Reproductive BioMedicine Online (2015) 31, 9–19

w w w. s c i e n c e d i r e c t . c o m
w w w. r b m o n l i n e . c o m

REVIEW

Impact of ovarian endometrioma on ovarian

responsiveness and IVF: a systematic review
and meta-analysis
Chun Yang 1, Yuhong Geng 1, Yanhui Li, Chunyan Chen, Ying Gao *

Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and
Technology, Wuhan 430022, China
* Corresponding author. E-mail address: 1211746863@qq.com (Y. Gao). 1 The two first authors contributed equally to this work.

Dr Yang is a doctor at the Assisted Reproductive Technology Center, Department of Obstetrics and Gynecology,
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, China. She obtained
her PhD from Tongji Medical College in 2011. Her current research interests include studies on endometriosis
and assisted reproduction.

Abstract In this systematic review and meta-analysis, the effect of ovarian endometrioma on ovarian responsiveness to stimulation
and on assisted reproduction outcomes was evaluated. Nine published studies (1039 cases) were included. The number of oocytes
retrieved (mean difference [MD] −1.50; 95% CI, −2.84 to −0.15, P = 0.03), metaphase II (MII) oocytes retrieved (MD −3.61; 95%
CI −4.44 to −2.78, P < 0.00001) and total embryos formed (MD −0.66; 95% CI −1.13 to −0.18, P = 0.007) were significantly lower in
women with ovarian endometrioma than the control group. Gonadotrophin dose, duration of stimulation, number of good-quality
embryos, implantation rate, clinical pregnancy rate and live birth rate were similar. Comparisons between ovaries with endome-
triomas and healthy ovaries of the same individuals were also made. Number of oocytes retrieved, MII oocytes retrieved and
total embryos formed were not statistically significantly different between the affected ovaries and contralateral normal ovaries.
Observational studies showed that ovarian endometrioma was associated with fewer oocytes retrieved, fewer MII oocytes retrieved
and fewer total formed embryos. Clinical pregnancy rate and live birth rates were not affected. Intra-patient comparisons in women
with unilateral endometrioma suggested the number of oocytes retrieved, MII oocytes retrieved and total embryos formed were
similar.
© 2015 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

KEYWORDS: in vitro fertilization, meta-analysis, ovarian endometrioma, ovarian responsiveness

