The Obstetrician & Gynaecologist 10.1111/tog.12043 http://onlinetog.

org Editorial

Editorial
Welcome to the July issue of TOG. I think I should should prepare the reader for what might prove to be Editorial board

start by updating you all on some of the changes that a series of challenging consultations. Jason Waugh MRCOG
Royal Victoria Infirmary, Newcastle
are afoot. Some of you will have already taken part in So, moving on from something very rare to a Upon Tyne
a TOG readership survey as part of our attempts to slightly more common problem in obstetrics – that of Mohamed Abdel-Fattah MRCOG
fully understand your needs and expectations from postpartum psychosis (page 145). Okay, so 1 in 1000 University of Aberdeen, Aberdeen

TOG and see if there are any changes we need to isn’t that common but there is, as you will know, a Jo Anthony MA FRCOG
Northampton General Hospital NHS Trust
make to satisfy these. This review is ongoing with a massive over-representation of psychotic illness in (Chair of the RCOG Revalidation
view to it being complete by the end of 2013 when I maternal mortality and morbidity reports and this Committee)

can relay our conclusions. Meanwhile, the editorial comprehensive clinical review is a useful reminder to Kate Harding FRCOG
Guy’s and St Thomas’ NHS Foundation
team is already putting in place some innovative us all that 50% of these women present from the very Trust, London
changes that we hope will appeal to you all. low risk population. As such, I’ve already tested this Justin Konje FMCOG (Nig) FWACS MRCOG
I cannot start without firstly acknowledging the article on some of our midwifery teams who found University of Leicester, Leicester (CPD Editor)
Kate Langford MA MD FRCOG
enormous contribution to the editorial board from it really easy to read and have begun to disseminate Guy’s and St Thomas’ NHS Foundation
retiring members Kay McAllister and Gary Frishman. it further. Trust, London
As they move on to new challenges it allows me to In gynaecology I enjoyed the review on Nicola Mullin MFFP MRCOG
Countess of Chester Hospital NHS
welcome Kristen Matteson and Nicola Mullin to the ambulatory hysteroscopy (page 159) which I felt Foundation Trust, Chester
board. I hope they will enjoy their time and help to complemented the RCOG Green-top guideline David Parkin MD FRCOG
shape TOG’s development over the coming years. nicely. It is nice to see the issues of comorbidities and Aberdeen Royal Infirmary, Aberdeen
Our latest step forward is the introduction of general anaesthesia brought into context in relation Mark Roberts MD MRCOG
Royal Victoria Infirmary,
‘early view’ whereby we publish our reviews online to risk, as well as a recognition that even a technique Newcastle Upon Tyne
first ahead of the print journal. We are working hard as ‘routine’ as hysteroscopy still requires further Thomas Tang MD MRCOG
to publish all our review articles on early view by research to establish its role in some clinical Regional Fertility Centre, Royal Maternity
Hospital, Belfast
2014, which will considerably reduce the time from management protocols.
International advisory board
acceptance to publication. We are also strengthening On page 177, for a different slant on reproductive
the links with BJOG by commissioning CPD medicine and oncology, we have a review of the Ben CP Chan FRCOG
Private practice and Queen Mary Hospital,
questions from selected articles in BJOG and these literature exploring the association between Hong Kong
are available now to complement the CPD material infertility, its treatment and the subsequent risk of Ki-Hong Chang MD PhD
from TOG. malignancy for either the mother or her fetus. Ajou University School of Medicine, Korea
Peter L Dwyer FRANZCOG FRCOG CU
Again, thank you for all your feedback and please Add to this the reviews on the management of vault Mercy Hospital for Women, Melbourne,
keep it coming. The board looks at all suggestions prolapse (page 167), pelvic congestion syndrome Australia
related to either content or format so no thoughts are (page 151) and polycystic ovary syndrome and Amr El-Shalakany MSc MD FRCOG
Ain Shams University Maternity Hospital,
too small. hyperandrogenism (page 171), and I think TOG Cairo, Egypt
So what of the content this time? Our authors for really is delivering something for all yet again. Kristen A Matteson MD MPH
this issue are drawn from the worlds of physicians, Beyond the reviews and ethics papers in this issue, Brown Medical School, Providence, USA

scientists, obstetricians, gynaecologists and look out for the website reviews this month on page Henry Murray MRCOG
Australia
neonatologists. I would like to draw your attention to 208. They are all based on revalidation websites to
Dimitrios Koleskas MRCOG
the two Ethics papers towards the back of the issue help guide you to the appropriate resources for your Euroclinic, Athens, Greece
on pages 184 and 189 which we have paired together individual needs. Duru Shah MD FCPS FICS FICOG DGO DFP FICMCH
as they present contrasting, but not conflicting, views So keep submitting those abstracts and letters. Let Jaslok Hospital, Sir Hurkinsondas Hospital
and Breach Candy Research Centers, India
on a specific clinical problem. One article relates to me know what’s right as well as where we could do David Shaker FRCSEd FRCOG FRANZCOG
the care of women where their fetus has a lethal better and hopefully we can keep your CPD read as University of Queensland, Rockhampton
anomaly and the accompanying article covers the enjoyable and valuable as possible. Base Hospital and Mater Private Hospital,
Australia
current position in the UK in relation to organ Ian Symonds DM MRCOG FRANZCOG ILTM
donation from the fetus in these circumstances. John Hunter Hospital, New South Wales,
Australia
Whilst not a situation encountered on a daily basis, it
Dirk Timmerman MD PhD
could be the next woman through the antenatal clinic University Hospitals Leuven, Belgium
door for any practising obstetrician and these articles

Editor-in-Chief

Jason Waugh

ª 2013 Royal College of Obstetricians and Gynaecologists iii

 DOI: 10.1111/tog.12041 2013;15:145–50
The Obstetrician & Gynaecologist
Review
http://onlinetog.org

Postpartum psychosis
a b c,
Arianna Di Florio MD PhD, Sue Smith MBBCh MRCPsych, Ian Jones MRCPsych PhD *
a
Clinical Research Fellow, MRC Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Neurology, School
of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN, UK
b
Consultant Perinatal Psychiatrist, Cardiff Mother and Baby Unit, Cardiff and Vale University Health Board, Cardiff, UK
c
Reader in Perinatal Psychiatry, MRC Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Clinical
Neurosciences, School of Medicine, Cardiff University, Henry Wellcome Building for Biomedical Research, Academic Avenue, Heath Park, Cardiff
CF14 4XN, UK
*Correspondence: Ian Jones. Email: [email protected]

Accepted on 30 July 2012

Key content Learning objectives

 Postpartum psychosis is a severe mental illness with a dramatic  To recognise women at high risk for severe postpartum mental
onset shortly after childbirth. illness.
 All women should be screened antenatally for the known risk  To recognise and appreciate the severity of postpartum psychosis
factors. and the need for prompt assessment and treatment.
 Women with bipolar disorder have at least a 1 in 4 risk and need
Ethical issues
close contact and review during the perinatal period even if they  Who should ultimately make decisions about taking medications
are well.
 Prompt recognition of the illness and rapid institution of
in pregnancy – the clinician or the woman and her family?
 What advice should a woman at high risk of postpartum psychosis
treatment are of vital importance.
be given if she is considering pregnancy?
Keywords: postpartum psychosis / puerperal psychosis / mood
disorders / bipolar disorder

Please cite this paper as: Di Florio A, Smith S, Jones I. Postpartum psychosis. The Obstetrician & Gynaecologist 2013;15:145–50.

Introduction commonly takes the form of mania, severe depression, or a

mixed picture with features of both high and low mood. In
Postpartum mood disorders are of great clinical and public
addition, women show evidence of psychosis with delusions
health importance, with suicide a leading cause of maternal
and hallucinations common, and also will often demonstrate
death in the UK. They are commonly divided into three
marked confusion or perplexity.2
categories: the ‘baby blues’, postnatal depression, and
postpartum (or puerperal) psychosis. This review focuses
on postpartum psychosis (PP), emphasising the importance Classification
of recognising women at high risk, and the early recognition
and prompt treatment of women who develop the illness. There is little consensus regarding the classification of
According to the Confidential Enquiries into Maternal postpartum psychosis. Modern classification systems do not
Deaths in the United Kingdom report,1 a diagnosis of recognise PP as a separate nosological entity. In the
severe affective illness was present in about 60% of the International Classification of Diseases (ICD-10),4 the
women who committed suicide. Although suicide after category ‘mental and behavioural disorders associated with
childbirth is rare, affecting about 1 pregnancy in 100 000, the puerperium, not elsewhere classified’ should only be used
suicide remains a leading cause of maternal death. Suicide in when unavoidable and includes only mental disorders
a new mother is a great tragedy, and for each woman who commencing within 6 weeks of delivery that do not meet
takes her life there are many near misses.2 the criteria for other diagnoses. In the Diagnostic and
Statistical Manual of Mental Disorders, fourth edition
(DSM-IV)5 postpartum affective episodes are treated as
The concept of postpartum psychosis
mood disorders with a postpartum trigger: patients must
The term ‘postpartum psychosis’ refers to a severe mental meet the criteria for a mood episode and the criteria for the
illness with a dramatic onset shortly after childbirth.3 It most postnatal-onset specifier. In DSM-IV a postnatal onset is

ª 2013 Royal College of Obstetricians and Gynaecologists 145

 Postpartum psychosis

considered to be within 4 weeks of delivery. Despite these the main, explanation.16 Given that there is little evidence of an
issues, however, the term postpartum (puerperal) psychosis association between PP and psychosocial factors, the
has remained in common clinical use. possibility remains that the effect of primiparity is, at least in
part, due to biological differences between first and subsequent
pregnancies. In this regard, the overlap with other pregnancy
Epidemiology
related disorders that also occur more frequently in first
Record-linkage studies estimate the admission rates to pregnancies, such as pre-eclampsia, is of interest. Hormonal,
psychiatric hospital in the postpartum as about 1–2 per immunological and other biological differences between first
1000 births in the general population.6 However, the true and subsequent pregnancies are interesting targets for further
incidence rates for severe postpartum affective disorder may investigation into the aetiology of PP.16
be higher, as at least some women with PP are likely to be
treated at home – particularly if facilities for admission with Changes in medications
the baby are not available.3 Women with BD often come off mood stabilisers, such as
There is consistent evidence of a specific relationship lithium, preconception or in early pregnancy because of
between PP and bipolar disorder (BD). Women with BD concerns over toxicity to the fetus. A survival analysis
have at least a 1 in 4 risk of suffering a severe recurrence comparing women with BD who stopped taking lithium
following delivery.7 Bipolar women with a personal or family because of pregnancy compared with age-matched
history of PP are at particularly high risk with greater than non-pregnant women who discontinued lithium for other
1 in 2 deliveries affected by PP.8 reasons, reported similar rates of recurrence during the first
40 weeks after lithium discontinuation for both groups.
However, among subjects who remained stable over the first
Aetiology and pathophysiology
40 weeks after lithium discontinuation, postpartum
Most episodes of PP can be considered as affecting women recurrences were 2.9 times more frequent than recurrences
with a bipolar disorder diathesis acted on by a specific in non-pregnant women during weeks 41–64 (70% versus
puerperal trigger.3 A number of factors have been suggested 24%).17 Thus, the increased risk of recurrence following
that increase vulnerability to the puerperal triggering of childbirth for women with BD does not appear to be merely a
episodes of BD. result of stopping mood-stabilising medication.

Genetic factors Hormonal factors

There is robust evidence that the vulnerability to the The lack of evidence implicating psychosocial factors and
triggering of affective psychosis by childbirth aggregates in consideration of the abrupt onset during a time of major
families and may define a genetically relevant subtype of physiological change suggest that biological, possibly
bipolar disorder.8 Evidence from family studies suggests that hormonal, factors are important. The role of several
episodes of PP are a marker for a more familial form of BD9 hormones (including estrogen, progesterone, prolactin,
and that a specific vulnerability to the puerperal triggering of follicular stimulating hormone and luteinising hormone)
BD is familial.8 Evidence from a linkage study indicated the has been considered, but the evidence pointing to hormones
possible location of a susceptibility gene on chromosome in the aetiology of PP remains predominantly circumstantial.
16.10 Particular candidate genes, such as those involved in the
serotoninergic11,12 hormonal13,14 and inflammatory15 Sleep deprivation
pathways, have also been investigated. It is hoped that A plausible hypothesis is that the sleep deprivation of delivery
identifying the genetic factors that increase risk will lead to and the immediate postpartum period is responsible for
more individualised risk assessment, earlier identification of puerperal triggering of illness.18 Sleep loss can effectively
women at risk, and improved treatments for women who trigger the onset of mania in people with BD and sleep loss is,
become ill. of course, common for new mothers.

Obstetric risk factors

Prevention
An increased risk of PP has been reported with a number of
obstetric factors including: primiparity; pregnancy and Screening for risk factors
delivery complications; delivery by caesarean section; having In addition to a history of BD or PP, other risk factors for PP
a female baby; and a shorter gestation period. However, include having a first-degree relative who has experienced PP
findings are consistent only for primiparity.16 The bias that and having a first degree relative with BD.7 For women who
women with a severe postpartum episode may be less likely to themselves have a history of mood disorder, particularly on
go on to have further children is unlikely to be the sole, or even the bipolar spectrum, a family history of severe postpartum

146 ª 2013 Royal College of Obstetricians and Gynaecologists

 Di Florio et al.

episodes is very important and may indicate a risk in excess period should also be developed and discussed with the
of 50%. For women who have not suffered episodes of woman and her family.19
psychiatric illness themselves, it is not so clear that family
history is relevant. While a risk of PP of 1–3% in such women Pre-conception
represents a considerable increase on the population rate of The possibility of future pregnancy should be considered in
around 1–2 in 1000 deliveries, it is unclear whether extensive all women with BD who are of childbearing age. Ideally the
efforts to identify women who are well but with a family pre-conception counselling should be conducted by a
history is a worthwhile strategy. These women may benefit perinatal psychiatrist,20 however, depending on availability,
from the risks being discussed with them if it is something other psychiatric teams or GPs can provide the necessary
they have identified as a concern, but it also is possible that it information to woman. The risks of illness following
may cause unnecessary worry in women who will not go on childbirth should be discussed with women and the
to develop illness. importance of seeking help emphasised. Decisions about
Because of the relapsing and remitting nature of BD, continuing or stopping medications before, or during,
women at high risk are often currently well and not in pregnancy are difficult and should be the result of a
contact with mental health services and may fail to recognise detailed and individualised risk analysis.19 Although there
the serious risk of their situation. Thus, all women should be are significant concerns about the teratogenic effects of the
screened for known important risk factors at their antenatal medications used to treat BD, the risks of stopping
booking visit.1 Protocols should be put in place to ensure that medication must also be considered. Data suggest that
women at potential risk receive a formal risk assessment and women with BD who stopped medication during pregnancy
management plan.19,20 were more than twice as likely to experience a recurrence
Women with schizophrenia also have an increased risk of than those who remained on medication.24 Data on the
hospitalisation after childbirth. However, the specificity of teratogenicity of psychotropic agents are often controversial
the childbirth trigger in schizophrenia is still controversial.21 and an exhaustive discussion is beyond the scope of this
Women with schizophrenia have a four-fold lower relative review. Consistent evidence suggest that valproate should be
risk of admission in the postpartum period compared with avoided, because of the high risk of malformations,25 and
those with BD.22 In many cases, schizophrenia is a severe because of negative effects on neurodevelopment.26 On the
chronic illness and women are commonly admitted for contrary, a recent meta-analysis found no significant
assessment of parenting or to help them to cope with the association between any major congenital abnormality and
newborn rather than for the acute onset of a new episode.21 lithium.27 However, due to the wide confidence limits,
considerable uncertainty about the risk of lithium remains.
Management of women at high risk
Women at high risk of PP need very careful care before During pregnancy and after childbirth
conception, throughout pregnancy and during the postpartum Perhaps the most important aspect of care is to maintain
period. The high risk of illness in the weeks following delivery close contact and review during the perinatal period. Women
in a woman with a history of BD must be recognised both by at high risk, even if they are well, should be referred in
healthcare professionals and by the woman herself.19,20 pregnancy for psychiatric assessment and monitored
regularly for at least 3 months following delivery. The good
Ethical issues practice guidelines developed by Royal College of
The management of women at risk raises ethical questions on Obstetricians and Gynecologists20 suggest that the following
the role of the patient and her family in the decision-making scenarios are indications for referral to specialised perinatal
process. Ethical principles of patient-centred care provide the mental health services where available, otherwise general
foundation for the doctor–patient relationship: autonomy, psychiatry services:
justice, beneficence and nonmaleficence.23 The clinician
 current severe psychiatric symptom
should avoid paternalistic attitude, exploring and
 a history of serious postpartum illness or bipolar disorder
considering the values and the expectations of the patient
or schizophrenia
and leaving the final informed decision to the woman. If the
 on complex psychotropic medications schemes.
woman wishes, family members can be involved in the
decision making process. The NICE guidelines suggest to Moreover, the guidelines suggest that referral should be
discuss the teratogenic risk explaining the background risk of considered for those with moderate symptoms developed in late
fetal malformations in the general population (around 2–4%) pregnancy or early postpartum or mild symptoms and a family
and to describe the risk using natural frequencies rather than history of bipolar disorder or puerperal psychosis (COG).
percentages (for example, 1 in 10 rather than 10%).19 A Psychiatric services should have priority care pathways for
written plan covering pregnancy, delivery and the postnatal pregnant and postpartum women and care by multiple

ª 2013 Royal College of Obstetricians and Gynaecologists 147

 Postpartum psychosis

psychiatric teams should be avoided.1 Ideally, women should be  Exogenous toxic substances or hormones: History of
managed by multiprofessional/multidisciplinary teams, with a therapeutic use and/or abuse of known causative
named obstetrician (possibly with special interest in perinatal substances or hormones, other symptoms and signs
mental health), midwives, perinatal psychiatrist, community specific to the substance or substances involved should
psychiatric nurse, health visitors and GP. All communication be investigated. Urine drug screen may be positive in
between maternity and mental health services should include substance abuse and identifies the substance taken,
primary care. A written care plan should be developed in although it is not definitive for drug misuse.
collaboration with all relevant healthcare professionals and  Other psychiatric disorders of the puerperium: Baby blues
recorded in all versions of the woman’s notes.19,20 affects 30–80% of births and causes transient emotional
It may also be important to address other avoidable factors lability during the first postpartum week. The mother
that may increase risk – such as decreasing general levels of typically presents mood swings ranging from elation to
stress and paying attention to sleep in late pregnancy and the sadness, insomnia, tearfulness, crying spells, irritability,
early postpartum weeks. Liaison with maternity services anxiety, and decreased concentration. Care of the baby is not
should involve discussion about how to manage the labour to impaired, hopelessness and worthlessness are not
reduce the sleep deprivation that can occur if labour is prominent, and women do not feel suicidal. It is
prolonged. For women with a history of BD who have been self-limiting, but assessment should ensure that the
off medication in pregnancy the introduction of prophylactic woman is not and does not become more severely depressed.
medication in the immediate postpartum period should be  Postnatal depression (for a review see Musters et al.29).
considered. Some evidence exists for the use of lithium in this The tendency for all postpartum episodes to be labelled
context, but the few studies have been open and retrospective as postnatal depression can lead to suboptimal care and,
and there are practical problems with reaching therapeutic in some cases, have dramatic consequences on mothers
levels quickly to cover the period of risk. These issues have and babies.
led some perinatal psychiatrists to use typical or atypical
Any psychotic symptoms, particularly delusions or
antipsychotics as prophylaxis.3
hallucinations, substantially increase risk for both mother
and child. The woman should be referred for a same day
Diagnosis of postpartum psychosis (PP) emergency appointment so that a detailed risk assessment can
be carried out.
History and examination
Although all women should be assessed antenatally for
known risk factors, such as personal or family history of BD Management of women with postpartum
and psychosis, it is important to bear in mind that 50% or psychosis (PP)
more of women who develop PP have no history that puts
them in a high-risk group.3
Hospital admission
PP is a psychiatric emergency. The clinical picture may
The distinctive clinical features include sudden onset and
mislead, quickly become extremely severe and vary
rapid deterioration. The vast majority of episodes have their
significantly from hour to hour. Admission is usually
onset within 2 weeks of delivery, with over 50% of symptom
necessary, even for women with the most supportive of
onsets occurring on days 1–3.28 The clinical picture often
families. The NICE guidelines19 recommend that women
changes rapidly, with wide fluctuations in the intensity of
within a year of childbirth should be offered admission to a
symptoms and severe swings of mood. Common symptoms
specialist mother and baby unit, however, the provision of
and signs include:
services across the UK is patchy and for the majority of
 A wide variety of psychotic phenomena such as delusions
women there is no option of admission with her baby.3
and hallucinations, the content of which is often related to
the new child.
 Affective (mood) symptoms, both elation and depression. Pharmacological treatment
 Disturbance of consciousness marked by an apparent A range of psychotropic medication may need to be
confusion, bewilderment or perplexity. employed. The treatment used depends on a number of
factors, including the symptoms that the woman experiences,
her level of disturbance and her previous response to
Differential diagnosis medication. For many women the severity of the illness
 Primary cerebral or systemic disease (such as eclampsia or does not allow breastfeeding. If breastfeeding is being
infection) should be excluded. The misattribution to considered, factors in the baby such as prematurity and
psychiatric disorder has led to a number of deaths in systemic illness should be considered in addition to the
new mothers.1 particular properties of the medication itself. Limited data

148 ª 2013 Royal College of Obstetricians and Gynaecologists

 Di Florio et al.

suggest that the use of lithium during breastfeeding is not as assessment. PP is a true psychiatric emergency and it is vital
problematic as once thought30 but is usually avoided because that it is recognised early and treated aggressively.
of the risk of toxicity in the baby.
Disclosure of interests
Follow-up ADF, IRJ and SS report no conflict of interest.

Prognosis
The short-term prognosis for PP is generally good. However, References
women need to be counselled about the risks they run of a
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23 Kols AJ, Sherman JE, Piotrow PT. Ethical foundations of client-centered 31 Robertson E, Jones I, Haque S, Holder R, Craddock N. Risk of puerperal
care in family planning. J Womens Health. 1999;8:303–12. and non-puerperal recurrence of illness following bipolar affective
24 Viguera AC, Whitfield T, Baldessarini RJ, Newport DJ, Stowe Z, puerperal (post-partum) psychosis. Br J Psychiatry 2005;186:
Reminick A, et al. Risk of recurrence in women with bipolar disorder 258–9.

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 DOI: 10.1111/tog.12031 2013;15:151–7
The Obstetrician & Gynaecologist
Review
http://onlinetog.org

Pelvic congestion syndrome

Mohamed Waseem Osman MBChB,a,* Ilias Nikolopoulos MBBS MRCOG,a Kannamannadiar Jayaprakasan MD
b,c
MRCOG MBChB PhD, Nicholas Raine-Fenning MBChB, PhDd,e
a
Specialty Registrar, Obstetrics and Gynaecology, Queen’s Medical Centre Campus, Nottingham University Hospital, Derby Road, Nottingham NG7
2UH, UK
b
Subspecialist and Honorary Associate Professor in Reproductive Medicine and Surgery, University of Nottingham, Nottingham, UK
c
Consultant Gynaecologist, Royal Derby Hospital, Derby, UK
d
Reader, Reproductive Medicine and Surgery, Division of Obstetrics and Gynaecology, School of Clinical Sciences, University of Nottingham, Derby
Road, Nottingham NG7 2UH, UK
e
Director of Research / Senior Consultant, Nottingham University Research and Treatment Unit in Reproduction (NURTURE), Derby Road,
Nottingham NG7 2UH, UK
*Correspondence: Mohamed Waseem Osman. Email: [email protected]

Accepted on 9 January 2013

Key content  To be able to discuss various management options and choose a

 Pelvic congestion syndrome is a poorly understood condition definitive mode of treatment tailored to individual need.
that forms part of chronic pelvic pain syndrome – this makes up
Ethical issues
10–40% of gynaecological outpatient department referrals.
 Are we doing justice to patients if we as clinicians are not actually
 Pelvic congestion syndrome is thought to affect 3.8% of women of
aware of this common and significant condition?
childbearing age yet the clinicians evaluating these patients are  Due to current gynaecological investigations not being able to
usually unaware of the condition and a significant number of
diagnose this condition and general unawareness of the current
trainees are not up to date with the current diagnostic and
available diagnostic tests, should we not be more aware of all the
management options.
investigative modalities and the most appropriate ones for our
Learning objectives patients so that a more definitive diagnosis can be made?
 To learn about the pathophysiology and the risk factors.
Keywords: pelvic congestion syndrome / pelvic pain / pelvic
 To learn to recognise the condition.
varicosities
Please cite this paper as: Osman MW, Nikolopoulos I, Jayaprakasan K, Raine-Fenning N. Pelvic congestion syndrome. The Obstetrician & Gynaecologist 2013;
15:151–7.

Introduction pain was suggested by Cotte1,2 in women with ovarian

varicosities. This relationship was subsequently confirmed by
Chronic pelvic pain is a common gynaecological complaint Taylor et al.3 in 1949 and then Allen et al.4 in 1955. Although
and may account for as many as 10–40% of all gynaecology PCS is well described in the literature, its existence as a
visits.1 There are many potential causes of chronic pelvic clinical entity remains controversial as there is no reference
pain but in a significant proportion of cases there is no standard and therefore valid diagnostic tests.5 In addition,
identifiable pathology or finding that may or may not many women found to have dilated pelvic veins at
account for the discomfort described. Pelvic congestion laparoscopy or during ultrasound examination are
syndrome (PCS) is a condition of pelvic varicosities in asymptomatic and most women with chronic pelvic pain
women with unexplained pelvic pain where it has been do not have prominent venous vasculature.5 The prevalence
suggested as a cause of the chronic pelvic pain. However, is difficult to define given this confusion but PCS is thought
there is a great deal of debate as to its definition and to affect 3.8% of women of childbearing age.6 PCS is less
associated clinical features. common than a varicocele, which is the corresponding entity
in men, although this obviously reflects the ease of diagnosis
rather than the clinical sequelae. Modern imaging techniques
Background are more sensitive and more readily available and so
PCS was first described by Richet in 1857 and shortly prevalence may increase. Less radical management options
afterwards by Aran in 1858.1 It was not until the mid-1930s, are also available and appear to be promising in terms of
however, that an association between congestion and pelvic symptom control.

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 Pelvic congestion syndrome

testicles and ovaries share a very similar venous drainage

Aetiology
pattern by means of the left gonadal vein in the male and the
The aetiology of PCS is poorly understood but is thought to left ovarian vein in the female draining into the left renal vein
be multifactorial. Three promising theories for the and the right gonadal vein and right ovarian vein draining
pathophysiology of PCS have been accepted by the authors directly into the inferior vena cava. This similarity in these
and are elaborated on further. venous drainage systems would explain the presentation of
ovarian varicoceles in women and a corresponding entity in
Ovarian varicoceles males, testicular varicoceles.3
The cause of ovarian varicoceles involves both mechanical and
hormonal factors.7 Absence of ovarian vein valves is an
Prevalence
important factor in PCS development.8 Venous valves may be
absent in the cranial portion of the ovarian vein in up to 15% of The only reported study in the English literature evaluating
the cases on the left side and in up to 6% on the right side.9 the incidence of PCS reported a prevalence of 9.9% in women
While the combination of ovarian vein reflux and PCS is in the age range of 18–76 years where the median age of the
diagnosed most frequently in multiparous women,10 study group was 43 years.16 The majority of these women
congenital absence of venous valves, leading to retrograde (59%) were symptomatic.16 This may reflect the true
ovarian vein flow and primary venous reflux may explain the prevalence of PCS, however, one has to bear in mind that
development of PCS in nulliparous women. It has been shown there is controversy with regard to the diagnosis of PCS as
that ovarian varices are symptomatic in only 59% of patients.11 some clinicians are unwilling to acknowledge the existence of
This supports earlier suggestions that pelvic congestion PCS as a clinical entity.
syndrome is due to a combination of factors.3 The presence
of ovarian vein reflux alone does not lead to the diagnosis of
The pain pathway
PCS,10 however, venous reflux in the ovarian veins of patients
with chronic pelvic pain with no other identifiable cause of In PCS the venous engorgement results in stretching of
organic disease makes the diagnosis of PCS more likely. the intima of the ovarian vein. This leads to distortion of
the endothelial and smooth muscle cells within the vessel
Pregnancy and hormonal factors with the resultant release of vasoactive substances, including
Pregnancy is believed to be one of the major risk factors for substance P which is a neuropeptide and also neurokinins
PCS. During pregnancy, ovarian vein flow may increase up to A and B which are involved in inflammatory processes
60 times.12 This increase in blood flow causes ovarian vein and pain.17
dilatation11 and may result in venous valve incompetence.11,13
The relaxant effect of progesterone on the pelvic veins and the
Clinical features and presentation
pressure effect of the gravid uterus may further increase the
engorgement. The retrograde flow from the ovarian vein into There are a wide variety of symptoms that PCS may present
the internal iliac vein is more common on the left than the with and this may be a reason why PCS is not considered often
right because the left ovarian vein drains directly into the left enough as a differential diagnosis of chronic pelvic pain (CPP).
renal vein whereas the right ovarian vein drains at a sharp PCS commonly presents in premenopausal multiparous
angle into the inferior vena cava. The fact that PCS only affects women.7,17 The most common feature is pain, which may be
premenopausal women suggests a strong correlation between unilateral or bilateral, can be acute and severe or chronic and
PCS and ovarian activity.6 dull.17 Patients present with pelvic pain without evidence of
inflammatory disease.7 The pain is worse during the
Nutcracker syndrome premenstrual period and pregnancy, and is exacerbated by
Nutcracker syndrome occurs when the left renal vein is fatigue and standing.7 Pain can also increase after intercourse
compressed between the superior mesenteric artery and the and may lead to patient anxiety and relationship difficulties.7
aorta. A depiction was given by Chait et al.14 describing the The dyspareunia due to endometriosis is usually with deep
aorta as two arms of a ‘nutcracker’ that can compress the left penetration during intercourse, whereas the dyspareunia due
renal vein. This dramatic description prompted a Belgian to PCS is usually worsened by intercourse resulting in a
physician to name this phenomenon the nutcracker throbbing ache afterwards.
syndrome.15 The syndrome, more frequently associated Symptoms mimicking urinary tract infection are not
with a varicocele in men, may manifest as a dragging unusual; this is due to varicosities in the bladder trigone region.
sensation in the scrotum with a dull aching pain and This organic disease can further manifest with
abnormalities in semen parameters and haematuria, psychological symptoms such as depression and anxiety.
abnormal menstruation and left flank pain in women. The This is partly because of the protracted time taken in making

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 Osman et al.

a diagnosis as PCS is often at the latter end of the differential users or across one or more menstrual cycles. One has to
diagnoses. PCS remains an under-diagnosed cause of chronic question their reproducibility and therefore further studies
pelvic pain.7 It is thought that psychological stress could be are required.
worsened by the release of substances such as substance P and
neurokinins A and B as part of the pathophysiology of PCS.17
Two studies have shown a 41–56% association of PCS with
polycystic changes in the ovaries, however, the significance of
these changes remains unclear.18,19

Investigations
Radiological imaging is essential in the assessment of PCS
and is frequently used to confirm the clinical suspicion of this
condition. Non-invasive modalities are recommended as a
first-line investigation, however, the gold standard remains
selective venography.7

Non-invasive imaging
Figure 1. Sagittal section: anteverted uterus with normal power
Pelvic ultrasound Doppler of the myometrium and subendometrium
Pelvic ultrasound has been found to be a simple yet valuable
first-line investigating tool for PCS as it can easily eliminate
the possibility of any other major abdomino-pelvic masses
that may present with PCS-like symptoms.7 To date there
have been no randomised controlled trials of distinguishing
the efficacy of transvaginal or transabdominal ultrasound
versus that of ovarian vein venography.7 It has been suggested
that assessing the patient in the standing position may
reproduce the venous dilation but as this is not the easiest
technique it is often preferable to ask the patient to perform
the Valsalva manoeuvre.20 The ultrasound images in
Figures 1 and 2 demonstrate a normal uterus, myometrium
and subendometrium, whereas Figures 3, 4 and 5 reveal
distended and dilated venous plexuses, iliac vessels and
arcuate veins.
The most common ultrasound criteria used for evaluating Figure 2. Sagittal section: normal anteverted uterus
PCS in the literature are:18,21,22
 Tortuous pelvic veins with a diameter of greater than
6 mm. Mean diameter in PCS ~8 mm.
 Slow blood flow < 3 cm/second or reversed caudal flow in
the left ovarian vein demonstrated by Doppler waveforms.
 Dilated arcuate veins in the myometrium that
communicate between the bilateral pelvic varicose veins.
 Polycystic changes within the ovaries. Features ranged
from the typical polycystic ovaries appearance to the
presence of clusters of four to six cysts of 5–15 mm in
diameter in bilaterally enlarged ovaries. Women with
polycystic changes of their ovaries secondary to PCS were
not hirsute or amenorrheic.
Despite these suggestions, there is no consensus on the
diagnostic criteria for PCS. Different authors use one or
more of the criteria outlined above. Furthermore, the
variability in these measures has not been tested between Figure 3. Power Doppler showing distended iliac vessels

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 Pelvic congestion syndrome

and missed one case where the patient was actually

symptomatic and had an abnormal magnetic resonance
phase contrast velocity mapping study.23 If the facilities and
expertise are available, magnetic resonance phase-contrast
velocity mapping may be preferred to venography as the
former is non-invasive.23

