Am J Obstet Gynecol. 2016 Feb;214(2):203-11. doi: 10.1016/j.ajog.2015.08.074.

Epub 2015 Sep

11.
Continuous versus cyclic oral contraceptives after
laparoscopic excision of ovarian endometriomas: a
systematic review and metaanalysis.
Muzii L1, Di Tucci C2, Achilli C2, Di Donato V2, Musella A2, Palaia I2, Panici PB2.
Author information

Abstract
In the lack of evidence consistently supporting the use of continuous vs cyclic
oral contraceptives after surgery for endometriosis, we conducted a systematic
review and metaanalysis with the objective of comparing a continuous vs a
cyclic oral contraceptive schedule administered after surgical excision of ovarian
endometriomas. A PubMed, MedLine, and Embase search through December
2014 was conducted, with the use of a combination of key words and text words
related to endometrioma, endometriosis, oral contraceptives, oral
estroprogestins, laparoscopy, and surgery. Studies directly comparing a
continuous vs a cyclic schedule administered after surgical treatment of
endometriomas were included, with pain and endometrioma recurrence rates as
the primary outcomes. Three reviewers independently assessed methodology
and extracted data from selected studies. The primary outcomes were
considered pain recurrence (evaluated separately for dysmenorrhea, noncyclic
chronic pelvic pain, and dyspareunia) and endometrioma recurrence evaluated
at ultrasonography. Dichotomous outcomes from each study were expressed as
risk ratio (RR) with a 95% confidence interval (CI). Three randomized clinical
trials and 1 prospective controlled cohort study were included, for a total of 557
patients with endometriosis, 343 patients of whom had ovarian endometriomas
completing the assigned treatment and follow-up. Lower recurrence rates for
dysmenorrhea were obtained with a continuous schedule (RR, 0.24; 95% CI,
0.06-0.91; P = .04). Nonsignificant differences were present for chronic pelvic
pain and dyspareunia. A continuous oral contraceptive schedule was associated
with a nonsignificant reduction of cyst recurrence rates compared with a cyclic
schedule (RR, 0.54; 95% CI, 0.28-1.05; P = .07). A continuous oral contraceptive
regimen, as opposed to a cyclic regimen, may be suggested after surgery for
endometriomas because of lower dysmenorrhea recurrence rates. Due to the
small number and small sample sizes of the included studies, further
randomized clinical trials are needed to confirm the findings of the present
systematic review. Also, outcomes related to patient satisfaction and quality of
life should be addressed.
Copyright 2016 Elsevier Inc. All rights reserved

Arch Gynecol Obstet. 2015 Jul;292(1):37-43. doi: 10.1007/s00404-015-3641-1. Epub 2015 Feb
3.
Continuous versus cyclic oral contraceptives for the
treatment of endometriosis: a systematic review.
Zorbas KA1, Economopoulos KP, Vlahos NF.
Author information

Abstract
PURPOSE:
Recurrence of endometriosis after conservative surgery has been observed in
40-50 % of patients within the first 5 years. A variety of regimens such as
combined oral contraceptives, GnRH agonists, danazol, and progestins have
been used postoperatively to reduce recurrence rates. Oral contraceptives (oCP)
have been used either in a cyclic or in a continuous (no pill-free interval) fashion.
The purpose of this article was to summarize the existing evidence on the
efficacy and patient compliance for the use of oCP in a continuous versus cyclic
fashion following conservative surgery for endometriosis.
METHODS:
A systematic search of Medline identified four eligible studies. Studies were
considered eligible, if they have evaluated oCP therapy, either in a cyclic or
continuous regimen, after conservative surgery for endometriosis. Specifically,
studies (1) reporting on women with endometriosis who were treated
postoperatively with both continuous oCP and cyclic oCP, (2) written in English,
(3) with minimum 6 months duration of medical treatment, and (4) with
minimum 12 months duration of follow-up were considered eligible for our
systematic review. Outcome measures of these eligible studies were tabulated
and then analyzed cumulatively. A purely descriptive approach was adopted
concerning all variables.
RESULTS:
Postoperative use of continuous oCP was associated with a reduction in the
recurrence rate of dysmenorrhea, delay in the presentation of dysmenorrhea,
reduction in nonspecific pelvic pain, and reduction in the recurrence rate for
endometrioma.
CONCLUSIONS:
Use of oCP in a continuous fashion following conservative surgery for
endometriosis is more beneficial to cyclic use.
Comment in
% Reply to: Continuous versus cyclic oral contraceptives for
endometriosis: any conclusive evidence? [Arch Gynecol Obstet. 2015]
% Reply to: Continuous or cyclic contraceptives for endometriosis:
a question still without an answer. [Arch Gynecol Obstet. 2015]
% Continuous or cyclic contraceptives for endometriosis: a
question still without an answer. [Arch Gynecol Obstet. 2015]
Continuous versus cyclic oral contraceptives for endometriosis: any
conclusive evidence? [Arch Gynecol Obstet. 2015]

Cochrane Database Syst Rev. 2016 Apr 20;4:CD012165. doi:

