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Impact of ovarian endometrioma on ovarian responsiveness and IVF: a systematic review and meta-analysis

Reproductive BioMedicine Online, Volume 31, Issue 1, Pages 9 - 19

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 endometriomas 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.

Keywords: in vitro fertilization, meta-analysis, ovarian endometrioma, ovarian responsiveness.

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 estimated to reach around 10–5% in reproductive-age women ( Macer and Taylor, 2012 ). Around 25–50% of women with infertility 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 outcomes is still a controversial issue. Some studies have shown that ovarian endometrioma could adversely affect the number of oocytes retrieved (Suzuki et al, 2005 and Yanushpolsky et al, 1998), oocyte quality, embryo quality and implantation rate (Azem et al, 1999 and Yanushpolsky et al, 1998). Studies, however, found no adverse effect of ovarian endometrioma on oocyte quality, embryo quality, implantation rate and pregnancy rate (Ashrafi et al, 2014 and Benaglia et al, 2013). Previous meta-analyses have shown inconsistent results and were focused on different stages of endometriosis or pregnancy outcome (Barnhart et al, 2002 and 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 injection (ICSI) outcomes between patients with and without endometrioma. 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 ‘assisted 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 exclusion 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 controlled trials, case-control, prospective and retrospective cohort studies) that assessed the association of ovarian response, 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 participants 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 subjectivity 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 additional 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 reviewers using the Newcastle–Ottawa Quality Assessment Scales, which is based on the recommendation of the Cochrane Collaboration for observational studies (Higgins, Green, 2011 and Wells et al, 2010). The quality checklist used awards a maximum of one star for each item except comparability, which can be given a maximum of two stars. An arbitrary 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 comparisons between the affected ovary and normal ovary.

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 heterogeneity 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. Dichotomous outcome data were reported as odds ratios with 95% confidence intervals (CI). Continuous data were synthesized 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 abstracts and titles. The literature search results are represented in Figure 1 . Eight original articles were excluded because five studies investigated women who underwent surgical interventions to treat ovarian endometrioma (Benaglia et al, 2012, Donnez et al, 2001, Mao et al, 2009, Nakahara et al, 1998, and 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 available ( Benaglia et al., 2011 ). Therefore, the total number of studies included in the meta-analysis was nine.

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Figure 1 The literature search. ICSI = intracytoplasmic sperm injection.

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 Assessment are presented in Table 1 and Table 2. The studies scored well on the Newcastle–Ottawa Quality Assessment Scale ( Table 2 ).

Table 1 Characteristics of studies of ovarian endometrioma versus control on ovarian response and IVF and inracytoplasmic perm injection outcome.

Study year Population Ovarian endometrioma group Control group Outcomes Study design
Ashrafi et al., 2014 (n = 104) Women undergoing ICSI at Royan Institute, Iran between 2005 and 2007. Women with either unilateral or bilateral ovarian endometrial cysts of less than 3 cm (n = 47) Patients with mild male factor infertility and without ovarian endometriomas (n = 57) Number of oocytes retrieved; number of MII oocytes retrieved; number of formed embryos; fertilization rate; implantation rate; number of good-quality formed embryos; clinical pregnancy rate. Cohort study
Benaglia et al., 2013 (n = 117) Women undergoing IVF at the Infertility Unit of the Fondazione Ca'Granda between 2006 and 2010. Women with unoperated bilateral endometriomas (n = 39) Patients without endometriotic or non-endometriotic ovarian cysts (n = 78) Number of oocytes retrieved; Number of formed embryos; Total dose of gonadotropin (IU); Number of good-quality formed embryos; Number of days of stimulation; implantation rate; clinical pregnancy rate; live birth rate. Cohort study
Bongioanni et al., 2011 (n = 316) Women undergoing IVF at three IVF units in Italy. 142 women with unoperated endometrioma (≤6 cm ) Women with tubal factor and without ovarian endometriomas (n = 174) Number of retrieved oocytes; fertilization rate; implantation rate; total dose of gonadotropin (IU). Cohort study
Reinblatt et al., 2011 (n = 52) Women undergoing IVF at the McGill