Invasive imaging

Venography
Venography remains the definitive imaging modality used to
evaluate patients with PCS.7 The presence of one or more of
the following venographic appearances is said to be
suggestive of PCS:22
 ovarian vein diameter >10 mm
Figure 4. Transverse view: demonstrating dilated and distended
 uterine venous engorgement
parametrial plexus – note the distention is more pronounced on the  congestion of the ovarian plexus
left side  filling of the pelvic veins across the midline and/or filling
of the vulvovaginal thigh varicosities.
While venography can be performed through the jugular
or femoral vein, the former approach is suggested as the
preferred option if embolisation is to be performed at the
same time.17 The reproducibility of venography has also not
been adequately tested. These procedures are invasive, and
may, however, albeit infrequently, result in complications
such as contrast extravasation, venepuncture site haematoma
and vessel injury.
A retrospective study evaluating time resolved imaging of
contrast kinetics (TRICKS) magnetic resonance venography
(MRV) revealed promising results in diagnosing ovarian
vein reflux, vein dilation with obvious advantages over
transfemoral venography, ultrasonography, computed
tomography and magnetic resonance imaging, such as the
lack of ionising radiation or intervention and improved 3D
Figure 5. Longitudinal view: Power Doppler of the uterus and the volume images dynamically over multiple phases.24 The
pronounced distension of the arcuate veins posteriorly [Source: All
study had limitations and inherent weaknesses that were
images are sourced from Mr Raine-Fenning’s archives with his
permission.] recognised by the authors but they concluded that TRICKS
MRV accurately and dynamically demonstrated ovarian vein
Computed tomography and magnetic resonance imaging reflux in patients with PCS but requires quiet respiration.
Both computed tomography and magnetic resonance imaging
demonstrate tortuous, dilated and enhancing tubular Laparoscopy
structures near the ovaries and uterus due to the PCS Diagnostic laparoscopy may enable the surgeon to visualise
varices.7 These imaging modalities have their limitation due the engorgement directly, but may provide false negative
to the need for the patient to be imaged in the supine position. results due to the supine positioning and insufflation of
This may result in less severe cases being missed as the venous pressurised carbon dioxide into the peritoneum, resulting in
distension may reduce and not be demonstrated.17 possible venous decompression.21 The data are limited on
Magnetic resonance phase-contrast velocity mapping was diagnostic laparoscopy and evaluating PCS.
demonstrated to be a useful tool in diagnosing pelvic
congestion syndrome compared with venography.23 A
Management
prospective study from 2011 showed that phase-contrast
velocity mapping diagnosed eight cases of PCS correctly, A multidisciplinary team approach should be implemented.
compared with venography which correctly diagnosed seven The disciplines involved should include: gynaecology,

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 Osman et al.

gastroenterology, the pain team, psychology, inter- increase in venous tone, improvement in lymphatic drainage
ventional radiology and physiotherapy. The treatment and a reduction in capillary hyperpermeability and therefore
options can be categorised into medical, surgical and ameliorate venous stasis.27 Simsek et al.27 performed a cross-
endovascular interventions. design study where 10 women with PCS received Daflon
500 mg twice daily for 6 months and another 10 received a
Medical treatment vitamin placebo first, and then crossover of treatment
Non-steroidal anti-inflammatory drugs are an acceptable occurred for another 6 months. This study showed a
first-line management. They offer a short-term solution and statistically significant improvement in pelvic pain scores in
may provide some relief while the patient awaits further both groups without any side effects.27
investigations or a more permanent treatment. The above studies have shown that medical management of
Ovarian suppression has been postulated to be beneficial PCS can prove to be beneficial for women, however, there is
for the treatment of women suffering from PCS. It has been insufficient evidence regarding their long-term effectiveness
suggested that estrogen may have some venodilatory effects in controlling their debilitating symptoms. Specifically,
and therefore hypo-estrogenic states can result in symptom GnRH agonist may be used for 6 months (without add-
resolution.17 However, the studies are of small sizes therefore back hormone replacement therapy [HRT]) or up to 2 years
firm conclusions cannot be drawn from just these studies with add-back HRT to reduce the risk of osteoporosis.
in isolation. Therefore, the use of progestins should be further evaluated
Medroxyprogesterone acetate (MPA) has been shown to be as a long-term treatment option for PCS, taking into account
beneficial both subjectively in terms of pain perception and that bone density is slightly reduced during its usage. The
objectively by assessing pelvic congestion using venography. reduction in bone density appears to be reversible and is
In a study, 30 mg MPA for 6 months was used in 22 women probably of minor clinical significance in women in their
to suppress the ovarian function.21 In 17 out of 22 women a second and third decade, however, there are some concerns
reduction in pelvic congestion was demonstrated by about the reversibility of bone mineral density reduction in
venography and in 16 women this was associated with women in their early and later reproductive years.
induction of amenorrhoea, which suggests that effective
ovarian suppression is an important component of successful Surgical management
treatment. In the 17 women who showed a reduction in Historically, gynaecological treatment for PCS focused on
venogram score, the median change in pain score was 75% uterine malposition (retroversion or retroflexion), as it was
compared with only 29% in the five women with no change thought that it caused venous kinking, obstruction and stasis.
in venogram score (P < 0.01).21 In a randomised controlled Therefore, surgical ventrosuspension was the treatment of
trial,25 treatment with MPA was associated with a statistically choice for women with retroverted uterus. Nowadays this
significant improvement of visual analogue pain scores procedure has been abandoned as it has been shown to have
compared with placebo, with the pain score reducing by little benefit in managing the symptoms of women suffering
58% in the MPA group compared with 28% in the placebo with PCS.28
group (P < 0.01). In 1984, Rundqvist et al.29 proposed extraperitoneal
Gonadotrophin-releasing hormone (GnRH) agonists have resection of the left ovarian vein as an effective treatment
also been suggested for the treatment of PCS. In a for PCS achieving a 73% cure rate and a 78% overall
prospective randomised controlled trial,26 47 patients symptomatic improvement. Out of 15 patients, 8 were
diagnosed with PCS were treated with either goserelin completely cured and 3 were significantly improved whereas
(GnRH agonist) without add-back hormone replacement 4 women showed no improvement with a mean period of
therapy (HRT) or MPA for 6 months. Both treatments follow-up of 5.6 years.29 More recently, laparoscopic bilateral
showed subjective and objective improvement of PCS as well transperitoneal ligation of ovarian veins has been proposed
as reduction in anxiety levels and improvement in sexual with reports of complete remission of pain and absence of
satisfaction. However, at a 12-month follow-up after pelvic varicosities for 12 months after this treatment
completion of the treatment, a statistical comparison of modality.30 However, as both studies referred to above had
these agents confirmed a better outcome for goserelin.26 The a very small sample size, no firm conclusions can be drawn
main side effects of progestins were weight gain and bloating, regarding the effectiveness of these surgical techniques.
whereas the use of GnRH analogues was associated with A non-randomised single-centre study demonstrated that
menopausal symptoms. hysterectomy and bilateral oophorectomy with hormone
Recently, venoactive drugs like micronised purified replacement therapy was an effective treatment for PCS
flavonoid fraction (Daflon 500 mg) have been investigated chronic pelvic pain as 35 of 36 women had complete
for the treatment of PCS.27 They provide a protective and resolution of their pelvic pain post-surgery.31 In a
tonic effect on the venous and capillary wall, resulting in an randomised controlled trial by Chung et al. in 2003,31 106

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 Pelvic congestion syndrome

women with pelvic congestion syndrome who failed to show psychological propensities, such as fear, and enable patients
any improvement with MPA for 4–6 months were randomly to develop coping strategies. A randomised controlled trial
assigned into three treatment groups: ovarian vein comparing MPA alone, MPA and psychotherapy, placebo
embolisation; hysterectomy and bilateral salpingo- alone and placebo and psychotherapy for 4 months showed
oophorectomy and HRT; and hysterectomy and unilateral that the combined effect of MPA and psychotherapy for the
salpingo-oophrectomy of the ovary with evidence of varices. treatment of PCS was superior, achieving a greater than 50%
The study showed statistically significant reduction in pain reduction in pain score that lasted for 9 months after the
scores after embolotherapy and hysterectomy with bilateral completion of treatment.25
salpingo-oophorectomy but not after unilateral ooph-
orectomy. Unfortunately, there are no studies that compare
the effectiveness of surgical management in women with pelvic Conclusion
congestion syndrome against medical management with
GNRH agonist. PCS remains a controversial clinical entity. It is an
unfamiliar condition to many clinicians and is seldom
Endovascular treatment considered in the differential diagnosis of the causes of
Transcatheter embolotherapy as a treatment for PCS was chronic pelvic pain in women. This probably reflects the lack
initially described in 1993.31 Ovarian and pelvic veins can be of consistent diagnostic criteria and acceptable, non-invasive
approached from a jugular or femoral vein and the tests. There are several hypotheses regarding the aetiology of
embolisation can be performed with different agents such PCS, which include ovarian varicoceles, hormonal factors
as steel coils, sclerosants (purified pork skin gelatine, sodium and structural factors including pregnancy and the
morrhuate) or glue. There are no published randomised nutcracker syndrome. The presence of the above
controlled trials comparing the different embolisation mentioned factors does not infer that a woman will have
techniques, however, a few prospective studies have been dilated pelvic vessels or the associated symptoms of PCS.
identified that demonstrate the various embolisation New diagnostic criteria need to be established and their
techniques and assess their effectiveness on pelvic pain.32–35 reproducibility and validity tested in accordance with
The results of these studies show significant improvement in guidelines for any test accuracy study.
pain ranging from 58% to 83%. The method of assessment of The management of PCS is also uncertain. Various medical
post-procedure symptoms was different in each study, and surgical options are available but a biopsychosocial
varying from clinical assessments to questionnaires and approach is paramount. A medical approach should be
pain-score scales. Therefore, no firm conclusions could be offered initially, reserving surgery for resistant cases and
drawn from them. those intolerant of side effects. Endovascular management
Overall endovascular management has been demonstrated with percutaneous embolisation of the ovarian/internal iliac
to be superior to the surgical option of hysterectomy and vein varicosities may prove to be the preferred treatment
bilateral oophorectomy.36 For symptom amelioration, it is option as it is minimally invasive and is associated with fewer
unclear whether embolisation should be performed only on complications than surgical management. The evidence base
the refluxing veins, on both ovarian veins, or on both the for the treatment of PCS is poor, however, and well-designed
ovarian and internal iliac veins. It is therefore apparent that randomised controlled trials are required. These require a
there is a need for well-designed randomised controlled trials revision of the diagnostic criteria as outlined above but also
to consistently assess the effectiveness of each technique. an awareness of the condition. Without these developments
The main complications that have been reported with PCS is likely to remain an enigma and women may be denied
transcatheter embolisation include coil migration that can be optimal diagnosis and treatment.
retrieved without any sequelae, ovarian vein perforation and
venupucture-site haematomas that can cause pain, and both Disclosure of interests
may be treated symptomatically.37 No significant changes None declared.
were noted in hormone levels or menstrual cycle after
embolotherapy and successful pregnancies following
treatment have also been reported.34,37 References
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21 Beard RW, Franks S, Reginald PW. Medroxyprogesterone acetate in the 37 Edward RD, Robertson IR, MacLean AB, Hemingway AP. Pelvic pain
treatment of pelvic pain due to venous congestion. Br J Obstet syndrome: successful treatment of a case by ovarian vein
Gynaecol 1989;96:1148–52. embolization. Clin Radiol 1993;47:429–31.

ª 2013 Royal College of Obstetricians and Gynaecologists 157

 DOI: 10.1111/tog.12039 2013;15:159–66
The Obstetrician & Gynaecologist
Review
http://onlinetog.org

Ambulatory hysteroscopy
a b,
Natalie AM Cooper MBChB, T Justin Clark MD, MRCOG *
a
Obstetrics and Gynaecology Specialty Trainee, Birmingham Women’s Hospital, Mindelsohn Way, Edgbaston, Birmingham B15 2TG, UK
b
Consultant Obstetrician and Gynaecologist and Honorary Reader, Birmingham Women’s Hospital, Mindelsohn Way, Edgbaston, Birmingham B15
2TG, UK
*Correspondence: T. Justin Clark. Email: [email protected]

Accepted on 15 February 2013

Key content hysteroscopy and facilitates operative procedures by improving

 Routine diagnostic hysteroscopy under general anaesthesia is an manipulation of miniature endoscopic equipment.
anachronism.  A contemporary outpatient hysteroscopy service should be able to
 Evidence-based RCOG guidance should be followed to ensure best provide surgical treatments for uterine polyps, small fibroids, lost
practice in outpatient hysteroscopy. coils, minor uterine anomalies, menstrual disorders and
 The role of hysteroscopy in the diagnostic work-up of abnormal permanent contraception.
bleeding and reproduction remains unclear and further research is
Ethical issues
required to elucidate where it can be used most cost-effectively.  Can we justify subjecting women, especially those with significant
Learning objectives medical co-morbidities, to the risks and inconvenience of general
 A ‘no touch’ vaginoscopic technique should be employed routinely anaesthesia for hysteroscopic procedures?
as this approach reduces pain during diagnostic rigid outpatient
Keywords: hysteroscopy / one-stop / outpatients / ‘see and treat’

Please cite this paper as: Cooper NAM, Clark TJ. Ambulatory hysteroscopy. The Obstetrician & Gynaecologist 2013;15:159–66.

proficient manner. As a result, the philosophy of efficient,

Introduction
safe and convenient ‘see and treat’, ‘one stop’ gynaecology in
Direct visualisation of the vagina, cervix and uterine cavity an ambulatory setting – the patient ‘ambulates’ in and
with the aid of an endoscope does not just facilitate diagnosis ‘ambulates’ out – has come of age.
of disease, but also provides therapeutic possibilities, either We will discuss in this article the advances in outpatient
directly (‘hysteroscopic surgery’) or indirectly (directing hysteroscopy, taking account of the evidence to support
‘blind procedures’ including global endometrial ablation). interventions and recent best practice guidance.
Such interventions were traditionally the domain of hospital
day-case wards with procedures performed under general
anaesthesia. This is no longer the case. The advent of small
Conducting outpatient hysteroscopy
diameter modern hysteroscopes (≤5.5 mm), allied with the A joint British Society for Gynaecological Endoscopy/ Royal
miniature 5–7 Fr ancillary instruments (mechanical College of Obstetricians and Gynaecologists (BSGE/RCOG)
instruments: scissors; graspers; biopsy cups; bipolar Green-top guideline addressing best practice in outpatient
electrodes, e.g. VersapointTM [Gynecare, Ethicon Inc., Menlo hysteroscopy has been recently published.1 The aim of the
Park, CA, USA]; morcellators: TRUCLEARTM[Smith & guideline is to provide clinicians with up-to-date, evidence-
Nephew Inc., Andover, MA, USA], MyoSure® [Hologic, based information regarding outpatient hysteroscopy, with
Marlborough, MA, USA]; and female sterilisation systems: particular reference to minimising pain and optimising
Essure® [Conceptus Inc., Mountain View, CA, USA]) has led women’s experience. Thus, by standardising best practice
the paradigm shift of surgical interventions being undertaken and identifying areas where evidence is lacking, we can hope
in an ‘inpatient’ general anaesthetic setting to an ‘outpatient’ to optimise both current and future patient experience. Box
environment with recourse to local anaesthesia if necessary. 1 summarises the key recommendations for best practice in
Thus, the modern gynaecologist is not restricted to efficient outpatient hysteroscopy and Box 2 summarises the key
outpatient diagnosis using hysteroscopy, transvaginal points of ‘no touch’ vaginoscopic hysteroscopy which
ultrasound and endometrial biopsy, but can institute should be the default technique in an outpatient
minimally invasive therapeutic interventions in an equally environment.2–4

ª 2013 Royal College of Obstetricians and Gynaecologists 159

 Ambulatory hysteroscopy

Box 1. Summary of recommendations for best practice in outpatient Box 2. Vaginoscopic ‘no-touch’ technique
hysteroscopy
The technique
1. All gynaecology units should provide a dedicated outpatient 1. Place the hysteroscope into the vagina and allow the distension
hysteroscopy service which is appropriately sized, equipped and media to flow in and distend the vagina.
staffed and located outside of the formal operating theatre 2. Advance the scope towards the posterior fornix and look for the
setting. The healthcare professional(s) should have the necessary cervix. If not immediately visible, work slowly backwards from the
skills and expertise to carry out diagnostic and/or therapeutic vault, angling the hysteroscope upwards as you go (most uteri are
outpatient hysteroscopy. anteverted) and sweeping side to side until you identify the cervix
2. Written patient information should be provided before the and find the external os.
appointment and consent for the procedure should be taken. 3. Steer the hysteroscope into the cervical os, along the canal and into
3. Women without contraindications should be advised to consider the uterine cavity under direct vision.
taking standard doses of NSAIDs 1 hour before their appointment, 4. Directed biopsies can be taken using a biopsy cup via the operating
but routine use of opiate analgesia should be avoided. channel of a rigid hysteroscope, or an H Pipelle can be used to take
a global biopsy through the hysteroscopic sheath.2,3
4. Routine cervical preparation before outpatient hysteroscopy
should not be used unless dilatation beyond Hegar 6 is
Tips to help identify the cervix vaginoscopically
anticipated.
 Mucus, blood or coil threads training from the cervical os can be
5. Miniature hysteroscopic systems (≤4 mm outer diameter) should be
followed to locate the cervix.
used for diagnostic outpatient hysteroscopy. Choice of
 A 30° angled hysteroscope makes it easier to identify the cervix.
hysteroscope (e.g. flexible or rigid; 0° or fore-oblique distal lenses)
should be left to the discretion of the operator.  If the cervix is difficult to locate consider eccentric placement, a
6. Carbon dioxide or normal saline can be used as distension media deficient cervix flush with the vault, an acutely retroverted uterus
for diagnostic outpatient hysteroscopy, but normal saline should with an anterior placed cervical os, or uterine prolapse with the
be used for operative procedures. cervix sited close to the introitus.
7. Routine, blind cervical dilatation should be avoided.  If you still cannot identify the cervix, perform a digital examination
to determine its position within the vagina.
8. Topical application of local anaesthetic to the ectocervix should be
considered where a cervical tenaculum is necessary. Routine
Advantages
administration of intracervical or paracervical local anaesthetic
 Vaginoscopy is significantly more comfortable for the patient than a
should be used where larger diameter hysteroscopes are being
hysteroscopy using a speculum, tenaculum and local anaesthesia
employed (outer diameter >5 mm) and where the need for
and it does not increase the number of failed procedures.4
cervical dilatation is anticipated (e.g. cervical stenosis). Standard
protocols regarding the type, maximum dosage and route of  It offers greater manoeuvrability for the operator as they are not
administration of anaesthesia should be implemented. restricted by the speculum. This is particularly useful when women
have a raised body mass index, acutely flexed uteri or when close
9. Conscious sedation should not be routinely used in outpatient
approximation of the hysteroscope to focal pathologies or access
hysteroscopic procedures.
the tubal ostia for sterilisation is required.
10. Vaginoscopy (avoiding the use of a vaginal speculum or cervical
instrumentation) should be the standard technique for outpatient  Vaginoscopy makes it possible to examine women who will not
hysteroscopy. tolerate a vaginal or speculum examination or who have medical co-
morbidities that prevent adequate positioning and vaginal access,
Source: RCOG/BSGE ‘Green-top guideline’ [http://www.rcog.org. thereby precluding endometrial assessment with endometrial
uk/files/rcog-corp/GTG59Hysteroscopy.pdf] biopsy.

Indications for diagnostic outpatient

biopsy and OPH is questionable and this is borne out in the
hysteroscopy
management algorithm produced by the National Institute
The main indications for diagnostic hysteroscopy are shown for Health and Clinical Excellence (NICE).6 However, women
in Box 3. The place of outpatient hysteroscopy (OPH) as a with HMB can have endometrial hyperplasia, submucous
third-line test after transvaginal ultrasound (TVU) and fibroids of various grades and sizes, uterine polyps, uterine
endometrial biopsy in the diagnostic work-up of women anomalies including uterine fibroids and adenomyosis and
with postmenopausal bleeding (PMB) is relatively well benign adnexal masses. Non-diagnosis of these pathologies
defined.5 However, for the most part, whereas there are prevents implementation of the many effective medical and
synergies between the available tests, there is also some surgical treatments for HMB and is therefore likely to result in
crossover in the information provided. For example, the place prolonged suffering, reduced health-related quality of life and
of OPH relative to TVU, endometrial biopsy and saline absenteeism from work with costs to the economy. Current
infusion sonography in heavy menstrual bleeding (HMB) and research involving decision analytical modelling hopes to
non-menstrual bleeding is unclear. By contrast with a PMB provide us with some answers as to which testing strategies are
population, women with HMB do not have a ‘normal’ the most cost-effective in HMB.7
endometrial thickness and the risk of endometrial cancer or Before leaving diagnostic indications, it is worth
atypia is low. Thus, the utility of routine TVU, endometrial considering the wider place of OPH in the management of

160 ª 2013 Royal College of Obstetricians and Gynaecologists

 Cooper and Clark

symptomatic relief. Thus, the woman can make a more

Box 3. Indications for diagnostic outpatient hysteroscopya
informed decision as to whether to opt for conservative
Abnormal uterine bleeding hysteroscopic surgery or proceed to hysterectomy.
 Postmenopausal bleeding with an endometrial thickness >4 mm or
irregular endometrium on TVU or a non-diagnostic endometrial
biopsy or on tamoxifen Operative hysteroscopy
 Recurrent postmenopausal bleeding
Polyps
 Unscheduled/intermenstrual bleeding with an abnormal
endometrium on TVU or refractory to medical treatment
The removal of uterine polyps appears to confer benefit in
 Heavy menstrual bleeding with fibroids or an abnormal endometrium
terms of resolving symptoms and obtaining tissue for
on TVU or refractory to medical treatment histological examination.8–11 Technological advances in
 Postpartum bleeding with suspected chronic retained products of imaging have resulted in better image quality, portability and
conception or arteriovenous malformation on TVU accessibility, improving the detection rate of focal uterine
pathologies. Improvements in hysteroscope design and
Reproductive problemsb
 Subfertility associated with an abnormal ultrasound or
ancillary instrumentation coupled with enhanced
hysterosalpingogram visualisation, due to improvements in fibre optics and digital
 Late miscarriage/preterm labour imaging, have enabled polyps to be removed under direct
hysteroscopic vision in an outpatient setting. Mechanical
Other instruments designed to pass down 5 and 7 Fr operating
 Glandular abnormalities on cervical smear
channels have been used successfully,12 but their utility is
 Identification (and retrieval) of lost intrauterine devices
affected by their size and relative fragility. In the late 1990s the
 Incidental finding of an abnormal uterine cavity on TVU (mass, fluid
development of bipolar intrauterine electrosurgical systems
etc.)
(e.g. VersapointTM bipolar electrosurgical system) facilitated
a
Hysteroscopy is only indicated under general or regional anaesthesia rapid resection of focal uterine lesions in a saline conducting
as day-cases where the outpatient setting has failed and the indication
remains sufficiently strong (i.e. benefits of diagnostic information
medium.13,14 It soon became clear that these rapid and versatile
outweigh potential risks); patient preference; virginal women and some electrosurgical approaches offered a wider repertoire of office
cardiac conditions where normal responses to vaso-vagal reactions are treatments including treatment for fibroids, adhesions and
blunted uterine anomalies in addition to endometrial polyps15 and
b
The role of hysteroscopy in investigating reproductive problems such
as subfertility or recurrent pregnancy loss is contentious. There is some have superseded mechanical approaches (Figure 1).
evidence from small RCTs that the use of hysteroscopy prior to in vitro Polyps within the uterus can be fibrous or glandular,
fertilisation cycles in women with previously failed cycles of treatment pedunculated or sessile, single or multiple and vary in size
may improve pregnancy rates by up to 60%. The European multicentre
from small with minimal uterine cavity distortion to large,
‘Trophy’ RCT5 is currently evaluating whether outpatient hysteroscopy
does indeed confer an advantage, although the reasons why it might filling the whole cavity. Location within the cavity can be a
remain unclear challenge especially fundally (due to difficulty accessing the
base) or isthmically (due to restrictions of movement) sited
lesions. Miniature hysteroscopic morcellators, which require
menstrual disorders, aiding safe intrauterine instrumentation a specific hysteroscope with an offset eyepiece, are the latest
(e.g. endometrial biopsy, levonorgestrel intrauterine system technologies to be introduced, e.g. TRUCLEARTM (Figure 2)
[LNG-IUS] insertion) and treatment planning. The latter role and MyoSure®. They can be used in the outpatient setting to
of OPH is often overlooked. For example, OPH may be simultaneously remove and retrieve polyps and submucous
useful in estimating the likely response of symptoms to fibroids16 and appear to be especially useful in removing
minimally invasive treatments with LNG-IUS and larger, fundally sited and multiple pathologies. Concerns over
endometrial ablation, based upon a hysteroscopic inability to establish histopathological diagnoses from
assessment of the endometrium, uterine size, capacity, morcellated specimens appear to be unfounded.17 The
shape and regularity. The test can also help determine the techniques available for outpatient uterine polypectomy are
most appropriate treatment setting (i.e. outpatient versus summarised in Table 1.
day-case under general anaesthesia), based upon patients’ The current literature on these outpatient hysteroscopic
tolerance of the procedure and any adverse anatomical techniques has demonstrated safety and feasibility, but evidence
factors. Similarly, in the case of submucous fibroid(s), OPH of effectiveness, patient acceptability and cost-effectiveness is
in conjunction with TVU allows an assessment of treatment lacking.14,18–20 A multicentre randomised controlled trial
setting and need for endometrial preparation based upon the (RCT) has randomised more than 500 women either to
size, vascularity, number and location. It aids patient outpatient with or without local anaesthesia treatment or to
counselling as to the likelihood of needing repeated day-case removal under general anaesthesia to compare
surgeries (2/3 stage resections) and the probability of effectiveness, cost-effectiveness and acceptability between

ª 2013 Royal College of Obstetricians and Gynaecologists 161

 Ambulatory hysteroscopy

(a) (b) (c)

Figure 1. VersapointTM (Gynecare, Ethicon Inc., Menlo Park, CA, USA) bipolar electrosurgery system: generator, foot pedals (a), spring (b) and
twizzle tipped electrodes (c). The chosen electrode is used down the 5 Fr working channel of a 5–5.5 mm rigid 30° continuous flow hysteroscope
or with the specifically designed alphascope (Gynecare, Ethicon Inc., Menlo Park, CA, USA) with a total outer diameter of less than 5 mm. All
images reproduced with permission from Ethicon Inc.

treatment settings.21 These patients, as well as 400 non- associated advantages of better visualisation with improved
randomised additional women who expressed a definite illumination and efficient continuous flow systems as well as
preference for treatment setting, will also allow effectiveness easier removal of treated fibroid tissue. However, it is not
and acceptability of treatments to be compared according to uncommon for failed removal of polyps under general
type of abnormal bleeding, menopausal status and treatment anaesthetic by curettage to be subsequently removed in the
technique. In time, therefore, we should have more idea as to outpatient setting by excising these misdiagnosed grade 0
how best to treat uterine polyps and whom we should treat. fibroids using bipolar electrosurgery.22 Smaller, sessile
fibroids can also be ablated in the office setting. Even if, for
Fibroids most submucous fibroids, larger diameter resectoscopes are
Submucous fibroids are commonly found in association optimal, outpatient hysteroscopic assessment is key; it allows
with menstrual and reproductive problems. Can we remove an assessment of treatment setting and need for endometrial
them hysteroscopically both safely and in entirety or do we preparation, based upon the size, vascularity, number and
offer repeat treatments? Do we need to prepare the location of myomas, to be assessed. The role of preliminary
endometrium with associated cost and morbidity? Do we incision of the ‘capsule’ of mucosa overlying the submucous
need to remove the ‘whole’ fibroid or just ‘normalise’ the fibroid precipitating expulsion of the fibroid into the uterine
contour of the uterine cavity (allowing any residual fibroid cavity (e.g. changing a grade 1 to a grade 0 submucous
to spontaneously extrude) reducing risk of inadvertent fibroid,23 thereby ‘preparing’ the fibroid for subsequent
uterine perforation and visceral injury? Appropriate resection under general anaesthesia, is unclear.
diagnostic work-up and consideration of patient views are
key to choosing how best to approach the management of Adhesions, septae and hypoplastic uteri
uterine fibroids. Hysteroscopic adhesiolysis can be achieved with scissors or
The removal of most intracavity fibroids requires general VersapointTM diathermy in an outpatient setting where scar
anaesthetic and often larger diameter hysteroscopes with their tissue is filmy and cavity distortion minimal.24 However,
published data are lacking for the safety and feasibility of
plastic operations on the uterus in an outpatient, local
(a)
anaesthetic setting.

Endometrial ablation
The development of ‘second-generation’ miniature, semi-
automated ablative technologies has allowed the concept of
outpatient local anaesthetic endometrial ablation to be
(b)
progressed. In the few centres able to offer both treatment
environments, outpatient local anaesthetic ablation is as
popular as traditional day-case general anaesthetic settings.25
Figure 2. The TRUCLEARTM hysteroscopic morcellator (a; Smith & Several observational studies have addressed the feasibility of
Nephew Inc., Andover, MA, USA): Hysteroscope showing off-set
outpatient local anaesthetic ablation for various technologies:
eyepiece and morcellator (b). The mechanical morcellator is attached
to external suction allowing simultaneous cutting and tissue HydroThermAblator System® (Boston Scientific Corp.,
extraction. All images reproduced with permission from Smith & Natick, MA, USA),26 Thermachoice® Endometrial Ablation
Nephew Inc. (TEA; Gynecare Inc., Somerville, NJ, USA),27,28 Thermablate

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ª 2013 Royal College of Obstetricians and Gynaecologists

Table 1. Techniques for outpatient hysteroscopic polypectomy

Comment

Technique and instruments Removal Retrieval Advantage Disadvantage

Blind
Mechanical (ring polyp Blind avulsion Simultaneous Cheap: does not require sophisticated instrumentation; suitable Painful; requires LA and cervical dilatation; risks
forceps/curette) for large, pedunculated, fundal lesions uterine perforation and failure to locate the
pathology
Hybrid
Hysteroscopic forceps + Hysteroscopic Blind location Useful for removing large, fibrous polyps and where there is Requires LA and cervical dilatation
ring polyp forceps or avulsion a narrow internal cervical os
curette
Hysteroscopic scissors + Hysteroscopic Blind location Useful for where there is a narrow internal cervical os Requires LA and cervical dilatation. Manipulating
ring polyp forceps or excision scissors difficult at uterine cornu and with larger,
curette fibrous lesions. Bleeding may obscure view
Hysteroscopic bipolar Hysteroscopic Blind location Useful for removing large, fibrous polyps and where there is a Requires LA and cervical dilatation. Disposable
electrosurgery + ring excision narrow internal cervical os electrodes more expensive than reusable mechanical
polyp forceps or curette instruments
Hysteroscopic
Hysteroscopic forceps or Hysteroscopic Simultaneous Quick, avoids LA, allows vaginoscopic approach. Costs minimal Not always possible to remove larger, fibrous polyps
polyp snare excision hysteroscopic especially with graspers alone through a narrow cervical os. Bleeding may
retrieval obscure view
Hysteroscopic scissors + Hysteroscopic Hysteroscopic Quick, avoids LA, allows vaginoscopic approach. Costs minimal Not always possible to remove larger, fibrous polyps
forceps or polyp snare excision retrieval especially with graspers alone through a narrow cervical os. Manipulating scissors
difficult at uterine cornu. Bleeding may obscure
view
Hysteroscopic bipolar Hysteroscopic Hysteroscopic Quick, avoids LA, allows vaginoscopic approach. Rapid, bloodless Not always possible to remove larger, fibrous polyps
electrosurgery + forceps excision retrieval and suitable for fibrous as well as glandular, vascular lesions through a narrow cervical os. Costs of disposable
or polyp snare electrode
Hysteroscopic polyp snare Hysteroscopic Simultaneous Avoids LA, allows vaginoscopic approach. Suitable for fibrous as Snaring larger lesions en bloc can be difficult. Needs
 monopolar current avulsion/ hysteroscopic well as glandular lesions return electrode plate + non-conducting fluid
excision retrieval medium if monopolar energy applied. Costs of
disposable snare
Hysteroscopic morcellator Hysteroscopic Simultaneous Avoids LA, allows vaginoscopic approach. Suitable for all types of Needs its own specific hysteroscope with an offset
morcellation hysteroscopic polyp including fundal large fibrous and pedunculated polyp eyepiece. Costs of disposable morcellator
retrieval and multiple lesions

LA = local anaesthesia

Cooper and Clark

The choice of approach depends in part upon the availability of equipment but also is dictated by the size, number, type and location of the focal pathology
163
 Ambulatory hysteroscopy

EASTM (Idoman Ltd, Dublin, Ireland),29 NovaSure® bipolar catheter which is passed down the 5 Fr operating channel of a
system (RFA) (Hologic, Marlborough, MA, USA).30 There are 30° 5–5.5 mm continuous flow rigid hysteroscope. The
also some RCTs comparing outpatient local anaesthetic procedure can be performed in the majority of women
ablation with day-case inpatient general anaesthetic settings: vaginoscopically using normal saline distension, without
TEA31 and Microwave Endometrial Ablation (MEA) system local anaesthesia and is completed in 5–10 minutes. The
(Microsulis Medical Ltd, Hampshire, UK).32 For the first time majority of women are discharged home within 1 hour.36
an RCT has been conducted and published directly comparing Occlusion of the narrow tubal lumen takes up to 3 months as
two of the leading second generation ablative technologies in the polyester fibres cause an inflammatory reaction with
this ‘novel’ outpatient local anaesthetic setting.33 The ‘COAT’ tissue ingrowth into the micro-insert and subsequent
trial showed that both thermal balloon ablation using the TEA blockage of the fallopian tube. Confirmatory radiology is
and radiofrequency impedance-controlled endometrial scheduled at 3 months to confirm the adequacy of
ablation using the RFA system were safe, acceptable and sterilisation; satisfactory device placement is checked by
effective in this setting. The RFA procedure was significantly abdominal X-ray or transvaginal ultrasound scan in the 85%
quicker, but no conclusive differences in pain or acceptability of procedures considered straightforward, and the remainder
were identified between technologies. Rates of amenorrhoea undergo more invasive hysterosalpingogram to confirm tubal
were higher with RFA at all time points post-surgery compared occlusion.37 In the last decade since its introduction, the
with TEA, but these differences only reached statistical feasibility,36,38 as well as the qualitative39 and economic40,41
significance at 12 months in favour of RFA. There were no benefits, of hysteroscopic sterilisation using the Essure®
differences in health-related quality of life between treatment system have been widely demonstrated. Women must be
modalities but it was significantly improved following both informed to continue using additional contraception until
treatments. Only one woman in each treatment arm had the results of radiological testing are available.
undergone a hysterectomy at 12 months. Successful bilateral device placement rates vary but are
Whereas the majority of women undergoing the outpatient consistently >90% and in many centres >95%36,41–43 for
ablation would recommend it to a woman with a similar techniques. No pregnancies have been reported from the
problem (82%), 13% of women found the procedure
unacceptable.33 We need to define more clearly the women (a)
most likely to have a positive and effective outpatient
experience. In addition to selecting the ‘right’ patients, we
need also to concentrate our efforts on reducing procedure-
related pain by manipulating analgesic, anaesthetic (topical,
intracervical and delayed paracervical blocks) and sedative
regimens.24 The use of intramyometrial injection of local
anaesthesia under direct hysteroscopic guidance in the
outpatient setting has been recently advocated, the so-called
‘focal–local’.34

Hysteroscopic sterilisation
Outpatient hysteroscopic sterilisation offers women long-
term, non-hormonal, effective, irreversible contraception
without the need for surgical incisions or anaesthesia,
thereby avoiding the small but significant risks of day-case,
laparoscopic surgery.35 Although it has long been recognised
that the transcervical route to occluding the tubal ostia offers
many potential advantages, it is only relatively recently that a
technique has become established in clinical practice. The
Essure® permanent birth control system is now widely used
(b)
across Europe, North America and Australasia with more
than 500 000 procedures being performed (Figure 3). The
procedure involves placing a micro-insert, consisting of a
Figure 3. The Essure (Conceptus Inc., Mountain View, CA, USA)
stainless steel inner coil with polyester fibres and a super- hysteroscopic sterilisation system: Hand piece, delivery system (a) and
elastic nitinol outer anchoring coil, into the intramyometrial micro-insert (b). All images reproduced with permission from
portion of each fallopian tube. This is done via a fine delivery Conceptus Inc.