http://dx.doi.org/10.1016/j.rbmo.2015.03.005
1472-6483/© 2015 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.
10
Introduction
Endometriosis is a chronic, painful disease caused by the
growth of endometrial-like tissue outside the uterus, which
induces a chronic inflammatory reaction (Kennedy et al.,
2005). The prevalence rate of endometriosis has been esti-
mated to reach around 10–5% in reproductive-age women
(Macer and Taylor, 2012). Around 25–50% of women with in-
fertility may be affected by endometriosis, and 30–50% of
women with endometriosis have infertility (Macer and Taylor,
2012).
Ovarian endometrioma (chocolate cyst) is a common and
specific manifestation of the disease; the effect of ovarian
endometrioma on assisted reproduction technique out-
comes is still a controversial issue. Some studies have shown
that ovarian endometrioma could adversely affect the number
of oocytes retrieved (Suzuki et al., 2005; Yanushpolsky et al.,
1998), oocyte quality, embryo quality and implantation rate
(Azem et al., 1999; Yanushpolsky et al., 1998). Studies,
however, found no adverse effect of ovarian endometrioma
on oocyte quality, embryo quality, implantation rate and preg-
nancy rate (Ashrafi et al., 2014; Benaglia et al., 2013). Pre-
vious meta-analyses have shown inconsistent results and were
focused on different stages of endometriosis or pregnancy
outcome (Barnhart et al., 2002; Harb et al., 2013). To better
explore the role of endometrioma in assisted reproduction
techniques, a systematic review and meta-analysis was carrued
out to evaluate the effects of ovarian endometrioma on ovarian
responsiveness and IVF and intracytoplasmic sperm injec-
tion (ICSI) outcomes between patients with and without en-
dometrioma. The comparisons were also made among patients
with unilateral disease.
Materials and methods
Search strategy
Related studies were identified by searching PubMed, Embase
and BIOSIS from January 1994 to June 2014. The following key
words and their synonyms were used: ‘endometriosis’ or
‘ovarian endometrioma’ or ‘endometriotic ovarian cyst’, ‘in-
vitro fertilization’ or ‘intracytoplasmic sperm injection’ or ‘as-
sisted reproductive technologies’, ‘infertility’, ‘fertilization’
and ‘oocyte’. The language of publication was restricted to
English. The reference lists of all publications and reviews were
hand-searched to indentify missing relevant publications. Two
authors (CY and YhG) independently conducted the search,
and reviewed titles, abstracts and full manuscripts. Each
article was independently assessed for inclusion and exclu-
sion criteria, and, when disagreements occurred, they were
arbitrated by the two-thirds agreement.
Study selection
The studies that were included in the meta-analysis met the
following criteria: (i) an original paper; (ii) a study of ovarian
endometrioma; (iii) a clinical study (including randomized con-
trolled trials, case-control, prospective and retrospective
C Yang et al.
cohort studies) that assessed the association of ovarian re-
sponse, oocyte quality, embryo quality and IVF outcome with
ovarian endometrioma; (iv) any type of ovarian stimulation
protocol was allowed; (v) the diagnosis of the endometriotic
cysts was performed by ultrasound; and (vi) control partici-
pants consisted of women who had not undergone previous
ovarian surgery and who did not have any ultrasonographic
evidence of ovarian cysts, including endometriomas, were
without a history of endometriosis.
The major exclusion criteria were literature reviews, non-
original articles; non-ovarian endometrioma; duplication of
a previous publication; and women who had received medical
or surgical treatment of their ovarian endometrioma before
IVF–ICSI cycles.
Data extraction
Two investigators independently extracted the data to ensure
homogeneity of the data collection and to rule out subjec-
tivity in data gathering and entry. The following data were
collected from all the included trials: the first author’s name,
the year of publication, the number of patients, total amount
of FSH used, duration of stimulation, total number of oocytes
retrieved, metaphase II (MII) oocytes retrieved, total formed
embryos, good-quality formed embryos, fertilization rates,
implantation rates, clinical pregnancy rates and the live birth
rates where available. Authors were not contacted for addi-
tional data. Continuous data were extracted in the form of
mean, SD, and population size. Data were collected from per
patient and per cycle outcomes.
Assessment of publication bias
The possibility of publication bias was assessed by two re-
viewers using the Newcastle–Ottawa Quality Assessment
Scales, which is based on the recommendation of the Co-
chrane Collaboration for observational studies (Higgins and
Green, 2011; Wells et al., 2010). The quality checklist used
awards a maximum of one star for each item except compa-
rability, which can be given a maximum of two stars. An ar-
