STANDARD TREATMENT

GUIDELINES

Management of Recurrent Spontaneous

Abortion
January 2017

Ministry of Health & Family Welfare

Government of India

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 Index

Scope .............................................................................................................................. 3
Background ..................................................................................................................... 4
Investigations for recurrent miscarriage......................................................................... 6
Recommendations .......................................................................................................... 7
Management of Recurrent Spontaneous Abortion (RSA) ............................................... 8
Treatment before Pregnancy .......................................................................................... 8
Treatment during Pregnancy ........................................................................................ 11
Treatment of RSA Patients with Antiphospholipid Syndrome ...................................... 12
Treatment of women presenting with RSA associated with inherited thrombophilia . 14
Treatment of women with unexplained RSA ................................................................ 15
Summary ...................................................................................................................... 17

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 STG Recurrent Miscarriage

Scope
Definition
Miscarriage is defined as a spontaneous loss of pregnancy before 20 weeks of gestation.

Group to be covered
Women with three or more first trimester and one or more second trimester miscarriage
(RCOG Greentop). Early evaluation is considered if fetal cardiac activity was present,
women >35 years with two or more abortions and the couple has had difficulty in
conceiving.
Group not covered
Two or more losses with one or more live issues.
Burden of the disease
In India, the prevalence of recurrent miscarriage is around 7.4%.
Rationale
Since the true prevalence of recurrent miscarriage is still unknown and the multimodality
approach being used at different levels of care by health care workers, this guideline
attempts to provide an evidence based platform to investigate and manage women with
recurrent miscarriage.
Financial constraints
A number of investigations related to recurrent miscarriage are expensive, so financial
constraints do come-up while investigating couple.
Target Users
All levels of healthcare including the primary, secondary and tertiary levels.
Main outcomes
Live pregnancy.
Key clinical issues
Causes, investigations and treatment of couples with recurrent miscarriage (RM).

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Collection of evidence
Evidence based existing guidelines which reviewed were Greentop, American Society of
Reproductive Medicine, National Clearing House and The Obstetrician and
Gynaecologist.
Criteria for referral
At the primary level, a thorough history and examination have to be carried out and the
patient has to be referred to the secondary care level for further management. If higher
modalities of treatment like surgery is required, the patient should be referred to the
tertiary care level.

Background

Introduction
Women with three or more first trimester and one or more second trimester miscarriage
are the one who have to be evaluated for recurrent miscarriage (Greentop Guidelines). It
affects 1% of fertile couples (Berry et al 1995). 1-2% of pregnancies miscarry before 24
weeks (RCOG). The mechanism of RM remains poorly understood. The cause remains
elusive in 50% of cases even after thorough investigations (TOG).

Causes of recurrent miscarriage

1) Epidemiological factors
· Advanced maternal age, number of previous miscarriages and advance paternal
age are independent risk factors for RM.
· The risk is highest if maternal age is >35 years and paternal age >40 years.
· The risk of miscarriage increases after each pregnancy loss reaching almost 30%
after two and 40% after three consecutive losses.
· Maternal smoking, alcohol consumption (5 units or more per week throughout
pregnancy or 3 or more per week in first trimester), caffeine consumption (3-5
cups per day, obesity, illicit drug use like cocaine (TOG)(ref) increase the risk.
· The evidence of the effect of anaesthetic gases in theatre workers is conflicting
(RCOG Ref12-13).

2) Acquired and inherited thrombophilias

Acquired thrombophilias are antiphospholipid syndrome (APS), hyperhomocysteinemia
and acquired protein C resistance (APCR).
· Antiphospholipid antibody syndrome is the most important treatable cause of RM.
· APL antibodies are present in 15% of RM in comparison to only 2% in women
with low risk obstetric history (RCOG 31-33).

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 · Inherited thrombophilias include Antithrombin-III, Protein C deficiency, Protein
S deficiency (uncommon and strongly thrombogenic), Factor-V Leiden,
Prothrombin gene mutation (20210A) (common and weekly thrombogenic).
· The association between fetal loss and inherited thrombophilia depends on the
type of thrombophilia and timing of fetal loss (Rey et al, Lancet 2003).