164 ª 2013 Royal College of Obstetricians and Gynaecologists

 Cooper and Clark

original pivotal trial of Essure®43 and the effectiveness of the honoraria for lecturing from Nordic Pharma. He has received
Essure® system is reported to be better than laparoscopic trial funding from Hologic and is currently a member of their
sterilisation44 with 5-year success rate of 99.7% from the European Advisory Board. He has received funding for travel
literature45 supported by data from commercial use (748 and accommodation at national and international
pregnancies reported/497 305 kits distributed worldwide; conferences from Ethicon, Hologic and Conceptus. He
99.9%)46 although the latter is likely to be an underestimate. receives research funding from the Department of Health
Longer term data pertaining to cumulative pregnancy rates and is an HTA Programme Elected West-Midlands member.
and complications are needed for the Essure® technology to
allow a fair comparison against laparoscopic approaches.
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demonstrate that now is the time to engage in outpatient ‘see treatment of symptomatic benign endometrial polyps: a feasibility
study. Gynaecol Endosc 2002;11:91–7.
and treat’ hysteroscopy.
15 Clark TJ. Outpatient hysteroscopy and ultrasonography in the
management of endometrial disease. Curr Opin Obstet Gynecol
Disclosure of interests 2004;16:305–11.
N.A.M. Cooper: none declared. T. J. Clark is a consultant to 16 Lukes AS. Myosure tissue removal system – comparative sedation
study in an office setting. J Minim Invasive Gynecol 2010;17(Suppl 1):
Conceptus. He received an honoraria from Hologic and S67.
Ethicon for clinician training which has been paid into a 17 Alhilli MM, Nixon KE, Hopkins MR, Weaver AL, Laughlin-Tommaso SK,
charitable account to fund research. He has also received an Famuyide AO. Long-term outcomes after intrauterine morcellation vs

ª 2013 Royal College of Obstetricians and Gynaecologists 165

 Ambulatory hysteroscopy

hysteroscopic resection of endometrial polyps. J Minim Invasive 35 Chapron C, Querleu D, Bruhat MA, Madelenat P, Fernandez H, Pierre F,
Gynecol 2013;20:215–21. et al. Surgical complications of diagnostic and operative
18 Marsh F, Kremer C, Duffy S. Delivering an effective outpatient gynaecological laparoscopy: a series of 29,966 cases. Hum Reprod
service in gynaecology. A randomised controlled trial analysing the 1998;13:867–72.
cost of outpatient versus daycase hysteroscopy. BJOG 36 Sinha D, Kalathy V, Gupta JK, Clark TJ. The feasibility, success and
2004;111:243–8. patient satisfaction associated with outpatient hysteroscopic
19 Capobianco G, Vargiu N, Dessole F, Milia L, Dessole S. Office sterilisation. Br J Obstet Gynaecol 2007;114:676–83.
hysteroscopy for uterine intracavitary pathologies: “see and treat” 37 National Institute for Health and Clinical Excellence. Hysteroscopic
approach. Gynecol Surg 2009;6:S1–S31. Sterilisation by Tubal Cannulation and Placement of Intrafallopian
20 Timmermans A, Veersema S. Ambulatory transcervical resection of Implants. London: NICE; 2009 [http://guidance.nice.org.uk/IPG315].
polyps with the Duckbill polyp snare: a modality for treatment of 38 Kerin JF, Carignan CS, Cher D. The safety and effectiveness of a new
endometrial polyps. J Minim Invasive Gynecol 2005;12:37–9. hysteroscopic method for permanent birth control: results of the first
21 Clark TJ, Daniels J, Gray R, Denny E, Roberts T. A Randomised Essure pbc clinical study. Aust NZ J Obstet Gynaecol 2001;41:
Controlled Trial of Outpatient Polyp Treatment for Abnormal Uterine 364–70.
Bleeding. Centre for Reviews and Dissemination; 2010 [http:// 39 Baxter N, Hudson H, Rogerson L, Duffy S. Hysteroscopic sterilisation: a
dx.doi.org/10.1186/ISRCTN65868569]. study of women’s attitudes to a novel procedure. Br J Obstet Gynaecol
22 Clark TJ, Mahajan D, Sunder P, Gupta JK. Hysteroscopic treatment of 2005;112:360–2.
symptomatic submucous fibroids using a bipolar intrauterine system: a 40 Levie MD, Chudnoff SG. Office hysteroscopic sterilization compared
feasibility study. Eur J Obstet Gynecol Reprod Biol 2002;100:237–42. with laparoscopic sterilization: a critical cost analysis. J Minim Invasive
23 A Di Spiezio Sardo, personal communication. Gynecol 2005;12:318–22.
24 Clark TJ, Gupta JK. Handbook of Outpatient Hysteroscopy. A 41 Hurskainen R, Hovi SL, Gissler M, Grahn R, Kukkonen-Harjula K, Nord-
Complete Guide to Diagnosis and Therapy. 1st ed. London: Hodder Saari M, et al. Hysteroscopic tubal sterilization: a systematic review of
Education; 2005. the Essure system. Fertil Steril 2010;94:16–19.
25 TJ Clark, personal communication. 42 Arjona JE, Mino M, Cordon J, Povedano B, Pelegrin B, Castelo-Branco
26 Farrugia M, Hussain SY. Hysteroscopic endometrial ablation using the C. Satisfaction and tolerance with office hysteroscopic tubal
HydroThermAblator in an outpatient hysteroscopy clinic: feasibility sterilization. Fertil Steril 2008;90:1182–6.
and acceptability. J Minim Invasive Gynecol 2006;13:178–82. 43 Cooper JM, Carignan CS, Cher D, Kerin JF, Selective Tubal
27 Clark TJ, Gupta JK. Outpatient thermal balloon ablation of the Occlusion Procedure 2000 Investigators Group. Microinsert
endometrium. Fertil Steril 2004;82:1395–401. nonincisional hysteroscopic sterilization. Obstet Gynecol
28 Varma R, Soneja H, Samuel N, Sangha E, Clark TJ, Gupta JK. 2003;102:59–67.
Outpatient thermachoice endometrial balloon ablation: long-term, 44 Peterson HB, Xia Z, Hughes JM, Wilcox LS, Tylor LR, Trussell J. The risk
prognostic and quality-of-life measures. Gynecol Obstet Invest of pregnancy after tubal sterilization: findings from the U.S.
2010;70:145–8. Collaborative Review of Sterilization. Am J Obstet Gynecol
29 Prasad P, Powell MC. Outpatients Thermablate EAS. A global thermal 1996;174:1161–8.
endometrial balloon ablation for menorrhagia. A retrospective review. 45 Bradley L. Long-term follow-up of hysteroscopic sterilization with the
Gynecol Surg 2009;6:S1–S31. Essure micro-insert. J Minim Invasive Gynecol 2008;15 Suppl:
30 Kalkat RK, Cartmill RSV. NovaSure endometrial ablation under local S14–S15.
anaesthesia in an outpatient setting: an observational study. J Obstet 46 Levy B, Veersema S, Munro M, Vleugels MPH. Reported pregnancies
Gynaecol 2011;31:152–5. after Essure hysteroscopic sterilization: a retrospective analysis of
31 Marsh F, Thewlis J, Duffy S. Randomized controlled trial comparing pregnancy reports worldwide during commercial distribution: 2001–
Thermachoice III* in the outpatient versus daycase setting. Fertil Steril 2010. Gynecol Surg 2011;8 Suppl 1:S71. [Abstract FC.13.8].
2007;87:642–50. 47 Saridogan E, Tilden D, Sykes D, Davis N, Subramanian D. Cost-analysis
32 Jack SA, Cooper KG, Seymour J, Graham W, Fitzmaurice A, Perez J. A comparison of outpatient see-and-treat hysteroscopy service with
randomised controlled trial of microwave endometrial ablation other hysteroscopy service models. J Minim Invasive Gynecol
without endometrial preparation in the outpatient setting: patient 2010;17:518–25.
acceptability, treatment outcome, and costs. Obstet Gynecol Surv 48 Kremer C, Duffy S, Moroney M. Patient satisfaction with outpatient
2005;60:792–3. hysteroscopy versus day case hysteroscopy: randomised controlled
33 Clark TJ, Samuel N, Malick S, Middleton LJ, Daniels J, Gupta JK. Bipolar trial. BMJ 2000;320:279–82.
radiofrequency compared with thermal balloon endometrial ablation 49 Varma R, Soneja H, Clark TJ, Gupta JK. Hysteroscopic myomectomy for
in the office: a randomized controlled trial. Obstet Gynecol menorrhagia using Versascope bipolar system: efficacy and prognostic
2011;117:109–18. factors at a minimum of one year follow up. Eur J Obstet Gynecol
34 Skensved H. Global–local anaesthesia: combining paracervical block Reprod Biol 2009;142:154–9.
with intramyometrial prilocaine in the fundus significantly reduces 50 RCOG. High Quality Women’s Health Care: A Proposal for Change.
patients’ perception of pain during radio-frequency endometrial London: RCOG; 2011 [http://www.rcog.org.uk/files/rcog-corp/
ablation (Novasure®) in an office setting. Gynecol Surg 2012;2:207–12. HighQualityWomensHealthcareProposalforChange.pdf].

166 ª 2013 Royal College of Obstetricians and Gynaecologists

 DOI: 10.1111/tog.12029 2013;15:167–70
The Obstetrician & Gynaecologist
Review
http://onlinetog.org

Management of vault prolapse

a, b
K Ramalingam MRCOG, * Ash Monga FRCOG
a
Consultant Obstetrician and Gynaecologist with a special interest in Urogynaecology, Kingston Hospital, Galsworthy Road, Kingston-upon-
Thames, Surrey KT2 7QB, UK
b
Consultant Gynaecologist and Subspecialist in Urogynaecology, Princess Anne Hospital, Tremona Road, Southampton SO16 5YD, UK
*Correspondence: K Ramalingam. Email: [email protected]

Accepted on 24 May 2012

Key content  Understand the limitations and complications of different

 Vaginal wall prolapse is increasing in incidence with improvement procedures and counsel patients appropriately.
in life expectancy.
Ethical issues
 Conservative and surgical treatments exist.
 Should procedures that improve quality of life be performed in
 Treatment should be tailored to individual needs depending on
elderly patients with comorbid conditions?
prolapse symptoms, sexual function and co-existing medical
 Should simpler surgical treatments such as colpocleisis or vaginal
conditions.
surgery be performed to be more cost-effective compared with
 Indications, expertise required and complications of different
laparoscopic or robotic procedures?
procedures should be explored with available evidence.
 How safe is it to use mesh in vault prolapse by the abdominal or
Learning objectives vaginal route?
 Recognise the presentation of vaginal vault prolapse.
Keywords: prolapse surgery / recurrent prolapse / vault prolapse
 Learn about different options available for the treatment of vaginal
vault prolapse.

Please cite this paper as: Ramalingam K, Monga A. Management of vault prolapse. The Obstetrician & Gynaecologist 2013;15:167–70.

Introduction Aetiology
Definition Age, menopause and childbirth have all been cited as
Vaginal vault prolapse is defined as descent of the vaginal cuff aetiological factors. Samuelsson revealed independent
below a point that is 2 cm less than the total vaginal length statistical associations with age, parity, maximal birth
above the plane of the hymen.1 Or simply, the uppermost weight, and pelvic floor muscle strength by multi-variate
part of the vagina descends from its normal position, analysis in a Swedish population study.5 Racial differences
sometimes out through the vaginal opening. have also been reported. It is reported to be more common in
Uterovaginal prolapse has been described as an entity as Asian women (67%) compared to Caucasian (26%) or
early as 1550 BC in ancient Egyptian literature and is a very African (28%) women.6 It is unclear if it is due to inherent
common condition. The incidence of vault prolapse is genetic or lifestyle factors.
expected to be on the increase as life expectancy increases.
It is difficult to ascertain the prevalence of the condition due Diagnosis
to inherent under-reporting as some patients often delay A good history from the patient and a detailed examination is
or do not seek care for vaginal prolapse. Vaginal required to establish diagnosis. It is also essential to establish
vault prolapse can have a significant impact on quality of the need to preserve coital function. The overall treatment
life due to discomfort and associated bowel, bladder and objective should be confirmed by the patient and the
sexual dysfunction. clinician at diagnosis; i.e. symptom relief from prolapse
There is an increasing prevalence of bothersome prolapse. sensation, improvement of apareunia or dyspareunia, urinary
The US Census Bureau estimates that it would increase from or bowel symptom improvement.
3.3 million in 2010 to 4.9 million in 2050.2 Population The most common symptom of presentation is a bulge or
studies by Swedish and Dutch clinicians have found the protrusion through the vagina. Varying degrees of bladder
prevalence to be between 8% and 12% for pelvic organ dysfunction may co-exist, such as, frequency, urgency,
prolapse by self reported questionnaires and pelvic organ voiding difficulty, the need to reduce the prolapse for
prolapse quantification (POP-Q) assessment.3,4 micturition, stress incontinence and urge incontinence.

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 Management of vault prolapse

Sexual dysfunction may be a feature in sexually active couples described. The ring and the shelf pessaries are the most
and may affect one or both partners. Either obstruction to commonly used. Newer forms such as the cube pessary, self-
intercourse and/or laxity is common. Obstructed defaecation introducing pessaries with handles and Gellhorn pessaries are
may also occur presenting with incomplete bowel emptying other options.
and pocketing with splinting. These patients present with an
inability to open their bowels on straining and a need to
Surgical management
splint the perineum for defaecation. These patients would
have had a prior hysterectomy by either the abdominal or The aim of surgical repair must address the need to preserve
vaginal route for varying indications. or improve function and should restore normal anatomy.
The need to investigate all patients presenting with vault The route of surgical management is rife with controversy.
prolapse with uroflow or cystometrogram is open to debate if There are different procedures that can be performed by the
stress incontinence or voiding difficulty is suspected. Twin vaginal, abdominal and the laparoscopic or robotic
channel cystometry can be helpful. If urodynamic stress laparoscopic approach.
incontinence (USI) is a major issue, treatment often
incorporates an incontinence procedure such as a mid Vaginal route
urethral tape. Some clinicians would routinely combine it Proponents of the vaginal approach claim that the presence
with an incontinence procedure. However, Maher’s review in of good pelvic floor tone and the presence of good endopelvic
2009 and then again in 2011 confirmed that there is no evidence fascia are prerequisites for a vaginal procedure.12 However,
to promote this practice.7,8 The management of vaginal the argument against this would be that it would seldom be
prolapse depends on the age at presentation, co-existent the case in patients with existing vault prolapse.
medical disorders that may impact on the type and duration of
anaesthesia, desire to preserve sexual function and the Sacrospinous fixation
preference of route and expertise of the surgeon. A longitudinal incision is made over the posterior vaginal
wall and extended to the apex of the vaginal wall. The vaginal
mucosa is dissected away from the rectovaginalis fascia until
Conservative management
the puborectalis muscle is identified. The sacrospinous
Physiotherapy ligament that runs from the ischial spine to the sacrum is
No specific guidance or evidence exists to assess the role of then identified by sharp and blunt dissection. Two sutures
pelvic floor physiotherapy in the management of vault are inserted through the sacrospinous ligament and secured
prolapse. A review of three randomised trials failed to find to the apex of the vagina.7 This has been made technically
sufficient evidence for judging the value of conservative easier by the introduction of newer devices to capture the
management of pelvic organ prolapse.9 suture during insertion into the sacrospinous ligament.
More recently, the POPPY trial has examined the role of A long-term follow-up of 55 patients reported a high rate
pelvic floor muscle training in a multicentre RCT and of sexual dysfunction. Good vault suspension was reported.
concluded that there is now sufficient evidence to conclude However, more than a third of the patients had prolapse of
that physiotherapy is effective and cost-effective in reducing the other compartments.13
prolapse symptoms and should be recommended as first-line A review of articles on sacrospinous fixation between 1996
management for prolapse.10 and 2010 concluded that sacrospinous fixation achieves good
long-term objective and subjective outcomes and improves
Pessary quality of life in women with pelvic organ prolapse. The
A systematic review on the use of pessaries in all types of complication rates were stated to be comparable to those
prolapse concluded that improvement in bulge sensation, of abdominal sacrocolpopexy and lesser than those
bladder symptoms and sexual behaviour occurred with a of transvaginal mesh procedures.14 Surgeons who approve of
reported satisfaction rate in 70–92%. It had similar outcomes this procedure argue that it is cost effective and time tested.
to surgery at 1 year follow-up.11 However, it could not be Maher et al.7 reviewed three trials and reported no
fitted in 15% of patients at presentation. The common side significant difference in prolapse outcomes with abdominal
effects reported are bleeding, vaginal discharge, pain, or vaginal sacrospinous colpopexy. However, subjective
constipation and odour in 56% of patients.11 failure of the procedure was twice as much in the vaginal
Pessary is a popular option especially in patients who do arm compared with abdominal sacrocolpopexy.
not wish to consider surgery due to comorbid conditions or
prior surgery. However, complications such as vaginal Iliococcygeal fixation
erosion and rare cases of migration into bladder, rectum or An incision is made in the posterior vaginal wall along with
soft tissue are reported. Various types of pessary have been an incision in each gluteal region. A tunnelling device is used

168 ª 2013 Royal College of Obstetricians and Gynaecologists

 Ramalingam and Monga

to insert the mesh through one buttock and with a finger stressed the need for specialist training before undertaking
in the vaginal incision, it is passed around the rectum. The these complex surgical procedures.20
mesh is then guided through the vagina and retrieved The use of vaginal mesh is a rapidly advancing and
through the contralateral gluteal incision. This is then evolving science. Well constructed trials should establish
sutured to the top of the vagina as a tension free mesh. patient selection criteria and the required surgical techniques
A prospective study of 21 patients reported that, in the to minimise complication rates.
short term, there was both subjective and objective
improvement in prolapse symptoms.15 The studies analysed Abdominal route
by the NICE guidance for iliococcygeal fixation concluded The proponents of this route for the treatment of vaginal
that failure occurred in 10% and 2–30% had further surgery. vault prolapse argue that it preserves vaginal length, prevents
Mesh erosion occurred in 7–21%, infection in 5% and rectal scarring and thereby improves sexual function by avoiding
perforation in 1%. The main criticism of this procedure by shortening and dyspareunia. Inherent to this approach,
surgeons preferring the abdominal route is a high incidence however, is longer recovery and hospital stay compared
of mesh erosion with the attendant complications of with the vaginal route.
bleeding, pain and dyspareunia.
Hence, NICE16 recommended that, due to inadequate data Abdominal sacrocolpopexy
on efficacy and safety of this procedure, it ‘should only be A long-term follow-up of 21 patients with a median of
used with special arrangements for clinical governance, 55 months concluded that abdominal sacrocolpopexy
consent and audit or research’. provided long-term symptom relief as well as anatomical
stability.21
Colpocleisis A review by Maher concluded on the basis of three
This was first described by Le Fort in the late 18th century. randomised trials that abdominal sacrocolpopexy had lesser
There has been renewed interest in the procedure in recent recurrence of vault prolapse and dyspareunia when
years. A short series of cases has reported good patient compared with sacrospinous fixation. However, an
satisfaction, objective improvement in prolapse outcomes abdominal procedure involves longer surgical and
and improved quality of life measures.17 Various recovery time and is less cost-effective.7 A more recent
modifications have been suggested including perineocleisis, update of the topic has confirmed that there are no
partial and near total vaginectomy and colpocleisis in ongoing randomised controlled trials currently.8 NICE
combination with incontinence procedures. This is often guidance recommends that the current evidence on the
the procedure of choice in older patients over 80 years of age, safety and efficacy of sacrocolpopexy using mesh for vaginal
with comorbid conditions. It restores quality of life, vault prolapse repair appears adequate to support the use
especially in patients with limited mobility, complications of this procedure.22
with the use of pessary such as ulceration and bleeding or
to aid care of such patients by carers in homes. Success Laparoscopic sacrocolpopexy
rates as high as 97% have been reported in a short-term This is becoming increasingly popular with the added
follow-up study.18 benefits of minimal access surgery such as shorter hospital
stay, lesser analgesia and quicker recovery which are often
Vaginal mesh kits criticisms when the open sacrocolpopexy is compared with
There has been a recent increase in the availability of trocar- and the vaginal procedures such as sacrospinous ligament
based vaginal devices for surgical treatment of vaginal fixation. It does take a longer surgical time in comparison to
prolapse. The FDA has reviewed the evidence and other procedures. A recent randomised trial between the total
concluded that ‘surgical mesh in the transvaginal repair of vaginal mesh and the laparoscopic sacrocolpopexy concluded
pelvic organ prolapse does not improve symptoms or quality that the laparoscopic sacrocolpopexy group had a longer
of life more than non-mesh repair’.19 The commonly operating time, reduced inpatient days, and quicker return to
reported complications were mesh erosion into the vagina activities of daily living compared with the total vaginal mesh
needing further surgery, mesh contraction with vaginal group. The follow-up review after 2 years concluded that
shortening, tightening and pain. Better quality meshes and both total objective prolapse rates for all compartments as
more robust evidence is required before widespread use of well as reoperation rates were considerably higher in the
this procedure. There is a need for these new procedures to vaginal mesh group.23
be research-driven rather than be industry-driven. The 1 year follow-up from the laparoscopic sacro-
A recent review by the Canadian Urogynaecology colpopexy trial in the UK concludes that the laparoscopic
Committee concluded that the vaginal mesh kits must be sacrocolpopexy with mesh is equivalent to open
considered novel until further evidence is available. It also sacrocolpopexy with regard to vaginal vault correction with

ª 2013 Royal College of Obstetricians and Gynaecologists 169

 Management of vault prolapse

inherent advantages of the laparoscopic approach for these 8 Maher CM, Feiner B, Baessler K, Glazener CM. Surgical management
of pelvic organ prolapse in women: the updated summary version
patients.24
Cochrane review. Int Urogynecol J 2011;22:1445–57.
9 Hagen S, Stark D, Maher C, Adams E. Conservative management of
Robotic laparoscopic sacrocolpopexy pelvic organ prolapse in women. Cochrane Database Syst Rev 2006;
A recent development is the robot-assisted laparoscopic (4):CD003882.
10 Hagen S, Stark D, Glazener C, Sinclair L, Wilson D, Norrie J, et al. A
approach. It offers better visualisation and precise
multicentre randomised controlled trial of a pelvic floor muscle
movements during surgery. The procedure itself is similar training intervention for women with pelvic organ prolapse. 41st
in principle to the abdominal sacrocolpopexy. The ports Annual Meeting of the International Continence Society, 29 August–2
include the central umbilical camera port, three surgical September 2011, Glasgow, Scotland. Abstract 000129
11 Lamers BH, Broekman BM, Milani AL. Pessary treatment for pelvic
robot ports and a port for the assistant. This has the added organ prolapse and health-related quality of life: a review. Int
benefit of shorter hospital stay, less bleeding and better Urogynecol J 2011;22:637–44.
patient satisfaction.25 The capital cost of setting up the 12 Uzoma A, Farag KA. Vaginal vault prolapse. Obstet Gynecol Int
service is very high. 2009;2009:275621.
13 Aigmueller T, Riss P, Dungl A, Bauer H. Long-term follow-up after
vaginal sacrospinous fixation: Patient satisfaction, anatomical results
and quality of life. Int Urogynecol J Pelvic Floor Dysfunct
Conclusion 2008;19:965–9.
Safer surgical procedures that are economical, with low 14 Petri E, Ashok K. Sacrospinous vaginal fixation – current status. Acta
Obstet Gynecol Scand 2011;90:429–36.
complication rates and high subjective and objective rates are 15 Krissi H, Stanton SL. Bilateral iliococcygeal fixation for vaginal vault
always desirable. Good randomised controlled trials prolapse and enterocele repair using a new suturing device – the
comparing the different routes and techniques are the way digital needle driver. BJOG 2005;112:1145–9.
16 National Institute for Health and Clinical Excellence. Infracoccygeal
forward. Also, vaginal kits will improve with time, when the
Sacropexy Using Mesh for Vaginal Vault Prolapse Repair.
ideal mesh that does not contract or cause erosion or pain Interventional Procedure Guidance 281. London: NICE; 2009.
can be found. Meanwhile, long-term follow-up data on 17 Marrero C, Aponte A, Torres R, Santos F, Rivera J. A preliminary report
abdominal and laparoscopic procedures should be ongoing. on pelvic floor reconstruction through colpocleisis from 2001 to 2007
at the University Hospital of the Puerto Rico Medical Center. P R Health
Sci J 2010;29:394–6.
Disclosure of interests 18 Cespedes RD, Winters JC, Ferguson KH. Colpocleisis for the treatment
None to declare of vaginal vault prolapse. Tech Urol 2001;7:152–60.
19 US Food and Drug Administration. FDA Safety Communication:
UPDATE on Serious Complications Associated with Transvaginal
References Placement of Surgical Mesh for Pelvic Organ Prolapse. Silver Spring,
MD: FDA; 2011 [http://www.fda.gov/medicaldevices/safety/
1 Abrams P, Cardozo L, Fall M, Griffiths D, Rosier P, Ulmsten U, et al. The alertsandnotices/ucm262435.htm].
standardisation of terminology of lower urinary tract function: report 20 Walter JE; Urogynaecology Committee, Lovatsis D, Walter JE, Easton
from the standardisation sub-committee of the International W, Epp A, et al. Transvaginal mesh procedures for pelvic organ
Continence Society. Urology 2003;61:37–49. prolapse. J Obstet Gynaecol Can 2011;33:168–74.
2 Wu JM, Hundley AF, Fulton RG, Myers ER. Forecasting the prevalence 21 Thomas AZ, Giri SK, Cox AM, Creagh T. Long-term quality-of-life
of pelvic floor disorders in U.S. women: 2010 to 2050. Obstet Gynecol outcome after mesh sacrocolpopexy for vaginal vault prolapse. BJU Int
2009;114:1278–83. 2009;104:1676–9.
3 Tegerstedt G, Maehle-Schmidt M, Nyr
en O, Hammarstro €m M. 22 National Institute for Health and Clinical Excellence. Sacrocolpopexy
Prevalence of symptomatic pelvic organ prolapse in a Swedish Using Mesh for Vaginal Vault Prolapse Repair. Interventional
population. Int Urogynaecol J Pelvic Floor Dysfunct 16:497–503. procedure guidance IPG 283. London: NICE; 2009.
4 Slieker-ten Hove MC, Pool-Goudzwaard AL, Eijkemans MJ, Steegers- 23 Geller EJ, Siddiqui NY, Wu JM, Visco AG. Short-term outcomes of
Theunissen RP, Burger CW, Vierhout ME, et al. The prevalence of pelvic robotic sacrocolpopexy compared with abdominal sacrocolpopexy.
organ prolapse symptoms and signs and their relation with bladder Obstet Gynecol 2008;112:1201–6.
and bowel disorders in a general female population. Int Urogynecol J 24 Pantazis K, Freeman R, Thomson A, Frappell J, Bombieri L, Moran P,
Pelvic Floor Dysfunct 2009;20:1037–45. et al. Open and laparoscopic sacrocolpopexy demonstrate clinical
5 Samuelsson EC, Victor FT, Tibblin G, Sv€ardsudd KF. Signs of genital equivalence: one year results from LAS trial, an RCT comparing the two
prolapse in a Swedish population of women 20 to 59 years of age and approaches for treating post hysterectomy vault prolapse. 41st Annual
possible related factors. Am J Obstet Gynecol 1999;180:299–305. Meeting of the International Continence Society, 29 August–2
6 Sewell CA, Chang E, Sultana CJ. Prevalence of genital prolapse in 3 September 2011, Glasgow, Scotland. Abstract 000131.
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7 Maher C, Feiner B, Baessler K, Glazener CMA. Surgical management of et al. Laparoscopic sacral colpopexy versus total vaginal mesh for
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170 ª 2013 Royal College of Obstetricians and Gynaecologists

 DOI: 10.1111/tog.12030 2013;15:171–6
The Obstetrician & Gynaecologist
Review
http://onlinetog.org

Polycystic ovary syndrome and the differential diagnosis

of hyperandrogenism
Claire L Meek MB ChB BSc(Med Sci) MSc MRCP,a,* Vassiliki Bravis MA (Hons) MBBS MRCP MRes,b
Abigail Don BMBCh and BA (Hons),c Felicity Kaplan MBChB, FCP(SA), FRCPd
a
Specialist Registrar, Chemical Pathology & Metabolic Medicine, Department of Clinical Biochemistry, Addenbrooke’s Hospital, Hills Road,
Cambridge CB2 0QQ, UK
b
Academic Clinical Fellow in Endocrinology and Diabetes, Department of Endocrinology, Lister Hospital, Corey’s Mill Lane, Stevenage SG1 4AB
and Department of Investigative Sciences, Imperial College, London, UK
c
FY2 Doctor in Endocrinology & Diabetes, Department of Endocrinology, Lister Hospital, Corey’s Mill Lane, Stevenage SG1 4AB, UK
d
Consultant in Endocrinology & Diabetes, Department of Endocrinology, Lister Hospital, Corey’s Mill Lane, Stevenage SG1 4AB, UK
*Correspondence: Claire Meek. Email: [email protected]

Accepted on 2 April 2012

Key content  To learn about the differential diagnosis of hyperandrogenism.

 The presence of clinical or biochemical evidence of  To learn about the limitations of biochemical testing for
hyperandrogenism is a defining feature of polycystic ovary testosterone in women.
syndrome (PCOS).
Ethical issues
 As the criteria for diagnosing PCOS becomes more inclusive, there
 Hyperandrogenism causing hirsutism and virilisation can have
is an increased risk of misdiagnosing women with other causes of
significant effects on physical and psychological wellbeing.
hyperandrogenism.
 Misdiagnosis can delay appropriate treatment and may affect
 Biochemical testing for serum testosterone concentrations in
future fertility.
women has important limitations.
 Patients with concerning features should be investigated for other Keywords: hirsutism / hyperandrogenism / polycystic ovary
causes of hyperandrogenism. syndrome
Learning objectives
 To review the different criteria for diagnosing PCOS and the
repercussions for disease prevalence.