bitrary score based on the assumption of equal weight of all
items included in the Newcastle–Ottawa Scale was used. The
score was used to give a quantitative assessment of the quality
of each study. The score ranged from 0 to 9, with a score of
either 0 or 1 for each item. Although no cut-off limit exists
to classify good or bad studies, a lower limit of five stars has
been suggested to identify studies at low risk of bias (Aziz
et al., 2006).
Outcome measures
Primary measures
Primary measures included the results of comparisons between
women with and without endometriomas.
Secondary measures
Secondary measures included the results of intra-patient com-
parisons between the affected ovary and normal ovary.
Impact of ovarian endometrioma on IVF
Statistical analysis
Data analyses were carried out using RevMan, version 5.1
(Cochrane, Collaboration, Oxford, UK). Heterogeneity was
evaluated graphically using forest plots and statistically using
the I2 statistic to quantify heterogeneity across studies. An
I2 > 50% was considered to represent substantial heteroge-
neity between studies. A random-effect model was used for
meta-analysis in cases of high heterogeneity, and a fixed-
effect model was used in cases of low heterogeneity. Di-
chotomous outcome data were reported as odds ratios with
95% confidence intervals (CI). Continuous data were synthe-
sized using weighted means with 95% CI.
Results
The search strategy yielded 832 studies. Of these, a total of
17 articles were found to be relevant by examining the ab-
stracts and titles. The literature search results are repre-
sented in Figure 1. Eight original articles were excluded
because five studies investigated women who underwent sur-
gical interventions to treat ovarian endometrioma (Benaglia
et al., 2012; Donnez et al., 2001; Mao et al., 2009; Nakahara
et al., 1998; Suzuki et al., 2005), one had a control group of
ovarian cysts (Kumbak et al., 2008), one had a control group
with endometriosis but without ovarian endometrioma (Isaacs
et al., 1997), and in one study, no extractable data were avail-
able (Benaglia et al., 2011). Therefore, the total number of
studies included in the meta-analysis was nine.
Figure 1 The literature search. ICSI = intracytoplasmic sperm
injection.
11
All of the nine included studies were observational studies,
with a total study population of 1039. The characteristics of
the nine studies and the Newcastle–Ottawa Quality Assess-
ment are presented in Tables 1 and 2. The studies scored
well on the Newcastle–Ottawa Quality Assessment Scale
(Table 2).
Primary outcomes
Total gonadotrophin consumption
Pooling of results from three studies (Almog et al., 2011;
Benaglia et al., 2013; Bongioanni et al., 2011) that reported
total dose of gonadotrophin (Figure 2A) did not show a dif-
ference between ovarian endometrioma group and control
group (weighted mean difference [WMD 108.56 IU; 95% CI
−207.06 to 424.17). Significant heterogeneity existed among
the studies, as indicated by an I2 value of 83% (P = 0.003).
Duration of stimulation
Pooling of results from three studies (Almog et al., 2011;
Benaglia et al., 2013; Yanushpolsky et al., 1998) that re-
ported the duration of stimulation (Figure 2B) did not show
a difference between the two groups (WMD 0.22 days; 95%
CI: −0.14 to 0.57). The I2 value was 0%, indicating that het-
erogeneity was unlikely between the studies.
Number of oocytes retrieved
Pooling of results from six studies (Almog et al., 2011; Ashrafi
et al., 2014; Benaglia et al., 2013; Bongioanni et al., 2011;
Reinblatt et al., 2011; Yanushpolsky et al., 1998) that re-
ported total number of oocytes retrieved (Figure 3A) found
1.50 fewer oocytes retrieved in those with ovarian endome-
trioma than in those without ovarian endometrioma (WMD
−1.50; 95% CI −2.84 to −0.15, P = 0.03). Significant variation
existed across studies as indicated by an I2 value of 91%
(P < 0.00001).
Number of MII oocytes
Pooling of results from two studies (Ashrafi et al., 2014;
Reinblatt et al., 2011) that reported number of MII oocytes
retrieved (Figure 3B) found 3.61 fewer MII oocytes re-
trieved in the ovarian endometrioma group than in control
group (WMD 3.61; 95% CI −4.44 to −2.78, P < 0.00001). The
I2 value was 0%, indicating that heterogeneity was unlikely
between the studies.
Number of total formed embryos
Pooling of results from two studies (Ashrafi et al., 2014;
Benaglia et al., 2013) that reported number of total formed
embryos (Figure 3C) suggested that 0.66 fewer total formed
embryos in the patients with ovarian endometrioma than
without ovarian endometrioma (WMD −0.66; 95% CI −1.13 to
−0.18, P = 0.007). Heterogeneity between the studies was
limited (I2 = 15).
Number of good-quality formed embryos
Pooling of results from two studies (Ashrafi et al., 2014;
Benaglia et al., 2013) that reported number of good-quality
formed embryos (Figure 3D) did not show a statistically

