Hindawi Publishing Corporation

BioMed Research International

Volume 2014, Article ID 264653, 9 pages
http://dx.doi.org/10.1155/2014/264653

Clinical Study
Impact of Medical and Surgical Treatment of Endometriosis on
the Cure of Endometriosis and Pain

Liselotte Mettler, R. Ruprai, and Ibrahim Alkatout

Department of Obstetrics and Gynecology, University Clinics of Schleswig-Holstein, Campus Kiel,
Arnold-Heller-Straße 3/24, 24105 Kiel, Germany

Correspondence should be addressed to Liselotte Mettler; [email protected]

Received 16 June 2014; Revised 3 September 2014; Accepted 9 October 2014; Published 15 December 2014

Academic Editor: Claude Hughes

Copyright © 2014 Liselotte Mettler et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

This endometriosis study evaluates three different treatment strategies (hormonal medication, surgical, or combined treatment)
and discusses the influence of endometriosis on the cure of this disease and pain relief. Four hundred and fifty patients with genital
endometriosis, aged 18–44 years, were randomly distributed to three treatment groups at the first laparoscopy. They were reevaluated
at a second-look laparoscopy (D 426/10), one to two months after the three-month hormonal therapy for groups 1 and 3 and five
to six months later for group 2 (surgical treatment alone). Outcome data focussed on the recurrence of symptoms and pain. The
three treatment options independent of the initial endoscopic endometriosis classification (EEC) stage including deep infiltrating
endometriosis (DIE) achieved an overall cure rate of 50% or higher. The highest cure rate of 60% was achieved by the combined
treatment, 55% by the exclusively hormonal therapy, and 50% by the exclusively surgical treatment. An overall pregnancy rate
between 55% and 65% was achieved with no significant difference in relation to the therapeutical option.

1. Introduction Inhibition of Mediators. Research work has focussed on

inhibiting the interaction of various mediators which main-
Pelvic endometriosis remains a late diagnosed complex and tain the illness by way of inflammatory processes, vascular-
mysterious disease that still gives rise to continuous research isation, and cell proliferation. Specific aromatase inhibitors
but can currently only be treated in up to 70% of cases with 3 (such as Letrozole, Anastrozole, or Exemestane) or selective
treatment options. COX-2 inhibitors (e.g., Celecoxib, Rofecoxib) are of great
interest and have been studied in clinical trials [6–8]. There
Medical Treatment. In the past, the main strategy was is no proven evidence that one medical therapy is superior
the induction of a pseudopregnancy and the application of to another in the treatment of the clinical symptoms of
gestagens and later danazol and GnRH analogues [1]. Up endometriosis or infertility.
to now, this theory “The production of pseudopregnancy”
has been regarded as the “gold standard,” but it is now sup- Surgical Treatment. As endometriosis is a progressive disease,
plemented by a simple progesterone (dienogest, 2 mg per which can cause the anatomic destruction of the reproductive
day) treatment or a GnRh analogue treatment with add-back organs, surgical therapy plays an important role. Laparoscopy
therapy [2]. To prevent side effects of the GnRH agonist, such provides the only possibility of ascertaining the expected
as bone demineralization, vasomotor symptoms, and mood diagnosis of endometriosis. Endometriosis has a varying phe-
swings, a serum estradiol concentration of approximately notype and can appear as raised flame-like patches, whitish
60 pg/mL is required [1, 3–5]. Every medical treatment today opacifications, yellow-brown discolorations, translucent blebs,
is well tolerable but should only be used as long as necessary. or reddish irregularly shaped spots (Figure 1) [9, 10]. In
In case it is used as long-time treatment, it should reduce the advanced stages, pain and sterility are predominantly caused
number of surgical interventions and improve the quality of by organ damage, fibrosis, and adhesions, thus constituting
life. a clear indication for surgical intervention. Early laparoscopy
 2738, 2014, 1, Downloaded from https://onlinelibrary.wiley.com/doi/10.1155/2014/264653 by Nat Prov Indonesia, Wiley Online Library on [10/03/2025]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
2 BioMed Research International

