University of Southampton, Human Development and Health, Southampton, UK.
University of Southampton, Complete Fertility, Princess Anne Hospital, Southampton, UK.
Hum Reprod Update. 2019 Sep 11;25(5):592-632. doi: 10.1093/humupd/dmz012.
The reproductive impact of adenomyosis and endometriosis is widely researched but the extent of these impacts remains elusive. It has been demonstrated that endometriosis, in particular, is known to result in subfertility but endometriosis and adenomyosis are increasingly linked to late pregnancy complications such as those caused by placental insufficiency. At the molecular level, the presence of ectopic endometrium perturbs the endometrial hormonal, cellular, and immunological milieu, negatively influencing decidualization, placentation, and developmental programming of the embryo. It is unclear if and how such early aberrant reproductive development relates to pregnancy outcomes in endometriosis and adenomyosis.
The aims of this systematic review and meta-analysis were to (i) investigate the association of adenomyosis and endometriosis with fertility, obstetric, and neonatal outcomes of women through both assisted reproduction and natural conception and (ii) determine whether endometriosis disease subtypes have specific impacts on different stages of the reproductive process.
A systematic literature review of NHS evidence electronic databases and the Cochrane database identified all comparative and observational studies between 1980 and December 2018 in any language on adenomyosis and endometriosis with fertility, obstetric, and neonatal outcomes (23 search terms used). A total of 104 papers were selected for data extraction and meta-analysis, with use of Downs and Black standardized checklist to evaluate quality and bias.
We found that endometriosis consistently leads to reduced oocyte yield and a reduced fertilization rate (FR), in line with current evidence. Milder forms of endometriosis were most likely to affect the fertilization (FR OR 0.77, CI 0.63-0.93) and earlier implantation processes (implantation rate OR 0.76, CI 0.62-0.93). The more severe disease by American Society for Reproductive Medicine staging (ASRM III and IV) influenced all stages of reproduction. Ovarian endometriosis negatively affects the oocyte yield (MD -1.22, CI -1.96, -0.49) and number of mature oocytes (MD -2.24, CI -3.4, -1.09). We found an increased risk of miscarriage in both adenomyosis and endometriosis (OR 3.40, CI 1.41-8.65 and OR 1.30, CI 1.25-1.35, respectively), and endometriosis can be associated with a range of obstetric and fetal complications including preterm delivery (OR 1.38, CI 1.01-1.89), caesarean section delivery (OR 1.98 CI 1.64-2.38), and neonatal unit admission following delivery (OR 1.29, CI 1.07-1.55).
Adenomyosis and the subtypes of endometriosis may have specific complication profiles though further evidence is needed to be able to draw conclusions. Several known pregnancy complications are likely to be associated with these conditions. The complications are possibly caused by dysfunctional uterine changes leading to implantation and placentation issues and therefore could potentially have far-reaching consequences as suggested by Barker's hypothesis. Our findings would suggest that women with these conditions should ideally receive pre-natal counselling and should be considered higher risk in pregnancy and at delivery, until evidence to the contrary is available. In order to expand our knowledge of these conditions and better advise on future management of these patients in reproductive and maternal medicine, a more unified approach to studying fertility and reproductive outcomes with longer term follow-up of the offspring and attention to the subtype of disease is necessary.
子宫腺肌病和子宫内膜异位症对生殖的影响已得到广泛研究，但这些影响的程度仍难以捉摸。已经证明，特别是子宫内膜异位症会导致生育能力下降，但子宫内膜异位症和子宫腺肌病与胎盘功能不全等晚期妊娠并发症的关系越来越密切。在分子水平上，异位子宫内膜扰乱了子宫内膜的激素、细胞和免疫环境，对蜕膜化、胎盘形成和胚胎发育编程产生负面影响。目前尚不清楚这些早期异常生殖发育是否以及如何与子宫内膜异位症和子宫腺肌病的妊娠结局相关。
本系统评价和荟萃分析的目的是：（i）通过辅助生殖和自然受孕，研究子宫腺肌病和子宫内膜异位症对妇女生育、产科和新生儿结局的影响；（ii）确定子宫内膜异位症疾病亚型是否对生殖过程的不同阶段有特定的影响。
对 NHS 证据电子数据库和 Cochrane 数据库进行系统文献检索，检索了 1980 年至 2018 年 12 月期间所有关于子宫腺肌病和子宫内膜异位症与生育、产科和新生儿结局的比较和观察性研究（使用了 23 个检索词）。共选择了 104 篇论文进行数据提取和荟萃分析，使用 Downs 和 Black 标准化清单评估质量和偏倚。
我们发现，子宫内膜异位症确实会导致卵子产量减少和受精率（FR）降低，这与目前的证据一致。较轻形式的子宫内膜异位症最有可能影响受精（FR OR 0.77，CI 0.63-0.93）和早期着床过程（着床率 OR 0.76，CI 0.62-0.93）。美国生殖医学学会分期（ASRM III 和 IV）更严重的疾病影响了生殖的所有阶段。卵巢子宫内膜异位症会对卵子产量（MD -1.22，CI -1.96，-0.49）和成熟卵子数量（MD -2.24，CI -3.4，-1.09）产生负面影响。我们发现子宫腺肌病和子宫内膜异位症都有较高的流产风险（OR 3.40，CI 1.41-8.65 和 OR 1.30，CI 1.25-1.35），子宫内膜异位症可能与一系列产科和胎儿并发症有关，包括早产（OR 1.38，CI 1.01-1.89）、剖宫产分娩（OR 1.98 CI 1.64-2.38）和新生儿分娩后入住新生儿病房（OR 1.29，CI 1.07-1.55）。
子宫腺肌病和子宫内膜异位症的亚型可能有特定的并发症特征，但需要进一步的证据才能得出结论。一些已知的妊娠并发症可能与这些情况有关。这些并发症可能是由功能性子宫变化引起的，导致着床和胎盘问题，因此，正如 Barker 假说所暗示的那样，它们可能会产生深远的影响。我们的研究结果表明，患有这些疾病的妇女在怀孕和分娩期间应接受产前咨询，并应被视为高风险，直到有相反的证据。为了扩大我们对这些疾病的了解，并在生殖和母胎医学方面更好地为这些患者的未来管理提供建议，有必要对生育和生殖结局进行更统一的研究，并对疾病的亚型进行更长期的随访，同时关注疾病的亚型，并关注疾病的亚型。