10.1002/14651858.CD012165.
Endometrial biomarkers for the non-invasive diagnosis of
endometriosis.
Gupta D1, Hull ML, Fraser I, Miller L, Bossuyt PM, Johnson N, Nisenblat V.
Author information
Abstract
BACKGROUND:
About 10% of reproductive-aged women suffer from endometriosis, which is a
costly, chronic disease that causes pelvic pain and subfertility. Laparoscopy is
the gold standard diagnostic test for endometriosis, but it is expensive and
carries surgical risks. Currently, there are no non-invasive tests available in
clinical practice that accurately diagnose endometriosis. This is the first
diagnostic test accuracy review of endometrial biomarkers for endometriosis
that utilises Cochrane methodologies, providing an update on the rapidly
expanding literature in this field.
OBJECTIVES:
To determine the diagnostic accuracy of the endometrial biomarkers for pelvic
endometriosis, using a surgical diagnosis as the reference standard. We
evaluated the tests as replacement tests for diagnostic surgery and as triage
tests to inform decisions to undertake surgery for endometriosis.
SEARCH METHODS:
We did not restrict the searches to particular study designs, language or
publication dates. To identify trials, we searched the following databases:
CENTRAL (2015, July), MEDLINE (inception to May 2015), EMBASE (inception to
May 2015), CINAHL (inception to April 2015), PsycINFO (inception to April 2015),
Web of Science (inception to April 2015), LILACS (inception to April 2015),
OAIster (inception to April 2015), TRIP (inception to April 2015) and
ClinicalTrials.gov (inception to April 2015). We searched DARE and PubMed
databases up to April 2015 to identify reviews and guidelines as sources of
references to potentially relevant studies. We also performed searches for
papers recently published and not yet indexed in the major databases. The
search strategies incorporated words in the title, abstract, text words across the
record and the medical subject headings (MeSH).
SELECTION CRITERIA:
We considered published peer-reviewed, randomised controlled or cross-
sectional studies of any size that included prospectively collected samples from
any population of reproductive-aged women suspected of having one or more of
the following target conditions: ovarian, peritoneal or deep infiltrating
endometriosis (DIE).
DATA COLLECTION AND ANALYSIS:
Two authors independently extracted data from each study and performed a
quality assessment. For each endometrial diagnostic test, we classified the data
as positive or negative for the surgical detection of endometriosis and calculated
the estimates of sensitivity and specificity. We considered two or more tests
evaluated in the same cohort as separate data sets. We used the bivariate
model to obtain pooled estimates of sensitivity and specificity whenever
sufficient data were available. The predetermined criteria for a clinically useful
test to replace diagnostic surgery was one with a sensitivity of 94% and a
specificity of 79%. The criteria for triage tests were set at sensitivity at or above
95% and specificity at or above 50%, which in case of negative results rules out
the diagnosis (SnOUT test) or sensitivity at or above 50% with specificity at or
above 95%, which in case of positive result rules in the diagnosis (SpIN test).
MAIN RESULTS:
We included 54 studies involving 2729 participants, most of which were of poor
methodological quality. The studies evaluated endometrial biomarkers either in
specific phases of the menstrual cycle or outside of it, and the studies tested the
biomarkers either in menstrual fluid, in whole endometrial tissue or in separate
endometrial components. Twenty-seven studies evaluated the diagnostic
performance of 22 endometrial biomarkers for endometriosis. These were
angiogenesis and growth factors (PROK-1), cell-adhesion molecules (integrins
31, 41, 1 and 6), DNA-repair molecules (hTERT), endometrial and
mitochondrial proteome, hormonal markers (CYP19, 17HSD2, ER-, ER-),
inflammatory markers (IL-1R2), myogenic markers (caldesmon, CALD-1), neural
markers (PGP 9.5, VIP, CGRP, SP, NPY, NF) and tumour markers (CA-125). Most of
these biomarkers were assessed in single studies, whilst only data for PGP 9.5
and CYP19 were available for meta-analysis. These two biomarkers
demonstrated significant diversity for the diagnostic estimates between the
studies; however, the data were too limited to reliably determine the sources of
heterogeneity. The mean sensitivities and specificities of PGP 9.5 (7 studies, 361
women) were 0.96 (95% confidence interval (CI) 0.91 to 1.00) and 0.86 (95% CI
0.70 to 1.00), after excluding one outlier study, and for CYP19 (8 studies, 444
women), they were were 0.77 (95% CI 0.70 to 0.85) and 0.74 (95% CI 0.65 to
84), respectively. We could not statistically evaluate other biomarkers in a
meaningful way. An additional 31 studies evaluated 77 biomarkers that showed
no evidence of differences in expression levels between the groups of women
with and without endometriosis.
AUTHORS' CONCLUSIONS:
We could not statistically evaluate most of the biomarkers assessed in this
review in a meaningful way. In view of the low quality of most of the included
studies, the findings of this review should be interpreted with caution. Although
PGP 9.5 met the criteria for a replacement test, it demonstrated considerable
inter study heterogeneity in diagnostic estimates, the source of which could not
be determined. Several endometrial biomarkers, such as endometrial proteome,
17HSD2, IL-1R2, caldesmon and other neural markers (VIP, CGRP, SP, NPY and
combination of VIP, PGP 9.5 and SP) showed promising evidence of diagnostic
accuracy, but there was insufficient or poor quality evidence for any clinical
recommendations. Laparoscopy remains the gold standard for the diagnosis of
endometriosis, and using any non-invasive tests should only be undertaken in a
research setting. We have also identified a number of biomarkers that
demonstrated no diagnostic value for endometriosis. We recommend that
researchers direct future studies towards biomarkers with high diagnostic
potential in good quality diagnostic studies.