Table 1 Characteristics of studies of ovarian endometrioma versus control on ovarian response and IVF and inracytoplasmic perm injection outcome.
Population
Study year
Ashrafi et al., 2014 Women undergoing ICSI at
(n = 104) Royan Institute, Iran between
2005 and 2007.
Benaglia et al., 2013 Women undergoing IVF at the
(n = 117) Infertility Unit of the
Fondazione Ca’Granda
between 2006 and 2010.
Bongioanni et al., 2011 Women undergoing IVF at three
(n = 316) IVF units in Italy.
Reinblatt et al., 2011 Women undergoing IVF at the
(n = 52) McGill
Reproductive Centre between
2006 and 2010.
Almog et al., 2011 Women undergoing IVF at
(n = 243) McGill University Health
Center, Montreal, between
2006 and 2009.
Yanushpolsky et al., 1998 Women undergoing IVF at
(n = 94) Harvard Medical School
between 1994 and 1995.
Filippi et al., 2014 Women undergoing IVF–ICSI at
(n = 29) the Infertility Unit of the
Fondazione Ca’Granda
between 2012 and 2013.
Esinler et al., 2012 Women undergoing ICSI at
(n = 28 cycles) Hacettepe University, Turkey.
Somigliana et al., 2006 Women undergoing IVF–ICSI at
(n = 56 cycles) Ospedale Maggiore Policlinico,
Mangiagalli and Regina Elena
between 2000 and 2004.
ICSI = intractoplasmic sperm injection; MII, metaphase II.
Ovarian endometrioma group
Women with either unilateral or
bilateral ovarian endometrial cysts
of less than 3 cm (n = 47)
Women with unoperated bilateral
endometriomas (n = 39)
142 women with unoperated
endometrioma (≤6 cm )
Women with bilateral
endometriomas (n = 13)
81 women with unilateral
endometrioma
37 women with endometriomas
Affected ovary (n = 29)
Affected ovary (n = 28)
Affected ovary (n = 56)
12
Control group Outcomes Study design
Patients with mild male Number of oocytes retrieved; number Cohort study
factor infertility and of MII oocytes retrieved; number of
without ovarian formed embryos; fertilization rate;
endometriomas (n = 57) implantation rate; number of good-
quality formed embryos; clinical
pregnancy rate.
Patients without Number of oocytes retrieved; Number Cohort study
endometriotic or non- of formed embryos; Total dose of
endometriotic ovarian gonadotropin (IU); Number of good-
cysts (n = 78) quality formed embryos; Number of
days of stimulation; implantation
rate; clinical pregnancy rate; live
birth rate.
Women with tubal factor Number of retrieved oocytes; Cohort study
and without ovarian fertilization rate; implantation rate;
endometriomas (n = 174) total dose of gonadotropin (IU).
Patients with male or Number of oocytes collected; Number Cohort study
tubal factor infertility of MII oocytes retrieved.
without endometriomas
(n = 39)
Women without Number of retrieved oocytes; total Cohort study
endometriomas (n = 162) dose of gonadotrophin (IU); Number
of days of stimulation;
Patients without any Number of retrieved oocytes; number Cohort study
ovarian endometriomas of days of stimulation; implantation
(n = 56) rate; clinical pregnancy rate; live
birth rate.
Intact ovary (n = 29) Number of co-dominant follicles; Cohort study
Number of oocytes retrieved; total
formed embryos; fertilization rate.
Intact ovary (n = 28) Number of oocytes retrieved; number Cohort study
of MII oocytes; fertilization rate.
Intact ovary (n = 56) Number of co-dominant follicles. Cohort study
C Yang et al.
Impact of ovarian endometrioma on IVF 13