3) Genetic causes
· Increased incidence of structural chromosomal anomalies to the tune of 2-5% is
seen in couples with RM. These are either balanced reciprocal or Robertsonian
translocations (RCOG 35,38). All the four factors low maternal age at second
miscarriage, history of three or more miscarriages, history of two or more
miscarriages in brothers and sisters and history of two or more miscarriages in
parents of either partner all increase the probability of carrier status (Franssen 2005).
· In couples with RM, chromosomal abnormalities of embryo account for 30-57%
of further miscarriages (RCOG 39,40).

4) Anatomic factors
a) Congenital uterine malformations
· Reported prevalence of uterine anomalies in recurrent miscarriage population
ranges between 1.8-37.6%.
· Women with arcuate uteri have more second trimester miscarriage and those with
septate uteri are more likely to miscarry in the first trimester (RCOG 45).

b) Cervical incompetence:
· Essentially a clinical diagnosis, with unknown true incidence, cervical
incompetence is a recognized cause of recurrent second trimester abortions.
· The diagnosis is usually suggested by a second trimester miscarriage preceding a
spontaneous rupture of membrane or painless cervical dilatation.

5) Endocrine factors
· Current evidence indicate that treated thyroid dysfunction and controlled diabetes
mellitus is not a risk factor for RM (RCOG 47,48) and the prevalence of diabetes
mellitus and thyroid dysfunction is similar to general population (RCOG 49,50).
· Obesity is also associated with statistically significant increased risk of first
trimester and recurrent miscarriage (Lashen 2004).
· Hypersecretion of LH, luteal phase defect, increased free androgen index and
hyperprolactinemia all have a role in recurrent miscarriage.
· Increased free androgen index appears to be a prognostic factor for a subsequent
miscarriage in women with RM (RCOG 55).

6) Immune factors
· There is no clear evidence to support the hypothesis of human leucocyte antigen
incompatibility between couples, the absence of maternal leucocytotoxic
antibodies or the absence of maternal blocking antibodies(RCOG).
· A no more than modest association between cytokine polymorphism and recurrent
miscarriage has been seen (RCOG 61).

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 · Mannan-binding lectin (MBL) is a C-type lectin that participates in the innate
immune defence by activating complement. Low MBL levels are associated with
RM and that low MBL is associated with significantly higher miscarriage rate in
next pregnancy (20%) (Kilpatric et al 1995, Cruz et al 2002). However, most women with low
MBL do not experience RM.

7) Infective factors
· The role of infection in recurrent miscarriage is unclear. Bacterial vaginosis is
consistently associated with recurrent second trimester abortions and preterm
delivery, but association with first trimester abortion is inconsistent.

Investigations for recurrent miscarriage

The women with recurrent miscarriage should be looked after by a trained and expert
health professional within a dedicated recurrent miscarriage clinic. Clearly written patient
leaflets are recommended to provide take home written information.

1) Antiphospholipid antibodies
· For diagnosis, a woman should have two positive tests at least 12 weeks apart of
either lupus anticoagulant or anticardiolipin (aCL) IgG/IgM in moderate to high
titres (>40 g/l).
· Dilute Russell Viper Venous Test (drVVT) along with platelet neutralization
procedure is a more sensitive and specific test than either activated prothrombin
times test (aPTT) or kaolin clotting time (KCT). aCL antibodies are detected
using ELISA (RCOG 31).

2) Inherited thrombophilias
· Women with any unexplained still birth and two or more second trimester losses
should be offered screening (Lavignee LG. Hematologica 2005).
· With only second trimester miscarriage women should be screened for inherited
thrombophilias for inherited thrombophilias including Factor V Leiden,
prothrombin gene mutation and protein S [D] (Meta-analysis by Rey et al).