Reproductive Centre between 2006 and 2010.
Women with bilateral endometriomas (n = 13) Patients with male or tubal factor infertility without endometriomas (n = 39) Number of oocytes collected; Number of MII oocytes retrieved. Cohort study
Almog et al., 2011 (n = 243) Women undergoing IVF at McGill University Health Center, Montreal, between 2006 and 2009. 81 women with unilateral endometrioma Women without endometriomas (n = 162) Number of retrieved oocytes; total dose of gonadotrophin (IU); Number of days of stimulation; Cohort study
Yanushpolsky et al., 1998 (n = 94) Women undergoing IVF at Harvard Medical School between 1994 and 1995. 37 women with endometriomas Patients without any ovarian endometriomas (n = 56) Number of retrieved oocytes; number of days of stimulation; implantation rate; clinical pregnancy rate; live birth rate. Cohort study
Filippi et al., 2014 (n = 29) Women undergoing IVF–ICSI at the Infertility Unit of the Fondazione Ca'Granda between 2012 and 2013. Affected ovary (n = 29) Intact ovary (n = 29) Number of co-dominant follicles; Number of oocytes retrieved; total formed embryos; fertilization rate. Cohort study
Esinler et al., 2012 (n = 28 cycles) Women undergoing ICSI at Hacettepe University, Turkey. Affected ovary (n = 28) Intact ovary (n = 28) Number of oocytes retrieved; number of MII oocytes; fertilization rate. Cohort study
Somigliana et al., 2006 (n = 56 cycles) Women undergoing IVF–ICSI at Ospedale Maggiore Policlinico, Mangiagalli and Regina Elena between 2000 and 2004. Affected ovary (n = 56) Intact ovary (n = 56) Number of co-dominant follicles. Cohort study

ICSI = intractoplasmic sperm injection; MII, metaphase II.

Table 2 Appraisal of methodological quality (Newcastle–Ottawa Scale) of included studies.

* Indicates that a feature is present.

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

Primary outcomes

Total gonadotrophin consumption

Pooling of results from three studies (Almog et al, 2011, Benaglia et al, 2013, and Bongioanni et al, 2011) that reported total dose of gonadotrophin ( Figure 2A ) did not show a difference 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).

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Figure 2 (A) Gonadotrophin consumption; (B) duration of stimulation between ovarian endometrioma group and control group.

Duration of stimulation

Pooling of results from three studies (Almog et al, 2011, Benaglia et al, 2013, and Yanushpolsky et al, 1998) that reported 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 heterogeneity 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, and Yanushpolsky et al, 1998) that reported total number of oocytes retrieved ( Figure 3A ) found 1.50 fewer oocytes retrieved in those with ovarian endometrioma 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).

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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.

Number of MII oocytes

Pooling of results from two studies (Ashrafi et al, 2014 and Reinblatt et al, 2011) that reported number of MII oocytes retrieved ( Figure 3B ) found 3.61 fewer MII oocytes retrieved 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 and 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 and Benaglia et al, 2013) that reported number of good-quality formed embryos ( Figure 3D ) did not show a statistically significant difference between the two groups (WMD −0.21; 95% CI −0.61 to 0.19), although the direction of effect suggested a reduction in good-quality formed embryos of patients with ovarian endometrioma. Heterogeneity between the studies was limited, as indicated by an I2 value of 8%.

Implantation rate

Four studies (Ashrafi et al, 2014, Benaglia et al, 2013, Bongioanni et al, 2011, and Yanushpolsky et al, 1998) reported implantation rate, but only two studies (Ashrafi et al, 2014 and Benaglia et al, 2013) reported it per patient. Pooling of results from the two studies ( Figure 4A ) did not show a difference in this outcome (odds ratio [OR] 1.11, 95% CI 0.68 to 1.81). The I2 value was 0%, indicating that heterogeneity was unlikely between the studies.

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Figure 4 (A) Implantation rate; (B) clinical pregnancy rate; and (C) live birth rate between ovarian endometrioma group and control group.

Clinical pregnancy rate

Pooling of results from three studies (Ashrafi et al, 2014, Benaglia et al, 2013, and Yanushpolsky et al, 1998) that reported 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 heterogeneity in this comparison (I2 = 0%).

Live birth rate

Pooling of results from two studies (Benaglia et al, 2013 and Yanushpolsky et al, 1998) that reported live birth rates ( Figure 4C ) did not show a significant difference in this outcome (OR 0.70, 95% CI 0.37 to 1.33). There was no heterogeneity in this comparison (I2 = 0%).

Secondary outcomes

Number of co-dominant follicles between ovary with endometrioma and normal ovary

Pooling of results from two studies (Filippi et al, 2014 and 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%).

rbmo1333-fig-0005

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.

