Impact of unilateral versus bilateral ovarian endometriotic cystectomy on ovarian reserve: a systematic review and meta-analysis

BACKGROUND Ovarian endometrioma is a frequent manifestation of endometriosis in women of reproductive age. Several issues related to its space occupying effects, local reactions and surgical removal continue to be actively debated today. The impact of ovarian endometrioma per se on ovarian reserve is still controversial and the effect of ovarian surgery is still actively discussed. Furthermore, the optimal biomarker of ovarian reserve estimation in women with ovarian endometrioma is still under examination. Additionally, there is no consistent agreement on the effect of endometrioma bilaterality on ovarian reserve. OBJECTIVE AND RATIONALE The objective of this systematic review and meta-analysis was to study the impact of unilateral versus bilateral ovarian endometrioma on ovarian reserve biomarkers before and after endometrioma cystectomy. SEARCH METHODS We performed an extensive electronic database search employing PubMed, EBSCO, Web of Science, ClinicalTrials.gov and the Cochrane Library, to identify published research articles published between January 2000 and October 2018. Search terms included endometriotic cyst OR endometrioma OR endometriomata, cystectomy OR resection OR stripping OR removal OR excision and infertility OR subfertility. Only prospective controlled studies that compared the impact of unilateral versus bilateral ovarian endometriotic cystectomy on ovarian reserve tests in the same setting were included. Studies which included cases with PCOS, ovarian failure, early menopause, oral contraception treatment, or prior chemotherapy and/or radiotherapy or ovarian surgery, were excluded from evaluation. We used the Newcastle-Ottawa Scale for assessing the quality of studies found eligible for meta-analysis. We registered the systematic review on PROSPERO and its number is CRD42018117170. OUTCOMES Twelve studies were eligible for meta-analysis including collectively 783 women: 489 and 294 in the unilateral and bilateral groups, respectively. The included studies had a low risk of bias. The pre-operative weighted mean difference (WMD) showed that serum AMH levels did not differ significantly between the groups. Conversely, AMH levels were significantly (P < 0.05) lower in bilateral groups than in unilateral groups at the early, intermediate and late post-operative periods, corresponding WMDs of 0.78 ng/ml (95% CI: 0.41-1.15), 0.59 ng/ml (95% CI: 0.14-1.04) and 1.08 ng/ml (95% CI: 0.63 to 1.52), respectively. Heterogeneity among eligible studies reporting on before the operation and at the early and intermediate post-operative periods was high. Pre-operative and post-operative AFC values were not significantly different between the groups. The heterogeneity among the studies reporting on AFC was high. Analysis of each of the unilateral and bilateral groups separately showed a significant and sustained serum AMH drop by 39.5% and 57.0%, respectively from baseline to after the operation. WIDER IMPLICATIONS Our results challenge the concept that endometrioma per se adversely affects ovarian reserve, whereas endometrioma cystectomy, especially as bilateral operation, has a deleterious and sustained effect on ovarian reserve. AMH seems to be a more appropriate biomarker of ovarian reserve than AFC in cases with endometrioma. Since low AMH implies a shorter reproductive lifespan, excision of endometrioma should be cautiously considered, especially in bilateral cases.