Cochrane Database Syst Rev. 2016 Jul 13;7:CD012281. [Epub ahead of print]
Combination of the non-invasive tests for the diagnosis of
endometriosis.
Nisenblat V1, Prentice L, Bossuyt PM, Farquhar C, Hull ML, Johnson N.
Author information
Abstract
BACKGROUND:
About 10% of women of reproductive age suffer from endometriosis, a costly
chronic disease causing pelvic pain and subfertility. Laparoscopy is the gold
standard diagnostic test for endometriosis, but is expensive and carries surgical
risks. Currently, there are no non-invasive tests available in clinical practice to
accurately diagnose endometriosis. This review assessed the diagnostic
accuracy of combinations of different non-invasive testing modalities for
endometriosis and provided a summary of all the reviews in the non-invasive
tests for endometriosis series.
OBJECTIVES:
To estimate the diagnostic accuracy of any combination of non-invasive tests for
the diagnosis of pelvic endometriosis (peritoneal and/or ovarian or deep
infiltrating) compared to surgical diagnosis as a reference standard. The
combined tests were evaluated as replacement tests for diagnostic surgery and
triage tests to assist decision-making to undertake diagnostic surgery for
endometriosis.
SEARCH METHODS:
We did not restrict the searches to particular study designs, language or
publication dates. We searched CENTRAL to July 2015, MEDLINE and EMBASE to
May 2015, as well as the following databases to April 2015: CINAHL, PsycINFO,
Web of Science, LILACS, OAIster, TRIP, ClinicalTrials.gov, DARE and PubMed.
SELECTION CRITERIA:
We considered published, peer-reviewed, randomised controlled or cross-
sectional studies of any size, including prospectively collected samples from any
population of women of reproductive age suspected of having one or more of the
following target conditions: ovarian, peritoneal or deep infiltrating endometriosis
(DIE). We included studies comparing the diagnostic test accuracy of a
combination of several testing modalities with the findings of surgical
visualisation of endometriotic lesions.
DATA COLLECTION AND ANALYSIS:
Three review authors independently collected and performed a quality
assessment of the data from each study by using the QUADAS-2 tool. For each
test, the data were classified as positive or negative for the surgical detection of
endometriosis and sensitivity and specificity estimates were calculated. The
bivariate model was planned to obtain pooled estimates of sensitivity and
specificity whenever sufficient data were available. The predetermined criteria
for a clinically useful test to replace diagnostic surgery were a sensitivity of 0.94
and a specificity of 0.79 to detect endometriosis. We set the criteria for triage
tests at a sensitivity of 0.95 and above and a specificity of 0.50 and above,
which 'rules out' the diagnosis with high accuracy if there is a negative test
result (SnOUT test), or a sensitivity of 0.50 and above and a specificity of 0.95
and above, which 'rules in' the diagnosis with high accuracy if there is a positive
result (SpIN test).
MAIN RESULTS:
Eleven eligible studies included 1339 participants. All the studies were of poor
methodological quality. Seven studies evaluated pelvic endometriosis, one study
considered DIE and/or ovarian endometrioma, two studies differentiated
endometrioma from other ovarian cysts and one study addressed mapping DIE
at specific anatomical sites. Fifteen different diagnostic combinations were
assessed, including blood, urinary or endometrial biomarkers, transvaginal
ultrasound (TVUS) and clinical history or examination. We did not pool estimates
of sensitivity and specificity, as each study analysed independent combinations
of the non-invasive tests.Tests that met the criteria for a replacement test were:
a combination of serum IL-6 (cut-off >15.4 pg/ml) and endometrial PGP 9.5 for
pelvic endometriosis (sensitivity 1.00 (95% confidence interval (CI) 0.91 to 1.00),
specificity 0.93 (95% CI, 0.80, 0.98) and the combination of vaginal examination
and transvaginal ultrasound (TVUS) for rectal endometriosis (sensitivity 0.96
(95% CI 0.86 to 0.99), specificity 0.98 (95% CI 0.94 to 1.00)). Tests that met the
criteria for SpIN triage tests for pelvic endometriosis were: 1. a multiplication of
urine vitamin-D-binding protein (VDBP) and serum CA-125 (cut-off >2755)
(sensitivity 0.74 (95% CI 0.60 to 0.84), specificity 0.97 (95% CI 0.86 to 1.00))
and 2. a combination of history (length of menses), serum CA-125 (cut-off >35
U/ml) and endometrial leukocytes (sensitivity 0.61 (95% CI 0.54 to 0.69),
specificity 0.95 (95% CI 0.91 to 0.98)). For endometrioma, the following
combinations qualified as SpIN test: 1. TVUS and either serum CA-125 (cut-off
25 U/ml) or CA 19.9 (cut-off 12 U/ml) (sensitivity 0.79 (95% CI 0.64 to 0.91),
specificity 0.97 (95% CI 0.91 to 1.00)); 2. TVUS and serum CA 19.9 (cut-off 12
U/ml) (sensitivity 0.54 (95% CI 0.37 to 0.70), specificity 0.97 (95% CI 0.91 to
1.0)); 3-4. TVUS and serum CA-125 (cut-off 20 U/ml or cut-off 25 U/ml)
(sensitivity 0.69 (95% CI 0.49 to 0.85), specificity 0.96 (95% CI 0.88 to 0.99)); 5.
TVUS and serum CA-125 (cut-off 35 U/ml) (sensitivity 0.52 (95% CI 0.33 to
0.71), specificity 0.97 (95% CI 0.90 to 1.00)). A combination of vaginal
examination and TVUS reached the threshold for a SpIN test for obliterated
pouch of Douglas (sensitivity 0.87 (95% CI 0.69 to 0.96), specificity 0.98 (95% CI
0.95 to 1.00)), vaginal wall endometriosis (sensitivity 0.82 (95% CI 0.60 to 0.95),
specificity 0.99 (95% CI 0.97 to 1.0)) and rectovaginal septum endometriosis
(sensitivity 0.88 (95% CI 0.47 to 1.00), specificity 0.99 (95% CI 0.96 to 1.00)).All
the tests were evaluated in individual studies and displayed wide CIs. Due to the
heterogeneity and high risk of bias of the included studies, the clinical utility of
the studied combination diagnostic tests for endometriosis remains unclear.
AUTHORS' CONCLUSIONS:
None of the biomarkers evaluated in this review could be evaluated in a
meaningful way and there was insufficient or poor-quality evidence. Laparoscopy
remains the gold standard for the diagnosis of endometriosis and using any non-
invasive tests should only be undertaken in a research setting.