Number of oocytes retrieved between ovary with endometrioma and normal ovary

Pooling of results from four studies (Almog et al, 2011, Ashrafi et al, 2014, Esinler et al, 2012, and Filippi et al, 2014) that reported the number of oocytes retrieved between affected ovary and intact ovary ( Figure 5B ) did not show a significant difference (WMD −0.11; 95% CI −0.25 to 0.03)]. The I2 value was 0%, indicating that heterogeneity was unlikely between the studies.

Number of MII oocytes between ovary with endometrioma and normal ovary

Pooling of results from two studies (Ashrafi et al, 2014 and Esinler et al, 2012) that reported the number of MII oocytes ( Figure 5C ) between the affected ovary and intact ovary did not suggest a significant difference (WMD −0.14; 95% CI −1.01 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 and 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, and Filippi et al, 2014) compared the fertilization rate between ovary with endometrioma and control ovary; however, only two of them (Ashrafi et al, 2014 and 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 heterogeneity 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 responsiveness 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 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, and Somigliana et al, 2008). Women who were previously operated on for ovarian endometrioma were excluded to protect our results from the confounding effects of previous surgery. Patients were included on the basis of a transvaginal ultrasonography diagnosis of endometrioma. Owing to their characteristic echogenic appearance, endometrioma could be easily distinguished from other ovarian cysts. Sensitivity and specificity of transvaginal ultrasonography 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 laboratory 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 clinical heterogeneity and insufficient power (low sample size) 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 endometriomas 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 compensated 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 performed. 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 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 and Lucena, Cubillos, 1999). Moreover, several studies reported that the density and diameters of primordial follicles 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, Kitajima et al, 2014, Kuroda et al, 2012, and 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 (Advanced 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, and Matsuzaki, Schubert, 2010). Our results indicated that the quality of the retrieved oocytes is not hampered by the presence of ovarian endometrioma.

As previously mentioned, a healthy ovary could compensate for ovarian function and fertility potential of the contralateral affected ovary in the same individual. The results from the studies of bilateral endometriomas should be particularly emphasized. Two studies (Benaglia et al, 2013 and Reinblatt et al, 2011) reported on IVF outcome in women with bilateral endometriomas. Reinblatt et al. (2011) failed to document any effect, whereas Benaglia et al. (2013) suggested a mild reduction in ovarian responsiveness but similar embryo development and pregnancy rates. Drawing definitive conclusions based on these conflicting reports is difficult; moreover, 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 inflammation, reactive oxygen species production that can impair ovarian responsiveness, but not the cyst of ovarian endometrioma itself. Esinler et al. (2012) reported that a single endometrioma 3 cm or less in diameter did not have a deleterious effect on ovarian reserve. The dimension of the endometriomas in women recruited for the intra-patient comparisons was relatively small (the mean diameter was less than 3 cm). We therefore cannot rule out that larger cysts may be detrimental. Further evidence is also required to address this point. On the other hand, in the comparisons of women with and without endometriomas, because of selection biases, the ovarian responsiveness might be enhanced in control group rather than reduced in women with endometriomas.

In this meta-analysis, we found that the clinical pregnancy and live birth rates were similar between the patients with and without ovarian endometrioma. It is consistent with the meta-analysis by Gupta et al. (2006) but in contrast to those from a meta-analysis by Barnhart et al. (2002) . The pooling results, however, did not suggest a significant difference of gonadotrophin consumption between the two groups, which was inconsistent with previous studies (Al-Azemi et al, 2000 and Kumbak et al, 2008). Surgery may diminish the ovarian reserve, reduce responsiveness to ovarian stimulation (Demirol et al, 2006 and Dilek et al, 2006). Our results suggest that surgical removal of endometriomas before assisted 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 responsiveness 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 outcomes. Ovaries with endometriomas, however, showed a similar response to stimulation compared with the contralateral healthy ovaries in the same individuals. In this regard, assisted reproduction techniques would provide a therapeutic approach for the ovarian endometrioma-related infertility rather than laparoscopic ovarian surgery. Further randomized controlled trials of patients with endometriomas would be needed to confirm our conclusions.