Assessment for eligibility (n = 523)

Excluded (n = 73)
Not meeting inclusion criteria (n = 11)
Declined to participate (n = 49)
Other reasons/not able to contact (n = 13)

Primary laparoscopy (n = 450)

Randomized (n = 450)

Medical treatment (n = 150) Surgical treatment (n = 150) Combined treatment (n = 150)

Lost to follow-up (n = 25) Lost to follow-up (n = 13) Lost to follow-up (n = 2)

Changed residence (n = 3) Declined to participate (n = 10) Declined to participate (n = 1)
Declined to participate (n = 14) Other reasons/not able to contact (n = 3) Other reasons/not able to contact (n = 1)
Other reasons/not able to contact (n = 8)

2. Laparoscopy (n = 125) 2. Laparoscopy (n = 137) 2. Laparoscopy (n = 148)

Reassessment ( n = 410)

Figure 1: Trial profile differentiating medical, surgical, and combined treatment of endometriosis (with permission of Alkatout et al. [17]).

can prevent any delays in diagnosis of the disease or symptom of Obstetrics and Gynecology. The evaluation aims at deter-
progression. The importance of laparoscopy with biopsy and/ mining the most successful of the available endometriosis
or resection is reinforced as visual diagnosis alone can often therapies.
lead to a misdiagnosis [11, 12]. Risk factors and disadvantages of
laparoscopy include damage of organs adjacent to the affected 2.1. Patients. Informed consent forms were completed by all
areas and postoperative complications, such as adhesion for- patients. This study, which included operation, medical treat-
mation or infection [13–17]. Symptom relief is achieved in ment, and a selected second-look operation, was approved by
most patients after successful ablation/resection of endo- the Ethical Committee of the Christian-Albrechts-University
metriosis and adhesiolysis. Nevertheless, the recurrence rate Kiel, Germany (D 426/10). Each patient signed an informed
is as high as 40% after a 10-year follow-up [16, 18–20]. consent form for the use of his specimen and clinical data.
The study comprised 450 symptomatic endometriosis
Combined Treatment. The combined treatment involves diag-
patients (18–44 years of age) for whom two consecutive
nostic laparoscopy, removing all visible endometriosis foci
laparoscopic interventions were to be assessed. There were
as far as possible, a 3- to 6-month endocrine therapy, and a
pain and/or infertility patients. 410 patients from the original
subsequent second-look laparoscopy with resection of resid-
collective returned for a second-look laparoscopy (Figure 1).
ual foci, adhesiolysis, and reconstruction of organs [8, 19–
23]. Despite maximal efforts, the therapy of first choice in the Endometriosis was diagnosed or confirmed by laparo-
management of endometriosis is still unclear [14, 24]. scopy and rated according to the endoscopic endometriosis
classification (EEC) introduced by Mettler (Figure 2) [25]
which compares completely to the r-AFS classification. It was
2. Material and Methods used as it is very easy and purely morphologically straightfor-
In the following we focus on current treatment possibilities, ward.
pain, fertility, and the obstetrical outcome in endometriosis
patients. 2.2. Exclusion Criteria. Previous surgery or hormone therapy
In a recent study, 450 endometriosis patients underwent for endometriosis was exclusion criterion, as was deep infil-
one of three different therapeutic strategies (medication, surgi- trating endometriosis with bladder or rectum excision. The
cal, or combined treatment) at the Kiel University Department treatment of deep infiltrating endometriosis with big lesions
 2738, 2014, 1, Downloaded from https://onlinelibrary.wiley.com/doi/10.1155/2014/264653 by Nat Prov Indonesia, Wiley Online Library on [10/03/2025]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
BioMed Research International 3

EEC
Endoscopic endometriosis classification

(I)

<5 mm

(II)

>5 mm

(III)

(IV)

Kiel University Department Obstet. Gynec. Mettler and Semm 1983

Figure 2: The EEC system used to classify endometriotic lesions. In contrast to the rASRM classification, the EEC classification includes
extragenital endometriosis and is divided into four stages.