significant difference between the two groups (WMD −0.21;

Score
95% CI −0.61 to 0.19), although the direction of effect sug-

9
9
9
9
9
8
9
9
9
gested a reduction in good-quality formed embryos of pa-
Duration of
tients with ovarian endometrioma. Heterogeneity between
follow-up
the studies was limited, as indicated by an I2 value of 8%.

* Implantation rate
*
*
*
*
*
*
*
*
Four studies (Ashrafi et al., 2014; Benaglia et al., 2013;
assessment
Outcome

Bongioanni et al., 2011; Yanushpolsky et al., 1998) reported

implantation rate, but only two studies (Ashrafi et al., 2014;
Benaglia et al., 2013) reported it per patient. Pooling of results
*
*
*
*
*
*
*
*
*
from the two studies (Figure 4A) did not show a difference
Comparability

in this outcome (odds ratio [OR] 1.11, 95% CI 0.68 to 1.81).

The I2 value was 0%, indicating that heterogeneity was un-
by analysis

likely between the studies.

Clinical pregnancy rate

*
*
*
*
*
*
*
*
*

Pooling of results from three studies (Ashrafi et al., 2014;

Comparability

Benaglia et al., 2013; Yanushpolsky et al., 1998) that re-

by designa

ported clinical pregnancy rates (Figure 4B) did not differ

between the group of ovarian endometrioma and the group
of control (OR 1.26, 95% CI 0.78 to 2.05). There was no het-
**
**
**
**
**

**
**
**

erogeneity in this comparison (I2 = 0%).

*
Outcome negative

Live birth rate

Pooling of results from two studies (Benaglia et al., 2013;
Yanushpolsky et al., 1998) that reported live birth rates
at start

(Figure 4C) did not show a significant difference in this

outcome (OR 0.70, 95% CI 0.37 to 1.33). There was no het-
Appraisal of methodological quality (Newcastle–Ottawa Scale) of included studies.

*
*
*
*
*
*
*
*
*

erogeneity in this comparison (I2 = 0%).

Ascertainment of

Secondary outcomes
exposure

Number of co-dominant follicles between ovary with

For comparability by design the checklist awards a maximum of two stars (**).

endometrioma and normal ovary

*
*
*
*
*
*
*
*
*

Pooling of results from two studies (Filippi et al., 2014;

Selection of non-exposed

Somigliana et al., 2006) that reported the number of co-

dominant follicles between affected ovary and intact ovary
(Figure 5A) suggested 0.81 fewer codominant follicles in the
affected ovary than intact ovary (WMD −0.81; 95% CI −1.41
to −0.21, P = 0.008). There was no heterogeneity between
the two studies (I2 = 0%).
control

Number of oocytes retrieved between ovary with

*
*
*
*
*
*
*
*
*

endometrioma and normal ovary

representative
Case –cohort

Pooling of results from four studies (Almog et al., 2011; Ashrafi

et al., 2014; Esinler et al., 2012; Filippi et al., 2014) that re-
ported the number of oocytes retrieved between affected
*Indicates that a feature is present.

ovary and intact ovary (Figure 5B) did not show a signifi-
cant difference (WMD −0.11; 95% CI −0.25 to 0.03)]. The I2
*
*
*
*
*
*
*
*
*

value was 0%, indicating that heterogeneity was unlikely

Yanushpolsky et al., 1998

between the studies.

Bongioanni et al., 2011

Somigliana et al., 2006

Reinblatt et al., 2011
Benaglia et al., 2013
Ashrafi et al., 2014

Esinler et al., 2012

Filippi et al., 2014
Almog et al., 2011

Number of MII oocytes between ovary with

endometrioma and normal ovary
Pooling of results from two studies (Ashrafi et al., 2014; Esinler
Table 2