References

  • Al-Azemi et al, 2000 M. Al-Azemi, A.L. Bernal, J. Steele, I. Gramsbergen, D. Barlow, S. Kennedy. Ovarian response to repeated controlled stimulation in in-vitro fertilization cycles in patients with ovarian endometriosis. Hum. Reprod. 2000;15:72-75 Crossref
  • Almog et al, 2011 B. Almog, F. Shehata, B. Sheizaf, Tan S.L., T. Tulandi. Effects of ovarian endometrioma on the number of oocytes retrieved for in vitro fertilization. Fertil. Steril. 2011;95:525-527 Crossref
  • Ashrafi et al, 2014 M. Ashrafi, T. Fakheri, K. Kiani, M. Sadeghi, M.R. Akhoond. Impact of the endometrioma on ovarian response and pregnancy rate in in vitro fertilization cycles. Int. J. Fertil. Steril. 2014;8:29-34
  • Azem et al, 1999 F. Azem, J.B. Lessing, E. Geva, A. Shahar, L. Lerner-Geva, I. Yovel, A. Amit. Patients with stages III and IV endometriosis have a poorer outcome of in vitro fertilization-embryo transfer than patients with tubal infertility. Fertil. Steril. 1999;72:1107-1109 Crossref
  • Aziz et al, 2006 O. Aziz, V. Constantinides, P.P. Tekkis, T. Athanasiou, S. Purkayastha, P. Paraskeva, A.W. Darzi, A.G. Heriot. Laparoscopic versus open surgery for rectal cancer: a meta-analysis. Ann. Surg. Oncol. 2006;13:413-424 Crossref
  • Barnhart et al, 2002 K. Barnhart, R. Dunsmoor-Su, C. Coutifaris. Effect of endometriosis on in vitro fertilization. Fertil. Steril. 2002;77:1148-1155 Crossref
  • Benaglia et al, 2011 L. Benaglia, R. Pasin, E. Somigliana, P. Vercellini, G. Ragni, L. Fedele. Unoperated ovarian endometriomas and responsiveness to hyperstimulation. Hum. Reprod. 2011;26:1356-1361 Crossref
  • Benaglia et al, 2012 L. Benaglia, A. Bermejo, E. Somigliana, C. Scarduelli, G. Ragni, L. Fedele, J.A. Garcia-Velasco. Pregnancy outcome in women with endometriomas achieving pregnancy through IVF. Hum. Reprod. 2012;27:1663-1667
  • Benaglia et al, 2013 L. Benaglia, A. Bermejo, E. Somigliana, S. Faulisi, G. Ragni, L. Fedele, J.A. Garcia-Velasco. In vitro fertilization outcome in women with unoperated bilateral endometriomas. Fertil. Steril. 2013;99:1714-1719 Crossref
  • Bongioanni et al, 2011 F. Bongioanni, A. Revelli, G. Gennarelli, D. Guidetti, L.D. Delle Piane, J. Holte. Ovarian endometriomas and IVF: a retrospective case-control study. Reprod. Biol. Endocrinol. 2011;17:81 Crossref
  • Coccia et al, 2014 M.E. Coccia, F. Rizzello, S. Barone, S. Pinelli, E. Rapalini, C. Parri, D. Caracciolo, S. Papageorqiou, G. Cima, L. Gandini. Is there a critical endometrioma size associated with reduced ovarian responsiveness in assisted reproduction techniques?. Reprod. Biomed. Online. 2014;29:259-266 Crossref
  • Demirol et al, 2006 A. Demirol, S. Guven, C. Baykal, T. Gurgan. Effect of endometrioma cystectomy on IVF outcome: a prospective randomized study. Reprod. Biomed. Online. 2006;12:639-643 Crossref
  • Di Emidio et al, 2014 G. Di Emidio, A. D'Alfonso, P. Leocata, V. Parisse, A. Di Fonso, P.G. Artini, F. Patacchiola, C. Tatone, G. Carta. Increased levels of oxidative and carbonyl stress markers in normal ovarian cortex surrounding endometriotic cysts. Gynecol. Endocrinol. 2014;17:1-5
  • Dilek et al, 2006 U. Dilek, O. Pata, C. Tataroglu, M. Aban, S. Dilek. Excision of endometriotic cyst wall may cause loss of functional ovarian tissue. Fertil. Steril. 2006;85:758-760 Crossref
  • Donnez et al, 2001 J. Donnez, C. Wyns, M. Nisolle. Does ovarian surgery for endometriomas impair the ovarian response to gonadotropin?. Fertil. Steril. 2001;76:662-665 Crossref
  • Esinler et al, 2006 I. Esinler, G. Bozdag, F. Aybar, U. Bayar, H. Yarali. Outcome of in vitro fertilization/intracytoplasmic sperm injection after laparoscopic cystectomy for endometriomas. Fertil. Steril. 2006;85:1730-1735 Crossref