affecting bowel and/or urinary tract, favorably diagnosed Histopathological assessment confirmed the site of origin,
before surgery, was performed via extensive laparoscopic that is, proliferative endometrium or endometrioma cyst wall,
resection. respectively.
Figure 3 differentiates stages I, II, and III in the laparo-
scopic appearance. 2.4. Interventions. The 450 patients were randomly distri-
buted to the following three treatment groups, 150 per group.
2.3. Tissue Samples. Samples of ectopic endometrium (𝑛 = 450) Of the original 450 patients, 410 returned for the second-look
were obtained from patients undergoing diagnostic hystero- pelviscopy and their findings were assessed.
scopy and laparoscopy for the treatment of endometrioma. Group 1 (𝑛 = 125) underwent hormonal treatment after
The patients ranged in age from 18 to 44 years and diagnostic laparoscopy with 3.75 mg of leuprorelin acetate
received no hormonal treatment prior to surgery. Cryostat depot which was injected subcutaneously in monthly inter-
sections were prepared and stained with hematoxylin-eosin. vals over 3 months. Leuprorelin acetate depot is a GnRH
 2738, 2014, 1, Downloaded from https://onlinelibrary.wiley.com/doi/10.1155/2014/264653 by Nat Prov Indonesia, Wiley Online Library on [10/03/2025]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
4 BioMed Research International

(a) (b)

(c)

Figure 3: Endoscopic image of endometriosis EEC stage I (a), EEC stage II (b), and EEC stage III ((c): (A)–(C)).

agonist and is commercially available in Germany as Enan- 2.5. Main Outcome Measures. The central issue for this study
tone Gyn Depot. was, Which endometriosis therapy is currently the most suc-
Group 2 (𝑛 = 137) underwent surgical laparoscopy with- cessful technique? The success of each therapeutic strategy
out any subsequent medical treatment. Endometriosis foci was assessed—independent of the original EEC stage—accord-
were totally excised, adhesions were removed, and the normal ing to the following criteria after the second-look laparo-
anatomy of the reproductive organs was restored. Ureter scopy:
and superficial bowel lesions were removed. For infertility
(1) a response rate to EEC stages 0 and I of at least 75%,
patients, tubal patency was checked and chromoperturbation
was performed at the second-look laparoscopy. Patients (2) the lowest recurrence rate,
with deep infiltrating endometriosis with bladder or rectum (3) the highest pregnancy rate.
resection were not included in the study.
Within the framework of this study, the endometriosis ther-
Group 3 (𝑛 = 148) underwent the same hormonal therapy
apy that fulfilled all of the criteria or at least two of them was
as group 1 over the same time period after surgical laparo-
regarded as the most successful therapy.
scopy. The combined or three-step therapy comprised diag-
nostic laparoscopy, removal of all visible endometriosis foci,
a 3-month endocrine therapy with GnRH agonists (e.g., 2.6. Statistical Evaluation and IRB Approval. Our results were
3.75 mg of leuprorelin acetate depot), and a subsequent sec- statistically evaluated with the chi-squared test and analysed
ond-look laparoscopy 1-2 months after conclusion of the with a significance level of 𝑃 < 0.05 and a confidence interval
hormonal therapy with resection of residual foci and recon- of 95%. Institutional review board approval was obtained at
structive surgery of organs. the beginning of the study.
The same team of physicians performed the primary and
secondary intervention as well as the primary and secondary 3. Results for Extent of Endometriosis,
endometriosis staging according to the EEC [25, 26]. For Fertility, and Pain
groups 1 and 3, a second-look laparoscopy was performed
1-2 months after hormonal therapy and, for group 2, 5 to 6 Results in the 3 treatment groups were analyzed to assess the
months after surgical endometriosis treatment. After the new endometriosis staging or EEC downstaging. There was
second-look laparoscopy, patients were monitored over a no significant difference between the groups insofar as distri-
period of 2 years and completed an extensive questionnaire to bution of EEC stages before treatment. After the individual
determine their recurrence of symptoms, new endometriotic treatment, the distribution of EEC stages indicated a signifi-
lesions determined laparoscopically, and confirmed preg- cant difference between the 3 groups (𝑃 = 0.01). The shift in
nancy rates. Also patients in group 2 were reevaluated with the CI is indicative of a higher rate of cure in patients in group
a second-look laparoscopy as endometriosis may reappear. 3 compared with groups 1 and 2. This was most remarkable
 2738, 2014, 1, Downloaded from https://onlinelibrary.wiley.com/doi/10.1155/2014/264653 by Nat Prov Indonesia, Wiley Online Library on [10/03/2025]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
BioMed Research International 5