Please cite this paper as: Meek CL, Bravis V, Don A, Kaplan F. Polycystic ovary syndrome and the differential diagnosis of hyperandrogenism. The Obstetrician &
Gynaecologist 2013;15:171–6.

inadequate conversion to estrogens or both. This review

Introduction
focuses on the pathophysiology, biochemistry and differential
Hyperandrogenism is one of the most common and diagnoses of hyperandrogenism in women.
distressing endocrine disorders in women of reproductive
age.1 Androgen excess results in the development of
Normal androgen production in females
hirsutism, androgenic alopecia, acne, ovulatory dysfunction,
and virilisation or masculinisation if prolonged or severe. Adrenal androgens
Bullock and Sequeira2 were the first to describe an association The adrenal gland is responsible for the production and
between masculinisation and endocrine pathology in 1905, secretion of aldosterone, cortisol, and androgens, as
linking the adrenals and gonads. Many conditions can cause summarised in Figure 1. Dehydroepiandrosterone (DHEA)
hyperandrogenism in women, but the most common cause is the predominant androgen produced by and released
worldwide is polycystic ovary syndrome (PCOS). from the adrenal gland. DHEA-sulfate (DHEA-S), the
Some androgen production occurs in all healthy women and sulfuric acid ester of DHEA, is predominantly produced in
is required for the synthesis of estrogens. In hyperandrogenic the adrenal gland and is therefore a useful measure of adrenal
states, there is either dysfunctional production of androgens or androgen production.3

ª 2013 Royal College of Obstetricians and Gynaecologists 171

 PCOS and hyperandrogenism

tissue.5 Most of the circulating testosterone is metabolised in

the liver into androsterone and etiocholanolone, which are
Negative Hypothalamus conjugated with glucuronic acid or sulfuric acid and excreted
feedback in the urine as 17-ketosteroids.
from cortisol
CRH GnRH
Androgen action
In the target tissues, androgens diffuse across cell membranes
and bind to nuclear androgen receptors. The androgen-
Pituitary Pituitary receptor complex attaches to a specific DNA site and
stimulates the production of messenger RNA, which, in
turn, stimulates the production of the enzymes and proteins
LH
ACTH necessary to affect androgen action.
FSH
In the brain, the highest concentrations of androgen
receptors are present in the preoptic area of the hypothalamus
– in close proximity to estrogen receptors – and are thought to
Adrenal glands Ovaries be involved in behaviour and sexual function. In bone,
androgens have an important role in bone mineralisation
both directly and through the aromatisation to estrogen.
Lower androgen concentrations have been associated with
bone loss in various age groups.6 Androgen receptors are also
Aldosterone Ovarian androgens
present in mammary epithelial cells in addition to estrogen
Cortisol Adrenal androgens Androstenedione and progesterone receptors. The role of androgens in human
DHEA and DHEA-S breast tissue remains unclear, although no increase in breast
cancer risk has been observed in hyperandrogenaemic
Figure 1. Androgen production in women. The secretion of
corticotrophin releasing hormone (CRH) by the hypothalamus
women with PCOS.7
stimulates the pituitary to release adrenocorticotrophic hormone
(ACTH). ACTH acts on the adrenal cortex and thus controls synthesis
rates of cortisol, aldosterone and adrenal androgens. Cortisol exerts a
Clinical assessment of hyperandrogenism
negative feedback on its own production. This is important in Symptomatic androgen excess in women of reproductive age
congenital adrenal hyperplasia (CAH). The release of gonadotrophin
releasing hormone (GnRH) from the hypothalamus stimulates release
is a common presentation to the general endocrinology
of luteinising hormone (LH) and follicle stimulating hormone (FSH) clinic. The physical effects of hyperandrogenism are
from the pituitary. These act upon the ovary and ovarian androgens distressing for many patients but nonetheless a detailed
are synthesised. The main ovarian androgen is androstenedione history and thorough clinical examination are essential.
Clinical assessment facilitates diagnosis of the underlying
cause of androgen excess and appropriate investigation and
management.
Ovarian androgens The history and examination should elucidate common
The ovary also produces and releases androgens, including symptoms and signs of hyperandrogenism including
20% of DHEA, 50% of androstenedione and 25% of hirsutism, acne, menstrual cycle irregularities, weight gain,
circulating testosterone. The control of ovarian androgen alopecia and virilisation (the development of classic male
production is summarised in Figure 1. characteristics). The chronology of symptom commencement
and progression is important and can be indicative of specific
Androgen metabolism disease processes. For example, rapid excessive hair growth,
In healthy women, 80% of circulating testosterone is bound deepened voice and breast atrophy would be more indicative
to sex hormone binding globulin (SHBG), 19% is bound to of an adrenal tumour, compared with the slow development
albumin, and 1% circulates freely in the blood stream. of hirsutism and menstrual irregularities occurring soon after
Traditionally, only the unbound fraction is considered puberty, classically due to PCOS. Disruption of the timing of
metabolically active although this is now disputed.4 Of the puberty can be associated with congenital adrenal hyperplasia
circulating androgens, only testosterone and its active (CAH) and Cushing’s syndrome. A family history is
metabolite dihydrotestosterone (DHT) are able to activate also important as both PCOS and CAH can occur in other
androgen receptors. The remaining androgens, DHEA-S, family members.
DHEA, and androstenedione are almost entirely bound to Clinical evaluation required in women with hyper-
albumin and can be converted to testosterone in peripheral androgenism is outlined in Box 1. An objective grading of

172 ª 2013 Royal College of Obstetricians and Gynaecologists

 Meek et al.

the severity of symptoms such as hirsutism is advisable due 100%.4 Suggested reasons for this include the presence of
to significant cultural and social differences in perceptions of cross-reacting compounds, which may include
normal body appearance. The most common scoring system immunoglobulins, drug metabolites and plasma proteins.4
used by clinicians for hirsutism is the Ferriman-Gallwey Unfortunately, the presence and degree of interference from
score,8 which rates hair growth severity from 0–4 and scores these cross-reactants is unpredictable.
11 different body areas (upper lip, chest, chin, lower The gold standard method for testosterone quantitation
back, upper back, lower abdomen, upper abdomen, is considered to be based upon mass spectrometry (MS), which
forearm, arm, thigh, and lower leg). A score of 8 or above is only available in some tertiary centres. However, this
defines hirsutism. technique requires expensive equipment and significant
operator skill, and currently lacks widespread standardisation.

Box 1. Clinical features associated with hyperandrogenism

Disorders associated with
 Height, weight and body mass index.
hyperandrogenism
 Distribution and extent of adiposity. The differential diagnoses of hyperandrogenism are
 Skin thinning or bruising (seen in Cushing’s syndrome). summarised in Box 2. Although PCOS is the most
 Acne, especially over the face, neck, back and chest. common cause in women of reproductive age, other
 Degree, pattern and severity of hirsutism. important disorders should be considered and excluded.
 Acanthosis nigricans (velvety skin hyperpigmentation), associated
with insulin resistance.
 Deepened voice. Box 2. Differential diagnoses of hyperandrogenism
 Male pattern balding.
 Breast atrophy.  PCOS
 Clitoromegaly.  Ovarian hyperthecosis
 Loss of normal feminine body shape.  Congenital adrenal hyperplasia
 Cushing’s syndrome
 Androgen-secreting tumour
- Adrenal origin
Biochemical assessment of - Ovarian origin
hyperandrogenism  Exogenous androgen administration
 Gestational hyperandrogenism
It is widely accepted that an elevated serum testosterone level
provides biochemical evidence of hyperandrogenism.
However, different analytical methods demonstrate
significant differences in analytical specificity for testosterone Polycystic ovary syndrome (PCOS)
– some methods have interference from non-testosterone PCOS is a heterogeneous condition associated with multiple
androgens. Many practitioners believe that a serum total ovarian cysts, menstrual irregularity, subfertility, mood
testosterone of <5.0 nmol/L, measured using an extraction disturbance, hyperandrogenism, obesity, acne and
immunoassay, makes serious pathology in a female unlikely.4 hirsutism.10 It is the most common reproductive
Mild hyperandrogenism with a serum total testosterone level endocrine disorder of women and has significant short-
of around 2–5 nmol/L is thought to be consistent with PCOS, term and long-term health sequelae. Although PCOS was
while marked elevations (>5 nmol/L) should first described in 1935 by Stein and Leventhal,11 its
prompt investigation for other causes, such as an androgen- diagnosis and management still represent a significant
secreting tumour. challenge to the clinician. This is partially due to the
Most laboratories in secondary care institutions in the UK heterogenous nature of the condition and the conflicting
use an immunoassay to measure total testosterone. This guidance on diagnostic criteria.12
method is fast, inexpensive and technically simple with the PCOS has also been associated with long-term metabolic
advantage of being suitable for automation.9 However, while effects, including the development of insulin resistance, diabetes
this method reliably identifies testosterone concentrations in mellitus, hyperlipidaemia, non-alcoholic steatohepatitis (NASH)
the adult male range, it often performs poorly in females, and an adverse risk profile for cardiovascular disease.13 As
where even in PCOS, concentrations are much lower. PCOS is common, perhaps affecting up to 10–20% of women of
Automatic immunoassays consistently overestimate the reproductive age, this represents a significant population
serum testosterone concentrations, some by as much as burden of disease for the future.

ª 2013 Royal College of Obstetricians and Gynaecologists 173

 PCOS and hyperandrogenism

Pathophysiology of PCOS exactly constitutes biochemical evidence of hyper-

There is controversy about the pathophysiology of PCOS. It is androgenism. The typical biochemical profile in PCOS
likely related to inherited and environmental susceptibilities, includes mild to moderate elevations in free and total
with possible excessive androgen stimulation in utero. Lifestyle testosterone, elevated DHEA-S and low SHBG
factors such as weight gain can exacerbate PCOS. concentrations. In some patients, the LH concentration is
Biochemically, there is hyperinsulinism beyond that expected elevated while the FSH concentration remains normal, giving
in an age- and BMI-matched group, which causes luteinising an elevated LH/FSH ratio.10
hormone (LH) hypersecretion and potentiates the action of LH
and the insulin-like growth factor-1 (IGF-1). Both LH and Ovarian hyperthecosis
IGF-1 upregulate synthesis of ovarian and adrenal Ovarian hyperthecosis accounts for most of the cases of
androgens causing production of testosterone and DHEA-S.10 hyperandrogenaemia in postmenopausal women,15 although
In the ovaries, hyperinsulinism, hyperandrogenism and its prevalence in younger women is much lower, affecting
disordered paracrine signalling cause arrest of follicular <1% of women with elevated androgens in their
development, typically when the follicle acquires aromatase reproductive years. Ovarian hyperthecosis describes the
activity and is around 7 mm in size. Excessive ovarian presence of luteinised theca cell nests in the ovarian
androgens impair aromatase function, which is required for stroma. When compared with the closely related condition
further follicular growth. Overproduction of anti-m€ ullerian of PCOS, hyperthecosis is typically associated with more
hormone (AMH) antagonises follicle-stimulating hormone severe hyperandrogenism and virilisation. Testosterone
(FSH) action and reduces availability of estrogen, which is concentrations are much higher than in PCOS and may
required for developing follicles.10 Arrest of follicular exceed 7 nmol/l.15
development leads to menstrual disturbance, anovulation
and subfertility. Congenital adrenal hyperplasia
CAH is a group of autosomal recessive disorders, each of
which involves a deficiency of one of five enzymes involved in
Diagnosing PCOS
the synthesis of cortisol in the adrenal cortex.16 In CAH,
Stein and Leventhal11 first described the association of
insufficient cortisol is produced, which stimulates
polycystic ovaries and menstrual disturbance. However, it
hypothalamic CRH secretion, due to the absence of normal
soon became apparent that some women with polycystic
feedback inhibition (see Figure 1). This leads to chronically
ovaries are otherwise healthy and do not have menstrual
elevated adrenocorticotrophic hormone (ACTH), which in
disturbance. Additionally, some patients with obesity,
turn stimulates the adrenal gland to become hyperplastic
menstrual disturbance and hirsutism resemble the PCOS
with excess androgen hormones and steroid precursors being
pattern but lack polycystic ovaries. This has made the
produced and secreted from the normally functioning
diagnosis of PCOS very challenging and many authorities
metabolic pathways. The most common form of CAH is
disagree on the value of different criteria in reaching
due to a deficiency of 21-hydroxylase activity, which accounts
a diagnosis.
for 90–95% of cases of CAH. It is associated with a wide
The Rotterdam international consensus group14 described
range of clinical effects and severity can vary depending on
PCOS as a syndrome of ovarian dysfunction, characterised by
the mutation.16
hyperandrogenism and polycystic ovaries. They
Classic 21-hydroxylase deficiency commonly presents in
recommended that the diagnosis be made if two of the
infancy. Female infants can be severely virilised leading to
following three criteria were met:
ambiguous genitalia. Salt wasting and adrenal crises can
 oligomenorrhoea or anovulation,
occur in some patients and are important causes of neonatal
 clinical and/or biochemical evidence of hyperandrogenism,
death. Non-classic 21-hydroxylase deficiency tends to present
 polycystic ovaries on ultrasonography: multiple peripheral
in puberty, or later in adult life. In this condition, the
follicles with ovarian volume >10 ml.
mutated enzymes in the cortisol biosynthetic pathways
Other diseases that can cause similar symptoms, such as maintain 20–60% of normal function.17 Typical patients
androgen secreting tumours, Cushing’s syndrome and have features of hyperandrogenism but have preserved
congenital adrenal hyperplasia must also be excluded. cortisol and aldosterone production, so salt wasting and
These criteria require a diagnosis to be reached on the basis adrenal crises are not common features of this condition.
of history-taking, clinical examination, blood testing for Many female patients can present in early adulthood with
hyperandrogenism and ovarian imaging. The role of menstrual disturbance or hirsutism.18 Affected males and
biochemistry in PCOS diagnosis is therefore crucial and females may exhibit precocious puberty with tall stature at
may provide the only objective measurement contributing to pubarche, advanced bone age with early epiphyseal fusion,
a diagnosis. However, there is also controversy about what infertility and severe acne, which is refractory to treatment. It

174 ª 2013 Royal College of Obstetricians and Gynaecologists

 Meek et al.

is responsible for around 2% of cases of hyperandrogenism in Exogenous androgen administration

women and occurs in around 1:100 Caucasians with increased Anabolic androgen steroids can be employed to enhance
prevalence in Eastern European Jews and Hispanic and athletic performance, increase libido in women or provide
Mediterranean populations. The remaining patients with cosmetic body building. Their administration can commonly
congenital adrenal hyperplasia have either 11-b-hydroxylase lead to acne vulgaris, hirsutism, seborrheic cutaneous
deficiency or 3-b-hydroxysteroid deficiency.17 changes and striae.22 Androgenic steroids can be
administered via tablets, injectable treatments, implants or
Cushing’s syndrome transdermal patches.
Cushing’s syndrome is a rare but important cause of
androgen excess. Hirsutism is present in approximately Gestational hyperandrogenism
80% of patients.19 Cushing’s syndrome results from increased Although total testosterone levels rise during pregnancy,
circulating concentrations of cortisol and can present serum SHBG also increases, which protects both the mother
insidiously with centripetal weight gain, facial plethora, and fetus from clinical hyperandrogenism. Overall,
supraclavicular fat pads, abdominal striae and signs of hyperandrogenism is rare during pregnancy23 but if it does
hyperandrogenism, such as hirsutism, acne and male occur, it is usually due to pregnancy-related causes. This is
pattern baldness. Cushing’s syndrome can be secondary to because subclinical or overt hyperandrogenism in a
an ACTH secreting pituitary tumour (Cushing’s disease), nonpregnant woman usually results in anovulation and
autonomous cortisol secretion by the adrenal glands due to infertility. The two most common causes of gestational
adrenocortical neoplasms or hyperplasia,20 exogenous hyperandrogenism are luteomas and theca lutein cysts of the
administration of glucocorticoids or ectopic ACTH ovary.23 Unilateral solid ovarian lesions complicated by
secretion in neoplasia including small cell lung carcinomas androgen excess have an increased risk of malignancy when
and carcinoid tumours. presenting in pregnancy.

Androgen secreting tumours

Androgen secreting tumours of the ovaries or adrenal
Conclusions
glands are rare causes of hyperandrogenism that often Hyperandrogenism in women is a common and distressing
mimic PCOS. Women with these tumours tend to have condition which is due to disruption of normal ovarian or
sudden onset and rapid progression of hyperandrogenism adrenal androgen production. The most common cause
and early development of frank virilisation. The most is PCOS, which is diagnosed using clinical, biochemical
common virilising ovarian tumours are Sertoli Leydig cell and ultrasonographic criteria. The biochemical quantitation
tumours and account for 0.5% of all ovarian neoplasms.15 of testosterone in females using the immunoassay
Other virilising ovarian tumours include granulosa cell, method is significantly flawed and clinical judgement is
hilar cell and Brenner tumours. Ovarian androgen-secreting crucial to prevent unnecessary investigation. Testosterone
tumours are characterised by striking elevations in serum concentrations around 2–5 nmol/l are associated with PCOS
testosterone but normal DHEA-S and urinary 17- while concentrations above 5 nmol/l should prompt
ketosteroids. Androgen-secreting adrenal neoplasms are investigation for another cause. MS-based methods will
less common than ovarian neoplasms and typically present usually achieve lower results due to reduced interference
with features of Cushing’s syndrome and simultaneous from non-testosterone androgens but are not widely
virilisation. Adrenal adenomas more frequently produce available. Prior to making a diagnosis of PCOS, other
cortisol and aldosterone while functional adrenal possible causes of hyperandrogenism should be excluded.
carcinomas produce androgens and cortisol. Pure
androgen-secreting adrenal tumors are rare. Adrenal
Disclosure of interests
carcinomas causing virilisation peak in incidence during
None to declare.
childhood and during the fourth/fifth decades of life.21
Markedly elevated serum testosterone, DHEA-S, and urinary
17-ketosteroid levels, which are not suppressed with
References
dexamethasone, suggest an androgen-secreting tumour.
Significantly elevated serum testosterone levels could 1 Knochenhauer ES, Key TJ, Kahsar-Miller M, Waggoner W, Boots LR,
indicate either an androgen-secreting adrenal or ovarian Azziz R. Prevalence of the polycystic ovary syndrome in unselected
black and white women of the southeastern United States: a
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3 Stanczyk FZ. Diagnosis of hyperandrogenism: biochemical criteria. Best manifestations that impacts on health across the lifespan. BMC Med
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Utility, limitations and pitfalls in measuring testosterone: An adrenarche. J Clin Endocrinol Metab 1986;62:840–8.
Endocrine Society position statement. J Clin Endocrinol Metab 19 Howlett TA, Rees LH, Besser GM. Cushing’s syndrome. Clin Endocrinol
2007;92:405–13. Metab 1985;14:911–45.
10 Goodarzi MO, Dumesic DA, Chazenbalk G, Azziz R. Polycystic ovary 20 Reyss AC, Dewailly D. Cushing’s Syndrome, Acromegaly, and Androgen
syndrome: etiology, pathogenesis and diagnosis. Nat Rev Endocrinol Excess. In: Azziz R, Dewailly D. Contemporary Endocrinology: Androgen
2011;7:219–31. Excess Disorders in Women: Polycystic Ovary Syndrome and Other
11 Stein I, Leventhal M. Amenorrhea associated with bilateral polycystic Disorders. 2nd ed. Totowa, NJ: Humana Press Inc. 2006. p. 85–90.
ovaries. Am J Obstet Gynecol. 1935;29:181–9. 21 Cordera F, Grant C, van Heerden J, Thompson G, Young W. Androgen-
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Ovarian Syndrome: The Rotterdam Criteria Are Premature. J Clin 22 Hartgens F, Kuipers H. Effects of androgenic-anabolic steroids in
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176 ª 2013 Royal College of Obstetricians and Gynaecologists

 DOI: 10.1111/tog.12040 2013;15:177–83
The Obstetrician & Gynaecologist
Review
http://onlinetog.org

The relationship between infertility treatment and cancer

including gynaecological cancers
Louay S Louis MRCOG,a,* Srdjan Saso MRCS,
a
Sadaf Ghaem-Maghami PhD MRCOG,
b
Hossam Abdalla FRCOG,
c

J Richard Smith MD FRCOGd

a
Clinical Research Fellow, Division of Surgery and Cancer, Institute of Reproductive and Developmental Biology, Imperial College London,
Hammersmith Hospital Campus, Du Cane Road, London W12 0HS, UK
b
Consultant in Gynaecological Oncology, West London Gynaecological Cancer Centre, Queen Charlotte’s and Chelsea Hospital, Hammersmith
Hospital Campus, Imperial College London, Du Cane Road, London W12 0HS, UK
c
Consultant Gynaecologist and Lead Reproductive Medicine Specialist, Lister Fertility Centre, the Lister Hospital, Chelsea Bridge Road, London
SW1W 8RH, UK
d
Consultant Gynaecological Surgeon, West London Cancer Centre and Queen Charlotte’s and Chelsea Hospital, Hammersmith Hospital Campus,
Imperial College London, Du Cane Road, London W12 0HS, UK
*Correspondence: Louay S. Louis. Email: [email protected]

Accepted on 31 January 2013

Key content  There is no strong evidence linking infertility treatment with

 Increasing availability and expanding usage of infertility treatment non-gynaecological or childhood cancers, with the possible
is a concern with regard to a possible increase in the risk of future exception of melanoma.
malignancy development for women and their offspring.
Learning objectives
 Infertile women are at significantly increased risk of developing
 To highlight the available evidence linking infertility treatment
ovarian and uterine cancers, especially nulliparous women.
 Earlier studies pointed to a possible increase in the risk of ovarian
with gynaecological, non-gynaecological and childhood cancers.
 How to counsel women about any possible risk of future neoplasia
cancer following large doses and multiple cycles of clomiphene citrate.
 Recent studies did not observe any increase in malignancy risk due
after infertility treatment.
to infertility medications. Other confounding factors, such as Ethical issues
infertility itself, may well be the reason for the increased percentage  Is it ethical to persevere with multiple fertility treatment cycles if it
of cancer cases noted in earlier studies. might be associated with increased risk of neoplasia in the future?
 Uterine cancer risk is possibly increased following multiple cycles
Keywords: assisted conception / cancer / epidemiology / infertility
and high doses of clomiphene citrate.

Please cite this paper as: Louis LS, Saso S, Ghaem-Maghami S, Abdalla H, Smith JR. The relationship between infertility treatment and cancer including
gynaecological cancers. The Obstetrician & Gynaecologist 2013;15:177–83.

Ovulation-inducing agents have been widely used to treat

Introduction infertility problems, either alone such as anti-estrogens
Debate has been continuing since the 1990s regarding the (e.g. clomiphene citrate [CC] and less frequently tamoxifen),
association between infertility, infertility treatment, use of or as part of IVF cycles including human menopausal
assisted reproductive techniques (ART), and cancer, gonadotrophins (hMG) and recombinant follicle-stimulating
especially gynaecological and breast cancers. hormone (rFSH) and human chorionic gonadotrophins (hCG)
With approximately 1 in 7 couples affected by infertility,1 We will discuss whether there is an association between
together with an annual increase in fertility treatment in the infertility, its treatment, and cancer. This will help when
UK and other developed countries, concerns have been raised counselling patients—who suffer from infertility, awaiting
as to the possible impact of fertility treatments on the infertility treatment, or are concerned about the impact of
development of cancer. A total of 39 879 women received IVF on developing cancer.
in vitro fertilisation (IVF) treatment in 2008 in the UK, an
increase of 8.2% on the previous year. These women had
Fertility treatment and ovarian cancer
50 687 cycles of treatment. There were 12 211 successful
births in 2008. Some of these births were twin or triplet Ovarian cancer is the fifth commonest cancer in women in
births, so a total of 15 082 babies were born.2 England, with 5535 new cases diagnosed in 2010.3 Risk

ª 2013 Royal College of Obstetricians and Gynaecologists 177

 Infertility treatment and cancer

factors include nulliparity, early menarche, late menopause, for 12 or more cycles with a relative risk (RR) of 2.3 in
and increasing age. Combined oral contraceptive (COC) pill general and 11.1 (with 12 or more cycles) compared with
use, pregnancy, lactation, and tubal ligation are associated infertile women with no CC use (95% CI 0.5–11.4 and 1.5–
with a reduced risk.4 Nulliparity increases the risk of 82.3 respectively). This cohort study included 3837 infertile
developing ovarian cancer by 1.5–2-fold (adjusted odds patients with a mean follow-up of 11.3 years. It reported 11
ratio [OR] 2.71, 95% confidence interval [CI] 1.33–5.52) for cases of invasive or borderline ovarian cancer (4.4 cases
untreated, infertile nulliparous women;5 and nulligravidas expected). It was limited by the small number of tumours
who received fertility treatment but failed to conceive are at and a heterogeneous histological mix.
increased risk of ovarian malignancy compared with those More studies observed a stronger association between
who did (OR 27.0, 95% CI 2.3–315.6).6,7 Furthermore, fertility drug use and borderline tumours of the
unexplained infertility has been associated with an increased ovary14,16,19,20 including hMG use.21 A recent large cohort
risk of developing ovarian and uterine cancers (standardised study by Sanner et al.16 reviewed 2768 infertile women; of
incidence ratio [SIR] 2.64, [95% CI 1.10–6.35] and 4.59 [95% whom 1150 did receive treatment in the form of CC and/or
CI 1.91–11.0] respectively).8 gonadotrophins, with a mean follow-up of 33 years.
COCs substantially decrease the risk of ovarian cancer even Fourteen patients developed ovarian cancer, nine of them
after a few months of use.9,10 The longer a woman has used were in the exposed group. The authors concluded that there
COCs, the greater this effect, with the reduction in risk is an increased risk of ovarian cancer after gonadotrophins
persisting for more than 30 years after cessation of COCs. (RR 5.28, 95% CI 1.91–13.75) and borderline tumours after
However, its effect becomes attenuated11 with OR of developing CC treatment (SIR 3.61, 95% CI 1.91–7.44).
ovarian cancer as low as 0.21 for women who took the pill for On the other hand, larger cohort and case–control studies
more than 10 years. It is estimated that each year of using the reported no association between fertility treatment and
pill brings an approximate 7% reduction in risk of ovarian ovarian cancer.22–27
cancer.12 However, women who undergo fertility treatment Modan et al.22 reviewed a cohort of 2496 infertile patients
may have used COCs far less than the general population.13 with a mean follow-up of 21.4 years. In all, 143 cancer cases
Whittemore et al.7 first noted that a small fraction of the were observed; 12 were ovarian (7.2 expected, 95% CI 0.6–
excess in ovarian cancer risk among nulliparous women is 3.8). However, the latter result was not significant (SIR 1.7 vs
because of infertility, and that any increased risk associated 1.6, v2 = 0.34) after correcting for nulliparity.
with infertility may be related to the use of fertility drugs. A historical cohort analysis by Dor et al.23 of 5026 patients
Conclusions were derived from 12 case–control studies of who had IVF using either CC with hMG, hMG alone, or
ovarian cancer, but only three of them reported data on gonadotrophin-releasing hormone (GnRH) agonist observed
infertility, infertility treatment, and ovarian cancer 27 cases of cancer (35.6 expected). No excess cancer risk was
development. The treatments used were outdated and noted, but the mean follow-up period was 3.6 years only. A
included diethylstilbesterol and conjugated estrogen. A similar cohort study was performed by Doyle et al.24 on 5556
follow-up analysis demonstrated an increased risk in patients, 75% of whom had CC either alone or in
tumours of low malignant potential in comparison to combination with gonadotrophins. After a mean follow-up
invasive tumours.14 Nonetheless, this conclusion was based period of 15.5 years, 118 cancers were identified (55 breast,
on only four ovarian cancer cases of low malignant potential four uterine, and six ovarian). There was no significant
(OR 4.0, 95% CI 1.1–13.9). Neither of the above two studies difference noted in the observed and expected incidence of
corrected for, nor took account of, confounding variables breast, uterine and ovarian cancers.
such as family history or use of COCs. Brinton et al.25 reported on a retrospective cohort of
Some historical as well as more recent cohort studies 12 193 patients treated with CC and/or hMG. The mean
showed an increased risk of ovarian cancer with the use of follow-up period was 19.4 years. A total of 581 cases of
infertility treatment, such as CC15 and gonadotrophins.16 cancer, including 45 cases of ovarian cancers, were identified.
This led some reviewers to conclude that the risk of ovarian After adjusting for patients’ characteristics, no strong link
cancer, if such a risk exists, is two to three times higher than was observed between ovulation-stimulating drugs and
the risk for the general population, with the lifetime risk of ovarian cancer (SIR 0.82 [95% CI 0.4–1.5] for CC and 1.09
ovarian cancer in the general population quoted at 1 in 70 [95% CI 0.4–2.8] for gonadotrophins).
(~1.43%)17; thus, an equivalent risk for patients treated with Four large studies since 2009 have sought to determine
fertility drugs may carry a 4–5% lifetime risk.18 whether there is an association between fertility treatment
The paper by Rossing et al.15 in 1994 led to significant and ovarian cancer. The first was a large Danish case–control
change in practice regarding the use of CC, as it concluded study by Jensen et al.26 who reviewed 54 362 patients during
that the latter increased the risk of borderline and invasive a 16 year (median) follow-up. Patients were treated with four
ovarian cancer. This was even more so when CC was taken different categories of fertility drugs including CC,

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 Louis et al.

gonadotrophins, hCG and GnRH. The authors concluded evidence that endometrial thickness is significantly reduced in
that there was no convincing association between fertility cycles using CC for ovulation induction compared with that in
treatment and ovarian cancer, including different drug non-CC cycles.31 Nonetheless, it is believed that CC increases
groups, length of follow-up or parity (rate ratios: serum estradiol levels during the follicular phase of menstrual
gonadotrophins [0.83, 95% CI 0.50–1.37], CC [1.14, CI cycles of induced ovulation,30 leading to the endometrium
0.79–1.64], hCG [0.89, CI 0.62–1.29] and GnRH [0.80, CI being exposed to increasing levels of estrogen, and hence
0.42–1.51]). The second study by Calderon-Margalit et al.27 increased mitotic activity, DNA replication errors, somatic
was a historical cohort study of 15 030 parous women treated mutations, and the possible development of malignancy.19
with CC and gonadotrophins, with a mean follow-up of This is a specific concern with regard to cases of anovulatory
29 years. The authors found no association between fertility infertility, a large number of which are due to polycystic ovary
treatment and ovarian cancer (age-adjusted hazard ratio syndrome (PCOS). However, contrary to general belief, the
[HR] of 0.61, 95% CI 0.08–4.42). evidence linking PCOS as an independent risk factor for
K€allen et al.28 reported an increased risk in ovarian cancer developing endometrial cancer is not conclusive.32
following IVF treatment. The risk nonetheless was lower than Interestingly, in one study, patients with primary infertility
that before treatment. This was a large study based on a cohort due to anovulation seemed to be particularly predisposed to
of 24 058 patients matched to a control group with all patients uterine cancers (RR 2.42, 95% CI 1.0–5.8). However, only 5%
having undergone IVF. A total of 1279 patients developed of women in that study would be classified as PCOS.33
cancer, 26 of which were ovarian cancers. There was a Reviewing the literature yields few relevant studies but they
statistically generalised decrease in cancer risk following IVF mostly demonstrate a persistent trend to an increased risk of
compared with prior to treatment (OR 0.74, 95% CI 0.67– uterine cancer, mainly with CC8,22,27,30,34,35 Chalderon-
0.82). This was even more so in women who had more than Malgarit et al.27 reported an increased risk of uterine cancer
one delivery. Van Leeuwen et al.29 reported on a historic with fertility treatment (adjusted HR: 3.39, 95% CI 1.28–8.97),
Dutch cohort of 19 146 subfertile women who received at least and the risk further increased with CC (HR 4.56, 95% CI 1.56–
one cycle of IVF between 1983 and 1995. This was compared 13.34). However, it is worth noting that ‘uterine cancer’ was
with 6006 women who did not undergo IVF treatment, and to not strictly defined in this study, though it implied cases of
the general population. After a mean follow-up period of endometrial carcinoma only.
14.3 years for the treatment group, the authors concluded that A study by Venn et al.8 of a large Australian cohort of
ovarian stimulation using IVF may increase the risk of ovarian 29 700 patients in total (20 656 were exposed to fertility
malignancies. The risk of borderline ovarian tumours (but not drugs including CC, hMG and GnRH agonist, whereas 9044
invasive ovarian cancer) was higher in the IVF-treated group patients were not) noted a transient increase in the risk of
compared with the general population (SIR 1.76, 95% CI 1.16– uterine cancer diagnosed in the first year after treatment,
2.56), whereas the risk of all ovarian malignancies was higher though the incidence overall was no greater than expected
compared with the untreated subfertile cohort (adjusted HR (SIR 1.09, 95% CI 0.45–2.61). This observation was based on
2.14, 95% CI 1.07–4.24). 12 cases with only 7 years of follow-up. Four of those cases
In conclusion, the increased risk in borderline and invasive were sarcomas and occurred in the unexposed group.
ovarian cancer noted in earlier studies following high doses In a retrospective case–control study by Althuis et al.,30
and multiple cycles of CC was not confirmed in larger and 8431 patients had been treated with CC and gonadotrophins,
more recent studies, the results of which are more reassuring with an average follow-up of 20 years. The authors identified
with respect to any increase in malignancy risk due to 39 uterine cancers (almost all of endometrial type), and
infertility medications (Table S1). concluded that CC may increase the risk of uterine cancer
(RR 1.79, 95% CI 0.9–3.4) in a dose-related fashion especially
when coupled with nulliparity (RR 3.49, 95% CI 1.3–9.3) and
Fertility treatment and uterine cancer
obesity (RR 6.02, 95% CI 1.2–30.0). This conclusion was
Uterine cancer is the fourth commonest cancer in women in more evident with doses of ≥900 mg (RR 1.93, 95% CI 0.9–
the UK with 6834 new cases diagnosed in 2010.3 As stated 4.0), six or more menstrual cycles of CC (RR 2.16, 95% CI
above, unexplained infertility has been associated with a 0.9–5.2) and time elapsed since the initial use (RR 2.5, 95%
diagnosis of uterine cancer (including both endometrial CI 0.9–7.2). Adjustments for anovulatory disorders in
carcinoma and sarcoma).8 The main concern regarding the multivariate models did not change the estimates of uterine
increased risk of uterine cancer with infertility treatment is the cancer risk associated with CC.
fact that the latter is associated with unopposed Jensen et al.34 concluded that gonadotrophins, and
supraphysiological levels of estrogen which may lead to possibly CC and hCG, may increase the risk of uterine
endometrial hyperplasia and possibly endometrial cancer. cancer. The higher the dose and the longer the follow-up, the
This is true in the case of tamoxifen.30 As for CC, there is greater was the risk especially after more than 10 years of