  • Esinler et al, 2012 I. Esinler, G. Bozdag, I. Arikan, B. Demir, H. Yarali. Endometrioma ≤3 cm in diameter per se does not affect ovarian reserve in intracytoplasmic sperm injection cycles. Gynecol. Obstet. Invest. 2012;74:261-264 Crossref
  • Eskenazi et al, 2001 B. Eskenazi, M. Warner, L. Bonsignore, D. Olive, S. Samuels, P. Vercellini. Validation study of nonsurgical diagnosis of endometriosis. Fertil. Steril. 2001;76:929-935 Crossref
  • Filippi et al, 2014 F. Filippi, L. Benaglia, A. Paffoni, L. Restelli, P. Vercellini, E. Somigliana, L. Fedele. Ovarian endometriomas and oocyte quality: insights from in vitro fertilization cycles. Fertil. Steril. 2014;101:988-993
  • Garrido et al, 2000 N. Garrido, J. Navarro, J. Remohí, C. Simón, A. Pellicer. Follicular hormonal environment and embryo quality in women with endometriosis. Hum. Reprod. Update. 2000;6:67-74 Crossref
  • Gupta et al, 2006 S. Gupta, A. Agarwal, R. Agarwal, J.R. Loret de Mola. Impact of ovarian endometrioma on assisted reproduction outcomes. Reprod. Biomed. Online. 2006;13:349-360 Crossref
  • Harb et al, 2013 H.M. Harb, I.D. Gallos, Chu J., M. Harb, A. Coomarasamy. The effect of endometriosis on in vitro fertilisation outcome: a systematic review and meta-analysis. BJOG. 2013;120:1308-1320 Crossref
  • Higgins et al, 2003 J.P. Higgins, S.G. Thompson, J.J. Deeks, D.G. Altman. Measuring inconsistency in meta-analyses. BMJ. 2003;327:557-560 Crossref
  • Higgins, Green, 2011 J.P.T. Higgins, S. Green. Cochrane handbook for systematic reviews of interventions version 5.1.0 (updated March 2011). http://handbook.cochrane.org/ (2011) The Cochrane Collaboration 2011. Available from
  • Isaacs et al, 1997 J.D. Isaacs Jr., R.S. Hines, V.M. Sopelak, B.D. Cowan. Ovarian endometriomas do not adversely affect pregnancy success following treatment with in vitro fertilization. J. Assist. Reprod. Genet. 1997;14:551-553
  • Jana et al, 2010 S.K. Jana, N.B. K, R. Chattopadhyay, B. Chakravarty, K. Chaudhury. Upper control limit of reactive oxygen species in follicular fluid beyond which viable embryo formation is not favorable. Reprod. Toxicol. 2010;29:447-451 Crossref
  • Karuputhula et al, 2013 N.B. Karuputhula, R. Chattopadhyay, B. Chakravarty, K. Chaudhury. Oxidative status in granulosa cells of infertile women undergoing IVF. Syst. Biol. Reprod. Med. 2013;59:91-98 Crossref
  • Kennedy et al, 2005 S. Kennedy, A. Bergqvist, C. Chapron, T. D'Hooghe, G. Dunselman, R. Greb, L. Hummelshoj, A. Prentice, E. Saridogan. ESHRE guideline for the diagnosis and treatment of endometriosis. Hum. Reprod. 2005;20:2698-2704 Crossref
  • Kitajima et al, 2011 M. Kitajima, S. Defrère, M.M. Dolmans, S. Colette, J. Squifflet, A. Van Langendonckt, J. Donnez. Endometriomas as a possible cause of reduced ovarian reserve in women with endometriosis. Fertil. Steril. 2011;96:685-691 Crossref
  • Kitajima et al, 2014 M. Kitajima, M.M. Dolmans, O. Donnez, H. Masuzaki, M. Soares, J. Donnez. Enhanced follicular recruitment and atresia in cortex derived from ovaries with endometriomas. Fertil. Steril. 2014;101:1031-1037 Crossref
  • Kumbak et al, 2008 B. Kumbak, S. Kahraman, G. Karlikaya, S. Lacin, A. Guney. In vitro fertilization in normoresponder patients with endometriomas: comparison with basal simple ovarian cysts. Gynecol. Obstet. Invest. 2008;65:212-216 Crossref
  • Kuroda et al, 2012 M. Kuroda, K. Kuroda, A. Arakawa, Y. Fukumura, M. Kitade, I. Kikuchi, J. Kumakiri, S. Matsuoka, I.A. Brosens, J.J. Brosens, S. Takeda, Yao T. Histological assessment of impact of ovarian endometrioma and laparoscopic cystectomy on ovarian reserve. J. Obstet. Gynaecol. Res. 2012;38:1187-1193 Crossref