Cochrane Database Syst Rev. 2015 Dec 23;(12):CD012019. doi: 10.1002/14651858.CD012019.

Urinary biomarkers for the non-invasive diagnosis of
endometriosis.
Liu E1, Nisenblat V, Farquhar C, Fraser I, Bossuyt PM, Johnson N, Hull ML.
Author information
Abstract
BACKGROUND:
About 10% of reproductive-aged women suffer from endometriosis which is a
costly chronic disease that causes pelvic pain and subfertility. Laparoscopy is the
'gold standard' diagnostic test for endometriosis, but it is expensive and carries
surgical risks. Currently, there are no simple non-invasive or minimally-invasive
tests available in clinical practice that accurately diagnoses endometriosis.
OBJECTIVES:
1. To provide summary estimates of the diagnostic accuracy of urinary
biomarkers for the diagnosis of pelvic endometriosis compared to surgical
diagnosis as a reference standard.2. To assess the diagnostic utility of
biomarkers that could differentiate ovarian endometrioma from other ovarian
masses.Urinary biomarkers were evaluated as replacement tests for surgical
diagnosis and as triage tests to inform decisions to undertake surgery for
endometriosis.
SEARCH METHODS:
The searches were not restricted to particular study design, language or
publication dates. We searched the following databases to 20 April - 31 July
2015: CENTRAL, MEDLINE, EMBASE, CINAHL, PsycINFO, Web of Science, LILACS,
OAIster, TRIP and ClinicalTrials.gov (trial register). MEDION, DARE, and PubMed
were also searched to identify reviews and guidelines as reference sources of
potentially relevant studies. Recently published papers not yet indexed in the
major databases were also sought. The search strategy incorporated words in
the title, abstract, text words across the record and the medical subject headings
(MeSH) and was modified for each database.
SELECTION CRITERIA:
Published peer-reviewed, randomised controlled or cross-sectional studies of any
size were considered, which included prospectively collected samples from any
population of reproductive-aged women suspected of having one or more of the
following target conditions: ovarian, peritoneal or deep infiltrating endometriosis
(DIE). We included studies comparing the diagnostic test accuracy of one or
more urinary biomarkers with surgical visualisation of endometriotic lesions.
DATA COLLECTION AND ANALYSIS:
Two authors independently collected and performed a quality assessment of the
data from each study. For each diagnostic test, the data were classified as
positive or negative for the surgical detection of endometriosis and sensitivity
and specificity estimates were calculated. If two or more tests were evaluated in
the same cohort, each was considered as a separate data set. The bivariate
model was used to obtain pooled estimates of sensitivity and specificity
whenever sufficient data sets were available. The predetermined criteria for a
clinically useful urine test to replace diagnostic surgery was one with a
sensitivity of 94% and a specificity of 79% to detect endometriosis. The criteria
for triage tests were set at sensitivity of equal or greater than 95% and
specificity of equal or greater than 50%, which in case of negative result rules
out the diagnosis (SnOUT test) or sensitivity of equal or greater than 50% with
specificity of equal or greater than 95%, which in case of positive result rules the
diagnosis in (SpIN test).
MAIN RESULTS:
We included eight studies involving 646 participants, most of which were of poor
methodological quality. The urinary biomarkers were evaluated either in a
specific phase of menstrual cycle or irrespective of the cycle phase. Five studies
evaluated the diagnostic performance of four urinary biomarkers for
endometriosis, including three biomarkers distinguishing women with and
without endometriosis (enolase 1 (NNE); vitamin D binding protein (VDBP); and
urinary peptide profiling); and one biomarker (cytokeratin 19 (CK 19)) showing
no significant difference between the two groups. All of these biomarkers were
assessed in small individual studies and could not be statistically evaluated in a
meaningful way. None of the biomarkers met the criteria for a replacement test
or a triage test. Three studies evaluated three biomarkers that did not
differentiate women with endometriosis from disease-free controls.
AUTHORS' CONCLUSIONS:
There was insufficient evidence to recommend any urinary biomarker for use as
a replacement or triage test in clinical practice for the diagnosis of
endometriosis. Several urinary biomarkers may have diagnostic potential, but
require further evaluation before being introduced into routine clinical practice.
Laparoscopy remains the gold standard for the diagnosis of endometriosis, and
diagnosis of endometriosis using urinary biomarkers should only be undertaken
in a research setting.