Table 1: Distribution of patients to EEC stages before (𝑃 = 0.105) and after therapy (𝑃 = 0.010).

EEC stage
Therapy methods
EEC 0 CI EEC I CI EEC II CI EEC III CI
Group 1, hormonal (𝑛 = 125)
Before therapy 0 — 50 (40%) 31.3–49.1 47 (38%) 29.1–46.7 28 (22%) 15.4–30.7
After therapy 62 (50%) 40.5–58.7 40 (32%) 23.9–40.9 16 (13%) 7.4–20.0 7 (5%) 2.3–11.2
Group 2, surgical (𝑛 = 137)
Before therapy 0 — 69 (50%) 41.7–59.0 44 (32%) 24.4–40.6 24 (18%) 11.5–24.9
After therapy 75 (55%) 46.0–63.3 20 (13%) 9.2–21.6 30 (23%) 15.3–29.8 12 (9%) 4.6–14.8
Group 3, combined (𝑛 = 148)
Before therapy 0 — 79 (53%) 45.0–61.1 36 (24%) 17.7–32.1 33 (23%) 15.9–29.9
After therapy 89 (60%) 51.3–68.1 26 (18%) 11.8–24.7 25 (17%) 11.2–23.9 8 (5%) 2.4–10.4
CI: confidence interval.

