Fundación IVI, Instituto de Investigación Sanitaria La Fe, Medicina Reproductiva, Valencia, Spain.
Departamento de Pediatría, Obstetricia y Ginecología, Universidad de Valencia, Valencia, Spain.
Hum Reprod Update. 2021 Aug 20;27(5):923-972. doi: 10.1093/humupd/dmab014.
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.
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.
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.
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.
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.
子宫内膜异位症患者常患有不孕症，体外受精（IVF）结局较差，受精率和妊娠率较低。尽管有许多理论试图解释这些患者不孕的机制，但没有一个是结论性的。
在这篇综述中，我们讨论了子宫内膜异位症可能导致不孕的病理机制，以及迄今为止用于治疗子宫内膜异位症相关不孕的治疗选择，从而改善子宫内膜异位症患者的 IVF 结局。
我们使用 PubMed 数据库对 1992 年至 2020 年 9 月发表的关于子宫内膜异位症的临床结局和导致卵子质量下降的分子机制的人类和动物研究进行了全面的文献检索，以确定纳入的研究。共纳入 123 篇论文。
虽然有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存在生育问题，但另一些理论则强调不孕可能与卵子改变和着床率降低有关。对子宫内膜异位症患者的卵子进行单细胞 RNA 测序，发现了类固醇代谢和生物合成、对氧化应激的反应以及细胞周期调节中涉及的失调机制。这些机制的失调可能导致子宫内膜异位症患者观察到的 IVF 结局不佳。此外，类固醇生成受损可能直接影响卵子和胚胎质量。子宫内膜异位症患者中氧化应激的增加也对卵泡微环境产生不利影响，导致卵子细胞周期失调、卵子质量差和不孕。此外，在子宫内膜异位症的背景下，颗粒细胞凋亡增加，细胞周期改变，这可能对卵泡发生、卵子和胚胎质量以及 IVF 结局产生不利影响。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 IVF 结局不佳直接相关。虽然使用 GnRH 类似物、孕激素和芳香化酶抑制剂的治疗选择并不能改善子宫内膜异位症相关的不孕，但抗炎药物和抗氧化剂补充剂可以改善子宫内膜异位症患者的卵子质量以及着床和临床妊娠率。
子宫内膜异位症是一种异质性疾病，其发病机制复杂，可能通过改变卵子中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。在患有子宫内膜异位症的个体中，卵泡环境和卵子中的类固醇生成、氧化应激、细胞周期进展、炎症和血管生成的失调，都可能是子宫内膜异位症相关不孕的原因。因此，针对这些机制的治疗方法可能是改善这些患者 IVF 结局的治疗选择。