Cochrane Database Syst Rev. 2016 Feb 26;2:CD009591. doi:

10.1002/14651858.CD009591.pub2.
Imaging modalities for the non-invasive diagnosis of
endometriosis.
Nisenblat V1, Bossuyt PM, Farquhar C, Johnson N, Hull ML.
Author information

Abstract
BACKGROUND:
About 10% of women of reproductive age suffer from endometriosis.
Endometriosis is a costly chronic disease that causes pelvic pain and subfertility.
Laparoscopy, the gold standard diagnostic test for endometriosis, is expensive
and carries surgical risks. Currently, no non-invasive tests that can be used to
accurately diagnose endometriosis are available in clinical practice. This is the
first review of diagnostic test accuracy of imaging tests for endometriosis that
uses Cochrane methods to provide an update on the rapidly expanding literature
in this field.
OBJECTIVES:
To provide estimates of the diagnostic accuracy of imaging modalities for the
diagnosis of pelvic endometriosis, ovarian endometriosis and deeply infiltrating
endometriosis (DIE) versus surgical diagnosis as a reference standard. To
describe performance of imaging tests for mapping of deep endometriotic
lesions in the pelvis at specific anatomical sites.Imaging tests were evaluated as
replacement tests for diagnostic surgery and as triage tests that would assist
decision making regarding diagnostic surgery for endometriosis.
SEARCH METHODS:
We searched the following databases to 20 April 2015: MEDLINE, CENTRAL,
EMBASE, CINAHL, PsycINFO, Web of Science, LILACS, OAIster, TRIP,
ClinicalTrials.gov, MEDION, DARE, and PubMed. Searches were not restricted to a
particular study design or language nor to specific publication dates. The search
strategy incorporated words in the title, abstracts, text words across the record
and medical subject headings (MeSH).
SELECTION CRITERIA:
We considered published peer-reviewed cross-sectional studies and randomised
controlled trials of any size that included prospectively recruited women of
reproductive age suspected of having one or more of the following target
conditions: endometrioma, pelvic endometriosis, DIE or endometriotic lesions at
specific intrapelvic anatomical locations. We included studies that compared the
diagnostic test accuracy of one or more imaging modalities versus findings of
surgical visualisation of endometriotic lesions.
DATA COLLECTION AND ANALYSIS:
Two review authors independently collected and performed a quality assessment
of data from each study. For each imaging test, data were classified as positive
or negative for surgical detection of endometriosis, and sensitivity and
specificity estimates were calculated. If two or more tests were evaluated in the
same cohort, each was considered as a separate data set. We used the bivariate
model to obtain pooled estimates of sensitivity and specificity when sufficient
data sets were available. Predetermined criteria for a clinically useful imaging
test to replace diagnostic surgery included sensitivity 94% and specificity
79%. Criteria for triage tests were set at sensitivity 95% and specificity
50%, ruling out the diagnosis with a negative result (SnNout test - if sensitivity is
high, a negative test rules out pathology) or at sensitivity 50% with specificity
95%, ruling in the diagnosis with a positive result (SpPin test - if specificity is
high, a positive test rules in pathology).
MAIN RESULTS:
We included 49 studies involving 4807 women: 13 studies evaluated pelvic
endometriosis, 10 endometriomas and 15 DIE, and 33 studies addressed
endometriosis at specific anatomical sites. Most studies were of poor
methodological quality. The most studied modalities were transvaginal
ultrasound (TVUS) and magnetic resonance imaging (MRI), with outcome
measures commonly demonstrating diversity in diagnostic estimates; however,
sources of heterogeneity could not be reliably determined. No imaging test met
the criteria for a replacement or triage test for detecting pelvic endometriosis,
albeit TVUS approached the criteria for a SpPin triage test. For endometrioma,
TVUS (eight studies, 765 participants; sensitivity 0.93 (95% confidence interval
(CI) 0.87, 0.99), specificity 0.96 (95% CI 0.92, 0.99)) qualified as a SpPin triage
test and approached the criteria for a replacement and SnNout triage test,
whereas MRI (three studies, 179 participants; sensitivity 0.95 (95% CI 0.90,
1.00), specificity 0.91 (95% CI 0.86, 0.97)) met the criteria for a replacement
and SnNout triage test and approached the criteria for a SpPin test. For DIE,
TVUS (nine studies, 12 data sets, 934 participants; sensitivity 0.79 (95% CI 0.69,
0.89) and specificity 0.94 (95% CI 0.88, 1.00)) approached the criteria for a
SpPin triage test, and MRI (six studies, seven data sets, 266 participants;
sensitivity 0.94 (95% CI 0.90, 0.97), specificity 0.77 (95% CI 0.44, 1.00))
approached the criteria for a replacement and SnNout triage test. Other imaging
tests assessed in small individual studies could not be statistically
evaluated.TVUS met the criteria for a SpPin triage test in mapping DIE to
uterosacral ligaments, rectovaginal septum, vaginal wall, pouch of Douglas
(POD) and rectosigmoid. MRI met the criteria for a SpPin triage test for POD and
vaginal and rectosigmoid endometriosis. Transrectal ultrasonography (TRUS)
might qualify as a SpPin triage test for rectosigmoid involvement but could not
be adequately assessed for other anatomical sites because heterogeneous data
were scant. Multi-detector computerised tomography enema (MDCT-e) displayed
the highest diagnostic performance for rectosigmoid and other bowel
endometriosis and met the criteria for both SpPin and SnNout triage tests, but
studies were too few to provide meaningful results.Diagnostic accuracies were
higher for TVUS with bowel preparation (TVUS-BP) and rectal water contrast
(RWC-TVS) and for 3.0TMRI than for conventional methods, although the paucity
of studies precluded statistical evaluation.
AUTHORS' CONCLUSIONS:
None of the evaluated imaging modalities were able to detect overall pelvic
endometriosis with enough accuracy that they would be suggested to replace
surgery. Specifically for endometrioma, TVUS qualified as a SpPin triage test. MRI
displayed sufficient accuracy to suggest utility as a replacement test, but the
data were too scant to permit meaningful conclusions. TVUS could be used
clinically to identify additional anatomical sites of DIE compared with MRI, thus
facilitating preoperative planning. Rectosigmoid endometriosis was the only site
that could be accurately mapped by using TVUS, TRUS, MRI or MDCT-e. Studies
evaluating recent advances in imaging modalities such as TVUS-BP, RWC-TVS,
3.0TMRI and MDCT-e were observed to have high diagnostic accuracies but were
too few to allow prudent evaluation of their diagnostic role. In view of the low
quality of most of the included studies, the findings of this review should be
interpreted with caution. Future well-designed diagnostic studies undertaken to
compare imaging tests for diagnostic test accuracy and costs are recommended.