3) Anatomic Factors
a) Uterine factors
· Suspected uterine anomalies may further require a confirmation with
hysteroscopy, laparoscopy or a 3D ultrasound [ü]. 3D ultrasound in particular has
become an accurate, reproducible, non-invasive outpatient method for diagnosis
(Saliim et al 2003)
.

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 · There is insufficient evidence to assess the effect of uterine septum resection in
females with RM and uterine septum to further prevent miscarriage [C].

b) Cervical incompetence
· There is currently no satisfactory objective test to clearly identify cervical
weakness in non-pregnant state.

4) Endocrine factors
· Role of estimation of serum progesterone, serum hCG, inhibin and actinin levels
is yet to be established.

Recommendations
1. Thorough history and Clinical examination is a must
2. Offer testing for APS with lupus anticoagulant (LAC) and anticardiolipin antibody
(aCL) ideally before the next pregnancy (HR Wilson 2006 and NGC) to any woman with
history of three or more pregnancy losses <10 weeks or one or more loss of a
morphologically normal fetus >10 weeks or one or more premature birth <34 weeks
due to severe preeclampsia or placental insufficiency.
3. Offer parental karyotype only when probability of carrier status is >2.2% (Franssen 2005).
4. Do not offer testing for human leucocyte antigen, maternal leucocytotoxic antibodies
and maternal blocking antibodies.
5. Do not offer TORCH investigations.
6. Do not offer investigations for hyperhomocysteinemia outside a research protocol.
7. Offer screening for inherited thrombophilias only if other causes have been ruled out,
with any unexplained still birth and two or more second trimester losses and if only
second trimester miscarriages are present.
8. Offer cytogenetic analysis on products of conception of third and subsequent
consecutive miscarriages.
9. Offer parental peripheral blood karyotyping of both partners in couples with RM
where testing of products of conception reveal an unbalanced structural chromosomal
translocations.
10. Consider pelvic ultrasound in all women with recurrent first trimester miscarriages
and with one or more second trimester miscarriages to assess uterine anomalies.

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Management of Recurrent Spontaneous Abortion (RSA)
The etiology of RSM is multifactorial. Appropriate treatment continues to be a challenge,
and there is need for larger well-planned double-blinded randomized controlled trials or
standardized research protocols for the investigations and treatment of RSA to effectively
resolve many of the problems which remain a source of dilemma for most treating
physicians. The investigation and management of women with recurrent spontaneous
abortion should be done in a centre well equipped with readily available facilities for all
ancillary investigations and well trained qualified personnel.
The management of RSA depends on the causative factor, though in 75% of the cases the
cause remains unexplained, thus only 25% of the women require treatment as per the
cause.
Management depends on the time of detection of these cases, before pregnancy and
during pregnancy.

Treatment before Pregnancy

1. Counseling the couple should be done regarding the investigations and the
outcome of the investigations, the treatment plan to be followed, and the outcome
of such treatment
2. Psychological support. Women with RSA are usually quite anxious and full of
uncertainty about the outcome of their next pregnancy. A strong psychological
support should be provided and should be dealt with tender loving care all
through the period of consultation
3. Those couples with abnormal karyotypes detected during the screening period
should be referred to a clinical geneticist, where available, for detailed counseling
about the outcome of future pregnancies.

4. Surgery for detected anatomical disorders (congenital and acquired):

Hysteroscopic resection of uterine septum preferably using cold scissors rather
than cautery or bipolar cutting devices, resection of submucous fibroids, and

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treatment of intrauterine adhesions presenting as Asherman syndrome can be
undertaken before another pregnancy is embarked upon.
Women who have multiple uterine fibroids with an uterine size more than 14
weeks’ size should be encouraged to secure appropriate treatment (including
myomectomy) before embarking on another pregnancy.
However, it should be noted that the exact role of a resection of the uterine
septum is still unresolved since there are no published controlled randomized
trials of the benefits of surgical correction of uterine abnormalities on pregnancy
outcome. Uncontrolled studies have indicated a positive effect on pregnancy
outcome.