ª 2013 Royal College of Obstetricians and Gynaecologists 179

 Infertility treatment and cancer

follow-up. This was based on the same large Danish cohort of treatment.41 However, a few other studies did report an
54 362 patients mentioned above who were treated with four increased risk following IVF.27,42,43
drug groups of CC, hCG, gonadotrophins and GnRH. A 1995 study by Venn et al.,40 extended in 1999 to include
Eighty-three uterine cancers were identified, with the 29 700 patients, of whom 20 656 were exposed to fertility
majority (79) being of the epithelial (endometrial) type. drugs with a mean follow-up of 7 years,8 reported 143 cases
This study also concluded that six or more cycles of hCG or of breast cancer. The authors concluded that women exposed
CC may increase the risk of uterine cancer (RR 1.96, 95% CI to fertility drugs have a transient increase in the risk of breast
1.03–3.72, and RR 2.18, 95% CI 1.16–4.08 respectively). The cancer diagnosed in the first year after treatment (SIR 1.96,
main limitation of this study was the patients’ mean age at 95% CI 1.22–3.15). However, the overall incidence was no
the end of the follow-up period being only 47 years. This is greater than expected.
well below the average age of 60 years for developing uterine A large cohort study from Denmark by Jensen et al.44 did
cancer.36 Other limitations included not adjusting for other not demonstrate an association between breast cancer and use
confounding factors such as histological subtype, obesity, of fertility drugs. Using the same cohort they had followed for
COC use or menopausal status, although adjustment of the the ovarian and uterine cancer mentioned earlier, they
RR with causes of infertility (when the results were available) identified 331 cases of breast cancer after a mean follow-up
did not significantly change that risk. period of 8.8 years. Nonetheless, there was some evidence of an
A study by Silva et al.35 of a British cohort of 7355 patients, increased risk of breast cancer in a subgroup of patients who
of whom 43% had received ovarian stimulatory drugs, had used progesterone (RR 3.36, 95% CI 1.3–8.6).
reported that CC conferred a 2.6-fold increase in the risk of Three studies from Israel reported an association between
developing cancer of the corpus uteri with a total dose of fertility treatment including IVF and breast cancer. Pappo
≥2250 mg (RR 2.62, 95% CI 0.94–6.82). There were no clear et al.42 reported a possible association between IVF therapy
trends with time since first treatment, i.e. latency, but there was and breast cancer in a cohort of 3375 IVF-treated women.
possibly an association with the number of cycles of CC (RR This was evident in: women aged ≥40 years at first IVF cycle,
2.2, 95% CI 0.24–9.80 with 10 or more cycles). Although high those with hormonal infertility, and those undergoing four or
doses of CC may have been preferentially given to women with more IVF cycles. This was all in comparison to the general
PCOS, adjustments for underlying diagnosis of the latter only population (SIR of 1.9, 95% CI 0.97–3.30; 3.1, 95% CI 0.99–
slightly reduced the magnitude of the estimated risk. The 7.22; and 2.0; 95% CI 1.15–3.27 respectively). The limitations
follow-up in this study was more than 20 years; but with only of this study include: small sample, relatively short follow-up
31 uterine cancer cases, and histology not ascertained, it is period of 8.1 years with only 35 cases identified, of whom
quite difficult to draw any concrete conclusions. 29% had a positive family history. The second study by Katz
In conclusion, multiple cycles and high doses of et al.43 reported an increased risk of breast cancer in women
clomiphene citrate may be associated with an increased risk who started their IVF treatment after age 30 years (RR 1.24,
of uterine cancers, but the evidence for this being an 95% CI 1.03–1.48). This was based on a cohort study of 7162
independent risk factor is inconclusive (see Table S2). patients from a single centre and only 41 cases of breast
cancer. The mean follow-up period was 12.9 years. Finally, a
historical cohort study by Chalderon-Malgarit et al.
Fertility treatment and breast cancer
including 15 030 parous women who were treated with CC
Breast cancer is the commonest cancer in women in England or gonadotrophin, and followed-up for 29 years, noted an
and worldwide, with 41 259 new cases diagnosed in 2010.3 increased risk of breast cancer of borderline significance
Estrogen and progesterone play an important role in (multivariate hazard ratio [HR] 1.42, 95% CI 0.99–2.05). The
tumorigenesis. As there is an increased risk of breast cancer risk was higher for patients who waited ≥12 months to
for infertile nulliparous women anyway, it is interesting to conceive (HR 2.36, 95% CI 1.30–4.27).27
focus on the role of ART and ovulation induction treatments A study by Orgeas et al.45 reported no association between
as a risk factor for breast cancer, with ART being associated fertility treatment and breast cancer. Even so, they did note
with supraphysiological and unopposed levels of estrogen. that women with non-ovulatory causes treated with
As early as 1977, Bolton published the first case report of high-dose CC therapy may have an elevated risk (SIR 1.9,
bilateral breast cancer associated with CC.37 Since then, a few 95% CI 1.08–3.35). The cohort sample was small with only
cohort and case–control studies have been published with 1135 patients, but the median time from fertility treatment to
contradictory conclusions. Some studies observed no breast cancer diagnosis was 26 years.
confirmatory association between fertility drugs and breast Gauthier et al.,46 in a prospective cohort study involving
cancer.8,38–40 Other studies found an increased risk in the 6602 patients treated for infertility, reported a possible
first year after fertility treatment which was attributed to the increased risk of breast cancer after fertility treatment in
probable presence of an occult lesion at the time of women with a family history of the disease. However, no

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 Louis et al.

overall significant association between treatment and breast (RR 2.29, 95% CI 1.16–5.52, and RR 3.26, 95% CI 1.50–7.09
cancer was observed (RR 0.95, 95% CI 0.82–1.11) despite respectively).50 The same group also reported that, for the
almost 10 years of follow-up. Furthermore, the association same cohort, CC and possibly progesterone may increase
between IVF and familial breast cancer was disputed in a thyroid cancer risk particularly among parous women (RR
case–control study by Kotsopoulos et al.47 who concluded 3.09, 95% CI 1.21–7.88). This was based on only 29 cases of
that fertility treatment, including IVF, did not increase the thyroid cancers out of a cohort of 54 362 women.51
risk of breast cancer among patients with BRCA mutation Another retrospective cohort study by Althuis et al. of
(OR 1.21, 95% CI 0.81–1.82). 8422 patients evaluated for infertility (1965–1998) and
It has been observed that women who gave birth after IVF followed up for a mean of 18.8 years reported that the risk
treatment had a decreased incidence of breast cancer, but this of cancer after CC or gonadotrophins did not increase
was not statistically significant (rate ratio 0.93, 95% CI 0.58– significantly for melanoma, thyroid, cervical, or colon cancer
1.43). This was a cohort of 8716 patients who gave birth with either drug. However, CC may impart stronger effects
following IVF and were followed up for a mean of on risks of melanoma (RR 2.0, 95% CI 0.9–4.6) and thyroid
6.2 years.48 The large British cohort study by Silva et al.35 cancer (RR 4.32, 95% CI 1.0–17.1) among women who
reported an increased risk of breast cancer compared with the remained nulliparous.52
general population (RR 1.13, 95% CI 0.97–1.30). In conclusion, there is no strong evidence linking infertility
Nevertheless, no significant differences between the exposed treatment with non-gynaecological cancers. Further studies
and non-exposed infertile cohort after mean follow up of are needed to evaluate any association between infertility,
21.4 years were observed. Evidently this implies that it may fertility treatment and melanoma.
well be infertility that is the cause for the increased risk;
furthermore, a case–cohort study by Rossing et al. concluded
Fertility treatment and childhood cancers
that using CC as a treatment for infertility lowers the risk of
breast cancer (adjusted RR 0.5, 95% CI 0.2–1.2).49 Several sporadic case reports53,54 highlighted a possible link
In conclusion, there is no strong evidence linking fertility between IVF and childhood cancer starting in 2001 with
treatment with breast cancer (Table S3). a report of unilateral retinoblastoma in one child among a
cohort of 47 children born after ART.53 Retinoblastoma is a
rare childhood cancer with only 41 new cases diagnosed in
Fertility treatment and other cancers
England in 2010.3
A few studies have reported an increased risk of developing In 2003 a small series of case reports55 noted an increased
non-gynaecological cancer after fertility treatment. However, risk of developing retinoblastoma in babies born following
the numbers are generally very small and one is unable to reach IVF. This was based on five cases of retinoblastoma and the
any reliable conclusions. This is also partly due to the lower estimation that 1–1.5% of babies in the general population
incidence of some of these cancers. One must note that the were born as a result of IVF (RR 7.2, 95% CI 2.4–17.1for 1%
effects of infertility may well extend beyond gynaecological estimate, and RR 4.9, 95% CI 1.6–11.3 for 1.5% estimate).
cancers, especially with thyroid cancers and melanomas, Though the same researchers observed no increase in risk
particularly when the cause of infertility is secondary to over an expanded study period of 5 years, they still found an
endometriosis, although the association is likely to be casual.33 increased risk of retinoblastoma based on the calculations
In 2010, a total of 5505 new cases were diagnosed with thyroid from the earlier cohort.56 The study provided no firm link
cancer and 1578 with malignant melanoma.3 between IVF treatment and retinoblastoma, other than
The aetiology of malignant melanoma, and to a lesser perhaps to question whether a change in the IVF
extent that of thyroid cancer, is known to involve procedure itself (such as the culture medium) had been
endogenous and exogenous hormones. It is also associated influential, or to speculate on some undefined genetic factors
with parity and COCs.50,51 It was therefore hypothesised that linking both infertility and retinoblastoma. This is in
the exogenous hormones administered for fertility treatment addition to the possibility that the association may be a
might be linked with both cancers. chance finding.55
The study by Silva et al. observed higher than expected Other larger studies were more reassuring57–60 and found
incidence of liver and biliary tract cancer but the results that children conceived using IVF and related procedures did
showed no statistical significance.35 not have a significantly increased incidence of cancer
Linkage of the large Danish cohort mentioned earlier to compared with the general population. In the largest of
different cancer registries yielded no strong association these studies by Bruinsma et al.57 who reviewed a cohort of
between use of fertility drugs and malignant melanoma. 5249 births with a median follow-up of 45 months, the
However, the results did indicate that use of gonadotrophins authors expected 4.33 cases of cancer and six cases were
or GnRH might increase melanoma risk in parous women observed (SIR 1.39, 95% CI 0.62–3.09).

ª 2013 Royal College of Obstetricians and Gynaecologists 181

 Infertility treatment and cancer

Another large record linkage study61 of 30 364 Danish Table S2. Principal studies examining infertility treatment
women evaluated for fertility concluded that there was no and risk of uterine cancer.
increase in the risk of any childhood malignancy. However, Table S3. Principal studies examining infertility treatment
it advised to continue monitoring the effects of and risk of breast cancer.
ovulation-stimulating drugs on future tumour incidence. Please access TOG online here: http://onlinetog.org.
In conclusion, there is no strong evidence linking infertility RCOG fellows and members can access TOG via the RCOG
treatment with childhood cancers. website.

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34 Jensen A, Sharif H, Kjaer SK. Use of fertility drugs and risk of uterine 56 Marees T, Dommering CJ, Imhof SM, Kors WA, Ringens PJ, van
cancer: results from a large Danish population-based cohort study. Leeuwen FE, Moll AC. Incidence of retinoblastoma in Dutch
Am J Epidemiol 2009;170:1408–14. children conceived by IVF: an expanded study. Hum Reprod
35 Silva Idos S, Wark PA, McCormack VA, Mayer D, Overton C, Little V, et 2009;24:3220–4.
al. Ovulation-stimulation drugs and cancer risks: a long-term 57 Bruinsma F, Venn A, Lancaster P, Speirs A, Healy D. Incidence of
follow-up of a British cohort. Br J Cancer 2009;100:1824–31. cancer in children born after in-vitro fertilization. Hum Reprod
36 Saso S, Chatterjee J, Georgiou E, Ditri AM, Smith JR, Ghaem-Maghami 2000;15:604–7.
S. Endometrial cancer. BMJ 2011;343:d3954. 58 Bradbury BD, Jick H. In vitro fertilization and childhood
37 Bolton PM. Bilateral breast cancer associated with clomiphene. Lancet retinoblastoma. Br J Clin Pharmacol 2004;58:209–11.
1977;2:1176. 59 Klip H, Burger CW, de Kraker J, van Leeuwen FE; OMEGA-project
38 Potashnik G, Lerner-Geva L, Genkin L, Chetrit A, Lunenfeld E, Porath A. group. Risk of cancer in the offspring of women who underwent
Fertility drugs and the risk of breast and ovarian cancers: results of a ovarian stimulation for IVF. Hum Reprod 2001;16:2451–8.
long-term follow-up study. Fertil Steril 1999;71:853–9. 60 Lerner-Geva L, Toren A, Chetrit A, Modan B, Mandel M, Rechavi G, Dor
39 Brinton LA, Scoccia B, Moghissi KS, Westhoff CL, Althuis MD, Mabie J. The risk for cancer among children of women who underwent in
JE, Lamb EJ. Breast cancer risk associated with ovulation-stimulating vitro fertilization. Cancer 2000;88:2845–7.
drugs. Hum Reprod 2004;19:2005–13. 61 Brinton LA, Kr€ uger Kjaer S, Thomsen BL, Sharif HF, Graubard BI, Olsen
40 Venn A, Watson L, Lumley J, Giles G, King C, Healy D. Breast and JH, Bock JE. Childhood tumor risk after treatment with
ovarian cancer incidence after infertility and in vitro fertilisation. Lancet ovulation-stimulating drugs. Fertil Steril 2004;81:1083–91.
1995;346:995–1000. 62 Mosgaard BJ, Lidegaard O, Kjaer SK, Schou G, Andersen AN. Ovarian
41 Salhab M, Al Sarakbi W, Mokbel K. In vitro fertilization and stimulation and borderline ovarian tumors: a case–control study. Fertil
breast cancer risk: a review. Int J Fertil Women’s Med 2005;50:259–66. Steril 1998 Dec;70:1049–55.

ª 2013 Royal College of Obstetricians and Gynaecologists 183

 DOI: 10.1111/tog.12027 2013;15:184–8
The Obstetrician & Gynaecologist
Ethics
http://onlinetog.org

Current status of potential organ donation in cases of

lethal fetal anomaly
Joe Brierley MBChB FRCPCH MA*

Paediatric and Neonatal Intensive Care Unit, Great Ormond Street Hospital for Children NHS Trust, Great Ormond Street, London
WC1N 3JH, UK
*Correspondence: Joe Brierley. Email: [email protected]

Accepted on 20 January 2012

Key content  Anencephalic donation does not occur in the UK, or indeed
 Anencephaly is the most severe form of neural tube defect with worldwide at present.
most pregnancies terminated following antenatal diagnosis and
Learning objectives
those carrying to term often stillborn.  This paper seeks to review the current UK position and possible
 Organ donation following anencephalic live birth has been
developments, and to provide guidance for obstetricians to reply to
undertaken worldwide, especially in the early years of infant
such requests.
transplantation. In the USA and Canada this ceased towards the
end of the last century. Ethical issues
 Although few UK transplants occurred, and the practice has  Can a pregnant women elect for her anencephalic infant to be
ceased, national guidelines still support organ retrieval from managed in such a manner – with organ support at delivery – that
anencephalic babies once certified dead. eventual donation after circulatory death can provide organs for
 With the current organ donation task-force linked drive, others on the subsequent death of the baby?
obstetricians are increasingly confronted with women carrying
Keywords: anencephaly / organ donation / severe fetal anomaly /
anencephalic fetuses who decline termination, perhaps for religious
transplantation
reasons, who would like to consider donation.

Please cite this paper as: Brierley J. Current status of potential organ donation in cases of lethal fetal anomaly. The Obstetrician & Gynaecologist 2013;15:184–8.

North America – as a result of UK policies on certification

Introduction
of infant death that inadvertently prevent organ donation
Anencephaly occurs when the cephalic end of the neural tube in infancy.2
fails to close, resulting in the absence of a major portion of Whether organ donation from anencephalic infants that
the brain, skull, and scalp. Infants with this disorder are born had been certified dead using neurological criteria ever
without a forebrain or cerebrum and although some are born occurred in the UK is unclear from the literature. In the US
with a rudimentary brain stem the absence of cerebral the controversial proposal of the removal of organs for
function precludes consciousness, and infants are either transplantation from anencephalic infants before they were
stillborn or die shortly after birth. certified dead3 was short-lived, falling rapidly in the court of
Antenatal identification of anencephalic infants has public opinion.4 Donation from formally ‘brain dead’
progressed from a-fetoprotein screening, via static anencephalic infants continued for a time, however all
B ultrasound to almost universal diagnosis by high-quality programmes in the US have stopped following further
real-time ultrasound, which permits cranial visualisation at debate and an influential Canadian ethical enquiry, which
12–14 weeks. Following such diagnoses, the majority of concurred that there are serious difficulties with using
anencephalic pregnancies are terminated. This, together with neurological criteria to certify death in anencephalic infants
the use of folic acid to prevent neural tube defects, has lead to and that this ought to preclude donation after brain death
a 96% reduction in anencephaly rates over the period (DBD).5 Indeed, no country seems to currently transplant
between 1975 and 1999.1 However, there are still in the organs from anencephalic infants with the most recent
region of 10–20 live born anencephalic infants in England European transplant reported being in Italy in 1999.6
and Wales per annum.1 Somewhat surprisingly, therefore, the most recent UK
Neonatal organ transplantation is, in itself, a rare guidelines from the Working Party on Organ
undertaking in the UK – more so than, for example, in Transplantation in Neonates,7 allows for such donation.

184 ª 2013 Royal College of Obstetricians and Gynaecologists

 Brierley

This guidance was unchanged, and therefore arguably The onset of mechanical ventilation led to the evolution of a
endorsed, by both the British Paediatric Association different method of the certification of human death: brain
document that established specific paediatric brain stem death. In the USA brain death is whole brain death, whereas in
death guidance for the UK,8 and the contemporary Academy the UK the more bedside-orientated brain-stem death is used.12
of Medical Royal Colleges national code of practice on the Brain death originally developed as a predictor of inevitable
diagnosis and confirmation of death.9 ‘somatic death’ in severely brain injured people on organ
The original Working party report suggested: support – notably mechanical ventilation – but has, via
clinical experience, a Presidential Commission in the US,13
‘….that the absence of the forebrain in anencephalic
professional guidance in the UK14 and court rulings,15,16
infants together with apnoea shall be recognised as death.’7
become an accepted method of certifying human death.
The document also stated that: Importantly, the development of brain death was remote from
any concept of the provision of organs for transplantation,17
‘…organs for transplantation may be removed from
though certification of death using neurological criteria
anencephalic infants when two doctors who are not
within intensive care has, without doubt, provided the
members of a transplant team agree that spontaneous
majority of organs used for human transplantation.
respiration has ceased.’7
One vital concept is that human death must be a uniform
Furthermore, such donation apparently remains lawful state, despite different methods being undertaken to
with parental consent, and causes no concerns for Her determine it. Philosophers have suggested, logically, that
Majesty’s Coroner or the Human Tissue Authority (HTA) one should first philosophically define human death, and
(Personal communication from Great Ormond St Hospital only then suggest criteria for its diagnosis before agreeing
Solicitor, 2009 [after seeking senior legal advice] and both tests to clinically verify death18 – whereas with brain death
Coronial and HTA communication, 2009). things arguably evolved in the converse manner.
The pertinence of this to anencephalic donation is that
for some philosophers anencephalic infants actually fulfil a
Dead donor rule
conceptual definition of human death – namely the irreversible
Apart from explicit living donation, the convention is that cessation of the capacity for consciousness19,20 – with its
organ retrieval for donation can only be performed after the corollary that the presence of a circulation and respiration in a
donor has been certified dead. Truog, amongst others, has phenotypical human are not enough to define human
questioned the inviolability of this ‘dead donor rule’,10 by existence. It follows that if we accept their neurological
arguing that brain death has no scientific basis, while also condition to be irreversible, those in a persistent vegetative
insisting that donation should continue from such patients state are also dead, with some suggesting that organ retrieval
who are, therefore, in the dying process rather than dead. In should be permitted in this circumstance.21
fact the entire question of the definitions of death, dying, and Irrespective of such philosophical debates, the concept that
for that matter, human life are extremely complex,11 with anencephalic infants are dead at delivery due to their
only the procedure of organ donation driving exact times or anatomy has been rejected by clinicians worldwide.5,22
indeed invasive testing to establish a diagnosis of death in the
clinical setting.
Anencephalic death
The current rather archaic UK guidelines permit certification
Human death
of death using neurological criteria in an infant known to be
It is worth setting any consideration of organ donation from anencephalic due to antenatal ultrasound findings once, after
anencephalic infants in the context of human death. Most birth, the infant has ‘irreversible apnoea’. In essence this
people who die have death certified using what have been attempt at modifying standard brain stem testing, with
termed cardiorespiratory criteria, though this also involves antenatal imaging replacing conditions necessary for the
confirmation of an absent pupillary response to light, as well diagnosis and confirmation of death as well as both motor
as the absence of heart sounds, breath sounds and a pulse. and brainstem components of the clinical testing together
Before organ support was possible, of course, cessation of with replacement of the apnoea test with the loose term
respiration or circulation were usual precursors to human irreversible apnoea, is clearly unworkable given the interim
death with established absence used to ‘pronounce’ those who advances in medicine.
had died. However, historical recovery from such ‘states’ led Furthermore, no other form of neurological condition is
to the setting up of devices to communicate from the grave currently accepted by neonatal clinicians in the UK as equating
and the building of charnel houses to allow witnessed to death, whereas in the US, Canada and Australia and indeed
putrefaction in those worried about being wrongly buried. other European countries this is standard practice.2

ª 2013 Royal College of Obstetricians and Gynaecologists 185

 Organ donation in fetal anomaly

Of course all live-born anencephalic infants born in the UK circulatory criteria has been an issue,28 although death is
die, having death certified using cardiorespiratory criteria. surely a uniform state, however it is verified. There also
Practically, around half of these babies have inadequate remains significant concern about tolerable warm ischaemic
brainstem formation and do not breathe adequately to times for successful DCD cardiac transplantation.
support organ function after birth, and half breathe It is worth considering whether – at parents’ request –
adequately for a short period then die in the subsequent hours.23 anencephalic infants might be managed in such a way to
facilitate DCD. While this avoids any controversy about brain
Donation death certification, there are a number of practical steps, and
Anencephalic donation after brain death (DBD) indeed ethical considerations.
Anencephalic DBD has been successfully undertaken leading One initial ethical challenge is the need to provide organ
to cardiac and renal transplantation,24 but has now stopped, support to such an infant at delivery. Currently, anencephalic
mainly due to the difficulties in certifying any form of infants are not intubated and ventilated at delivery, as this is
neurological death in these infants. considered futile in that it merely prolongs an inevitable
Organ donation from anencephalic infants following dying process. The clinical standard is that children are
brain death surely needs contemporary review, though managed in what is determined to be their ‘best interests’.
whether the UK position on this following the organ For dying children, as with adults, it is rarely considered that
retention scandal at Alder Hey Children’s Hospital would attempts to provide invasive – and so burdensome – organ
be different from elsewhere is unclear, however given current support is an appropriate intervention. However, if the
appropriate deference to parental autonomy in this area this parents of an anencephalic infant ask for ventilation of their
is potentially possible. baby to try to help another dying infant, surely this is
As already highlighted, neonatal organ donation does not compatible with the legal standard that parental
currently occur in the UK, though such practice is routine in responsibility permits parents to make decisions for their
mainland Europe, Canada, the USA and Australia. This has children, as they are considered the most likely to decide in
led to the anomaly of UK cardiac transplant teams retrieving their child’s best interests, unless their decision is overtly
organs from European infants to transplant into British harmful to the child. While anencephalic children are not
babies, whilst babies dying in the UK cannot donate organs, considered to be dead, it is unclear what degree of pain they
irrespective of parental wishes because of neonatology could ever appreciate without a neocortex, especially given
practices.25 As part of a current ethical address of this by appropriate analgesia. Therefore, it is also unclear what harm
the Royal College of Paediatrics and Child Health’s Ethical would be caused to them. Furthermore, given extended best
and Law Advisory Committee and the Academy of Medical interests appropriately advanced by the courts29 with weight
Royal College Donation Ethics Committee, amongst others, given to social and cultural best interests, not just limited
the entire topic of an agreed UK viewpoint on anencephalic medical best interests, familial altruism is potentially an
DBD warrants attention. overriding determinant in these cases.
Given the recent success of infant cardiac DCD it is worth
Anencephalic donation after circulatory death (DCD) exploring the limits of parental consent and whether an
Over the past decade, the shortage of organs for anencephalic infant might be practically and ethically
transplantation has led to a resurgence of DCD, whereby managed in such a way that they may have intensive care
organ donation can occur within a short interval of death support provided at delivery, and then withdrawn and their
certified by cardiorespiratory criteria. As the circulation has death certified in such a way that facilitated organ donation.
been interrupted prior to death the organs are inevitably
exposed to a period of warm ischaemia, which if prolonged
or exacerbated by antecedent significant hypoxia and/or
Alder Hey and relevance
ischaemia during the dying process, can preclude successful Due to the controversy at Alder Hey and other children’s
transplantation. Consequently, most DCD donation occurs hospitals involving organ retention from children who had
after elective withdrawal of organ support within the died without parents being aware or consenting the Human
intensive care unit, and is standard in both adult and Tissue Act30 has changed UK practice. Whilst organ donation
paediatric intensive care units. Importantly, fewer organs are was not involved in this controversy, the subsequent
currently transplantable following DCD, with no cardiac legislation ensures that UK parents have unprecedented
donation occurring in the UK. In fact, this is not undertaken control over where and how organs and tissues from children
in adults, though of course was involved with Barnard’s first that die are ultimately disposed. It cannot be logical to allow
cardiac transplant,26 but has recently been successfully a family to receive their child’s liver after autopsy to their
reported in three infants in the US.27 For some, the ethical home address, yet not to permit another family to donate a
complexity of donating the heart after certifying death using healthy organ from their dying child to another person.

186 ª 2013 Royal College of Obstetricians and Gynaecologists

 Brierley

The future References

Clearly the current guidance suggesting that irreversible 1 Botting B. Trends in neural tube defects. Health Statistics Quarterly
apnoea in a newborn with known anencephaly equates to 2011;10:5–13.
2 Brierley J. Neonatal organ donation: has the time come? Arch Dis Child
death is unsustainable, not least because irreversible apnoea
Fetal Neonatal Ed 2011;96:F80–3.
remains undefined and practically challenging. Ventilation of 3 [No authors listed] The use of anencephalic neonates as organ donors.
anencephalic infants at delivery to permit more leisurely Council on Ethical and Judicial Affairs, American Medical Association.
diagnosis of a neurological state compatible with death, akin JAMA 1995;273:1614–8.
4 American Medical Association. Council on Ethical and Judicial Affairs.
to brain death, is feasible but internationally has been largely The Use of Anencephalic Neonates as Organ Donors—Reconsidered.
rejected.5 If the Rubicon of ventilating such infants (not in Unpublished meeting proceedings, AMA Interim Meeting, December
their narrow medical best interests, but in some extended 1995, Chicago, IL, USA.
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Paediatr Child Health 2005;10:335–7.
can be crossed, then DCD of heart and kidneys has already 6 Parisi F, Squitieri C, Carotti A, Di Carlo D, Gagliardi MG. Heart
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organs may be feasible. Indeed the FIGO Committee for the Pediatr Transplant 1999;3:150–1.
Ethical Aspects of Human Reproduction and Women’s 7 Department of Health and Social Security. Report of a working party
on organ transplantation in neonates. In: Proceedings of the
Health has recently stated that: Conference of Medical Royal Colleges and their Faculties in the
 The purpose of organ donation constitutes an ethical ground United Kingdom. London: Department of Health and Social Security;
for a woman to choose to maintain an anencephalic 1988
8 British Paediatric Association. Diagnosis of Brain-Stem Death in Infants
pregnancy. Counseling of women and couples regarding
and Children. London; Conference of Medical Royal Colleges and their
organ donation should be undertaken by persons with no Faculties in the United Kingdom; 1991.
conflict of interest. 9 Academy of Medical Royal Colleges. A Code of Practice for the
 When an infant is born with signs of life but has no forebrain Diagnosis and Confirmation of Death. London: Academy of Medical
Royal Colleges; 2008
(anencephaly) and hence has no prospect of survival, with
10 Truog RD, Miller FG. The dead donor rule and organ transplantation. N
parental permission, the child may be placed on a ventilator Engl J Med 2008;359:674–5.
for the purpose of organ donation following natural death. 11 Bernat JL, Culver CM, Gert B. Defining death in theory and practice.
Any local legal definition of death is binding, but it may have Hastings Cent Rep 1982;12:5–8.
12 Wijdicks EF. Brain death worldwide: accepted fact but no
to be reviewed in the light of scientific development of criteria global consensus in diagnostic criteria. Neurology 2002;58:
concerning brain death in neonates.31 20–5.
13 Uniform Determination of Death Act 1980.
14 Diagnosis of brain death. Statement issued by the honorary
Conclusion secretary of the Conference of Medical Royal Colleges and their
Faculties in the United Kingdom on 11 October 1976. Br Med J
Organ donation from anencephalic infants does not currently 1976; 2:1187–8.
occur in the UK, or indeed worldwide. However, national 15 Re A [1992] 3 Med LR 303. 2010.
16 R v Malcherek and Steel [1981] 2 All ER 422. 2011.
guidance does support such donation but clearly needs
17 Machado C, Kerein J, Ferrer Y, Portela L, de la CG, Manero JM. The
contemporary review given the events since it was provided. concept of brain death did not evolve to benefit organ transplants. J
Internationally, the key ethical issue has been the Med Ethics 2007;33:197–200.
determination of death before donation in anencephalic 18 Bernat JL, Culver CM, Gert B. On the definition and criterion of death.
Ann Intern Med 1981;94:389–94.
infants using neurological criteria, and it is generally accepted 19 Puccetti R. Does anyone survive neocortical death. In: Zaner R, editor.
that this is not possible. However, DCD might be realised in Death: Beyond Whole-Brain Criteria. Dordrecht, Netherlands: Kluwer
such cases, though this requires research and new national Academic Publishers; 1988. p. 75–90.
guidance. Obstetricians approached by women carrying an 20 Veatch R. The impending collapse of the whole-brain definition of
death. Hastings Cent Rep 1993;23:18–24.
anencephalic fetus should contact their local senior nurse in 21 Hoffenberg R, Lock M, Tilney N, Casabona C, Daar AS, Guttmann RD
organ donation, though the advice is likely to be that organ et al. Should organs from patients in permanent vegetative state be
donation is not currently possible, but that heart valve used for transplantation? International Forum for Transplant Ethics.
donation after death may be undertaken. Any other Lancet 1997;350:1320–1.
22 Truog RD, Fletcher JC. Anencephalic newborns. Can organs be
donation, such as stem cells or hepatocytes must be under transplanted before brain death?. N Engl J Med 1989;321:
the auspices of formally reviewed research projects. 388–91.
23 Peabody JL, Emery JR, Ashwal S. Experience with anencephalic
Disclosure of interests infants as prospective organ donors. N Engl J Med 1989;321:
344–50.
JB is the clinical lead for organ donation at Great Ormond St 24 The Medical Task Force on Anencephaly. The infant with anencephaly.
Hospital. N Engl J Med 1990;322:669–74.

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 Organ donation in fetal anomaly

25 Brierley J, Larcher V. Organ donation from children: Time for 28 Bernat JL. The boundaries of organ donation after circulatory death. N
legal, ethical and cultural change. Acta Paediatr 2011;100: Engl J Med 2008;359:669–71.
1175–9. 29 Re A (Male Sterilisation) [2000] 1 FLR 549. 2000. 2011.
26 Hoffenberg R. Christiaan Barnard: his first transplants and their impact 30 The Human Tissue Act 2004.
on concepts of death. BMJ 2001;323:1478–80. 31 FIGO Committee for the Study of Ethical Aspects of Human
27 Boucek MM, Mashburn C, Dunn SM, Frizell R, Edwards L, Reproduction and Women’s Health. Ethical Issues in Obstetrics and
Pietra B et al. Pediatric heart transplantation after declaration Gynecology. London: FIGO; 2012 [http://www.figo.org/files/figo-corp/
of cardiocirculatory death. N Engl J Med 2008;359: English%20Ethical%20Issues%20in%20Obstetrics%20and%
709–14. 20Gynecology.pdf].