Gynecol Endocrinol. 2015 Jun;31(6):454-7. doi: 10.3109/09513590.2015.1017812.

Surgical technique of endometrioma excision impacts on
the ovarian reserve. Single-port access laparoscopy
versus multiport access laparoscopy: a case control study.
Angioni S1, Pontis A, Cela V, Sedda F, Genazzani AD, Nappi L.
Author information

Abstract
Several recent studies report the detrimental effect of endometrioma excision on
the ovarian reserve. Surgical technique and the excessive use of bipolar
coagulation could be the key factors. Single-port access laparoscopy (SPAL)
ovarian cystectomy has been reported as a comparable procedure to
conventional laparoscopy in terms of operative outcomes. The aim of this study
was to evaluate whether the single-port surgery affects the ovarian reserve
whilst performing laparoscopic ovarian cystectomy for unilateral endometrioma.
This was a prospective, case-control study of 99 women with unilateral
endometrioma. Forty-nine women underwent single-port cystectomy and 50
women underwent multiport laparoscopic (MPL) conventional cystectomy. The
primary outcome was the assessment of the ovarian reserve. We evaluated the
serum anti-Mullerian hormone (AMH) levels before, 4-6 weeks and 3 months
after surgery. At T2 we performed an ultrasound assessment of the antral
follicular count (AFC). We have drawn attention to a statistically significant
decrease of the mean AMH value and AFC in the SPAL group at the 4-6-week and
3-month follow-up compared to the conventional laparoscopy group. In
conclusion, our results suggest that SPAL cystectomy should not be
recommended to patients undergoing surgery for endometrioma excision who
want to preserve their fertility.

Fertil Steril. 2016 Jun 22. pii: S0015-0282(16)61299-2. doi: 10.1016/j.fertnstert.2016.06.003.