for stage EEC 0 (Table 1). The definition of cure rate is that after the end of all therapeutic activities as a second outcome
laparoscopically there were no more endometriotic lesions measure [27].
visible for stage EEC 0. Results in the 3 treatment groups were analyzed to assess
At the onset of the study, in the 125 patients in group 1 the treatment effect considering the recurrence of symptoms
(hormone therapy), disease stage was EEC I in 40%, ECC of endometriosis. There was no significant difference between
II in 38%, and EEC III in 22%. After hormone therapy and the groups insofar as distribution of symptoms before treat-
independent of the previous EEC stage, disease stage was EEC ment (𝑃 = 0.61 for dysmenorrhea, 𝑃 = 0.59 for dyspareunia,
I in 32% of patients, EEC II in 13%, and EEC III in 5%. In 50% and 𝑃 = 0.54 for abdominal pain).
of the patients, second-look laparoscopy showed no signs of After the individual treatment, the distribution of recur-
endometriosis (EEC 0). In these patients, the disease seemed rence of symptoms highlights a general reduction in symp-
to be cured (cure rate = 50%). In the 137 patients in group 2 toms, with the greatest benefit observed in the combined
(surgical treatment), disease stage was EEC I in 50%, EEC II treatment group. There was a difference, statistically not sig-
in 32%, and EEC III in 18%. At second-look laparoscopy, the
nificant, for dysmenorrhea between the therapeutic groups
disease could be downstaged to EEC I in 13% of patients, EEC
(𝑃 = 0.05) after treatment. The 95% CI demonstrated a
II in 23%, and EEC III in 9%.
remarkable difference in the treatment effect in all 3 groups.
The cure rate for the exclusively surgically treated group
Nevertheless, the treatment effect was strongest in group 3,
was 55% (EEC 0). In the 148 patients in group 3 (combined
followed by group 2. Insofar as dyspareunia, a significant
treatment), disease stage was EEC I in 53%, EEC II in 24%,
difference was noted between the 3 treatment groups (𝑃 =
and EEC III in 23%. After combined surgical and hormone
0.007). The CIs demonstrated the biggest treatment effect in
therapy, disease stage was EEC I in 18% of the patients, EEC
group 3, followed by group 2. Abdominal pain could not
II in 17%, and EEC III in 5%. With combined treatment, the
be reduced significantly (𝑃 = 0.284). Nevertheless, the CIs
cure rate was 60% (EEC 0).
showed the biggest effect in group 3, followed by group 1. In
The 3 treatment options achieved, independent of the ini-
group 1 (hormone therapy), at the onset of the study, 60%
tial EEC stage, an overall cure rate of ≥50%. With combined
of the 125 patients had dysmenorrhea, 56% had dyspareunia,
treatment, the cure rate was 60%, with exclusively hormonal
and 48% had abdominal pain. The group that received exclu-
therapy was 55%, and with exclusively surgical treatment was
50%. Within the framework of the study, cure was defined as sively hormonal therapy had the highest recurrence rates:
a reduction in disease stage to EEC 0. This new endometriosis dysmenorrhea in 28% of the patients, abdominal pain in 26%,
downstaging was confirmed at second-look laparoscopy. The and dyspareunia in 22%. In group 2 (surgical treatment), 57%
best total cure rate was achieved with combined treatment of the 137 patients had dysmenorrhea, 50% had dyspareunia,
(Table 1). and 42% had abdominal pain. After follow-up, 20% of the
In a second step, we differentiated light, intermediate, and women in this group reported dysmenorrhea, 15% reported
advanced endometriosis and evaluated therapeutic strategies. dyspareunia, and 24% reported abdominal pain.
An improvement of at least 75% to EEC stage 0 or stage 1 was In group 3 (combined treatment), 54% of the 148 women
defined as highly efficient. These conditions were met with the had dysmenorrhea, 51% had dyspareunia, and 42% had
exclusively hormonal therapy, with a rate of 82% (50% EEC 0 abdominal pain. Patients in the combined treatment group
and 32% EEC I), and with the combined treatment (3-step achieved the lowest general recurrence rate and the lowest
therapy), with a response rate of 78% (60% EEC 0 and 18% recurrence rate per symptom: 16% of the patients reported
EEC I) (Table 1). dysmenorrhea, 8% reported dyspareunia, and 17% reported
Because endometriosis generally causes recurrent pain, abdominal pain at 1-year follow-up (Figure 4). In comparison
we asked our study patients to complete an extensive ques- with groups 1 and 2, group 3 had significantly better results
tionnaire and report recurrent symptoms, before and at 1 year after treatment (𝑃 < 0.001).
 2738, 2014, 1, Downloaded from https://onlinelibrary.wiley.com/doi/10.1155/2014/264653 by Nat Prov Indonesia, Wiley Online Library on [10/03/2025]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
6 BioMed Research International

Table 2: Comparison of recurrence rates for the three therapy methods before and after one year.

Recurrent symptoms (in %)/CI

Therapy
methods Dysmenorrhea Dyspareunia Abdominal pain
Before (𝑃 = 0.613) After (𝑃 = 0.053) Before (𝑃 = 0.0593) After (𝑃 = 0.007) Before (𝑃 = 0.0540) After (𝑃 = 0.284)
Group 1,
hormonal 75 (60%)/50.9–68.7 35 (28%)/20.3–36.7 70 (56%)/46.8–64.9 28 (22%)/15.4–30.7 60 (48%)/40.0–57.1 33 (26%)/18.9–35.0
(𝑛 = 125)
Group 2,
surgical 78 (57%)/48.2–65.4 27 (20%)/13.4–27.3 69 (50%)/41.7–59.0 21 (15%)/9.7–22.5 58 (42%)/33.9–51.1 33 (24%)/17.2–32.1
(𝑛 = 137)
Group 3,
combined 80 (54%)/45.7–62.3 24 (16%)/10.7–23.2 75 (51%)/42.3–59.0 12 (8%)/4.2–13.7 62 (42%)/33.8–50.3 25 (17%)/11.2–23.9
(𝑛 = 148)
CI: confidence interval.