Evidence
· There is insufficient evidence to assess the effect of uterine septum resection
in women with recurrent miscarriage and uterine septum to prevent further
miscarriage (RCOG)
· Almost 65% to 85% of patients with bicornuate or septate uteri have a
successful pregnancy outcome after metroplasty. However, 59.5% of the
patients with such anomalies have a successful subsequent pregnancy without
surgery, with a cumulative live birth rate of 78.0%. Further evidence is needed
to recommend metroplasty surgery in these women (Evidence level II).
· Correction of septate defects in particular may have beneficial effects (live
birth rate 83.2%, range from 77.4%- to 90.9%) and should be considered in
women with RPL. The primary limitation of existing data is the lack of
randomized, controlled therapeutic trials ASRM)
· Because randomized trials in this area are lacking and difficult to conduct,
the general consensus is that surgical correction of significant uterine
cavity defects should be considered
· The clinical management of pregnancy-loss patients with Asherman
syndrome/intrauterine synechiae, uterine fibroids, and uterine polyps is also
controversial, and there is no conclusive evidence that surgical treatment

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 reduces the risk of pregnancy loss. Minimally invasive surgeries are the better
option for the treatment of structural defects.(RCOG)
· There are no published randomised trials assessing the benefits of surgical
correction of uterine abnormalities on pregnancy outcome. Open uterine
surgery has never been assessed in prospective trials but is associated with
postoperative infertility and carries a significant risk of uterine scar rupture
during pregnancy. These complications are less likely to occur after
transcervical hysteroscopic resection of uterine septae; experience from case
series appears promising However, before a clear judgement can be made, this
procedure must be evaluated in a prospective controlled trial
· In the event of irreparable anatomic uterine abnormalities and RPL, IVF
with transfer of embryos to an appropriately selected gestational carrier
also may be a clinical consideration(ASRM)

Repair of cervical lacerations: Abdominal Cerclage

Surgical correction of traumatic cervical lacerations should be undertaken before
further pregnancies are planned. Transabdominal cerclage can be offered as an
alternative treatment for patients presenting with second-trimester miscarriage or
early preterm labour who have had unsuccessful transvaginal cerclage because of
a short or scarred cervix. A systematic review comparing abdominal with vaginal
cerclage has indicated a lower risk of delivery before 24 weeks’ gestation
although the timing of performing transabdominal cerclage before or during
pregnancy remains unresolved

5. Medical treatment: Endocrine disorders including thyroid dysfunction and

diabetes mellitus should be well controlled before another pregnancy is planned.
Patients presenting with PCOS should be appropriately managed with medical
and surgical methods to achieve regular ovulation, and assisted reproductive
technology may be indicated in some of these patients with PCOS.

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 Treatment during Pregnancy
1. Psychological support: Psychological support and tender loving care should be
continued all through the pregnancy. The women should be encouraged for more
frequent antenatal visits (usually 2 weekly appointments) and should be reassured and
to be well supported
2. Treatment for the thyroid dysfunction and diabetes mellitus should be continued to
ensure that these endocrine disorders are well controlled
3. Treatment of RSA Patients with Cervical Disorders: Cervical cerclage
Because of conflicting evidence, the management of women presenting with RSA,
usually late in the first trimester, and with second-trimester miscarriages is really
difficult for the treating physician who needs to decide on the definitive treatment
for such patients.
· A meta-analysis of 4 randomized controlled trials reported that prophylactic
cerclage did not reduce the risk of miscarriage or preterm delivery in women at
risk of such disorders because of cervical weakness.
· Another meta-analysis on women from 4 randomized controlled trials with a short
cervix (<25 mm diagnosed by transvaginal ultrasound examinations) and a history
of previous second-trimester miscarriage confirmed that cervical cerclage may
reduce second-trimester miscarriages and the incidence of preterm delivery. It has
been documented that cervical cerclage may be associated with some minor
maternal morbidity.
· Prophylactic cerclage can be applied in women who present with a history of
recurrent second-trimester abortions, a history of a typical single second-trimester
abortion, or with ultrasound-indicated cervical weakness where a cervical length
of 25 mm or less has been detected by transvaginal ultrasound.
· In women with a less specific history, serial cervical ultrasonographic monitoring
can be carried out in the index pregnancy and prophylactic cerclage can be
performed in women with a short cervix (cervical length of <25 mm).