[Epub ahead of print]
Fertility outcome of laparoscopic treatment in patients
with severe endometriosis and repeated in vitro
fertilization failures.
Soriano D1, Adler I2, Bouaziz J3, Zolti M3, Eisenberg VH3, Goldenberg M4, Seidman DS5,
Elizur SE5.
Author information

Abstract
OBJECTIVE:
To evaluate fertility outcomes in infertile women with severe endometriosis (The
revised American Fertility Society classification [AFS] 3-4) and repeated IVF
failures, who underwent surgery due to exacerbation of endometriosis-related
symptoms.
DESIGN:
Retrospective cohort study.
SETTING:
University hospital.
PATIENT(S):
All women who failed IVF treatment before surgery and who underwent
laparoscopic surgery for severe endometriosis between January 2006 and
December 2014.
INTERVENTION(S):
All patients were operated by highly skilled surgeons specializing in laparoscopic
surgery for advanced endometriosis. Only patients with evidence of
endometriosis in the pathology specimens were included in this study.
MAIN OUTCOME MEASURE(S):
Delivery rate after surgery.
RESULT(S):
Seventy-eight women were included in the present study. All women were
diagnosed with severe endometriosis during surgery (AFS 3-4) and all women
had experienced failed IVF treatments before surgery. All women were
symptomatic before their surgery. After surgical treatment 33 women (42.3%)
delivered. Three women (9%) conceived spontaneously and all other women
conceived after IVF treatment. Women who delivered were younger (32.5 [4.1]
years vs. 35.5 [3.8] years), were less often diagnosed with diminished ovarian
reserve before surgery (6% vs. 28.8%), and were more often diagnosed with
normal uterine anatomy (by preoperative transvaginal ultrasound and during
operation). In addition, performing salpingectomy during surgery was associated
with a trend of improvement in delivery rates after surgery (70% in women who
delivered vs. 51% in women who failed to deliver).
CONCLUSION(S):
Symptomatic women with severe endometriosis and repeated IVF implantation
failures may benefit from extensive laparoscopic surgery when performed by an
experienced multidisciplinary surgical team to improve IVF outcome.
Copyright 2016 American Society for Reproductive Medicine. Published by
Elsevier Inc. All rights reserved.

Hum Reprod. 2015 Aug;30(8):1831-41. doi: 10.1093/humrep/dev136. Epub 2015 Jun 16.
Artificial oocyte activation to improve reproductive
outcomes in women with previous fertilization failure: a
systematic review and meta-analysis of RCTs.
Sfontouris IA1, Nastri CO2, Lima ML2, Tahmasbpourmarzouni E3, Raine-Fenning N4,
Martins WP5.
Author information

Abstract
STUDY QUESTION:
In couples with previous fertilization failure, are reproductive outcomes improved
using ICSI followed by artificial oocyte activation (ICSI-AOA) compared with
conventional ICSI?
SUMMARY ANSWER:
There is insufficient evidence available from RCTs to judge the efficacy and
safety of ICSI-AOA for couples with previous fertilization failure.
WHAT IS KNOWN ALREADY:
In cases with previous low fertilization rates or total fertilization failure using ICSI
due to sperm-related, oocyte activation deficiency, several methods of AOA have
been described, which employ mechanical, electrical or chemical stimuli.
Reported fertilization and pregnancy rates appear to be improved after ICSI-AOA
compared with conventional ICSI; however, the small studies performed to date
make it difficult to assess the clinical efficacy or safety of AOA.
STUDY DESIGN, SIZE, AND DURATION:
The present systematic review and meta-analysis identified RCTs that compared
ICSI-AOA and conventional ICSI. The last electronic search was conducted in
August 2014 and there was no limitation regarding language, publication date,
or publication status. We included studies that randomized either oocytes or
women and included them in two different parts of this review: a women-based
review and an oocyte-based review. For the women-based review, the primary
outcome of effectiveness was live birth per randomized woman and the primary
outcome for safety was congenital anomalies per clinical pregnancy. For the
oocyte-based review, the primary outcome was embryo formation per oocyte
randomized.
PARTICIPANTS/MATERIALS, SETTING, AND METHODS:
Record screening and data extraction were performed independently by two
authors and risk of bias was assessed by three authors. The effects of ICSI-AOA
compared with conventional ICSI were summarized as risk ratio (RR) and the
precision of the estimates was evaluated by the 95% confidence interval (CI).
MAIN RESULTS AND THE ROLE OF CHANCE:
A total of 14 articles were assessed for eligibility and 9 included in the meta-
analysis: 2 studies comprised the woman-based review (n = 168 women) and 7
studies the oocyte-based review (n = 4234 oocytes). Only four studies evaluated
AOA due to fertilization failure after conventional ICSI: these were included in the
quantitative analysis. In two studies evaluating couples with a history of
fertilization failure in a previous cycle, ICSI-AOA was associated with an increase
in the proportion of cleavage stage embryos (RR 5.44, 95% CI 2.98-9.91) and
top/high quality cleavage stage embryos (RR 10.02, 95% CI 2.45-40.95). There
was no evidence of effect on fertilization rate (RR 2.97, 95% CI 0.84-10.48). In
the two studies that evaluated ICSI-AOA as a rescue method for unfertilized
oocytes after conventional ICSI, ICSI-AOA was associated with an increase in
fertilization (RR 8.26, 95% CI 1.28-53.32, P = 0.03) and cleavage rates (RR 8.65,
95% CI 2.28-32.77) although there was no significant effect on the likelihood of
blastocyst formation (RR 1.97, 95% CI 0.11-34.99). The remaining five studies
evaluated ICSI-AOA for reasons other than fertilization failure and were excluded.
LIMITATIONS AND REASONS FOR CAUTION:
The majority of the studies were not considered to be similar enough for meta-
analysis due to different AOA methods and patient inclusion criteria, thus limiting
the possibility of pooling studies and achieving a more robust conclusion. Only
two studies examined ICSI-AOA in couples with previous fertilization failure, and
only one of these included couples with proven male-related, oocyte activation
deficiency, which is the primary indication for AOA. The resulting evidence was
considered to be of very low quality and should be interpreted with caution.
WIDER IMPLICATIONS OF THE FINDINGS:
There is insufficient evidence available from the currently available RCTs to judge
the efficacy or safety of ICSI-AOA on key reproductive outcomes in couples with
previous fertilization failure. Such interventions should be further examined by
well-designed RCTs before the introduction of ICSI-AOA as a standard treatment.
STUDY FUNDING/COMPETING INTERESTS:
No funding was obtained. No competing interests to declare.
REGISTRATION NUMBER:
PROSPERO CRD42014007445.
The Author 2015. Published by Oxford University Press on behalf of the
European Society of Human Reproduction and Embryology. All rights reserved.
For Permissions, please email: journals.permissions@oup.com.