188 ª 2013 Royal College of Obstetricians and Gynaecologists

 DOI: 10.1111/tog.12028 2013;15:189–94
The Obstetrician & Gynaecologist
Ethics
http://onlinetog.org

Antenatal and intrapartum care of pregnancy complicated

by lethal fetal anomaly
Karen McNamara MBBCh BAO MRCPI MSc,a Keelin O’Donoghue MB BCh BAO FRCOG PhD,b
Orla O’Connell RGN RM BA Psych MIACP,c Richard A Greene MBBCh BAO FRCOG FRCPId,*
a
Registrar, Anu Research Centre, Department of Obstetrics and Gynaecology, University College Cork and Cork University Maternity Hospital,
Cork, Ireland
b
Consultant Obstetrician Gynaecologist, Senior Lecturer, Anu Research Centre, Department of Obstetrics and Gynaecology, University College Cork
and Cork University Maternity Hospital, Cork, Ireland
c
Bereavement Midwife, Cork University Maternity Hospital, Cork, Ireland
d
Professor of Clinical Obstetrics and Director, National Perinatal Epidemiology Centre, Department of Obstetrics and Gynaecology, University
College Cork and Cork University Maternity Hospital, Cork, Ireland
*Correspondence: Richard Greene. Email: [email protected]

Accepted on 12 February 2013

Key content  To provide a framework for the management of a pregnancy

 Congenital anomalies are the number one cause of infant mortality involving a lethal fetal anomaly.
in the developed world. Antenatal diagnosis of lethal fetal  To increase the awareness of the emotional and spiritual needs of
abnormality is likely to have a profound psychological impact. the family.
 The multidisciplinary team should aim to meet the medical,
Ethical issues
emotional and spiritual needs of the family, through appropriate  The dilemma of psychological impact of carrying a pregnancy with
referral in the latter aspect.
a lethal fetal anomaly for a mother and a family.
Learning objectives  The issues around care including feeding the liveborn baby with an
 To consider the psychological impact of an antenatal diagnosis of anomaly.
lethal fetal abnormality.
Keywords: anomaly / lethal / multidisciplinary care / perinatal
 To review the principles of informing parents about the diagnosis.
hospice / individualised care

Please cite this paper as: McNamara K, O’Donoghue K, O’Connell O, Greene RA. Antenatal and intrapartum care of pregnancy complicated by lethal fetal
anomaly. The Obstetrician & Gynaecologist 2013;15:189–94.

in this area. A handful of authors have studied outcomes in

Introduction
pregnancies complicated by lethal fetal anomaly,2,3 while
Congenital anomalies are the number one cause of infant even fewer have proposed a strategy on how to care best for
mortality in the developed world, accounting for 20% of these babies and their parents.1 The first published report on
infant deaths.1 Lethal fetal anomalies encompass a wide range the maternal grief reaction in stillbirth was published in 1968
of conditions, which, mainly as a result of advances in and the first report on parental grief following neonatal death
ultrasonography, are now routinely detected in the antenatal was published in 1970.4,5 Before these publications, the
period. These conditions include brain anomalies such as implications of perinatal deaths were often ignored, with
anencephaly, skeletal anomalies, genetic disorders including clinicians underestimating the significant impact on parental
triploidy and trisomies 13, 15 and 18, and bilateral renal tract morbidity in terms of post-traumatic stress disorder,
anomalies such as renal agenesis, multicystic or dysplastic relationship difficulties, anxiety, depression and suicidal
kidneys and polycystic kidney disease. ideation.6,7 There is now also much evidence on the
The diagnosis of lethal fetal anomaly poses significant concomitant morbidity in both the existing children and
challenges for obstetricians, paediatricians, and the subsequent siblings in terms of attachment disorders,
bereavement and loss team, as parents struggle to come to behavioural difficulties and depression.8,9
terms with the reality of the diagnosis. Currently, there is a In a study based in the United Kingdom (UK) in 2007
paucity of literature addressing the management of these Breeze et al. reported that only 40% of women faced with a
pregnancies, and clinicians in training realise little experience diagnosis of lethal fetal anomaly chose to continue with their

ª 2013 Royal College of Obstetricians and Gynaecologists 189

 Care of pregnancy complicated by lethal fetal anomaly

pregnancies,2 with the other 60% electively terminating the Core to this approach is the multidisciplinary team who
pregnancy. The authors, who are based at a large tertiary- together aim to meet the medical, emotional and spiritual
referral university teaching hospital in the Republic of Ireland needs of the family, and who continue to liaise with them
(ROI), report their experience. Termination of pregnancy is after the death of the baby.12 Bereavement and loss midwives
not legalised in Ireland, which contributes to clinicians develop an ongoing relationship providing support
having more experience in managing ongoing pregnancies throughout pregnancy, delivery, the postnatal period and
affected by lethal anomalies. The legal right to life of the fetus where possible, into a subsequent pregnancy. The primary
is enshrined within the Irish Constitution, with an equal right obstetrician leads and directs the care providing a sense of
to life being accorded to both fetus and mother. There is no continuity and security. Input from neonatologists prioritises
universal policy of prenatal screening for fetal anomaly and the identity of the fetus as an individual. Ethnicity, culture
while screening for aneuploidy is privately available, a and religious beliefs also have a profound effect on the grief
minority of pregnant women access this service. While reaction to perinatal loss. Lathrop et al.13 describe recent
parents can travel abroad in order to obtain a termination of developments in bereavement theory focusing particularly on
pregnancy the dominant parental choice is to continue with a way to restore the parents’ sense of meaning and self-
these pregnancies.10 The experience gained by clinicians in purpose in life. In considering this process it is clear that
the ROI, provides learning for other clinicians and teams chaplaincy or spiritual support has a valuable role to play
where continuation of the pregnancy is less common. in addition to traditional religious ministry. It is vital
The antepartum and intrapartum care of pregnancies that parents take control and exercise as much choice as
complicated by lethal fetal anomaly is unique and requires an possible in areas such as birth planning, creating memories
individualised management plan to meet the significant and burial arrangements.
obstetric and psychosocial needs. A multidisciplinary team
approach is the ideal, involving obstetricians, neonatologists,
Antenatal management
sonographers, bereavement and loss midwives, social support
services and pastoral care support. The parents need to be Diagnosis and breaking news
assisted and supported from the time of initial diagnosis Informing parents of the diagnosis of lethal fetal anomaly is
through stages of shock, denial, anger and grief to a level of perhaps the most difficult interaction in the early relationship
adaptation whereby they can begin to cope with their loss between the clinician and parents. If the diagnosis is
and even engage with the positive aspects of their experience. suspected but not confirmed it is best to be honest and
Significant time and emotional support is needed around advise the parents there is a concern and you will organise a
the time of antenatal diagnosis and in preparing the parents specialist opinion as soon as possible. To avoid the woman
for delivery and the postnatal period. Frank, open and returning alone for the scan and diagnosis, she should be
informed discussions need to be held with the parents advised to bring her partner or support person. Similarly, the
regarding the difficulty predicting the time of fetal or diagnosis may not be confirmed until after results are
neonatal death, the complications that may arise in the available from invasive testing. Once confirmed, parents need
antenatal period, as well as timing of delivery and to hear the information regarding the pregnancy in simple,
management of labour. non-medical language and usually, more than once. The
information is delivered in an appropriately private space
with both partners present if possible. The clinician needs to
Perinatal hospice and multidisciplinary
takes cues from the parents and proceed gently, checking on
approach
existing knowledge and concerns. Some parents will require a
The most striking difference between ‘normal’ pregnancies lot of information while more than the minimum facts would
and pregnancies complicated by lethal fetal anomaly is the overwhelm others. Parents value both visual images and
profound psychological effect these pregnancies can leave on written information to enhance their understanding at this
affected families. The cornerstone of caring for these time.14 The introduction of other team members (specialist
families should not just involve monitoring for the midwifery, counselling, pastoral care) at this stage may be
physical side effects of pregnancy but also focus on helpful in initiating a relationship that will provide ongoing
psychological needs. In 2001, Hoeldtke et al.11 introduced support. Communication with the GP and community
the concept of perinatal hospice. In this paper the authors midwife is very important as they will be involved with the
proposed that families who were carrying pregnancies care and be a resource for the parents. Regular updates to
complicated by lethal fetal anomalies be likened to those these healthcare professionals, ensures appropriate care
of a terminally ill child. They proposed extending the responses to new symptoms.
traditional hospice model to care for families anticipating a Parent support networks and/or advocacy groups (such as
perinatal loss. UK Stillbirth and Neonatal Death or Antenatal Results and

190 ª 2013 Royal College of Obstetricians and Gynaecologists

 McNamara et al.

Choices) may be of benefit depending on the parent’s emotional wellbeing of some mothers, for others it may be
individual needs. Providing written information may also be necessary to diagnose complications in a timely manner. As
appropriate in aiding parents with their decision of whether well as the more common pregnancy complications (pre-
to terminate the pregnancy or continue on to term. It is eclampsia, gestational diabetes, maternal anaemia), certain
appropriate, even in countries where termination is not anomalies are associated with increased rates of specific
readily available, that both options be discussed and complications. In their report on anencephaly, Obeidi et al.3
presented to the parents using a non-biased and non- found that 27% of pregnancies developed polyhydramnios.
judgmental approach. It is recognised that termination of Polyhydramnios has also been associated with the lethal
pregnancy at this stage is associated with significant parental skeletal dysplasias.16 Certain trisomies (such as trisomy 13)
grief reactions15 and support following termination should be and triploidy can lead to hydrops and there is a specific
continued for as long as necessary. association of fetal hydrops with polyhydramnios17 and
severe early onset maternal pre-eclampsia. The Ballantyne
Antenatal care Syndrome, also known as the maternal hydrops syndrome or
If the parents choose continuation of pregnancy then a well- mirror syndrome, can affect women pregnant with a
documented plan of care for the pregnancy should be agreed hydropic fetus. This syndrome is characterised by maternal
on. This should be an individualised plan based on the ‘mirroring’ of the hydropic state – hypertension, severe
diagnosis, certainty of the diagnosis and likely prognosis. oedema, and can progress to maternal eclampsia. The exact
Consideration should be given to the fact that not all patients pathophysiological basis for this disorder is unknown but the
will want a comprehensive holistic package and an maternal condition dramatically improves upon delivery.
appropriate plan with selected components should be Polyhydramnios can cause significant problems both
developed to meet their needs also. antenatally and during labour and induction. Maternal
The importance and appreciation of continuity of care is discomfort can be severe with tense polyhydramnios, and
stressed. It is important to manage this period as sensitively this may itself be an indication for amnioreduction.
as possible, as it may be the only opportunity that the parents Polyhydramnios also increases the risk of placental
will have to bond with the baby and create memories while he abruption, unstable fetal lie, ineffective uterine activity
or she is still living. It may also be worthwhile for example if during labour and postpartum haemorrhage.
the parents wish to establish the gender or use the baby’s Amnioreduction may be needed several times during the
given name. Flexibility when seeing these families for pregnancy and although it relieves maternal discomfort, is
antenatal care is hugely important. Some women will not without complications. It has been associated with a 1.2–
request to be seen outside of the usual antenatal clinic 3%18,19 procedure-related complication rate, which can
times, when there are fewer pregnant women in the clinical include prolonged pre-labour rupture of the membranes
areas, and this request should be accommodated wherever (PPROM), chorioamnionitis, placental abruption and
possible. Women will often need to be seen for more frequent maternal visceral injury. While providing comfort,
visits than the usual antenatal care schedule. This is both for amnioreduction may delay labour onset and thus not be in
ongoing reassurance that the fetus is alive, and for early the best interest of the patient.
diagnosis of any developing pregnancy complications. The substantial risk of intrauterine fetal death (IUFD) is
A meeting with a senior neonatologist is important in the another complication that needs to be discussed with parents.
antenatal care schedule. It is key that the parents are fully This risk has been reported at 15–35% in the literature,
aware of the supportive nature of care that will be given to depending on the type of anomaly.3,20 Obeidi et al. reported
the neonate should he/she be born alive and that they a 23% IUFD rate in their anencephaly population3 and
understand that resuscitation is not appropriate should the for trisomy 21 it is estimated that 40% of affected fetuses die
baby be born alive. Analgesia requirements, neonatal unit in utero.21
facilities and visits prior to delivery should also be discussed.
The outcome of this meeting needs to be clearly documented
Intrapartum care
in the antenatal notes and an outline of the care to be given
to the neonate recorded as part of the intrapartum care plan. How and when to deliver, both ongoing pregnancies with
Ideally, both parents should be involved at this meeting, as lethal anomalies and those already complicated by IUFD
this helps to lessen parental anxiety in the postnatal period. needs to be addressed in detail with the parents. Ideally,
vaginal delivery with minimal intervention should be
Pregnancy complications encouraged. If induction of labour is necessary (IUFD, no
Monitoring for the appearance of pregnancy complications is spontaneous onset), the majority of clinical protocols now
another vital facet in the management of these pregnancies. rely on initial mifepristone and later misoprostol. This is
Although repeated ultrasonography may impact on the primarily based on a study by Wagarachachi et al.,21

ª 2013 Royal College of Obstetricians and Gynaecologists 191

 Care of pregnancy complicated by lethal fetal anomaly

published in 2002. This study found that the combined use of In one case series where four labours associated with lethal
mifepristone and misoprostol was not only safe but also had fetal anomalies were managed with continuous fetal heart
an average time to delivery interval less than any of the other rate auscultation, the authors reported that mothers found
induction regimens in use at the time of publication. significant comfort in the live births and the time spent with
There is little consensus on the appropriate timing of the neonate before death. In these cases, the maternal desire
induction of labour and decisions have to be based on the to avoid an intrapartum stillbirth was deemed so strong that
specific needs of each pregnancy. Each case should be it ‘would result in significant psychological impairment if it
examined individually and maternal discomfort and requests, occurred.’22 There has also been another case report where a
parity and suitability for induction, and presence or absence CS for an abnormal fetal heart trace in a baby with lethal fetal
of pregnancy complications should all be taken into account. anomaly was carried out.2 Again this was at maternal request,
Local legal and ethical practice need also to be given due and was determined by clinicians involved to have benefited
consideration. Early induction of labour where the fetus has a the mother psychologically.
lethal anomaly is not an option in the UK; it may in some There are certain scenarios, where elective CS delivery is
jurisdictions be considered termination of pregnancy and not clearly the best and safest method of delivery. Women with
be legally possible. If early induction is planned then the three previous CS scars have a high chance of uterine scar
woman should be fully aware of the potential for failure,3 rupture and unless very premature spontaneous labour
which may necessitate repeat attempts at induction at a later occurs these women are best delivered by CS. Some units
date, or even caesarean section (CS). do undertake induction of labour in this clinical situation,
Consideration also needs to be given to the location of under strict protocol and commonly using mechanical
labour. Ideally women should be given the opportunity to devices (balloon catheter) for cervical dilatation. Women
labour in private, in a single room. A senior midwife who has with two or fewer uncomplicated caesarean sections may be
had experience in dealing with pregnancies complicated by allowed attempt a vaginal birth after caesarean (VBAC),
lethal fetal anomaly should be present. This helps to reduce assuming the risk of scar rupture, and increased risk of blood
both parental and staff stress and anxiety at this crucial time. transfusion is addressed.23 Other indications for elective CS
All usual forms of analgesia should be available – entonox, include spontaneous labour with a transverse lie, or if there is
pethidine, diamorphine, epidural analgesia. Also if a high suspicion of birth dystocia, for example pregnancies
polyhydramnios has been an issue or maternal pre- with severe fetal hydrops. Shoulder dystocia is a significant
eclampsia is present it may be necessary to site an risk factor with macrosomic or hydropic babies and can
intravenous cannula, check haematology and biochemistry result in both physical and psychological maternal trauma.
indices and have blood cross-matched, in anticipation of the Some parents may request elective CS in the absence of any
increased risk of postpartum haemorrhage. maternal medical condition. This request should be treated
Continuous monitoring of the fetal heart is not routinely the same as a request for CS in a routine pregnancy.
advocated during labour and women should be appropriately Following appropriate counselling, the lead obstetrician and
counselled in this regard. There should be a detailed the mother may decide that elective CS is in the maternal best
discussion including an agreed approach with the parents interest and proceed to same, however, wherever possible,
and neonatologists on the issue of monitoring. This should vaginal delivery should be advocated and CS limited to
be clearly documented and provision made for care around appropriate indications.
delivery if the on-call team are uncomfortable with the Certain fetal anomalies increase the time spent in labour
approach. This is mainly to avoid emergency CS for an and increase the risk of dystocia. Anencephaly can be
abnormal fetal heart rate during labour. CS is associated with associated with inadequate cervical dilation or inadequate
significant maternal complications including venous descent of the presenting part. Because of this, a longer
thromboembolism, postoperative infection and potential passive second stage of labour has been advocated. This aims
damage to the maternal structures and vessels. It also has a to ensure good descent of the fetal head and prevent CS at
significant psychological impact on the mother given the full dilatation. The use of Neville-Barnes forceps has also
persistence of a CS scar and the implications for risk of been associated with anencephalic vaginal deliveries.
uterine rupture in a subsequent pregnancy. Nevertheless, Destructive procedures such as craniotomy, decapitation,
some women will request the option of an emergency and cleidectomy were common in the 19th century to enable
caesarean section in labour; although not the preferred vaginal delivery of a dead baby that had become obstructed in
option, it may be appropriate after detailed discussion. It is the pelvis during labour.23 These procedures have almost
usual practice to auscultate the fetal heart intermittently, for completely disappeared from western medicine although are
parental information, and in the second stage of labour, so still carried out in the developing world. Fluid drainage
that the parents as well as neonatologists can be updated on procedures should be considered where fluid filled cavities
the condition of the fetus immediately prior to delivery. are a cause for obstruction or dystocia. A senior obstetrician

192 ª 2013 Royal College of Obstetricians and Gynaecologists

 McNamara et al.

should be ether available or in attendance at delivery. Active as a vital milestone in their grieving process. Receiving
management of the third stage of labour is advised, using postmortem reports and other test results may also allow
oxytocics to ensure adequate uterine tone. some sense of closure. For most parents it will also be an
The experience of delivery when the parents see their baby opportunity to begin to invest in the future and raise the
for the first time will always be remembered. They may have subject of subsequent pregnancies. They will need to be
lost their baby but they have still become parents and this reassured that the team are aware that any subsequent
needs to be acknowledged. The first half hour while the baby pregnancy will be very stressful and that a plan for additional
is still soft and warm is a vital time and can never be support is available. This is also an opportunity to address
recaptured.25 The parents may need to be supported in significant physical and emotional issues, which presented in
holding and caring for their baby if they wish and helped the postnatal period that may be traumatic to both the
with creating memories such as time alone together. While it mother and her family.
is common practice to encourage the parents and siblings to Routine postnatal care in relation to observing lochia,
hold the baby; it is not evidence based and in fact may have ensuring adequate healing of perineal tears or episiotomies
adverse effects including post-traumatic stress disorder.26 needs to be continued. Lactation can be a sensitive issue for
mothers in the postnatal period. It has been shown that
cessation of lactation can cause moderate to severe breast
Neonatal care
engorgement in 66% of women when no treatment is given.
If the neonate is born alive then senior neonatal input is This can progress to mastitis in a minority. There is no
necessary to avoid inappropriate attempts at resuscitation consensus on whether agents to suppress lactation should be
from more inexperienced members of the neonatal team. The used in this setting. One of the more common drugs used is
presence of an agreed and documented plan of care is vital. If the dopamine receptor agonist Cabergoline; while unlicensed
the baby is born alive then comfort care should be offered. it is found effective in clinical practice and could be used if
The neonate should be kept warm and comfortable and if there are no contraindications (such as, hypersensitivity,
needed analgesia may be offered. Human touch is important CYP450 drug interaction potential, liver abnormalities).
both for soothing the infant and for creating a bond between If the diagnosis of fetal anomaly was suspected but not
baby and parents. Not all parents will wish for this approach confirmed antenatally then a postmortem examination
and in certain conditions it may be reasonable for the should be offered and encouraged. This is both important
neonate to be admitted to the neonatal unit for further care. in helping the family come to terms with the loss and in
Other family members such as siblings should be encouraged helping to estimate a recurrence risk for subsequent
to be involved. pregnancies. If a postmortem is declined then a placental
Whether to feed the baby can be of significant concern to or cord biopsy should be sent for cytogenetic analysis and
the parents. If the baby suckles then feeding can be DNA storage (more and more conditions are amenable to
encouraged as this can be a source of comfort to the genetic diagnosis) and consideration should be given to
neonate. If the baby dies in hospital, where possible this further investigations, including X-rays, computerised
should happen in a private setting, making provision for all tomography or magnetic resonance imaging, and geneticist
family members to attend. review according to local protocols.
Some babies are born with anomalies that are not Finally, continued liaison between the family and the
immediately fatal and in these cases provision can be made bereavement and loss services is encouraged and a postnatal
to allow the parents to bring the baby home. This aids with follow-up appointment with clinicians to discuss events
bonding, can profoundly help with the parental grief reaction surrounding the death of the baby should be arranged when
and can allow older siblings time to adjust to the perinatal the parents are ready. Subsequent pregnancies may need to
death. Home care can be utilised in liaison with the hospice be managed by a fetal medicine specialist with anomaly
team or with the neonatal team, depending on local ultrasound and/or invasive prenatal diagnostic techniques. It
protocols. A visit from the bereavement and loss team, who may also be necessary to refer the family to a clinical
have been liaising with the family, may also be helpful. geneticist for genetic counselling and/or testing. As
Taking the baby home may not be an option for parents and subsequent pregnancies are associated with significant
hospice care may be provided in the neonatal unit or local depression and anxiety,6 multidisciplinary support should
hospice if suitable for babies. be continued.

Postnatal parental follow-up Staff debriefing

Postnatal follow-up, ideally by the same team who looked It is important to note that often during the process of caring
after the mother during pregnancy is experienced by parents for parents who have experienced a lethal fetal anomaly

ª 2013 Royal College of Obstetricians and Gynaecologists 193

 Care of pregnancy complicated by lethal fetal anomaly

resulting in a stillbirth or neonatal death, or indeed any 7 Barr P, Cacciatore J. Personal fear of grief and death in bereaved
mothers. Death Stud 2008;32:445–60.
pregnancy loss, staff members can also be affected. This can
8 Hughes P, Turton P, Hopper E, McGauley GA, Fonagy P. Disorganised
be hugely traumatic for all staff members involved. Given the attachment behaviour among infants born subsequent to stillbirth.
lack of adequate training in this field of obstetrics and J Child Psychol Psychiatry 2001;42:791–801.
midwifery, particularly if it is their first time involved in the 9 O’Connor TG, Heron J, Golding J, Beveridge M, Glover V. Maternal
antenatal anxiety and children’s behavioural/emotional problems at
management of these pregnancies, junior staff members are
4 years; report from the Avon Longitudinal Study of Parents and
particularly at risk. All units involved in delivering these Children. Br J Psychiatry 2002;180:502–8.
babies should have adequate provisions in place for 10 Lalor J, Begley CM, Galavan E. Recasting hope: a process of
debriefing staff not just following stillbirth but all adverse adaption following fetal anomaly diagnosis. Soc Sci Med
2009;68:462–72.
pregnancy outcomes. 11 Hoeldtke NJ, Calhoun BC. Perinatal hospice. Am J Obstet Gynaecol
2001;185:525–9.
12 Kilby MD, Pretlove SJ, Bedford Russell AR. Multidisciplinary palliative
Conclusion care in unborn and newborn babies. BMJ 2011;342:d1808.
13 Lathrop A, VandeVause L. Continuity and change.in mothers’
In summary, the diagnosis of a lethal fetal anomaly is a narratives of perinatal hospice. J Perinat Neonatal Nurs 2011;25:
difficult time for both parents and clinicians. Options, 21–31.
including termination of pregnancy and continuation of 14 Lalor JG, Devane D, Begley CM. Unexpected diagnosis of fetal
the pregnancy with palliative care of the infant, should be abnormality: woman’s encounters with caregivers. Birth 2007;34:
80–8.
discussed in a non-judgmental manner and parents 15 Kenyon SL, Hackett GA, Campbell S. Termination of pregnancy
supported through the necessary decision-making process. following diagnosis of fetal malformation: the need for improved
A multidisciplinary approach with continuity of care is follow up services. Clin Obstet Gynecol 1988;31:97–100.
16 Chen CP, Chern SR, Shih JC, Wang W, Yeh LF, Chang TY, et al. Prenatal
essential in helping these families understand and adjust to
diagnosis and genetic analysis of type I and type II thanatophoric
the diagnosis, and is also necessary to ensure quality of care dysplasia. Prenat Diagn 2001;21:89–95.
through pregnancy, labour and delivery. The emotional and 17 Boyd PA, Lindenbaum RH, Redman C. Pre-eclampsia and trisomy 13:
spiritual needs of the family are just as important as the a possible association. Lancet 1987;2:425–7.
18 O’Donoghue K, Giorgi L, Pontello V, Pasquini L, Kumar S.
physical management of these pregnancies. There is a paucity
Amniocentesis in the third trimester of pregnancy. Prenat Diagn
of published literature to guide clinicians in the management 2007;27:1000–4.
of these difficult and sometimes complex pregnancies. This 19 Leung WC, Jouannic JM, Hyett J, Rodeck C, Jauniaux E. Procedure
review aims to provide a framework for the management of related complications of rapid amniodrainage in the treatment of
polyhydramnios. Ultrasound Obstet Gynecol 2004;23:154–8.
pregnancies complicated by lethal fetal anomaly. 20 Carpenter MW, Corrado F, Sung J. Lethal fetal renal anomalies and
obstetric outcome. Eur J Obstet Gynecol Reprod Biol 2000;89:
Disclosure of interests 149–52.
None declared. 21 Wagaarachchi PT, Ashok PW, Narvekar NN, Smith NC, Templeton A.
Medical management of late intrauterine death using a combination
of mifepristone and misoprostol. BJOG 2002;109:443–7.
22 Spinatto JA, Cook VD, Cook CR, Voss DH. Aggressive intrapartum
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2 Breeze ACG, Lees CC, Kumar A, Missfelder-Lobos HH, Murdoch M. 23 Royal College of Obstetricians and Gynaecologists. Greentop
Palliative care for prenatally diagnosed lethal fetal abnormality. Arch Guideline No. 45. Birth after Previous Caesarean Birth. London: RCOG;
Dis Child Fetal Neonatal Ed 2007;92:F56–8. 2007.
3 Obeidi N, Russell N, Higgins JR, O’Donoghue K. The natural history of 24 Sikka P, Chopra S, Kalpdev A, Jain V, Dhaliwal L. Destructive
anencephaly. Prenat Diagn 2010;30:357–60. operations-a vanishing art in modern obstetrics: 25 year experience
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doctors. J R Coll Gen Pract 1968;16:103–12. 2011;283:929–33.
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194 ª 2013 Royal College of Obstetricians and Gynaecologists

 DOI: 10.1111/tog.12038 2013;15:195–9
The Obstetrician & Gynaecologist
CPD
http://onlinetog.org

CPD questions for volume 15, number 3

CPD credits can be claimed for the following questions In the treatment of postpartum psychosis,
online via the TOG CPD submission system. You must be a 11. the woman should not breastfeed. ThFh
registered CPD participant of the RCOG CPD programme 12. lithium is the gold standard. ThFh
(available in the UK and worldwide) in order to submit your 13. referral to safeguarding teams should be
answers. Participants will need to log in to the RCOG website routine. ThFh
(www.rcog.org.uk) and go to the ‘Our Profession’ tab. 14. the whole range of psychotropic medication
Participants can claim 2 credits per set of questions if at may need to be employed. ThFh
least 70% of questions have been answered correctly. At least
In the prevention of puerperal psychosis,
50 credits must be obtained in this way over the 5-year cycle.
15. a woman who has experienced an episode
Please direct all questions or problems to the CPD Office.
should be advised about both the risk of
Tel: +44(0) 20 7772 6307 or email: [email protected]
postpartum and non-postpartum recurrence. ThFh
The blue symbol denotes which source the questions refer
16. only women with psychiatric symptoms at
to including the RCOG journals, TOG and BJOG, and RCOG
their antenatal booking visit should be
guidance, such as Green-top Guidelines (GTG) and Scientific
screened for risk factors. ThFh
Impact Papers (SIPs). All of the above sources are available to
17. women at high risk, even if they are well,
RCOG members and fellows via the RCOG website.
should be referred in pregnancy for psychiatric
assessment and management. ThFh
TOG Postpartum psychosis
With regard to postpartum mood disorders in
Postpartum psychosis complicating childbirth occurs in the UK,
approximately, 18. suicide is a leading cause of maternal
1. 1–2 in 1000 women in the general population. T h F h mortality. ThFh
2. 1 in 4 women with bipolar disorder. ThFh 19. a survival analysis comparing women with
bipolar disorders who stopped taking lithium
The definition of postpartum psychosis includes,
because of pregnancy compared with age-
3. the continuation of a chronic schizophrenic
matched non-pregnant control, has shown
illness into the postpartum period. ThFh
similar recurrence rates during the first 40
4. the onset of a severe obsessive–compulsive
weeks after lithium discontinuation. ThFh
illness in the first 2 weeks following delivery. ThFh
20. women with schizophrenia have a similar risk
5. an episode of major depression with onset in
of admission for this disorder in the
the first postpartum month. ThFh
postpartum period compared to those with
6. acute onset in the first postpartum week of an
bipolar disorders. ThFh
episode with marked manic and psychotic
features. ThFh
7. acute onset 2 years postpartum of an episode
TOG Pelvic congestion syndrome
with manic and psychotic features, including
delusional thoughts of harming the baby. ThFh The following aetiological factors have been associated
with pelvic congestion syndrome:
The postpartum onset specifier in Diagnostic and
1. ovarian varicoceles. ThFh
Statistical Manual of Mental Disorders (DSM-IV-TR)
2. pregnancy. ThFh
identifies postpartum episodes as those with an onset
3. estrogen and progesterone. ThFh
following delivery within:
4. nutcracker syndrome. ThFh
8. 1 month. ThFh
9. 6 months. ThFh Regarding pelvic congestion syndrome (PCS),
10. 3 months. ThFh 5. it is a widely accepted clinical condition. ThFh

ª 2013 Royal College of Obstetricians and Gynaecologists 195

 CPD

6. more than 75% of affected individuals are Vaginoscopy,

symptomatic. ThFh 4. refers to a ‘no touch’ technique for
hysteroscopy that bypasses the routine
Regarding the clinical presentation of PCS,
requirement for a vaginal speculum or
7. pain is the most common feature. ThFh
instrumentation of the cervix. ThFh
8. psychological symptoms such as anxiety and
5. requires a hysteroscope with a 30° offset distal
depression are common. ThFh
lens. ThFh
Regarding investigations for PCS, 6. is useful in women with atrophic lower genital
9. selective venography is recommended first line. T h F h tracts or restricted vaginal access. ThFh
10. tortuous pelvic veins greater than 4 mm in
diameter are diagnostic of PCS on ultrasound. T h F h Outpatient hysteroscopic removal of endometrial polyps,
7. requires infiltration into or around the cervix
Regarding the medical management of PCS,
with a local anaesthetic. ThFh
11. ovarian suppression can cause venous
8. has evidence to support feasibility, but not
vasoconstriction. ThFh
effectiveness. ThFh
12. medroxyprogesterone acetate (MPA) has only
9. is limited to some degree by the size, location
been shown to subjectively reduce pelvic pain. ThFh
and number of lesions. ThFh
13. gonadotropin-releasing hormone (GnRH)
10. with Versapoint® bipolar diathermy requires
agonists shave been shown to subjectively and
continuous flow hysteroscopes >5 mm in
objectively improve pelvic pain. ThFh
outer diameter. ThFh
14. MPA has been proven to be more effective
11. using bipolar electrosurgery needs a non-
treatment than GnRH agonist at 12 months. ThFh
conducting distension media. ThFh
15. psychotherapy has been shown to have an
12. using the new morcellator systems is
additive benefit to the treatment of pelvic pain
compatible with standard hysteroscopes. ThFh
compared with MPA alone. ThFh
Regarding submucous fibroids,
Regarding the surgical management of PCS,
13. most can be removed in an outpatient setting. T h F h
16. there is good evidence to suggest the
14. formal resection of fibroids usually requires
application of laparoscopic bilateral
general anaesthesia. ThFh
transperitoneal ligation of ovarian veins. ThFh
15. the likelihood of complete excision of a
17. hysterectomy and bilateral oophorectomy has
grade 1 submucous fibroid (>50% visible
not been shown to achieve a statistically
within the uterine cavity) is increased with
significant reduction in pelvic pain in women
preliminary capsular incision in the outpatient
with PCS. ThFh
setting following diagnosis. ThFh
Regarding the role of endovascular treatment in PCS,
Hysteroscopic sterilisation with the Essure® system:
18. transcatheter embolotherapy has been shown
16. is not feasible in approximately 20% of
to improve overall pain perception by more
women. ThFh
than 60%. ThFh
17. is completed in less than 15 minutes. ThFh
19. only the refluxing ovarian vein should be
18. requires routine dilatation of the cervix. ThFh
embolised. ThFh
19. has a higher cumulative pregnancy rate
20. there has been no significant hormonal
compared with laparoscopic sterilisation. ThFh
disturbance after embolotherapy. ThFh
20. needs a routine hysterosalpingogram to
confirm tubal occlusion. ThFh

TOG Ambulatory hysteroscopy

Pain can be minimised during diagnostic outpatient TOG Management of vault prolapse
hysteroscopy by the routine use of, Regarding the role of conservative treatment in vaginal
1. a vaginal speculum. ThFh vault prolapse,
2. conscious sedation. ThFh 1. physiotherapy has been shown in trials to be
3. non-steroidal anti-inflammatory agents beneficial. ThFh
1-hour pre-procedure. ThFh 2. pessary use has a high patient satisfaction rate. T h F h