et al., 2012) that reported the number of MII oocytes

Study

(Figure 5C) between the affected ovary and intact ovary did
not suggest a significant difference (WMD −0.14; 95% CI −1.01
a
14
Figure 2 (A) Gonadotrophin consumption; (B) duration of stimulation between ovarian endometrioma group and control group.
t 0.73). The I2 value was 0%, indicating that heterogeneity was
unlikely between the studies.
Total number of embryos formed between ovary with
endometrioma and normal ovary
Pooling of results from two studies (Ashrafi et al., 2014; Filippi
et al., 2014) that reported the number of total formed embryos
(Figure 5D) between the affected ovary and intact ovary did
not show a significant difference (WMD −0.32; 95% CI −0.91
t 0.27). There was no heterogeneity between the two studies
(I2 = 0%).
Fertilization rate between ovary with endometrioma and
normal ovary
Three studies (Ashrafi et al., 2014; Esinler et al., 2012; Filippi
et al., 2014) compared the fertilization rate between ovary
with endometrioma and control ovary; however, only two of
them (Ashrafi et al., 2014; Filippi et al., 2014) reported it per
patient. Pooling of results from the two studies did not show
a difference (Figure 5E) between the two groups (OR 1.06,
95% CI 0.71 to 1.60). The I2 value was 0%, indicating that het-
erogeneity was unlikely between the studies.
Discussion
Main findings
The present study is the first meta-analysis to investigate
the effect of ovarian endometrioma on ovarian responsive-
ness to stimulation and IVF outcomes. The results of the study
indicated that the presence of ovarian endometrioma reduces
the number of oocytes retrieved, MII oocytes retrieved and
formed embryos. The outcome, however, was similar in terms
of implantation, clinical pregnancy or live birth rates. The
C Yang et al.
within-patient comparisons indicated that the number of
oocytes retrieved, MII oocytes retrieved and total formed
embryos were not significantly different between the ovary
with endometrioma and the contralateral normal ovary.
Strengths and imitations
A previous meta-analysis (Gupta et al., 2006) did not exclude
the studies in which the patients had undergone excision of
ovarian endometrioma before IVF–ICSI. It is now widely known,
however, that any type of surgery could cause additional
damage to already compromised ovarian function, even when
the surgery is carried out by a skilful gynaecological surgeon
(Esinler et al., 2006; Raffi et al., 2012; Somigliana et al., 2008).
Women who were previously operated on for ovarian endo-
metrioma were excluded to protect our results from the con-
founding effects of previous surgery. Patients were included
on the basis of a transvaginal ultrasonography diagnosis of en-
dometrioma. Owing to their characteristic echogenic appear-
ance, endometrioma could be easily distinguished from other
ovarian cysts. Sensitivity and specificity of transvaginal ul-
trasonography have been reported to be 84–100% and 90–100%,
respectively (Eskenazi et al., 2001). In this study, the results
from affected ovary and intact ovary were analysed. It allows
each patient to serve as her own control, thereby reducing
the effect of potentially important confounders, such as age,
ovarian stimulation, oocyte and sperm quality and labora-
tory conditions. The Newcastle–Ottawa Quality Assessment
Scale to rate the quality of the included studies was used, and
the included studies scored well on this scale, suggesting low
risk of bias.
Because clinical and methodological diversity always occur
in a meta-analysis, statistical heterogeneity is inevitable
(Higgins et al., 2003). Methodological problems caused by clini-
cal heterogeneity and insufficient power (low sample size)
Impact of ovarian endometrioma on IVF 15

Figure 3 (A) Number of oocytes retrieved; (B) number of metaphase II oocytes; (C) number of total formed embryos; and (D) number
of good-quality formed embryos between ovarian endometrioma group and control group.

cause difficulty in drawing inferences from the meta-analysis.
The heterogeneity among the studies, calculated using the
I2 statistic, was high in the number of oocytes retrieved. This
finding may be explained by the size of the studies (ranging
from 52 to 316 participants) and the size of endometrioma.
Coccia et al. (2014) reported that in patients with ovarian en-
dometriomas 3 cm or greater, the size of endometrioma was
the most influential contributor to the total number of oocytes
retrieved. Other sources of clinical heterogeneity included
the endometriomas origin from unilateral or bilateral ovaries.
Data from women with unilateral endometrioma are poorly
informative because the contralateral intact ovary compen-
sated for ovarian function and fertility potential. We used a
random-effects model for combined outcomes in cases of high
heterogeneity. Owing to the limited data, a subgroup meta-
analysis to reduce the heterogeneity could not be per-
formed. Therefore, further randomized controlled trials with
larger sample size will be helpful for the corroboration of these
results.
Interpretation
Our results indicated that the number of oocytes retrieved,
MII oocytes, total formed embryos in patients with ovarian
endometrioma were significantly lower. Some mechanisms
16
Figure 4 (A) Implantation rate; (B) clinical pregnancy rate; and (C) live birth rate between ovarian endometrioma group and control
group.
such as changes in autoimmune factors, accumulation of
interleukin-6 or silencing of vascular endothelal growth factor
in the follicular fluid were considered as negative factors for
follicular growth and oocyte maturity (Garrido et al., 2000;
Lucena and Cubillos, 1999). Moreover, several studies re-
ported that the density and diameters of primordial fol-
licles are decreased in the cortex from ovaries with
endometrioma, and the vasculature network is distorted when
the ovarian cortex surrounding endometrioma (Kitajima et al.,
2011, 2014; Kuroda et al., 2012; Schubert et al., 2005). Also
of relevance is the observation that the amount of oxidative
and carbonyl stress markers such as FOXO3A, oxidized DNA
adduct 8-OHdG (8-hydroxy-2’-deoxyguanosine), AGEs (Ad-
vanced Glycation End products) and reactive oxygen species
production in the ovarian cortex surrounding endometrioma
is markedly higher than in other types of cysts (Barnhart et al.,
2002; Di Emidio et al., 2014; Jana et al., 2010; Karuputhula
et al., 2013; Matsuzaki and Schubert, 2010). Our results in-
dicated that the quality of the retrieved oocytes is not ham-
pered by the presence of ovarian endometrioma.
C Yang et al.
As previously mentioned, a healthy ovary could compen-
sate for ovarian function and fertility potential of the con-
tralateral affected ovary in the same individual. The results
from the studies of bilateral endometriomas should be par-
ticularly emphasized. Two studies (Benaglia et al., 2013;
Reinblatt et al., 2011) reported on IVF outcome in women with
bilateral endometriomas. Reinblatt et al. (2011) failed to docu-
ment any effect, whereas Benaglia et al. (2013) suggested a
mild reduction in ovarian responsiveness but similar embryo
development and pregnancy rates. Drawing definitive con-
clusions based on these conflicting reports is difficult; more-
over, the sample sizes of the two studies are small. More
women with bilateral endometriomas should be recruited for
further studies.
Interestingly, the differences of the number of oocytes
retrieved, MII oocytes and total formed embryos between
the ovary with endometrioma and contralateral normal ovary
were not significant, although fewer codominant follicles were
formed in the endometrioma ovary group. It might be due
to the microenvironment of endometriosis such as
Impact of ovarian endometrioma on IVF 17