70 80
Dyspareunia Dysmenorrhea
60 70
60
50
50
40 (%)
(%)

40
30
30
20 20
10 10
0 0
Hormonal Surgical Combined Hormonal Surgical Combined

Before Before
After After
(a) (b)

60
Abdominal pain
50

40
(%)

30

20

10

0
Hormonal Surgical Combined

Before
After
(c)

Figure 4: Comparison of recurrence rates of symptoms including dyspareunia (a), dysmenorrhea (b), and abdominal pain (c) for each of the
3 treatment groups before 1 year after treatment. Therapeutic benefit is supported by the marked confidence intervals.

The third outcome measure was the pregnancy rate. We There was no statistical significance between these results.
determined an overall pregnancy rate over 2 years of 55% to Of these 245 pregnancies, 41 (17%) were not carried to
65% in the 3 treatment groups, independent of ECC stage term (6 ectopic pregnancies and 35 abortions). However, 205
(Table 2). The pregnancy rate after the exclusively surgical children, including 1 set of twins, were born. There was no
restoration was 55%, after combined treatment was 60%, and statistically significant difference between the 3 therapeutic
after exclusively hormonal therapy was 65%. strategies insofar as the pregnancies and their course.
 2738, 2014, 1, Downloaded from https://onlinelibrary.wiley.com/doi/10.1155/2014/264653 by Nat Prov Indonesia, Wiley Online Library on [10/03/2025]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
BioMed Research International 7

