Reproductive Medicine, Department of Obstetrics and Gynecology, Baruch-Padeh Medical Center, Poriya, Israel.
Azrieili Faculty of Medicine, Galilee, Bar-Ilan University, Israel.
Hum Reprod Update. 2019 May 1;25(3):375-391. doi: 10.1093/humupd/dmy049.
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.
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.
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.
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.
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.
卵巢子宫内膜异位症是生育期妇女中子宫内膜异位症的常见表现。目前仍在积极讨论与该病变占位效应、局部反应和手术切除相关的多个问题。卵巢子宫内膜异位症本身对卵巢储备功能的影响仍存在争议，卵巢手术的影响也在积极讨论中。此外，用于评估卵巢子宫内膜异位症患者卵巢储备功能的最佳生物标志物仍在研究中。另外，关于双侧卵巢子宫内膜异位症对卵巢储备功能的影响，目前尚无一致的共识。
本系统评价和荟萃分析的目的是研究单侧和双侧卵巢子宫内膜异位症囊肿切除术前后，卵巢储备生物标志物的变化。
我们通过 PubMed、EBSCO、Web of Science、ClinicalTrials.gov 和 Cochrane Library 进行了广泛的电子数据库检索，以确定 2000 年 1 月至 2018 年 10 月期间发表的研究文章。检索词包括子宫内膜异位症囊肿或子宫内膜异位瘤、囊肿切除术或切除术或剥离术或切除术或切除术和不孕或不育。仅纳入前瞻性对照研究，比较单侧和双侧卵巢子宫内膜异位症囊肿切除术对同一环境中卵巢储备测试的影响。排除多囊卵巢综合征、卵巢衰竭、早绝经、口服避孕药治疗或先前化疗和/或放疗或卵巢手术的病例。我们使用纽卡斯尔-渥太华量表评估符合荟萃分析条件的研究的质量。我们在 PROSPERO 上注册了该系统评价，其编号为 CRD42018117170。
共有 12 项研究符合荟萃分析条件，共纳入 783 名女性：单侧组 489 名，双侧组 294 名。纳入的研究存在低偏倚风险。术前加权均数差（WMD）显示两组血清 AMH 水平无显著差异。相反，双侧组在术后早期、中期和晚期的 AMH 水平明显（P<0.05）低于单侧组，相应的 WMD 分别为 0.78ng/ml（95%CI：0.41-1.15）、0.59ng/ml（95%CI：0.14-1.04）和 1.08ng/ml（95%CI：0.63-1.52）。报告术前和术后早期和中期 AMH 值的研究之间存在高度异质性。术前和术后 AFC 值无显著差异。报告 AFC 值的研究之间存在高度异质性。分别对单侧和双侧组进行分析显示，血清 AMH 分别从基线下降 39.5%和 57.0%，具有显著和持续的下降趋势。
我们的研究结果挑战了这样一种概念，即子宫内膜异位症本身会对卵巢储备产生不良影响，而子宫内膜异位症囊肿切除术，尤其是双侧手术，对卵巢储备具有有害和持续的影响。在子宫内膜异位症患者中，AMH 似乎比 AFC 更适合作为卵巢储备的生物标志物。由于低 AMH 意味着生育寿命缩短，因此应谨慎考虑切除子宫内膜异位症，尤其是双侧病例。