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Evidence
· Cervical cerclage is associated with potential hazards related to the surgery and
the risk of stimulating uterine contractions and hence should be considered only in
women who are likely to benefit (RCOG)

· Women with a history of second-trimester miscarriage and suspected cervical

weakness who have not undergone a history-indicated cerclage may be offered
serial cervical sonographic surveillance. (RCOG)
· In women with a singleton pregnancy and a history of one second-trimester
miscarriage attributable to cervical factors, an ultrasound-indicated cerclage
should be offered if a cervical length of 25 mm or less is detected by transvaginal
scan before 24 weeks of gestation. (RCOG)

Treatment of RSA Patients with Antiphospholipid Syndrome

APS, the most frequently diagnosed immunological cause of RSA and the only
proven thrombophilia associated with an adverse pregnancy outcome, has also been
identified as the most treatable cause of RSM.

LDA & LMWH

· Low doses of acetylsalicylic acid and low molecular weight heparin (LMWH) are
the best solution in women suffering from recurrent spontaneous miscarriage.
This treatment combination of low dose aspirin and low molecular weight heparin
reduces the miscarriage rate by 54%.
· The efficacy of low molecular weight heparin plus aspirin remains unproven as
LMWH data were based on only two trials. These trials were criticized as studies
were not blinded and the randomization procedure had been criticized in one of
the trials and inclusion criteria were very different.
· Third trial showed no significant difference in live birth rate with LMWH
treatment versus aspirin or a combination of both versus aspirin in women with
recurrent miscarriage.

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· A meta-analysis showed the combination of unfractionated heparin and aspirin
confers a significant benefit in live births (RCOG, ASRM).
· A small trial showed comparable results with LMWH plus aspirin as an
alternative to unfractionated heparin and aspirin in the management of recurrent
miscarriage secondary to APS.
· The consensus is combination of low molecular weight heparin and aspirin is
superior to aspirin alone in achieving more live births. Therefore, it is
recommended treatment for recurrent miscarriages with antiphospholipid
syndrome (Evidence level I).

Evidence
· Pregnant women with antiphospholipid syndrome should be considered for
treatment with low-dose aspirin plus heparin to prevent further miscarriage
(RCOG)
· The combination of twice daily unfractionated heparin and low-dose aspirin
appears to confer a significant benefit in pregnancies with aPLs and otherwise
unexplained recurrent pregnancy loss; comparable efficacy of low molecular
weight heparin has not been established (ASRM,2012).

Treatment with heparin and LDA should be commenced as soon as a pregnancy

test is positive and continued all through pregnancy and into the puerperium with
specific breaks. LDA should be stopped at 35 weeks’ gestation because of some
adverse neonatal effects of LDA, and heparin should not be administered during
labour and operative obstetric operations because of the risk of hemorrhage.

Glucocorticoids :
Glucocorticoids should not be given in antiphospholipid antibodies syndrome without
connective tissue disorder. Low-dose prednisone is given when lupus is present and
with the advice of rheumatologist. Prednisone does not prevent recurrent fetal death
in women with antiphospholipid antibody. Corticosteroids administered to women
during pregnancy presenting with RSA associated with APS do not improve the live

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 birth rate compared with heparin and LDA, and such therapy should not be
encouraged, especially as corticosteroids are associated with significant fetal and
maternal morbidity.