196 ª 2013 Royal College of Obstetricians and Gynaecologists

 CPD

Regarding the vaginal route for the surgical treatment of 20. laparoscopic sacrocolpopexy has been shown
vaginal vault prolapse, to have similar reoperation rates as those after
3. objective outcomes for sacrospinous fixation treatment with a vaginal mesh. ThFh
are poor. ThFh
4. complications of sacrospinous fixation are
comparable to those of sacrocolpopexy. ThFh TOG Polycystic ovary syndrome and the
5. NICE recommends the use of routine differential diagnosis of hyperandrogenism
iliococcygeal fixation. ThFh
Androgen excess in women is associated with,
6. colpocleisis is the procedure of choice in the
1. menstrual irregularity. ThFh
frail and elderly. ThFh
7. erosion is a recognised complication in cases With regard to normal androgen physiology in women,
treated with a mesh. ThFh 2. the adrenal medulla makes
dehydroepiandrosterone sulfate. ThFh
Regarding sacrocolpopexy,
3. less than 10% of testosterone is bound to sex
8. open abdominal sacrocolpopexy has a lower
hormone binding globulin. ThFh
incidence of recurrent prolapse compared to
vaginal sacrospinous fixation. ThFh With regard to androgen action and metabolism,
9. laparoscopic sacrocolpopexy has a shorter stay 4. androgens are excreted unchanged in the urine. T h F h
and quicker recovery in comparison to the 5. testosterone binds to a nuclear receptor. ThFh
open procedure. ThFh
With regard to the clinical presentation of hyperandrogenism,
10. robotic laparoscopic sacrocolpopexy involves
6. the Ferriman-Gallwey score is useful in
more ports. ThFh
objectively assessing the severity of hirsutism. T h F h
11. robotic procedures have poorer visualisation
7. deepening voice and breast atrophy are
of the surgical field. ThFh
features suggestive of an adrenal tumour. ThFh
12. capital cost is high for laparoscopic
sacrocolpopexy in comparison to the robotic Regarding the biochemical assessment of hyperandrogenic
surgery. ThFh patients,
Risk factors for vault prolapse include: 8. serum testosterone >5 nmol/l should prompt
13. body mass index. ThFh further investigation. ThFh
With regard to the use of pessaries in the treatment of Regarding the pathophysiology of polycystic ovary
vault prolapse, syndrome,
14. the outcome (in terms of success) is similar to 9. a combination of genetic and lifestyle factors
that of surgery at 1 year. ThFh are likely to be causative. ThFh
15. difficulties in fitting them are encountered in 10. arrest of follicular development is
less than 10% of patients at presentation. ThFh characteristic. ThFh
16. spontaneous expulsion is one of the
Regarding the differential diagnoses of hyperandrogenism,
commonly reported side effects. ThFh
11. ovarian hyperthecosis is a disease of
With regard to colpocleisis, childhood. ThFh
17. when undertaken, the reported success rate is 12. congenital adrenal hyperplasia is often
approximately 75%. ThFh diagnosed in infancy. ThFh
13. the most common virilising adrenal tumours
Regarding the vaginal routine for the surgical treatment of are the Sertoli-Leydig cell type. ThFh
vaginal vault prolapse,
With regard to the pathophysiology of hyperandrogenism,
18. when mesh is used, its contraction is not a 14. approximately 50% of circulating androgens
recognised complication. ThFh are conjugated with either glucuronic or
sulfuric acid. ThFh
With regard to the abdominal approach to surgery for
vaginal vault prolapse, In hyperandrogenaemic women with PCOS,
19. sacrocolpopexy has a lower recurrent prolapse 15. it has been shown that there is an increased
rate compared to sacrospinous fixation. ThFh risk of breast cancer. ThFh

ª 2013 Royal College of Obstetricians and Gynaecologists 197

 CPD

With regard to the quantification of androgens in 10. there is evidence showing that ever use of
secondary care institutions in the UK, gonadotropins is associated with increased
16. automated immunoassays on whole serum are risk. ThFh
known to consistently overestimate serum 11. IVF, particularly after multiple IVF cycles,
testosterone concentrations. ThFh increases risk. ThFh
In case of hyperandrogenism, Regarding infertility treatment and breast cancer,
17. ovarian hyperthecosis accounts for less than 12. most studies observed an increased risk
50% of cases in postmenopausal women. ThFh following the use of fertility drugs. ThFh
18. the non-classic 21-hydroxylase deficiency 13. there is strong evidence showing an increased
tends to typically present in childhood. ThFh risk following fertility treatment in women
19. luteomas of the ovary are one of the most with family history of the disease. ThFh
common causes of gestational 14. there is strong evidence linking the
hyperandrogenism. ThFh development of the cancer with increased
20. unilateral solid ovarian lesions as a cause have maternal age at first IVF cycle. ThFh
an increased risk of malignancy when 15. there is robust evidence linking the
presenting in pregnancy. ThFh development of the cancer with multiple IVF
cycles. ThFh
16. there is good evidence that women exposed to
TOG The relationship between infertility fertility drugs have a transient increase in the
treatment and cancer including risk of the cancer diagnosed in the first year
gynaecological cancers after treatment. ThFh
Infertile patients, Regarding infertility treatment and non gynaecological
1. are at increased risk of developing ovarian cancers,
cancers. ThFh 17. there is evidence linking fertility treatment
with increased risk of melanoma. ThFh
Nulliparity,
18. the evidence linking thyroid cancer with
2. is associated with a ten-fold increase in the
clomiphene citrate is weak. ThFh
risk of developing ovarian cancer. ThFh
Regarding fertility treatment and childhood cancer,
Regarding infertility treatment and ovarian cancer,
19. there is a consistently increased risk of
3. when clomiphene citrate is given for more than
retinoblastoma. ThFh
12 cycles, it is associated with an increased risk
20. children born following IVF are at a
of borderline and invasive cancer. ThFh
significantly increased risk of developing
4. nulligravidae who received fertility treatment
cancer compared with the general
have been shown to be at an increased risk of
population. ThFh
ovarian cancer regardless of whether they
conceived or not. ThFh
5. there is strong evidence linking multiple
in vitro fertilisation (IVF) cycles and an BJOG Delivery outcomes for nulliparous

increased risk of developing the cancer. ThFh women at the extremes of maternal age – a
6. treatment with fertility drugs does not cohort study
increase risk compared with non treated Vaughan DA, Cleary BJ, Murphy DJ. Delivery outcomes for nulliparous
infertile women. ThFh women at the extremes of maternal age – a cohort study. BJOG 2013; DOI:
7. compared with the general population, those 10.1111/1471-0528.12311
who have IVF treatment are at an increased
With regard to the epidemiology of maternal age in
risk of ovarian cancer. ThFh
pregnancy,
Regarding infertility treatment and uterine cancer, 1. the live birth rate in young women aged 20
8. there is a persistent trend linking usage of years and under has halved in the UK between
clomiphene citrate and increased risk. ThFh 1997 and 2007. ThFh
9. there is some evidence pointing to a transient 2. the number of live births in women aged
increase in risk in the first year following between 40 and 44 years has almost doubled in
infertility treatment. ThFh the UK between 1997 and 2007. ThFh

198 ª 2013 Royal College of Obstetricians and Gynaecologists

 CPD

With regard to maternal risk factors, compared to women 9. young teenagers are no more likely to have
aged 20 to 34 years, small for gestational age babies (<10th
3. young teenagers (under 18 years) are more percentile) when potential confounding
likely to be underweight (BMI <18.5 kg/m2) factors are taken into account. ThFh
when assessed at the first antenatal visit. ThFh 10. young teenagers are more likely to have an
4. young teenagers are more likely to report instrumental delivery by vacuum or forceps. ThFh
smoking cigarettes when questioned at the
first antenatal visit. ThFh Supporting information
5. women aged 40 years and over are more likely
CPD questions for the BJOG article ‘Timing of prophylactic
to abstain from alcohol in pregnancy. ThFh
antibiotics for caesarean section: a systematic review and
6. women aged 40 years and over are more likely
meta-analysis’ were published in TOG Vol 15 No 2.
to have hypertension in pregnancy. ThFh
Additional supporting information regarding the CPD
7. women aged 40 years and over are more
questions may be found in the online version of this article.
likely to be of higher socioeconomic
Please read the supporting information before attempting the
status. ThFh
questions.
When compared to women aged 20 to 34 years, Please access TOG online here: http://onlinetog.org.
8. young teenagers are more likely to deliver RCOG fellows and members can access TOG via the RCOG
preterm (<37 weeks of gestation). ThFh website.

ª 2013 Royal College of Obstetricians and Gynaecologists 199

 DOI: 10.1111/tog.12037 2013;15:200–7
The Obstetrician & Gynaecologist
Letters and emails
http://onlinetog.org

Please note that letters and emails to

the editor should be no more than
500 words with a maximum of five
references.

following the cup application, the proximal marking (near the

Vacuum extraction
cup) on the tube connecting the palmpump and the cup should
Dear Sir be at the introitus. In OP position, the cup should be inserted as
I would like to thank Tracey A Johnston and Tara Selman for deep as possible posteriorly, such that the distal marking (near
their excellent article on vacuum extraction, offering helpful the palmpump) on the tube is at the introitus. One hand is used
tips to improve success rate and reduce morbidity.1 I wish to to apply traction while the forefinger and the thumb of the
add a few more helpful tips. other hand rest on the fetal scalp and the cup respectively. The
Placement of the vacuum cup on the flexion point is forefinger detects the beginnings of any cup detachment. The
associated with high success rate and reduction in maternal and traction should be applied in such a way that the tube is always
fetal morbidity. Before one can locate the flexion point, one has at right angles to the outer surface of the cup. This means that in
to be absolutely certain of the fetal position. As the article OP positions, the initial traction is directed almost vertically
points out, in the presence of significant caput and moulding, downwards. As the fetal head descends, auto-rotation to OA
the fetal ears are a very useful landmark, acting as a guide to the position takes place just before crowing. In general, cup
feasibility of the vacuum extraction. The curve of the ear points application to delivery time should not exceed 20 minutes. In
to the occiput and can be very useful in determining the fetal case of a cup slip-off, it should not be reapplied more than once.
position, especially if the sagittal suture is in the midline but the So long as there is descent with each pull, the vast majority of
fontanelles are difficult to define due to caput and moulding. deliveries with a vacuum device will occur within four pulls.
Ultrasound on the labour ward can be a very helpful tool
in situations where the fetal position is difficult to define.2 It
is relatively very simple to get a four chamber view of the fetal References
heart on the ultrasound scan. The fetal spine points towards 1 Johnston TA, Selman T. Vacuum extraction. The Obstetrician &
the direction of the occiput. Similarly, by placing the Gynaecologist 2012;14:275–6.
ultrasound transducer transversely on the mother’s 2 Akmal S, Tsoi E, Nicolaides H. Intrapartum sonography to determine
fetal occipital position: interobserver agreement. Ultrasound Obstet
supra-pubic region, both the fetal orbits are readily seen in Gynecol 2004;24:421–4.
a direct occipito-posterior (OP) position. These ultrasound 3 Baskett TF, Calder AA, Arulkumaran S. (2007) Munro Kerr’s Operative
skills are not difficult to acquire and can be easily learned on Obstetrics. Saunders. London.
the labour ward under the supervision of someone already
trained in the procedure. Ultrasound should be used only as
Ajay Poddar MD MRCOG
an adjunct to the clinical findings whilst determining the fetal
position. It should never replace clinical examination.
The flexion point is located on the midline sagittal suture,
Authors’ reply
approximately 3 cm from the posterior fontanelle. As most
vacuum cups are 5–6 cm in diameter, if the cup is applied so Dear Sir
that the rear edge overlaps the posterior fontanelle, the centre We thank Dr Poddar for his interest in our article, and for his
of the cup will be over the flexion point. The flexion point is comments. As stated, the purpose of the article was not to
approximately 6 cm from the anterior fontanelle. When the rehearse the basic techniques of vacuum extraction but to
cup is correctly placed, over the sagittal suture, in the inform the readership of some tips to improve the success rate
midline, the leading edge of the cup should be about 3 cm (2 and reduce morbidity when vacuum is used. We agree that
finger breadths) from the anterior fontanelle.3 ultrasound used by appropriately trained individuals can
The Kiwi Omnicup (Clinical Innovations Inc., Salt Lake assist with determining the position of the vertex in labour,
City, UT, USA) is an excellent device for delivering babies in but would strongly caution that knowing where the occiput is
occipito-anterior (OA) or OP positions. In OA position, does not necessarily help with determining the position of the

200 ª 2013 Royal College of Obstetricians and Gynaecologists

 Letters and emails

flexion point. A vacuum cup should not be placed unless the asymptomatic postmenopausal women but have failed to
flexion point can be identified. If a clinician is unable to clarify this issue. In their useful review of management of
determine the position on vaginal examination and requires women with postmenopausal bleeding, Bakour et al.2 cite
the assistance of ultrasound, we would question the ability to evidence that follow up and/or treatment of endometrial
accurately determine where the flexion point is in most cases, polyps incidentally diagnosed in asymptomatic
and would therefore suggest that a cup should not be applied. postmenopausal patients could safely be restricted to a few
If the reason for not being able to determine the position is select cases based on polyp diameter. However, Annan et al.1
excessive caput, as explained in the article this may suggest a recommend removal of all such polyps. Given that 10% of
degree of disproportion, and can also prevent a good seal with asymptomatic women are diagnosed with endometrial polyps,
the cup being achieved, and in these cases careful selection of this represents a massive potential workload for hysteroscopic
the correct instrument to achieve delivery is paramount. services. The main dilemma for clinicians is that the majority
With respect to choice of vacuum equipment, we would again of asymptomatic postmenopausal polyps are diagnosed
like to point out that not all devices are the same, and choosing because of incidental finding of increased endometrial
the appropriate instrument for individual clinical cases is thickness on scans performed for investigation of non
essential. There must therefore be a choice if outcomes are to be gynaecological symptoms. Bakour et al. appear to support a
maximised. Caution must be exercised when relying on the Kiwi policy of offering hysteroscopy to all asymptomatic women
Omnicup versus alone. In randomised controlled trials, the with endometrial thickness over 6 mm, based on
Kiwi device has a higher failure rate compared to conventional interpretation of data from the UK Collaborative Trial for
(metal or silastic cup) ventouse (30.1% versus 19.2%1; 34% Ovarian Cancer Screening (UKCTOCS).3 The latter
versus 21%2), especially with malposition (48%1 and 56%2), a case-control study measured endometrial thickness in over
higher association with sequential use of instruments (22% 40 000 women, 133 of whom went on to develop endometrial
versus 10%1), a higher number of detachments1 (44% versus cancer or atypical hyperplasia within 1 year of follow-up. Of
18% of at least one detachment) but no difference in trauma the control group, 4878 women (13.3%) had endometrial
rates. Although individual operators have demonstrated thickness between 5 and 10 mm and 1116 (3%) between
excellent outcomes with the Kiwi device, the results of these 10 and 20 mm but did not go on to develop cancer.
randomised controlled trials must be acknowledged. Asymptomatic postmenopausal thickening is most
On a final note, the markings on the tubing of the Kiwi device commonly due to presence of a polyp and the
in relation to the introitus depend upon the station of the vertex overwhelming majority of such polyps are entirely benign.1,2
and how deflexed the head is. The cup must always be placed Surely the current recommendation should be that
over the flexion point which does not necessarily equate with asymptomatic endometrial thickening in postmenopausal
placing the cup ‘as deeply as possible posteriorly’. The key to women should normally be ignored unless there are other
success is appropriate patient selection, use of the correct features of concern and women reassured that the
instrument, and ensuring cup placement over the flexion point. appearance is due to the presence of a small polyp which
is most unlikely to do them any harm in the absence of any
warning sign of bleeding? To do otherwise is to cause
References
unnecessary worry, inconvenience and potential risk to
1 Groom KM, Jones BA, Miller N, Paterson-Brown S. A prospective thousands of women and add to the burden of already
randomised controlled trial of the Kiwi Omnicup versus conventional overstretched services.
ventouse cups for vacuum-assisted vaginal delivery. BJOG
2006;113:183–9.
2 Attilakos G, Sibanda T, Winter C, Johnson N, Draycott T. A randomised
References
controlled trial of a new handheld vacuum extraction device. BJOG
2005;112:1510–5. 1 Annan JJ, Aquilina J, Ball E. The management of endometrial polyps
in the 21st century. The Obstetrician & Gynaecologist 2012;14:33–
Tracey Johnston MD FRCOG 8.
2 Bakour SH, Timmermans A, Mol BW, Khan KS. Management of
Tara Selman PhD MRCOG women with postmenopausal bleeding: evidence-based review. The
Obstetrician & Gynaecologist 2012;14:243–9.
3 Jacobs I, Gentry-Maharaj A, Burnell M, Manchanda R, Singh N,
Sharma A, et al. Sensitivity of transvaginal ultrasound screening
Asymptomatic endometrial thickening in for endometrial cancer in postmenopausal women: a case-control
study within the UKCTOCS cohort. Lancet Oncology 2011;12:
postmenopausal women 38–48.
Dear Sir
Two recent articles 1,2 in TOG have addressed the problem of Christine P West MD FRCOG
how to manage incidental abnormal endometrial findings in Royal Infirmary of Edinburgh, UK

ª 2013 Royal College of Obstetricians and Gynaecologists 201

 Letters and emails

Authors’ reply endometrial carcinoma and atypical endometrial

hyperplasia were 0.62% (95% CI, 0.42–0.82%) and 0.59%
Dear Sir (95% CI, 0.22–0.96%), respectively. Summary estimates for
The authors of the two articles1,2 read with interest the sensitivity and specificity of TVS endometrial thickness
comments from Dr West and decided to formulate this joint measurement in the prediction of endometrial carcinoma
response to address the issue of management of asymptomatic were 0.83 (95% CI, 0.19–1.00) and 0.72 (95% CI, 0.23–0.95)
thickened endometrium/polyps in postmenopausal women for a 5 mm cut-off and 0.33 (95% CI, 0.04–0.85) and 0.94
embracing the challenging implication of over investigating (95% CI, 0.92–0.96) for a 6 mm cut-off. The authors of this
on the resources but at the same time envisaging that a case of systematic review concluded that the risk of endometrial
cancer would not be missed. cancer in asymptomatic postmenopausal women with
Measurement of endometrial thickness on transvaginal thickened endometrium is not any higher than that of the
scan is an important tool in the assessment of women with background population thus does not justify the use of
postmenopausal bleeding, but the role of endometrial endometrial thickness as a screening test for endometrial
thickness measurement by ultrasound in asymptomatic carcinoma and atypical endometrial hyperplasia in
women is unclear. At the time we submitted our articles asymptomatic postmenopausal women not using HRT.
(both groups) 12 months ago, this statement held true. In On a second look, and following from recent verbal personal
attempting to answer the question: should we investigate communication with the authors of this systematic review, it is
asymptomatic thickened endometrium in postmenopausal their belief that this conclusion has to be interpreted with
women, our reviews then could not ignore the preliminary caution taking into consideration the following: (i) the
data from The UK Collaborative Trial for Ovarian Cancer indication of the pelvic scan: e.g abdominal pain, (ii) other
Screening (UKCTOCS), the world’s largest collaborative risk factors for endometrial cancer: i.e diabetes, obesity, and
screening trial, involving more than 200 000 UK unopposed estrogen replacement, (iii) other co morbidity that
women that reports in 2015. Data from the assessment of might determine the level of intervention.
endometrial thickness and morphology in the course of this In cautiously interpreting the result of this systematic
trial has provided invaluable information on endometrial review, the authors of the systematic review would advise to
thickness in asymptomatic women and the risk of reassure and refrain from over investigating postmenopausal
endometrial cancer in this population. The logistic women with asymptomatic thickened endometrium found
regression model identified 25% of the population as at incidentally on transvaginal scan provided that: (i) they do
high risk and 39.5% of endometrial cancer or atypical not display other possible symptoms of endometrial cancer
endometrial hyperplasia cases were identified within this high such as pelvic pain, and (ii) they do not have other
risk group. In this high-risk population, a cut-off at 6.75 mm characteristic risk factors for endometrial cancer such as
achieved sensitivity of 84.3% (71.4–93.0) and specificity of obesity and/or diabetes. The authors of the systematic
89.9% (89.3–90.5). These findings concluded that reviews, we were told, would have low threshold in those
transvaginal sonography (TVS) screening for endometrial given scenarios to revert to outpatient hysteroscopy.
cancer has good sensitivity in postmenopausal women. We We (the authors of the two articles) feel that the
acknowledged that there are complex and challenging issues recommendation for polyp removal regardless of
around balancing the cost, positive health impact and symptomatology has to be now modified in the light of the
unwanted consequences of screening which require careful review from Breijer et al.. However we are still concerned
study and analysis but these findings are of immediate value about larger polyps (15 mm or more) as a risk factor in
in the management of increased endometrial thickness in asymptomatic women and are not sure that Breijer et al.’s
postmenopausal women undergoing pelvic scans for reasons review allows extrapolation of threshold for increased risk,
other than vaginal bleeding.3 because cut-off values examined for malignancy were much
Since our review was submitted, a new meta-analysis4 is lower. There is only scanty evidence on large polyps and
awaiting publication as we are writing this reply. The aims of cancer risk in asymptomatic women. Ferrazzi et al.5 quote
this study were to determine: (i) the normal endometrial size of polyp as malignancy risk, based on the finding of one
thickness measured by ultrasonography, (ii) the prevalence of very large cancerous polyp detected in 1152 women. This trial
serious endometrial pathology, and (iii) the sensitivity and was not included in the meta-analysis.
specificity of endometrial thickness measurement by TVS for The two group authors would like jointly to concur with
diagnosing premalignant and malignant endometrial disease the judicious evaluation of the new information, and now
in asymptomatic postmenopausal women. This meta-analysis would go with the recommendation not to hysteroscopically
reviewed 32 studies reporting on 11 100 women. The assess and remove all polyps in asymptomatic women but on
estimated mean endometrial thickness was 2.9 mm (95% the other hand not to reassure and discharge all women with
CI, 2.6–3.3 mm). The pooled estimated prevalence of an incidental finding of thickened endometrium.

202 ª 2013 Royal College of Obstetricians and Gynaecologists

 Letters and emails

We support the caveat on individual risk factors and on Several reviews of non medical treatments have been
lowering the threshold for investigation based on a case by carried out for women undergoing natural menopause as well
case assessment. This rational conclusion resonates with our as those experiencing vasomotor symptoms following breast
regional cancer network guideline6 that states: cancer treatments. A recent review concluded that outcomes
‘Asymptomatic thickening of the endometrium/polyps of vitamins, herbal remedies or acupuncture for women with
does not routinely justify further investigation. In the hot flushes following breast cancer treatment were either
absence of evidence to support further testing in inconsistent or not statistically significant, i.e. could have
asymptomatic postmenopausal women, decisions for occurred by chance.2 Similarly, reviews of complementary
further investigation should be made on an individual therapies, such as vitamins, herbal remedies and reflexology,
basis.’ This would be more rational than the blanket for women transitioning through menopause find insufficient
‘reassure and discharge’ policy suggested by the letter above. evidence of effectiveness.3–5 On the basis of current evidence
We all should note that any recommendation may have to Black Cohosh, vitamin E, evening primrose oil, dong quai,
be modified with the publication of the final UKCTOCS data ginseng, or wild yam are not recommended.6 There is mixed
in 2015. evidence and some support for acupuncture,7,8 yoga9,10 and
for mindfulness.11 Moreover, the evidence from three recent
RCTs, that cognitive behavior therapy is effective in reducing
References the impact of hot flushes12–14 both for well women and breast
1 Bakour SH, Timmermans A, Mol BW, Khan KS. Management of cancer patients, was not included.
women with postmenopausal bleeding: evidence-based review. The Perhaps TOG should review its editorial processes and
Obstetrician & Gynaecologist 2012;14:243–9. press releases, which depart from best practice,15,16 thus
2 Annan JJ, Aquilina J, Ball E. The management of endometrial polyps
in the 21st century. The Obstetrician & Gynaecologist 2012;14:
failing to help gynaecologists or their patients.
33–8.
3 Jacobs I, Gentry-Maharaj A, Burnell M, Manchanda R, Singh N,
Sharma A, et al. Sensitivity of transvaginal ultrasound screening References
for endometrial cancer in postmenopausal women: a case-control
study within the UKCTOCS cohort. Lancet Oncology 2011;12: 1 Tong IL. Nonpharmacological treatment of postmenopausal
38–48. symptoms. The Obstetrician & Gynaecologist 2013;15:19–25.
4 Breijer MC, Peeters JA, Opmeer BC, Clark TJ, Verheijen RH, Mol BW, 2 Rada G, Capurro D, Pantoja T, Corbalan J, Moreno G, Letelier LM., et al.
Timmermans A. Capacity of endometrial thickness measurement to Non-hormonal interventions for hot flushes in women with a history of
diagnose endometrial carcinoma in asymptomatic postmenopausal breast cancer. Cochrane Database Syst Rev 2010;9:CD004923.
women: a systematic review and meta-analysis. Ultrasound Obstet 3 Geller SE, Studee L. Botanical and dietary supplements for menopausal
Gynecol 2012;40:621–9. symptoms: what works, what does not. J Womens Health (Larchmt)
5 Ferrazzi E, Zupi E, Leone FP, Savelli L, Omodei U, Moscarini M, et al. 2005;14:634–49.
How often are endometrial polyps malignant in asymptomatic 4 Carroll DG. Non-hormonal therapies for hot flushes in menopause. Am
postmenopausal women? A multicenter study. Am J Obstet Gynecol Fam Physician 2006;73:457–64.
2009;200:1–235. 5 Borrelli F, Ernst E. Alternative and complementary therapies for the
6 The Pan Birmingham Cancer Network Guideline for the Management menopause. Maturitas 2010;66:333–43.
of Post Menopausal Bleeding (PMB). Version 2.0, September 2011. 6 Pachman DR, Jones JM, Loprinzi CL. Management of
menopause-associated vasomotor symptoms: Current treatment
Shagaf H Bakour MD FRCOG options, challenges and future directions. Int J Womens Health
City Hospital, Birmingham, UK 2010;2:123–35.
7 Lee MS, Kim KH, Choi SM, Ernst E. Acupuncture for treating hot
flashes in breast cancer patients: a systematic review. Breast Cancer
Elizabeth Ball MD PhD MRCOG Res Treat 2009;115:497–503.
Barts and The London NHS Trust, London, UK 8 Dos Santos S, Hill N, Morgan A, Smith J, Thai C, Cheifetz O.
Acupuncture for treating common side effects associated with
breast cancer treatment: a systematic Review. Medical Acupuncture
2010;22:81–97.
Recommending treatments that don’t work patronises 9 Chattha R, Raghuram N, Venkatram P, Hongasandra NR. Treating the
women climacteric symptoms in Indian women with an integrated approach
to yoga therapy: a randomized control study. Menopause 2008;15
It is wrong to recommend treatments that have little evidence (5):862–70.
on the basis that they cause no harm and many women use 10 Carson JW, Carson KM, Porter LS, Keefe FJ, Seewaldt VL. Yoga of
Awareness program for menopausal symptoms in breast cancer
them. In the January 2013 issue of TOG, Tong1 recommends survivors: results from a randomized trial. Support Care Cance
herbal treatments for menopausal women, claiming there are 2009;17:1301–9.
no significant associated adverse side effects, as long as they 11 Carmody JF, Crawford S, Salmoirago-Blotcher E, Leung K, Churchill L,
Olendzki N. Mindfulness training for coping with hot flashes: results of
are used in women who do not have a personal history of
a randomized trial. Menopause 2011;18:611–20.
breast cancer, are not at high risk for breast cancer, and are 12 Mann E, Smith MJ, Balabanovic J, Hellier J, Hamed H, Grunfeld B,
not taking tamoxifen. Hunter MS. Efficacy of a cognitive behavioural intervention to treat

ª 2013 Royal College of Obstetricians and Gynaecologists 203

 Letters and emails

menopausal symptoms following breast cancer treatment (MENOS 1): reducing hot flush symptoms.1 In reviewing treatment options
a randomised controlled trial. Lancet Oncol 2012;13:309–18.
with women experiencing hot flushes, the data suggest that soy
13 Ayers B, Smith M, Hellier J, Mann E, Hunter MS. Effectiveness of group
and self-help cognitive behaviour therapy to reduce problematic may be a reasonable option is some women.
menopausal hot flushes and night sweats (MENOS 2): a randomised Medication trials inherently have limitations, and
controlled trial. Menopause 2012;19:749–59. providers need to interpret trial data to the best of their
14 Duijts SF, van Beurden M, Oldenburg HS, Hunter MS, Kieffer JM,
ability in order to provide the best care for their patients.
Stuiver MM, et al. Efficacy of cognitive behavioral therapy and physical
exercise in alleviating treatment-induced menopausal symptoms in Medications in trials with positive results may not be effective
patients with breast cancer: results of a randomized, controlled, in some patients, and likewise, trials with negative results
multicenter trial. J Clin Oncol 2012;30:4124–33. may not completely eliminate the therapy as a treatment
15 Anon (2013). Quackery http://en.wikipedia.org/wiki/Quackery
(accessed 24th January 2013).
option. For example, trials on the pharmaceutical agents
16 Bewley S. Doctors should prescribe treatments that work. The known to be effective for hot flushes (venlafaxine,
Obstetrician & Gynaecologist 2010;12:216. gabapentin, and several selective serotonin receptor
inhibitors) demonstrate a statistically significant reduction
in hot flush symptoms when compared to placebo.2–8 The
Myra Hunter PhD CPsychol FBPS
short duration of these trials (average 4–8 weeks) and their
King’s College London, 5th Floor Bermondsey Wing, Guy’s Hospital,
London, UK
sponsorship by pharmaceutical companies are significant
limitations, which need to be considered by providers when
interpreting these results. Trials on soy have been much
Susan Bewley MA MD FRCOG
longer in duration (average of 12 weeks, ranging up to
Women’s Health Academic Centre, Kings Health Partners (KHP), St
Thomas’ Hospital, London, UK 52 weeks), and some have demonstrated no significant effect
over placebo.9,10 Many providers may conclude that trial data
demonstrates that pharmacologic agents are effective in the
Debra Bick RM, BA MMedSci PhD
Kings College London, London, UK
treatment of hot flush symptoms and that soy is not. The
question to ask is, if the pharmaceutical trials were as long as
the soy trials, would there still be a therapeutic effect?
Margaret McCartney MRCGP
The practice of medicine involves the interpretation of
Fulton St Medical Centre, Glasgow, UK
available trial data, and this interpretation by different
providers is often varied and controversial. If the authors
Disclosure of interests also approach positive trials with equal scrutiny when
considering treatment options for their patients, then
MH has published extensively on the menopause and perhaps we do not differ in our opinions as much as we think.
received grant funding from Cancer Research UK, NIHR
and Prostate Cancer UK but has no other competing
interests. DB and SB are Trustees of the charity References
Healthwatch-UK (for treatments that work).
1 Taku K, Melby MK, Kronenberg F, et al. Extracted or synthesized
soybean isoflavones reduce menopausal hot flash frequency and
severity: systematic reviw and meta-analysis of randomized controlled
Author’s reply
trials. Menopause 2012;19:776–790.
Dear Sir 2 Loprinzi CL, Kugler JW, Sloan JA, et al. Venlafaxine in management of
hot flashes in survivors of breast cancer: a randomised controlled trial.
I respect and appreciate the comments made by Myra Lancet 2000;356:2059–63.
Hunter, Susan Bewley, Debra Bick, and Margaret McCartney. 3 Evans ML, Pritts E, Vittinghoff E, et al. Management of
To clarify, I am not recommending all herbal treatments for postmenopausal hot flushes with venlafaxine hydrochloride: a
menopausal women, as the authors suggest. As stated in my randomized controlled trial. Obstet Gynecol 2005;105:161–6.
4 Stearns V, Slack R, Greep R, et al. Paroxetine is an effective treatment
review, I agree with the authors that there are limited data for hot flashes: results from a prospective randomized clinical trial.
with respect to the effect of many complementary therapies Journal of Clinical Oncology 2005;23:6919–8930.
on vasomotor symptoms and that the available data 5 Stearns V, Beebe KL, Iyengar M, et al. Paroxetine controlled release in
the treatment of menopausal hot flashes: a randomized controlled
demonstrate that these options are not superior to placebo.
trial. JAMA 2003;289:2827–34.
However, I do believe that the data on phytoestrogens – in 6 Loprinzi CL, Sloan JA, Perez EA, et al. Phase III evaluation of fluoxetine
particular soy – are worthy of further consideration when for treatment of hot flashes. J Clin Oncol 2002;20:1578.
choosing options for women interested in non-pharmacologic 7 Freeman EW, Guthrie KA, Cann B, et al. Efficacy of Escitalopram for
Hot Flashes in Healthy Menopausal WomenA Randomized Controlled
treatment of hot flushes. A recent systematic review and
Trial. JAMA, January 2011;305:267–74.
meta-analysis of randomised controlled trials demonstrated 8 Loprinzi CL, Kugler JW, Baron DL, et al. Phase III Trial of Gabapentin
that soy was significantly more effective than placebo in Alone or in Conjunction With an Antidepressant in the Management

204 ª 2013 Royal College of Obstetricians and Gynaecologists

 Letters and emails

of Hot Flashes in Women Who Have Inadequate Control With an occurs. As an illustration, I cite the much-maligned ‘Breech
Antidepressant Alone. J Clin Oncol 2007;25:308–312.
Trial’ by Hannah et al.3 Here is a piece of research that was
9 Newton KM, Reed SD, LaCroix AZ, et al. Treatment of vasomotor
symptoms of menopause with black cohosh multibotnicals, soy, rapidly taken into common practice from the day it was
hormone therapy, or placebo. Ann Intern Med 2006;145:869–79. published, because the results of the trial agreed with the past
10 Nelson HD, Vesco KK, Haney E, et al. Nonhormal therapies for accumulated experience of the profession (there was
menopausal hot flashes: systematic review and meta-analysis. JAMA
reinforcement).
2006;295:2057–71.
I would like to ask the authors this: do they see a difference
Iris Tong MD between research evidence and best practice for an individual
The Warren Alpert Medical School of Brown University, USA patient?
And if they don’t: what point do they see in training
Editorial response doctors?