Figure 5 (A) Number of codominant follicles; (B) number of oocytes retrieved; (C) number of metaphse II oocytes; (D) total number
of embryos formed; and (E) fertilization rate between affected ovary and contralateral ovary.

inflammation, reactive oxygen species production that can a deleterious effect on ovarian reserve. The dimension of
impair ovarian responsiveness, but not the cyst of ovarian the endometriomas in women recruited for the intra-
endometrioma itself. Esinler et al. (2012) reported that a patient comparisons was relatively small (the mean diam-
single endometrioma 3 cm or less in diameter did not have eter was less than 3 cm). We therefore cannot rule out that
18
larger cysts may be detrimental. Further evidence is also re-
quired to address this point. On the other hand, in the com-
parisons of women with and without endometriomas, because
of selection biases, the ovarian responsiveness might be en-
hanced in control group rather than reduced in women with
endometriomas.
In this meta-analysis, we found that the clinical preg-
nancy and live birth rates were similar between the pa-
tients with and without ovarian endometrioma. It is consistent
with the meta-analysis by Gupta et al. (2006) but in con-
trast to those from a meta-analysis by Barnhart et al. (2002).
The pooling results, however, did not suggest a significant dif-
ference of gonadotrophin consumption between the two
groups, which was inconsistent with previous studies (Al-Azemi
et al., 2000; Kumbak et al., 2008). Surgery may diminish the
ovarian reserve, reduce responsiveness to ovarian stimula-
tion (Demirol et al., 2006; Dilek et al., 2006). Our results
suggest that surgical removal of endometriomas before as-
sisted reproduction techniques does not provide any benefit
to IVF treatment success.
In conclusion, the meta-analysis was conducted to assess
the effect of ovarian endometrioma on ovarian responsive-
ness to stimulation and IVF outcomes. The results of the meta-
analysis indicated that ovarian endometrioma had adverse
effects on oocytes retrieved, MII oocytes retrieved and total
formed embryos but not on quality of embryos and IVF out-
comes. Ovaries with endometriomas, however, showed a
similar response to stimulation compared with the contra-
lateral healthy ovaries in the same individuals. In this regard,
assisted reproduction techniques would provide a therapeu-
tic approach for the ovarian endometrioma-related infertil-
ity rather than laparoscopic ovarian surgery. Further
randomized controlled trials of patients with endometrio-
mas would be needed to confirm our conclusions.
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Declaration: The authors report no financial or commercial con-
flicts of interest.
Received 16 October 2014; refereed 8 March 2015; accepted 10 March
2015.