Evidence
· Neither corticosteroids nor intravenous immunoglobulin therapy improve the
live birth rate of women with recurrent miscarriage associated with
antiphospholipid antibodies compared with other treatment modalities; their
use may provoke significant maternal and fetal morbidity (RCOG)
· Administration of prednisone does not improve pregnancy rates and may
be associated with an increased risk of gestational hypertension and
gestational diabetes (ASRM)

Treatment of women presenting with RSA associated with inherited

thrombophilia
· Role of anticoagulation therapy in the treatment of RSA with hereditary
thrombophilia is debatable. Treatment of women presenting with RSA associated
with inherited thrombophilia poses many challenges because there is no strong
evidence to support the treatment of these patients with aspirin and/or heparin.
· Few studies suggested low molecular weight heparin therapy during pregnancy
may improve the live birth rate of women with second-trimester miscarriage
associated with inherited thrombophilia. However, there is currently no evidence
supporting treatment, because observational research is hampered by poor
methodology or inconsistent results. (RCOG,ASRM.. insufficient evidence) .
· Recent meta-analysis showed that the use of LMWH in women with inherited
thrombophilia with recurrent pregnancy loss is not indicated.
· Women with thrombophilia should be followed closely without routine
prophylactic low molecular weight heparin other than for prevention of venous
thromboembolism in limited circumstances (Evidence level I).

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 · Although some studies have indicated that heparin may improve live birth rates in
women with inherited thrombophilia , a more recent has stated that there was no
significant difference in the live birth rate in women with RSA and inherited
thrombophilia who have been treated with a combination of aspirin and LMWH
or aspirin alone.

4. Luteal support Role of Progesterone

In spite of the fact that progesterone has been identified as being essential for the
implantation and maintenance of pregnancy, great controversy still exists about the role
of progesterone supplementation in supporting early pregnancy and in the prevention
and/or reduction of first-trimester miscarriages/recurrent early spontaneous first-trimester
miscarriages.

Treatment of women with unexplained RSA

It should be recalled that in about 50–60% of patients presenting with RSA, in spite of
comprehensive investigations, no etiological factor is identified, and these are classified
as unexplained or idiopathic RSM. Therapy for these cases of idiopathic RSA remains a
great challenge and increases the state of dilemma which the treating physicians confront
on a regular basis. Therapy for many of these patients is empirical, the treating physician
faces a lot of pressure in deciding on whether to offer some other forms of controversial
therapy to these patients. A psychological support and tender loving care should be part
of the treatment offered to these patients. Efforts should be made to find an appropriate
therapy for patients with idiopathic RSA

· Psychological support: should be offered tender loving care, psychological

support as well as dedicated intensive monitoring and comprehensive care and
they should be reassured that a successful future pregnancy could be in the range
of 75%. Women should be reassured for a successful future pregnancy with
supportive care.(Evidence level III)

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· Aspirin 75 mg OD: Evidence is debatable. There is paucity of evidence to make
any recommendation on aspirin for treating recurrent miscarriage in women
without antiphospholipid syndrome. Few RCT suggested clear benefit of using
aspirin for such women. Recent trial failed to support any role of Aspirin in
unexplained recurrent miscarriage. Aspirin helps in improving uterine perfusion.
Aspirin is useful in many undiagnosed implantation failure patients. However, in
the absence of strong evidence, routine use of Aspirin is not recommended
(Evidence level II)
· LMWH: Use of LMWH to prevent miscarriage is not recommended in the
absence of antiphospholipid syndrome (Evidence level II).
· The role of low molecular weight heparin and aspirin treatment specifically for
the prevention of recurrent miscarriage remains controversial.
Two recent randomized controlled trials reported that low molecular weight
heparin and aspirin treatment showed no improvement in the live birth rate
among women with unexplained recurrent miscarriage Proper RCT should
be done to test the efficacy of this treatment (RCOG)
The combination of twice daily unfractionated heparin and low-dose aspirin
appears to confer a significant benefit in pregnancies with otherwise
unexplained recurrent pregnancy loss (ASRM).