The TOG Editorial Board is confident in the rigorous Reference

double-blind peer review process it follows. It continues to
develop ways in which to optimise and perfect this process 1 Latibeaudiere M, Phillips J, Siassakos D, Winter C, Draycott T.
Implementation strategies – moving duidance into practice. The
and would like to thank Dr Bewley for her comments and Obstetrician & Gynaecologist 2013;15:51–7
input. 2 Haykin S. Neural Networks and Learning Machines 3rd ed. Upper
Saddle River, NJ: Prentice Hall, 2008.
3 Hannah ME, Hannah WJ, Hewson SA, Hodnett ED, Saigal S, Willan AR.
Planned caesarean section versus planned vaginal birth for breech
Re: Implementation strategies – moving guidance into presentation at term: a randomised multicentre trial. Term Breech Trial
practice Collaborative Group. Lancet 2000; 356:1375–83.

Dear Sir
I disagree with the philosophy which provoked the a recent Glenn Blanchette MBChB FRANZCOG FRCOG BSc DipPG
article in TOG.1 As Latibeaudiere et al. point out, many
authors have complained about the difficulties of
implementing research evidence in clinical practice. The
Authors’ reply
disparaging term inertia has been used, most commonly to
describe those of us who are aging practitioners. I would like Dear Sir
to present a complementary opinion. We thank Glenn for reading our paper and it does seem as
My PhD research interest is in artificial neural networks. though he thought about every word – which is good. Words
Artificial intelligence is a younger science than medicine but I are important. Implementation science is still a new field
believe it offers an objective view of learning. Machine within health care and active discussion of its terminology,
learning in a supervised context relies on a delta of the methodology and culture is to be especially welcomed. We
present experience (the current research), which is the identified four points in Glenn’s letter and we would like to
difference between the desired output and the actual make the following comments:
output. However, any machine which trains using this delta 1. Glenn seems to think we were attacking the aged when we
alone is likely to fail. The best algorithms include a wrote of inertia. As well as being multiprofessional, our
mathematical term representing the past accumulated team is multigenerational. Although some of us are a little
experience of the machine.2 This adaptive factor carries the slowed by shot knees, we would probably all agree that our
machine forward across ‘pot holes in the problem surface’, preparedness to engage with and act upon new guidance is
which are inadequate solutions. Researchers in the field of not a function of the number of candles on our cake, even
machine learning have not so disparagingly used the term; though they might seem a little harder to extinguish with
momentum, a protection to the machine against the each passing year. So no, we do not believe greater age
possibility of getting stuck in blind allies (or in the equates with an increased lag time to implementation.
mathematical parlance – local minima). What we meant by inertia were those things that get in the
Moreover, the concepts of inertia and momentum have a way of local adoption of best practice; lack of time, lack of
subtle difference. Inertia can only be negative; it only results system support, lack of ambition. But yes, there is a
in delay. Momentum can both limit or accelerate change. In negative connotation to inertia; delay in the availability of
situations where the current evidence is at odds with past safe effective care.
experience it reduces the change in direction that might be 2. Artificial neural network science lies outwith our
expected from the evidence. However, in situations where the experience and expertise but it does sound interesting.
direction of the past and present coincide, reinforcement Different scientific disciplines do well to share concepts.

ª 2013 Royal College of Obstetricians and Gynaecologists 205

 Letters and emails

Implementation science took ideas from academics in

industry. Re: Ovarian hyperstimulation syndrome (OHSS)
3. When reviewing evidence, it is important to be sure that Dear Sir
what we view as reinforcing our beliefs is not simply We welcome the timely article by Prakash and Mathur1 on the
confirmation bias. The Hannah example is interesting management of OHSS and agree with the authors on the need
because the reaction of the academic community to those for the RCOG to update its guidelines on this topic. We also
data seemed to work to remove the woman’s choice for agree with the need for a unified management strategy despite
vaginal breech birth but we would question whether that the lack of high-quality evidence, as OHSS can be serious (no
was in the best interest of women? It could be that if need to do a blind RCT on parachute jumping) and cost
service users had been involved in the interpretation of implications may dictate that patients will not agree to be
the results, that a wide range of opinions might have included in randomised trials. Prevention must be the primary
become evident. Academic judgments can also be at odds objective of the fertility specialists with strict individualisation
with clinicians in practice. After a debate at the RCOG in of COS protocol, and strategies to reduce the OHSS risk, such
2002, just one member of the audience of 200 clinicians as costing, freezing all embryos, use on GnRH agonist as a
put their hand up to support the conclusions of surrogate to hCG to achieve final oocyte maturation and
the Hannah breech trial. Perhaps, we need to consider release and others listed by the authors. All of these strategies
more sophisticated means of synthesising evidence must be part of the protocols that IVF centres should have as
into guidance? part of their adherence to the HFEA code of practice.
4. Yes, we do see a difference between research evidence However, the adherence and effectiveness of each individual
and best practice for the patient though we might phrase fertility unit’s protocol varies widely and the true incidence of
it slightly differently. Good research provides moderate and severe form of OHSS is still unknown to the
information that helps define interventions that can be fertility specialists, centres, and the regulators.
offered to women, but we need to be cautious as to who What is more relevant and as part of a duty of care to those
makes that interpretation, ensuring that service users are in the NHS (A&E and gynaecology services) is what is involved
involved. We also hold that whilst healthcare workers are in the management of the women who have OHSS symptoms
bound by the spirit of co-created guidance, those seeking and present to them in an emergency. We suggest a different
healthcare are not. When advising an individual woman, approach to significantly reduce the need for women to be
we need to use our expertise to take account of her seen in emergency rooms and in inpatient gynaecology wards.
individual circumstance, but we must also use our The evidence is strong in support of outpatient treatment
wisdom to allow her the freedom to line up her needs, and very early intervention by transvaginal paracentesis in the
wishes and beliefs alongside the guidance for herself. Put management of women with moderate OHSS to prevent the
another way, national recommendations guide a doctor occurrence of the most severe and the critical stages. In 2000
or midwife on how to advise a woman, but they do not Fluker et al.2 advocated outpatient early treatment of OHSS.
tell the woman what to do. Put in a slightly heartless way This was later confirmed by two large observational studies by
– clinicians advise, patients decide. It might be that an Aboulghar3 and Smith et al.4 This approach involves early
individual woman does view a 1 in 300 risk to her recognition of the patients at risk or those who present early
singleton term breech baby as being high, but then again, symptoms, with the onus of the outpatient care on the centre
she might not. that provided the fertility treatment. The fertility centre
Robert Fox MD MRCOG
should have daily contact with the patients at risk or with
Taunton and Somerset Hospital, Taunton, UK symptoms, see the patients early and perform early outpatient
transvaginal aspiration of ascites that is deemed more than
1000 ml, or less if causing symptom of discomfort, especially
Dimitrios Siassakos MD MRCOG
Southmead Hospital, Bristol, UK in those with pelvic adhesions. The fertility centres that
provided the fertility treatment should offer the outpatient
management at no extra cost or a very small one, as it should
Tim Draycott MD MRCOG
Southmead Hospital, Bristol, UK
be part of the package (treat and are responsible for the
complications). Transvaginal aspiration may be repeated if
necessary. Thromboprophylaxis should be started and
Justin Phillips MB FRCA
continued at least until the end of the first trimester or for a
Taunton and Somerset Hospital, Taunton, UK
further 2 weeks from a negative pregnancy test result.
The outpatient management of OHSS will reduce the
Cathy Winter RCM
incidence of the most severe forms and therefore the need for
Southmead Hospital, Bristol, UK

206 ª 2013 Royal College of Obstetricians and Gynaecologists

 Letters and emails

hospital admission, saving the NHS expensive care and hyperstimulation syndrome (OHSS). We are unable to
valuable bed space. At the same time, the IVF centres will be agree with them that trials on the most effective
responsible for implementing effective strategies that by management of OHSS are not required; indeed the
reducing their OHSS incidence will also contribute to the potentially serious nature of OHSS should require us to
reduction of multiple pregnancies. develop and use management strategies supported by the best
Finally, we believe the HFEA should impose a more quality evidence.
structured monitoring of OHSS occurrence in the fertility We agree with the correspondents that there is (mostly
units with the severe cases reported (or better reported) to a retrospective) evidence concerning outpatient management
national register. OHSS occurrence in each fertility unit of severe OHSS including outpatient paracentesis of
should become part of the structured HFEA fertility unit ascites.1–4 The efficacy and cost-effectiveness of this are not
monitoring with information made available publicly clear and it has not yet been widely applied in UK practice.
alongside the pregnancy outcome league table. This will This aspect is covered in detail in forthcoming guidelines for
allow a level-up of the quality of care at a national level as management of OHSS from the British Fertility Society.5
well as a proper informed decision by the public looking for The correspondents make an interesting point as to
treatment. The HFEA need to step up to ensure high quality whether the clinic providing the fertility treatment should
care in reducing risks and improving results, and not to shy also be financially responsible for managing severe OHSS
away from demanding centres to improve quality or resulting from the treatment. This clearly requires further
threatened with penalties as any Government watchdog discussion between NHS Trusts and private providers and
organisation is asked to do in these days of austerity and was outside the remit of our clinical review article. We agree
demands by patients for quality care and not just any care. with them about the need for consistent and reliable
We also have many reservations about the proposed reporting of cases of severe OHSS. Our understanding is
management strategies suggested and some of the suggestions that this is already required by the Human Fertilisation and
in the article, but due to lack of space will restrict this letter to Embryology Authority, which licenses fertility clinics in the
the pure management of moderate and severe OHSS. UK.
We would welcome the opportunity to respond to their
‘many reservations’ about the management suggested in our
References
article, but we cannot of course guess what these might be
1 Prakash A, Mathur R. Ovarian hyperstimulation syndrome. The without further details!
Obstetrician & Gynaecologist 2013;15:31–5.
2 Fluker MR, Copeland JE, Yuzpe AA. An ounce of prevention:
outpatient management of the ovarian hyperstimulation syndrome. References
Fertil Steril 2000;73:821–4.
3 Mohamed Aboulghar, Treatment of Ovarian Hyperstimulation 1 Fluker MR, Copeland JE, Yuzpe AA. An ounce of prevention:
Syndrome. Semin Reprod Med 2010;28:532–9. outpatient management of the ovarian hyperstimulation syndrome.
4 Smith LP, Hacker MR, Alper MM. Patients with severe ovarian Fertil Steril 2000;73:821–4.
hyperstimulation syndrome can be managed safely with aggressive 2 Aboulghar MA, Mansour RT, Serour GI, Amin Y. Ultrasonically guided
outpatient transvaginal paracentesis, Fertil Steril 2009;92:1953–9. vaginal aspiration of ascites in the treatment of severe ovarian
hyperstimulation syndrome. Fertil Steril 1990;53:933–5
3 Smith LP, Hacker MR, Alper MM. Patients with severe ovarian
K Sivanesan MRCOG hyperstimulation syndrome can be managed safely with aggressive
outpatient transvaginal paracentesis. Fertil Steril 2009;92:1953–9.
Independent Consultant Gynaecologist, Sri Lanka
4 Csokmay JM, Yauger BJ, Henne MB, Armstrong AY, Queenan JT,
Segars JH (2010). Cost analysis model of outpatient management of
Luca Sabatini MD MRCOG ovarian hyperstimulation syndrome with paracentesis: “tap early and
The Barts Centre for Reproductive Medicine, St.Bartholomew’s Hospital, often” versus hospitalization. Fertil Steril 2010;93:167–73.
London, UK 5 Tan B, Mathur R Management of ovarian hyperstimulation syndrome.
Hum Fertil. In press.

Talha Al-Shawaf FRCOG FRCS (Edin) Raj Mathur FRCOG MD

The Barts Centre for Reproductive Medicine, St.Bartholomew’s Hospital, Addenbrooke’s Hospital, Cambridge, UK
London, UK
Alka Prakash MRCOG MD
Addenbrooke’s Hospital, Cambridge, UK
Authors’ reply

Dear Sir
We thank Sivanesan et al. for their comments on our recent
review on the prevention and management of ovarian

ª 2013 Royal College of Obstetricians and Gynaecologists 207

 DOI: 10.1111/tog.12042 2013;15:208–10
The Obstetrician & Gynaecologist
Website reviews
http://onlinetog.org

Website reviews@TOG
Website reviews editors Thomas Tang / Anna Fabre-Gray / David Parkin
Thomas Tang MD MRCOG
(Website Reviews Editor)
Consultant Gynaecologist
Regional Fertility Centre, Royal Maternity Hospital,
Grosvenor Road, Belfast, BT12 6BA, UK
E-mail: [email protected]

Anna Fabre-Gray MRCOG

ST5 in Obstetrics and Gynaecology
Royal United Hospital, Bath, UK

David Parkin MD FRCOG

Consultant Gynaecological Oncologist
Aberdeen Royal Infirmary, Aberdeen, UK

specifically for SAS doctors or those in locum posts is

www.gmc-uk.org/doctors/revalidation
lacking. The section for patients and the public helpfully
outlines their role in the use of structured feedback and the
importance of complaints and compliments.
In conclusion, this subsection of the GMC website is
useful, well thought out and fairly exhaustive when used in
conjunction with specialty literature. It should be continually
updated as the revalidation process continues and problems
are encountered.
Anna Fabre-Gray
www.aomrc.org.uk/revalidation
The GMC website is a familiar interface for most doctors, the
layout is logical and easy to navigate. Information on
revalidation is under the tab ‘registration and licensing’. As
expected, the GMC is an authority on revalidation and under
this subsection it provides a single point of reference on the
subject, providing links to relevant literature.
Information is helpfully divided into sections for; licensed
doctors, doctors in training, responsible officers and
employers, and the patients and public. To the right are
quick links to all the GMC published guidance. The Academy of Medical Royal Colleges (AoMRC) website
The section for licensed doctors reads a little like a ‘how to’ has a clear homepage with a series of options available across
guide and is less extensive and personalised than the section for the title bar. Revalidation is one such option and the sub-
doctors in training but it is well organised and the subsections sections are found by hovering over the title (there is not a
are logical. FAQs are hidden in the ‘help and guidance’ section. drop-down menu which could be confusing for some users).
For trainees there is extensive information on the key areas The AoMRC aims to share information and experiences of
likely to cause confusion, for example: changing of completion revalidation between medical colleges, thereby establishing
of training (CCT) dates and time out of programme. There is a best practice. This is achieved through regular meetings
good section on FAQs and the opportunity to email the GMC if where each college is represented; the RCOG are well
your specific question remains unanswered. Information represented as it is chaired by RCOG president Tony

208 ª 2013 Royal College of Obstetricians and Gynaecologists

 Website reviews

Falconer. The site defines the role of each college by directing Information aimed at the responsible officers is extensive.
the reader to each medical college’s website, this makes it There are case studies with difficult cases and FAQs. The
clear that each specialty has independent advice on subsection for appraisers is currently empty. The information
revalidation and that the academy serves as an ‘umbrella’ for the employers is useful and provides an organisation
on the subject. Helpfully the link takes you directly to the readiness self-assessment (ORSA) tool and specific advice for
RCOG section on revalidation, not the homepage. locum agencies. The sub-section for patients provides an
There is an extensive subsection on the published overview but does not mention the role of feedback,
documentation and guidance. This is disorganised and the compliments and complaints.
subsections are not very clear, but there is interesting In conclusion, this is a user-friendly website with some
information and resources to be found here. For example, useful links and resources, however its major feature are the
there is a template for reflective practice and a report on the appraisal tools.
Anna Fabre-Gray
effectiveness of CPD.
There is further guidance by specialty and here our college www.rcog.org.uk/our-profession/
outlines clearly the supporting information and revalidation
documentation required by specialists revalidating. The
tabulated format is easy to follow. The FAQs are extensive
and cover subjects omitted by the GMC such as locum doctors
and doctors working abroad at the time of their revalidation.
In conclusion, this website is a useful resource but the
layout is messy and at times illogical. The user can find
helpful information and experiences from other specialties
but can easily be overwhelmed by too much information.
However, the FAQs are an excellent resource and
compliment other information available. This is a useful, logically laid out and fairly easy to use site.
Anna Fabre-Gray Though there is relatively little original content within the
revalidation pages, they link appropriately to the sites of the
www.revalidationsupport.nhs.uk GMC, NHS etc. There is little obstetrics and gynaecology
specific content apart from the CPD programme, but that is
of little concern as revalidation is essentially generic. It does
have a specific page for SAS doctors and trainees.
It is certainly a useful way to commence your revalidation
but does not remove the need for collecting a large amount of
data as well as patient assessment and 360° multi-source
feedback. It could be recommended as the starting point for
revalidation but it provides little that is not available on
The NHS revalidation support team (RST) website is employer’s websites or the Scottish Online Appraisal
modern, interactive and engaging. There is generous use of Resource (SOAR; http://www.scottishappraisal.scot.nhs.uk/)
multimedia resources and colour-coded subsections for; pages in Scotland.
doctors, responsible officers, appraisers, employers, and David Parkin
patients. It is easy to use and the homepage has sections
for recent news and relevant document publication. www.rcplondon.ac.uk/e-learning/
The RST works in partnership with the Department of revalidation-module
Health, GMC and designated bodies to deliver an effective
This package is aimed at guiding and helping you through
system of revalidation to doctors in England. The subsection
the steps that have to be completed for appraisal and
for doctors states that the GMC is the primary source of
information on revalidation, so material found here is an
adjunct. It is not specialty specific and there is no specific advice
for trainees. There is a helpful ‘10 steps to revalidation’ section,
a clear example of an appraisal portfolio and extensive FAQs.
The website houses the medical appraisal guide (MAG)
model appraisal form. This is supported with a user guide
and extensive information for organisations collating
appraisal information using them.

ª 2013 Royal College of Obstetricians and Gynaecologists 209

 Website reviews

revalidation. Finding it was not terribly easy as the e-learning Preparing for revalidation is an e-learning tool developed
package is one of a list of options you are given when by the RCP, aiming at secondary care doctors who are going
entering the CPD page and I was not used to the layout of the through the revalidation process as an appraisee. It can be
Royal College of Physicians (RCP) website. I suspect that easily downloaded with a small charge of £90 for non-
once you have purchased the package it might be more members or fellows of the RCP. The package offers a
straightforward to find. comprehensive description of the principles of the
It is divided into three learning paths, which are accessed revalidation process through interactive tutorials,
through ‘Your learning plan page’. These are: understanding workbooks supported by informative reading material.
revalidation, preparing your portfolio, and appraisal. Each of Furthermore, the package provides practical guidance on
these should take around 1.5 hours to complete. Within these collecting appropriate high-quality supporting information
three areas there are e-lessons (interactive tutorials), key for annual appraisal.
readers, interactive workbooks, videos (which wouldn’t play The package is user-friendly and easily accessible
on an NHS computer!) and a series of tests to see if you compared with some other hospital and university e-
understand the process. learning modules I have come across in recent time. Users
The advice is easy to follow and navigation is can collect non-clinical CPD credits after completion. The
straightforward once you have entered the package but the content is logically and clearly delivered, although can be
corporate blue colour-scheme became a bit tiring after an repetitive in places. There is also a mobile companion setup
hour or so. It immediately has one useful feature that will allowing users to access the modules through iPhone
take you back to wherever you finished any part of the or Android.
tutorials. There is an online support service, which will reply Undoubtedly, this package offers an in-depth explanation
in two working days. of the whole revalidation/appraisal process and enhances the
It will undoubtedly help a busy consultant prepare for learning experience. It is invaluable for post-CCT members
appraisal/revalidation. Whilst some of the examples given gaining an insight of the revalidation process, especially
are specific to physicians they are easily adaptable to our preparing for consultant interviews. Nevertheless, for a
specialty. Much, however, was not new to anyone who has more established clinician who has kept up to date with the
kept an appraisal folder for any length of time. In Scotland development of the revalidation process through the RCOG
we have SOAR which contains much the same material and and the GMC website as well as the local hospital support
is free of charge. Though the e-learning package is systems, they would be unlikely to find that this online tool
comprehensive, easy to use and well presented there is adds much further benefit. The only way to learn is to have
little that can’t be found from the RCOG website in the a go and to actively take part in the process. The most
revalidation section or from the associated links. The RCP is taxing challenge a lot of my consultant colleagues
charging £90 for their members to access this package. At have encountered is not a lack of understanding of the
that price I feel that fellows and members of the RCOG principles of revalidation, but rather inadequate time
would be advised to try our website first and only look to a and resource allocated at workplaces to collect the
commercial package if problems were encountered. The supporting information.
problem with all these web based services is although they
tell you what to collect, they don’t do it for you! Thomas Tang

David Parkin

210 ª 2013 Royal College of Obstetricians and Gynaecologists

 DOI: 10.1111/tog.12036
The Obstetrician & Gynaecologist
2013;15:211
Book review
http://onlinetog.org

Book review

Anesthesia and the Fetus fetal assessment methods – possibly the chapter on validity
of endpoint measurement may be a little detailed for some.
Editors Yehuda Ginosar, Felicity Reynolds, The third section is a major focus of the book and looks at
Stephen Halpern, Carl P Weiner the effects of anaesthesia, drugs and analgesia on the fetus
including considerations for non obstetric surgery and
assisted reproduction techniques. This section is
particularly detailed and looks in depth at the evidence
behind the choices and modifications in conduct of
anaesthesia for caesarean section and analgesia for labour
from the fetal perspective. The fourth section, entitled The
Compromised Fetus, covers details of multiple pregnancies,
pre-eclampsia and fetal distress. The fifth section looks
primarily at resuscitation guidance including perimortem
delivery, the management of trauma and the principles and
practice of intrauterine fetal resuscitation. The final section
touches on ethical decision-making and the law as applied to
the fetus.
Most anaesthetic textbooks concentrate on the impact of
anaesthesia on the mother with little detail on the effects of This book is hardback with good quality printing and easy to
analgesia and anaesthesia on the fetus. Textbooks in read layout. The illustrations are mainly in black and white
obstetrics, perinatology, neonatology and midwifery often with just a few in colour – unfortunately some are not
give little detailed consideration of the effect of anaesthetic particularly well reproduced.
interventions on the fetus and newborn. I believe that this
book has successfully integrated into one textbook the impact Unusually for a medical textbook, I believe this book will
of anaesthesia on the fetus and newborn as well as detailed have true multidisciplinary appeal. It will be of interest to
information on fetal pharmacology, physiology, development specialist obstetric anaesthetists, obstetricians – particularly
and monitoring. those with a fetal medicine interest – neonatologists and
specialist midwives. As such, I believe it has found a unique
This book is well constructed and written by an international place in the current market.
group of well renowned clinicians and scientists from USA,
Canada, Israel, UK, Australia and New Zealand. One The only negative aspect is the relatively high price –
disadvantage of such an international authorship is a lack although not unreasonable for such a well constructed
of focus on specific UK drugs and practice including specific hardback book, this will likely reduce demand on an
resuscitation guidance, but it is interesting to look at the individual basis. Clearly this book will be ideal for reference
interpretation of the evidence that defines international in departmental and hospital libraries and I will be
practice and aspects such as the law as it affects the fetus in recommending this to ours.
different countries.
Hilary Swales MBChB
The book is well laid out in a traditional format and is easy to Anaesthetic Consultant
read. Each section covers basic knowledge but also looks in University Hospitals Southampton Foundation Trust,
depth at the available evidence and recent advances. Southampton, UK

The first section covers in appropriate depth fetal Wiley-Blackwell, 2013

physiology, pharmacology and the changes at birth. The ISBN: 978-1444337075
second section covers detail on antenatal and intrapartum Hardback, 418 pages, £94.99

ª 2013 Royal College of Obstetricians and Gynaecologists 211

 DOI: 10.1111/tog.12034
The Obstetrician & Gynaecologist
2013;15:212
Book review
http://onlinetog.org

Book review

Oncofertility Medical Practice: Clinical There are numerous articles about the options of fertility
preservation, but they provide little guidance on clinical
Issues and Implementation application. In Part 2, the authors have explored in depth the
advantages and disadvantages, and the implications for the
Editors Clarisa Gracia, Teresa K Woodruff present and future, in order to bridge the gap in the practical
application of the different fertility preservation options. The
authors have provided a good source for devising clinical
guidelines that are tailored to individual settings.

Part 3 describes cancer in pregnancy and outlines the treatment

of the more common cancers encountered by the obstetrician
made complex by the risks of chemotherapy or radiotherapy to
the fetus, and possible need to terminate pregnancy.

Part 4 is perhaps the most impressive and useful section in the

book. Though the authors are all from the USA, and therefore
write about health care in that country, their clinical experience
has enabled them to provide invaluable advice with remarkable
attention to detail of oncofertility in clinical practice.

Oncofertility is a developing branch of reproductive Part 5 presents and discusses well selected cases to highlight
medicine but globally there are still only a few centres not only the challenges that are encountered in fertility
providing a structured service, which requires coordination preservation but also the pitfalls and how these can be avoided
of multidisciplinary specialties in a limited time period. to provide the best all round management of the case.

Oncofertility Medical Practice: Clinical Issues and In the appendix the authors have shared all the templates for
Implementation has successfully contrived to bring together documentation from consent forms for treatment and
an understanding of the theoretical principles of gonadal research, to applications for financial assistance for the
effects of cancer therapy with all the clinical and practical inevitable additional financial burden of fertility preservation.
aspects of fertility preservation for cancer survivors. The book
should be read by both oncologist and fertility specialists, as This is a comprehensive and very well-written book by
it presents clearly the degree of overlap that is required by the authors who have a wealth of clinical expertise in their
different healthcare providers to achieve a meaningful different fields. It is not often that a book provides
outcome for the cancer patient. The book has been divided information for different medical specialties and part 4
into different sections that discuss the implementation of (oncofertility in clinical practice) is highly recommended
fertility preservation. reading for all healthcare providers who currently offer or
wish to build an oncofertility practice.
Part 1 deals briefly with the gonadotoxicity of cancer therapy
explained in a simple manner, having sieved through Reviewer Nivedita Reddy MRCOG
numerous publications to include the factual evidence that Associate Specialist Reproductive Medicine,
is currently available. This understanding is a basic requisite Assisted Conception Unit, Guy’s Hospital, London, UK
for the reproductive physician who will be the key person in
managing the patient. It also makes easy reading for any Springer, 2012
oncologist who wishes to further his knowledge of fertility ISBN: 978-1441994240
risks of oncotherapy. Hardback, 290 pages, £126.00

212 ª 2013 Royal College of Obstetricians and Gynaecologists

 DOI: 10.1111/tog.12044 2013;15:213
The Obstetrician & Gynaecologist
UKOSS Update
http://onlinetog.org

UKOSS Update

 Pre-eclampsia developed in 24% compared with 4% of a

Incidence and risk factors for placenta
comparison cohort.
accreta/increta/percreta1
 52% of women with kidney transplants delivered preterm,
 The presence of placenta accreta/increta/percreta is significantly higher than the national rate of 8%.
associated with major pregnancy complications, and is  Twenty-four infants (24%) were small for gestational age
thought to be becoming more common, due to a number (<10th centile).
of factors including rising maternal age at delivery and an  Potential predictive factors for poor pregnancy outcome
increasing proportion of deliveries by caesarean. included >1 previous kidney transplant (P = 0.03), first
 The aims of this study were to estimate the incidence of trimester serum creatinine >125 mmol/L (P = 0.001), and
placenta accreta/increta/percreta in the UK and to diastolic BP >90 mmHg in the second (P = 0.002) and
investigate and quantify the associated risk factors. third trimesters (P = 0.05).
 134 women were diagnosed with placenta accreta/increta/  This study shows that most pregnancies in the UK in
percreta between May 2010 and April 2011 and 256 women with kidney transplants are successful but rates of
control women; an estimated incidence of 1.7 per 10 000 maternal and neonatal complications remain high.
maternities.
 Women who had a previous caesarean delivery (adjusted
Marian Knight MA DPhil FFPH
odds ratio [aOR], 14.41; 95% confidence interval [CI], Head of UKOSS/NIHR Research Professor in Public Health,
5.63–36.85), other previous uterine surgery (aOR, 3.40; National Perinatal Epidemiology Unit,
95% CI, 1.30–8.91), an IVF pregnancy (aOR, 32.13; 95% Department of Public Health, University of Oxford,
CI, 2.03–509.23) and placenta praevia diagnosed Old Rd Campus,
antepartum (aOR, 65.02; 95% CI, 16.58–254.96) had Oxford, OX3 7LF, UK
Email: [email protected]
raised odds of having placenta accreta/increta/percreta.
 There were also raised odds of placenta accreta/increta/
percreta associated with older maternal age in women References
without a previous caesarean delivery (aOR, 1.30; 95% CI,
1 Fitzpatrick KE, Sellers S, Spark P, Kurinczuk JJ, Brocklehurst P, Knight M.
1.13–1.50 for every one year increase in age). Incidence and risk factors for placenta accreta/increta/percreta in the
 The estimated incidence is 577 per 10 000 in women with UK: a national case–control study. PLoS One 2012;7:e52893.
both a previous caesarean delivery and placenta praevia; 2 Bramham K, Nelson-Piercy C, Gao H, Pierce M, Bush N, Spark P, et al.
Pregnancy in renal transplant recipients: A UK national cohort study.
there is a need to maintain a high index of suspicion of
Clin J Am Soc Nephrol 2013 Feb;8:290–8.
abnormal placental invasion in such women and
preparations for delivery should be made accordingly.
Acknowledgement
Thank you to all members who contributed information to
Pregnancy in renal transplant recipients2 these studies.
 Most studies reporting pregnancy outcomes in women with
kidney transplants are either single-centre studies, small, or
Further information
report historical cohorts identified over long periods.
 The aim of this study was to collect information about Details of these and other UKOSS study results can
pregnancy outcomes among a current cohort of all kidney be obtained from the UKOSS website http://
transplant recipients in the UK. www.npeu.ox.ac.uk/ukoss/completed-surveillance. If you
 There were 105 pregnancies identified in 101 recipients would like a reprint of any UKOSS publications please
between January 1, 2007 and December 31, 2009. contact [email protected].

ª 2013 Royal College of Obstetricians and Gynaecologists 213

 DOI: 10.1111/tog.12035
The Obstetrician & Gynaecologist
2013;15:214
And finally…
http://onlinetog.org

Girls, girls, girls!

James Drife MD FRCOG FRCPEd FRCSEd FCOGSA FFSRH

Emeritus Professor of Obstetrics and Gynaecology, Leeds, UK

When our first grandchild was born a few months ago we knew that my talent for algebra was vastly inferior to that of her
already knew that the baby was a girl. Even before the news favourite pupil, a quiet girl who started a family shortly
was confirmed by the wonders of ultrasound, we had sort of afterwards.
expected it. All the other recent arrivals in our extended
family have been girls: a grand-niece for us, a second
Catwalk interns
grand-daughter for my songwriting partner (a collaborator is
almost a blood relative), and a daughter for my wife’s Things have changed a lot in 50 years. In the mining industry
language tutor (related to us by the future perfect women have yet to break the glass ceiling (if that’s the right
subjunctive, a tie that my wife says is thicker than water). cliche) but they are well established in the professions. Among
Advance knowledge of the baby’s gender is said to help the medical specialties the pace of feminisation has varied, with
bonding process, though I doubt that it can make much sexual and reproductive health in the vanguard and surgery in
difference to such a primordial emotion. What it does do is the rear. General medicine is somewhere in between. When I
decide the colour of the babygro. ‘Pink for a girl’ is a tradition took ill in The Netherlands a couple of years ago I was
that goes all the way back to the 1940s, but it gives pause to admitted to a splendid hospital and was unsurprised to find
modern grandparents who aspire to gender-blindness. Is it the that the whole team of junior physicians was female. What
first step in social imprinting? Should we go instead for black took me aback was that they all dressed like fashion models.
or yellow? But then she might grow up to be a Goth or a Even with my life in danger I found it hard to take the ward
Liberal Democrat. Not that there’s anything wrong with round seriously.
either, of course. In the end we chose a blue-free pattern.
Mr Lazy
Take that
Aha, I hear you say, that’s irrational masculine prejudice: as a
Having realised that mine was the first UK generation to be bow tie wearer you’re hardly in a position to criticise Jimmy
colour-coded after inspection of its genitalia, I began to Choo shoes. OK, point taken, but I do think that one of the
wonder how the expectations of the 1940s and 1950s have few biological differences between the male and female brains
affected me. Our school had two doors with ‘GIRLS’ or is an interest in clothes. This was why, no matter how long I
‘BOYS’ carved in stone above them. The playground was hung around the delivery suite as consultant on call, I could
divided by railings and inside, at least in some classrooms, never really join in the midwives’ conversations. My wife
the girls sat on one side and the boys on the other. This remembers what she was wearing on every significant
sexual segregation, however, was half-hearted compared to occasion during our married life. So could I, I suppose, but
Scotland’s religious demarcation. There was a separate school only because I make each jacket last a decade.
for Roman Catholics even in our small village. This is not a big deal but there is one male/female
At our primary school the girls tended to be at the top of the difference that worries me. In my youth I always had my nose
class, but not for long. Academic achievement is determined in a book, but somewhere along the line the habit died.
less by brainpower than by parental expectations, and in that Today the Amazon man calls regularly but his parcels are all
mining community girls were not expected to go to university. for my wife. We’re not atypical. Most fiction is bought by
Nor were boys, come to that, and the frustration felt by the women and book groups around the country are
teachers was obvious even to us kids. On leaving for a senior predominantly, if not exclusively, female. Being bored by
school I won most of the prizes, which prompted a dose of stories seems to be a feature of the ageing male. Perhaps
corporal punishment – ‘the strap’ – from a vengeful lady maths reading the Mr Men to our new grand-daughter will reignite
teacher. (On my hands: we weren’t barbarians.) She and I both my enthusiasm for literature.

214 ª 2013 Royal College of Obstetricians and Gynaecologists