BACKGROUND Patients with endometriosis often experience infertility and have poor IVF outcomes, with low fertilization and pregnancy rates. Although many theories have tried to explain the mechanisms underlying infertility in these patients, none of them is conclusive. OBJECTIVE AND RATIONALE In this review, we discuss the pathologic mechanisms through which endometriosis likely leads to infertility along with the therapeutic options used to date to treat endometriosis-related infertility and, thereby, to improve IVF outcomes in patients with endometriosis. SEARCH METHODS We performed a comprehensive literature search of clinical outcomes in endometriosis and the molecular mechanisms contributing to oocyte quality using the PubMed database to identify human and animal studies published from 1992 until September 2020. In total, 123 manuscripts were included. OUTCOMES While some theories propose that endometriosis patients may have fertility problems as a result of decreased endometrial receptivity, others reinforce the idea that infertility could be associated with oocyte alterations and lower implantation rates. Single-cell RNA sequencing of oocytes from patients with endometriosis has identified dysregulated mechanisms involved in steroid metabolism and biosynthesis, response to oxidative stress and cell cycle regulation. Dysregulation of these mechanisms could result in the poor IVF outcomes observed in patients with endometriosis. Further, impaired steroidogenesis may directly affect oocyte and embryo quality. Increased oxidative stress in patients with endometriosis also has a detrimental effect on the follicular microenvironment, inducing cell cycle dysregulation in oocytes, poor oocyte quality, and infertility. Moreover, granulosa cells in the context of endometriosis undergo increased apoptosis and have an altered cell cycle that could adversely affect folliculogenesis, oocyte and embryo quality, and IVF outcomes. Endometriosis is also associated with inflammatory damage and impaired angiogenesis, which could be directly correlated with poor IVF outcomes. While therapeutic options using GnRH analogues, progestins and aromatase inhibitors do not improve endometriosis-related infertility, anti-inflammatory agents and antioxidant supplementation could improve oocyte quality as well as implantation and clinical pregnancy rates in patients with endometriosis. WIDER IMPLICATIONS Endometriosis is a heterogeneous disease whose pathogenesis is complex and could affect fertility by altering a collection of molecular mechanisms in oocytes. Thus, a single model is not sufficient to describe endometriosis-related infertility. Dysregulation of steroidogenesis, oxidative stress, cell cycle progression, inflammation and angiogenesis in the follicular environment and oocytes in individuals with endometriosis are all possible contributors to endometriosis-related infertility. Therefore, treatments targeting these mechanisms could be therapeutic alternatives to improve IVF outcomes for these patients.

中文翻译：

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改善子宫内膜异位症患者体外受精结果的新治疗靶点：回顾和未来前景

背景 子宫内膜异位症患者经常经历不孕症，IVF 结局较差，受精率和妊娠率低。尽管许多理论试图解释这些患者不孕的机制，但没有一个是决定性的。目的和理由 在这篇综述中，我们讨论了子宫内膜异位症可能导致不孕症的病理机制，以及迄今为止用于治疗子宫内膜异位症相关不孕症的治疗方案，从而改善子宫内膜异位症患者的体外受精结果。搜索方法 我们使用 PubMed 数据库对子宫内膜异位症的临床结果和影响卵母细胞质量的分子机制进行了全面的文献搜索，以确定从 1992 年到 2020 年 9 月发表的人类和动物研究。总共，收录了 123 篇手稿。结果 虽然一些理论认为子宫内膜异位症患者可能由于子宫内膜容受性降低而出现生育问题，但其他理论则强调不育可能与卵母细胞改变和较低的植入率有关。来自子宫内膜异位症患者的卵母细胞的单细胞 RNA 测序已经确定了涉及类固醇代谢和生物合成、对氧化应激反应和细胞周期调节的失调机制。这些机制的失调可能导致在子宫内膜异位症患者中观察到不良的 IVF 结果。此外，类固醇生成受损可能直接影响卵母细胞和胚胎质量。子宫内膜异位症患者的氧化应激增加也会对卵泡微环境产生不利影响，诱导卵母细胞周期失调、卵母细胞质量差和不育。此外，子宫内膜异位症的颗粒细胞凋亡增加，细胞周期发生改变，这可能对卵泡发生、卵母细胞和胚胎质量以及体外受精结果产生不利影响。子宫内膜异位症还与炎症损伤和血管生成受损有关，这可能与不良的 IVF 结果直接相关。虽然使用 GnRH 类似物、孕激素和芳香酶抑制剂的治疗选择不能改善子宫内膜异位症相关的不孕症，但抗炎剂和抗氧化剂补充剂可以改善子宫内膜异位症患者的卵母细胞质量以及植入率和临床妊娠率。更广泛的影响 子宫内膜异位症是一种异质性疾病，其发病机制复杂，可通过改变卵母细胞中的一系列分子机制来影响生育能力。因此，单一模型不足以描述子宫内膜异位症相关的不孕症。类固醇生成的失调、氧化应激、细胞周期进程、卵泡环境中的炎症和血管生成以及子宫内膜异位症患者的卵母细胞都可能导致子宫内膜异位症相关的不孕症。因此，针对这些机制的治疗可能是改善这些患者体外受精结果的治疗选择。细胞周期进展、卵泡环境中的炎症和血管生成以及子宫内膜异位症患者的卵母细胞都是子宫内膜异位症相关不孕症的可能因素。因此，针对这些机制的治疗可能是改善这些患者体外受精结果的治疗选择。细胞周期进展、卵泡环境中的炎症和血管生成以及子宫内膜异位症患者的卵母细胞都是子宫内膜异位症相关不孕症的可能因素。因此，针对这些机制的治疗可能是改善这些患者体外受精结果的治疗选择。