IVI-RMA Global Research Alliance, IVI Foundation, Instituto de Investigación Sanitaria La Fe (IIS La Fe), Av. Fernando Abril Martorell 106, Torre A, Planta 1ª, Valencia, 46026, Spain.
IVI-RMA Rome, Rome, 00197, Italy.
Reprod Biol Endocrinol. 2024 Nov 30;22(1):152. doi: 10.1186/s12958-024-01323-6.
The decline in women's fertility becomes clinically relevant between 35-40 years old, when there is insufficient ovarian activity, and it becomes more difficult to achieve pregnancy naturally and through artificial reproductive technologies. A competent endometrium is required for establishing and maintaining a pregnancy to term, however, experts in the field underestimate the contribution of endometrial age and its impact on reproductive outcomes remains unclear.
A systematic search of full-text articles available in PubMed was conducted to retrieve relevant studies published until March 2023. Search terms included: endometrium, uterus, age, aging, pregnancy, and oocyte donation. Terms related to reproductive pathologies were excluded. Eligibility criteria included original, rigorous, and accessible peer-reviewed work, published in English on the effect of age on the uterus and endometrium.
From 11,354 records identified, 142 studies were included for systematic review, and 59 were eligible for meta-analysis of endometrial thickness (n = 7), pregnancy rate (n = 22), implantation rate (n = 10), live birth rate (n = 10) and pregnancy loss rate (n = 11). Studies for the meta-analysis of reproductive outcomes only included transfers of embryos from ovum donation (ovum donors < 36 years old). Age shrinks the uterus; depletes endometrial blood supply through narrow uterine veins and a progressive loss of uterine spiral arteries; disrupts endometrial architecture and cellular composition; alters hormone production, shortening menstrual cycle length and impeding endometrial progression to the secretory stage; and dysregulates key endometrial functions such as adhesion, proliferation, apoptosis, and receptivity, among others. Women over 35-40 years old had significantly thinner endometrium (MD 0.52 mm). Advanced maternal age is associated with lower odds of achieving implantation (27%) and clinical pregnancy (20%), or higher odds of experiencing pregnancy loss (44%).
Due to the effect of age on endometrium reported in this review, managing patients with advanced maternal age may require considering the endometrial factor as a potential tissue to treat with anti-aging strategies. This review provides researchers and clinicians with an updated and in-depth summary of this topic, encouraging the development of new tailored anti-aging and preventive strategies for precision medicine in endometrial factor in infertility.
PROSPERO 2023 (CRD42023416947).
女性生育能力的下降在 35-40 岁之间变得具有临床意义，此时卵巢活动不足，自然怀孕和通过人工生殖技术怀孕变得更加困难。一个有能力的子宫内膜是建立和维持足月妊娠所必需的，然而，该领域的专家低估了子宫内膜年龄的贡献，其对生殖结局的影响仍不清楚。
对 PubMed 全文文章进行了系统检索，检索截至 2023 年 3 月发表的相关研究。检索词包括：子宫内膜、子宫、年龄、衰老、妊娠和卵母细胞捐赠。排除与生殖病理相关的术语。纳入标准包括原创、严格和可获取的同行评议工作，以英文发表，内容为年龄对子宫和子宫内膜的影响。
从 11354 条记录中，有 142 项研究被纳入系统综述，59 项研究符合纳入标准，可进行子宫内膜厚度（n=7）、妊娠率（n=22）、着床率（n=10）、活产率（n=10）和流产率（n=11）的荟萃分析。仅纳入了卵母细胞捐赠（卵母细胞捐赠者<36 岁）的胚胎移植研究进行生殖结局的荟萃分析。年龄会使子宫缩小；通过狭窄的子宫静脉和逐渐丧失子宫螺旋动脉使子宫内膜血供减少；破坏子宫内膜结构和细胞组成；改变激素产生，缩短月经周期长度，阻碍子宫内膜向分泌期进展；以及扰乱关键的子宫内膜功能，如粘连、增殖、凋亡和容受性等。35-40 岁以上的女性子宫内膜明显变薄（MD 0.52mm）。高龄产妇的着床率（27%）和临床妊娠率（20%）较低，流产率（44%）较高。
由于本综述中报道的年龄对子宫内膜的影响，对高龄产妇的管理可能需要考虑将子宫内膜因素作为一种潜在的治疗组织，采用抗衰老策略进行治疗。本综述为研究人员和临床医生提供了该主题的最新和深入总结，鼓励为子宫内膜因子不孕症开发新的个体化抗衰老和预防策略，以实现精准医学。
PROSPERO 2023（CRD42023416947）。