um Reprod Update. 2015 Nov-Dec;21(6):809-25. doi: 10.1093/humupd/dmv035. Epub 2015 Jul

12.
The impact of endometrioma on IVF/ICSI outcomes: a
systematic review and meta-analysis.
Hamdan M1, Dunselman G2, Li TC3, Cheong Y4.
Author information

Abstract
BACKGROUND:
Endometriosis is a disease known to be detrimental to fertility. Women with
endometriosis, and the presence of endometrioma, may require artificial
reproductive techniques (ART) to achieve a pregnancy. The specific impact of
endometrioma alone and the impact of surgical intervention for endometrioma
on the reproductive outcome of women undergoing IVF/ICSI are areas that
require further clarification. The objectives of this review were as follows: (i) to
determine the impact of endometrioma on IVF/ICSI outcomes, (ii) to determine
the impact of surgery for endometrioma on IVF/ICSI outcome and (iii) to
determine the effect of different surgical techniques on IVF/ICSI outcomes.
METHODS:
We performed a systematic review and meta-analysis examining subfertile
women who have endometrioma and are undergoing IVF/ICSI, and who have or
have not had any surgical management for endometrioma before IVF/ICSI. The
primary outcome was live birth rate (LBR). Our secondary outcomes were clinical
pregnancy rate (CPR), mean number of oocyte retrieved (MNOR), miscarriage
rate (MR), fertilization rate, implantation rate, antral follicle count (AFC), total
stimulating hormone dose, and any rates of adverse effects such as cancellation
and associated complications during the IVF/ICSI treatment.
RESULTS:
We included 33 studies for the meta-analysis. The majority of the studies were
retrospective (30/33), and three were RCTs. Compared with women with no
endometrioma undergoing IVF/ICSI, women with endometrioma had a similar
LBR (odds ratio [OR] 0.98; 95% CI [0.71, 1.36], 5 studies, 928 women, I(2) = 0%)
and a similar CPR (OR 1.17; 95% CI [0.87, 1.58], 5 studies, 928 women, I(2) =
0%), a lower mean number of oocytes retrieved (SMD -0.23; 95% CI [-0.37,
-0.10], 5 studies, 941 cycles, I(2) = 37%) and a higher cycle cancellation rate
compared with those without the disease (OR 2.83; 95% CI [1.32, 6.06], 3
studies, 491 women, I(2) = 0%). Compared with women with no surgical
treatment, women who had their endometrioma surgically treated before
IVF/ICSI had a similar LBR (OR 0.90; 95% CI [0.63, 1.28], 5 studies, 655 women,
I(2) = 32%), a similar CPR (OR 0.97; 95% CI [0.78, 1.20], 11 studies, 1512
women, I(2) = 0%) and a similar mean number of oocytes retrieved (SMD -0.17;
95% CI [-0.38, 0.05], 9 studies, 810 cycles, I(2) = 63%).
CONCLUSIONS:
Women with endometrioma undergoing IVF/ICSI had similar reproductive
outcomes compared with those without the disease, although their cycle
cancellation rate was significantly higher. Surgical treatment of endometrioma
did not alter the outcome of IVF/ICSI treatment compared with those who did not
receive surgical intervention. Considering that the reduced ovarian reserve may
be attributed to the presence of endometrioma per se, and the potential
detrimental impact from surgical intervention, individualization of care for
women with endometrioma prior to IVF/ICSI may help optimize their IVF/ICSI
results.
The Author 2015. Published by Oxford University Press on behalf of the
European Society of Human Reproduction and Embryology. All rights reserved.
For Permissions, please email: journals.permissions@oup.com