  • Lucena, Cubillos, 1999 E. Lucena, J. Cubillos. Immune abnormalities in endometriosis compromising fertility in IVF-ET patients. J. Reprod. Med. 1999;44:458-464
  • Macer, Taylor, 2012 M.L. Macer, H.S. Taylor. Endometriosis and infertility: a review of the pathogenesis and treatment of endometriosis-associated infertility. Obstet. Gynecol. Clin. North Am. 2012;39:535-549 Crossref
  • Mao et al, 2009 Mao Y.H., Zhou C., A. Zaccabri. Outcome of the IVF for the patients with endometrioma associated infertility. J. Reprod. Contracep. 2009;20:19-26 Crossref
  • Matsuzaki, Schubert, 2010 S. Matsuzaki, B. Schubert. Oxidative stress status in normal ovarian cortex surrounding ovarian endometriosis. Fertil. Steril. 2010;93:2431-2432 Crossref
  • Nakahara et al, 1998 K. Nakahara, H. Saito, T. Saito, M. Ito, N. Ohta, T. Takahashi, M. Hiroi. Ovarian fecundity in patients with endometriosis can be estimated by the incidence of apoptotic bodies. Fertil. Steril. 1998;69:931-935 Crossref
  • Raffi et al, 2012 F. Raffi, M. Metwally, S. Amer. The impact of excision of ovarian endometrioma on ovarian reserve: a systematic review and meta-analysis. J. Clin. Endocrinol. Metab. 2012;97:3146-3154 Crossref
  • Reinblatt et al, 2011 S.L. Reinblatt, L. Ishai, F. Shehata, W.Y. Son, T. Tulandi, B. Almog. Effects of ovarian endometrioma on embryo quality. Fertil. Steril. 2011;95:2700-2702 Crossref
  • Schubert et al, 2005 B. Schubert, M. Canis, C. Darcha, C. Artonne, J.L. Pouly, P. Déchelotte, D. Boucher, G. Grizard. Human ovarian tissue from cortex surrounding benign cysts: a model to study ovarian tissue cryopreservation. Hum. Reprod. 2005;20:1786-1792 Crossref
  • Somigliana et al, 2006 E. Somigliana, M. Infantino, F. Benedetti, M. Arnoldi, G. Calanna, G. Ragni. The presence of ovarian endometriomas is associated with a reduced responsiveness to gonadotropins. Fertil. Steril. 2006;86:192-196 Crossref
  • Somigliana et al, 2008 E. Somigliana, M. Arnoldi, L. Benaglia, R. Iemmello, A.E. Nicolosi, G. Ragni. IVF-ICSI outcome in women operated on for bilateral endometriomas. Hum. Reprod. 2008;23:1526-1530 Crossref
  • Suzuki et al, 2005 T. Suzuki, S. Izumi, H. Matsubayashi, H. Awaji, K. Yoshikata, T. Makino. Impact of ovarian endometrioma on oocytes and pregnancy outcome in in vitro fertilization. Fertil. Steril. 2005;83:908-913 Crossref
  • Wells et al, 2010 G.A. Wells, B. Shea, D. O'Connell, J. Peterson, V. Welch, M. Losos, P. Tugwell. The Newcastle-Ottawa Scale (NOS) for assessing the quality of cohort studies. http://www.medicine.mcgill.ca/rtamblyn/Readings/The%20Newcastle%20-%20Scale%20for%20assessing%20the%20quality%20of%20nonrandomised%20studies%20in%20meta-analyses.pdf (2010) Available from
  • Yanushpolsky et al, 1998 E.H. Yanushpolsky, C.L. Best, K.V. Jackson, R.N. Clarke, R.L. Barbieri, M.D. Hornstein. Effects of endometriomas on ooccyte quality, embryo quality, and pregnancy rates in in vitro fertilization cycles: a prospective, case-controlled study. J. Assist. Reprod. Genet. 1998;15:193-197 Crossref
rbmo1333-fig-5001

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.

Footnotes

Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China

* Corresponding author.

1 The two first authors contributed equally to this work.

Editorial comment by Bruce Dunphy:

This article by Heitmann et al highlights the importance of stringent quality control measures in the ART laboratory and the beneficial impact of improving laboratory conditions. The important principles of quality control in the ART laboratory are discussed in video interviews with Dr David Mortimer, which can be viewed here.