· Progesterone: Meta-analysis of 4 randomized trials and only 132 women in total

showed a statistically significant reduction in miscarriages. Further, the evidence
is awaited before making recommendation on use of progesterone in explained
miscarriage. (Evidence level III).
· Human chorionic gonadotrophin (hCG): Recent Cochrane review failed to find
quality evidence to support use of hCG for preventing miscarriage. A well-
designed randomized controlled trial of adequate power and methodological
quality is required. Therefore, the use of hCG is not recommended (Evidence
level II.
· Steroids: The effect of prednisolone therapy for some women with recurrent
miscarriage may be due to altered endometrial angiogenic growth factor

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 expression and reduced blood vessel maturation. The role is mostly limited to
recurrent miscarriage with known connective tissue disorders. Rheumatologic
advice should be taken with patients diagnosed having recurrent pregnancy loss
and connective tissue disorder. The results from the Prednisolone Trial are
awaited; it is a randomized controlled trial of prednisolone for women with
idiopathic recurrent miscarriage and raised uNK cells in the endometrium. There
is no robust evidence to recommend steroid use for unexplained recurrent
miscarriage (Evidence level III)
· Immunoglobulins: IVIG administration for treatment of recurrent miscarriage is
not justified outside the context of research as discussed earlier (Evidence level II)
· Intravenous intralipid solution: No evidence of benefit with use of intralipid. Well
controlled, large-scale, and confirmatory studies required before it can be
recommended for routine use (Evidence level III)
Recent randomized controlled trials have indicated that interventions with the drugs
stated above do not improve live birth rates in women with unexplained/idiopathic RSA.
As clearly recommended, empirical treatment of patients with unexplained RSM with the
drugs stated above should be resisted and discontinued, and restate that in spite of the
challenges we face in finding suitable evidence-based therapy for our patients with RSA,
we should resist offering empirical treatment.

Summary
· The management of RSA is quite varied and challenging.
· The use of LDA and heparin, an established treatment for APS, has been associated
with a live birth rate of 54–74%.
· The role of LDA and heparin therapy in congenital thrombophilia remains
controversial.
· Surgical treatment for uterine anatomical disorders requires further studies.
· The management of unexplained or idiopathic RSA remains a clinical dilemma, and
although psychological care has been associated with a favorable outcome, the

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 empirical use of LDA and heparin and/or intravenous immunoglobulin, should be
discouraged because available results do not support this line of management.
· There is a need for larger, randomized, double-blinded, multi-centred, placebo-
controlled studies to establish an evidence-based basis for the aetiology, diagnosis
and treatment of RSA, and the definition of RSA should be standardized in such
studies.
One of the major setbacks in the field of the management and research in RSA is the lack
of large, well-conducted, double-blinded, randomized, placebo-controlled and preferably
multi-centred trials with well-defined objectives and dealing with patients with
standardized definitions of RSA.

Treatment RCOG (2012) ASRM(2012) ESHRE(2006)

Aspirin plus Recommended Recommended Insufficient
heparin therapy Evidence Level: 2+ Live birth rates with evidence
for Abortion rate 74% vs without 42.9%
antiphospholipid Decreased to 54%
antibodies
Aspirin plus Not recommended Recommended _
heparin therapy
in women with
unexplained
recurrent abortion
Resection of Insufficient evidence Should be considered -
uterine septum
Supportive care Insufficient evidence Recommended Recommended
for women with
unexplained
recurrent
miscarriage

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Other Treatment
RCOG ASRM ESHRE
Anticoaggulants for Insufficient - Insufficient evidence
hereditary evidence
thrombophilias
Immunotherapy Not Recommended Not Recommended Insufficient evidence
Progesterone Insufficient Insufficient -Insufficient
supplementation evidence evidence evidence
HCG Insufficient _ _
supplementation evidence
Folic acid _ _ Insufficient evidence
supplementation for
hyperhomocytenemia
Vitamin - - Not Recommended
supplementation
Steroid treatment Not Recommended Not Recommended Not Recommended
Cervical pessary Not Recommended - -
Serial sonographic Not Recommended - -
surveillance

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