Laboratory of Development and Plasticity of the Neuroendocrine Brain, University of Lille, Inserm, CHU Lille, Lille Neuroscience and Cognition, UMR-S 1172, Lille, France.
Department of Reproductive Medicine and Fertility Preservation, AP-HP-Université Sorbonne Paris-Nord, Jean Verdier Hospital, Bondy, France.
Hum Reprod. 2023 May 2;38(5):938-950. doi: 10.1093/humrep/dead050.
What are the changes in serum concentration of total and cleaved anti-Muüllerian hormone (AMH) molecular forms and of androgens before and throughout pregnancy in women with and without polycystic ovary syndrome (PCOS) in a longitudinal follow-up investigation?
Serum levels of total and cleaved AMH are higher from preconception to the third trimester of pregnancy in women with PCOS as compared to controls, whereas testosterone and androstenedione levels are higher in women with PCOS than in control women before pregnancy and during the second and third trimester of pregnancy.
Cross-sectional or partial longitudinal studies have shown higher AMH and androgen levels in pregnant women with PCOS as compared with non-PCOS women. To date, no complete longitudinal dynamic monitoring of the circulating forms of AMH and androgens from pre-conception to the third trimester of pregnancy have compared women with and without PCOS.
STUDY DESIGN, SIZE, DURATION: This systematic prospective quarterly longitudinal monocentric study was a comparative follow-up of 30 women with PCOS and 29 controls before and during pregnancy from April 2019 to July 2022.
PARTICIPANTS/MATERIALS, SETTING, METHODS: Women aged 18-43 years with a pre-conception measurement of AMH were included during the first trimester of a singleton pregnancy. The PCOS group was defined according to the Rotterdam diagnostic criteria. The control group patients included in the study had normal ovarian reserves. Circulating total and cleaved AMH, and serum estradiol, LH, and androgen levels were measured during the first, second, and third trimester of pregnancy in all study participants.
Before pregnancy, patients with PCOS had higher levels of AMH than controls. The total and cleaved AMH forms were significantly higher in women with PCOS than controls from pre-conception to the third trimester of pregnancy (all P < 0.001). Androgens (total testosterone and androstenedione) were higher in women with PCOS than controls from mid-pregnancy onwards.
LIMITATIONS, REASONS FOR CAUTION: Our control population was a population of infertile women with no ovarian problems but most of them had undergone ART treatments to achieve pregnancy.
These results strengthen the hypothesis that gestational hyperandrogenism as well as exposure to elevated AMH levels in utero could be driving forces predisposing female progeny to develop PCOS.
STUDY FUNDING/COMPETING INTEREST(S): Funding was provided by INSERM, France (grant number U1172) and the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program, ERC-2016-CoG to P.G. grant agreement n° 725149/REPRODAMH. The authors have nothing to declare.
NCT03483792.
在一项纵向随访研究中，在患有和不患有多囊卵巢综合征（PCOS）的女性中，从受孕前到整个妊娠期间，血清总抗缪勒管激素（AMH）和裂解 AMH 分子形式以及雄激素的浓度变化如何？
与对照组相比，患有 PCOS 的女性从受孕前到妊娠第 3 期的血清总 AMH 和裂解 AMH 水平均较高，而在受孕前和妊娠第 2、3 期，PCOS 女性的睾酮和雄烯二酮水平高于对照组。
横断面或部分纵向研究表明，患有 PCOS 的孕妇的 AMH 和雄激素水平高于非 PCOS 女性。迄今为止，尚无关于 AMH 和雄激素循环形式从受孕前到妊娠第 3 期的完整纵向动态监测比较患有和不患有 PCOS 的女性。
研究设计、大小和持续时间：本系统前瞻性季度纵向单中心研究是对 2019 年 4 月至 2022 年 7 月期间患有 PCOS 的 30 名女性和 29 名对照者在妊娠前和妊娠期间的比较随访。
参与者/材料、设置和方法：在单胎妊娠的孕早期，纳入 AMH 预妊娠测量值为 18-43 岁的女性。根据鹿特丹诊断标准定义 PCOS 组。研究中纳入的对照组患者卵巢储备正常。所有研究参与者在妊娠第 1、2 和第 3 期均测量血清总 AMH 和裂解 AMH 及雌二醇、LH 和雄激素水平。
受孕前，PCOS 患者的 AMH 水平高于对照组。从受孕前到妊娠第 3 期，PCOS 组的总 AMH 和裂解 AMH 形式均明显高于对照组（均 P<0.001）。从妊娠中期开始，PCOS 患者的雄激素（总睾酮和雄烯二酮）水平高于对照组。
局限性、谨慎的原因：我们的对照组是一群没有卵巢问题的不孕妇女，但她们大多数人都接受了辅助生殖技术（ART）治疗以实现妊娠。
这些结果进一步证实了这样一种假说，即妊娠期高雄激素血症以及宫内暴露于升高的 AMH 水平可能是促使女性后代易患 PCOS 的驱动力。
研究资金/竞争利益：该研究由法国 INSERM（拨款号 U1172）和欧洲研究理事会（ERC）资助，ERC 根据欧盟地平线 2020 研究和创新计划，通过 ERC-2016-CoG 向 P.G. 提供资金，资助协议号为 725149/REPRODAMH。作者没有什么可申报的。
NCT03483792。