4. Discussion Regidor found a significant improvement of the r-AFS

score after treatment with triptorelin (GnRH analogue).
The presented clinical studies comparing medical, surgical, Sixty-three percent of these patients were no longer diag-
and combined therapy and the assessment of how endomet- nosed with endometriosis, 30% presented with stage I resid-
riosis can affect pregnancy and deliveries show the current ual endometriosis according to the AFS classification, and
needs for the treatment of endometriosis and point out some only 7% had stage II endometriosis [33]. It could be demon-
advice for future therapeutic modalities. strated that after administration of buserelin (GnRH ana-
In the presented study, 450 endometriosis patients, aged logue) the average AFS score went down from 17.4 ± 12.9
18–44 years, were randomly assigned to one of the three dif- before therapy to 7.2 ± 8.2 after a 6-month therapy [31, 34].
ferent therapeutic strategies (medical, surgical, or combined Although up to 90% of patients experience some symptom
treatment) at the Kiel University Department of Obstetrics relief with medical therapy, medical treatment alone neither
and Gynecology, Germany. The success of each therapeutic enhances fertility, diminishes pelvic mass, nor removes adhe-
strategy was assessed—independent of the original EEC stage sions [1, 10].
[25]—according to the following criteria: Similar to Schweppe [30] and Römer and Schwesinger
[35], we also determined a significantly lower recurrence
(i) the therapy after which the patients achieved the
rate after application of the three-step therapy. Römer and
highest cure rate (EEC stage 0),
Schwesinger reported that retrospective analyses 12–48
(ii) a response rate to EEC stages I and 0 of 75% or higher, months after endometriosis therapy presented a recurrence
(iii) the lowest recurrence rate, rate for hormonal and surgical treatment (three-step concept)
(iv) the highest pregnancy rate. of only 16.7%, whereas the recurrence rate for exclusively
surgically treated patients was 47%.
Within the framework of this study, the endometriosis Regidor et al. showed in a long-term follow-up study that
therapy that fulfilled the majority of the criteria, or at least 70 of 112 patients (62.5%) again reported ailments and that the
two of them, was regarded as the most successful therapy. recurrence-free interval amounted to an average of 11 months
The three treatment options reached an overall cure rate of after finishing the three-step therapy (with the GnRH ana-
50% or higher. There was no statistically significant difference logue leuprorelin acetate) [36]. In another long-term follow-
(𝑃 > 0.05), but with a cure rate of 60% the combined therapy up study, Schindler et al. established recurrent endometriosis
ranks first. The combined (three-step) and the exclusively in 62 of 112 patients (55%) after a combined surgical-hor-
hormonal therapy managed to surpass the 75% response rate monal therapy [1, 37]. Our recurrence rate (41%) was lower
with 78% and 82%, respectively. Nevertheless, the combined than Regidor’s rate (62.5%) and Schindler’s rate (55%) for the
treatment reached the lowest recurrence rate per symptom combined therapy. Zupi et al. were able to show that patients
at a statistically significant level. No statistically significant treated with GnRH agonists had a significantly higher rate
difference was recorded for the pregnancy rate which ranged of symptom reduction (pelvic pain, dysmenorrhea, and dys-
between 55% and 65%, independent of the therapeutic strat- pareunia) than women treated with continuous estrogen-
egy. As an overall result, we have been able to confirm the progestin oral contraceptives. Quality of life was increased by
high efficacy of the combined endometriosis therapy in this extending the GnRH treatment to include add-back therapy
study. [3]. Other investigations comparing oral contraceptives to
Medical therapy can be applied prior to surgery to GnRH agonists found an equal reduction of pain [38]. Abbott
decrease the size of endometriotic implants and the extent of et al. 2004 and Sutton et al. 1994 performed a second-look
the operation [28]. However, so far there is no clear evidence laparoscopy 6–12 months after the primary operation and
that perioperative hormonal treatment decreases the extent found that 29–45% of the patients had disease progression
of operation necessary to remove endometriotic implants, and 22–29% disease regression, and in 33–42% the disease
remained static [18, 39].
delays or prevents recurrence, or increases pregnancy rates.
Endometriosis can reduce the fecundability rate without
In contrast, several trials were able to report an increased
completely preventing conception. Impaired fertility might
duration of pain relief and delayed recurrence rates using
be due to anatomic variations after adhesion formation
postoperative medical therapy [10, 28, 29]. Schweppe con-
and endometriomas [40]. An enhancement of fertility rates
cluded that, in all cases of active endometriosis, pelviscopic
through ovulation suppression has not yet been proven [1].
treatment alone is not sufficient [30]. Schindler et al. demon- In our study, after the combined therapy, we had 89 (60%)
strated that the primary surgical intervention reduced the pregnancies in 148 patients and 13 abortions and 3 extrauter-
total r-AFS (revised American Fertility Society) score by 34%, ine pregnancies. Sixteen (18%) of the 89 pregnancies did
whereas the combined therapy brought about a reduction of not lead to a live birth (13 abortions and 3 extrauterine preg-
66% [31]. nancies). Regidor reported 55 (60%) pregnancies for 91
Thus the combined hormonal and surgical treatment of patients for the same therapeutic strategy [36]. Nineteen
endometriosis gave best results in stopping the progressing (34.5%) of the 55 pregnancies were not carried to term (5
of the disease, as already found by our group [32]. extrauterine pregnancies, 14 abortions). Our pregnancy rate
Our study showed only a weak and statistically nonsignif- was comparable to Regidor’s rate, but our abortion rate was
icant difference between the combined treatment (decrease significantly lower than his. After the exclusively surgical
in EEC stage by 60%) and the solitary surgical treatment treatment, we registered a pregnancy rate of 55%. In compar-
(decrease in EEC stage by 55%). ison, Marcoux et al. presented a pregnancy rate of 29% [41].
 2738, 2014, 1, Downloaded from https://onlinelibrary.wiley.com/doi/10.1155/2014/264653 by Nat Prov Indonesia, Wiley Online Library on [10/03/2025]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
8 BioMed Research International

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and after surgical procedures, their prevention and impact on
The authors declare that there is no conflict of interests womens health,” Women’s Health, vol. 8, no. 5, pp. 495–498,
regarding the publication of this paper. 2012.
[17] I. Alkatout, T. Schollmeyer, M. Doniec, J. Egberts, and W. Jonat,
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