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生殖年龄较大女性的卵巢储备生物标志物与不孕症之间的关联

Association Between Biomarkers of Ovarian Reserve and Infertility Among Older Women of Reproductive Age.

作者信息

Steiner Anne Z, Pritchard David, Stanczyk Frank Z, Kesner James S, Meadows Juliana W, Herring Amy H, Baird Donna D

机构信息

Department of Obstetrics and Gynecology, University of North Carolina, Chapel Hill.

Department of Biostatistics, University of North Carolina, Chapel Hill.

出版信息

JAMA. 2017 Oct 10;318(14):1367-1376. doi: 10.1001/jama.2017.14588.

Abstract

IMPORTANCE

Despite lack of evidence of their utility, biomarkers of ovarian reserve are being promoted as potential markers of reproductive potential.

OBJECTIVE

To determine the associations between biomarkers of ovarian reserve and reproductive potential among women of late reproductive age.

DESIGN, SETTING, AND PARTICIPANTS: Prospective time-to-pregnancy cohort study (2008 to date of last follow-up in March 2016) of women (N = 981) aged 30 to 44 years without a history of infertility who had been trying to conceive for 3 months or less, recruited from the community in the Raleigh-Durham, North Carolina, area.

EXPOSURES

Early-follicular-phase serum level of antimüllerian hormone (AMH), follicle-stimulating hormone (FSH), and inhibin B and urinary level of FSH.

MAIN OUTCOMES AND MEASURES

The primary outcomes were the cumulative probability of conception by 6 and 12 cycles of attempt and relative fecundability (probability of conception in a given menstrual cycle). Conception was defined as a positive pregnancy test result.

RESULTS

A total of 750 women (mean age, 33.3 [SD, 3.2] years; 77% white; 36% overweight or obese) provided a blood and urine sample and were included in the analysis. After adjusting for age, body mass index, race, current smoking status, and recent hormonal contraceptive use, women with low AMH values (<0.7 ng/mL [n = 84]) did not have a significantly different predicted probability of conceiving by 6 cycles of attempt (65%; 95% CI, 50%-75%) compared with women (n = 579) with normal values (62%; 95% CI, 57%-66%) or by 12 cycles of attempt (84% [95% CI, 70%-91%] vs 75% [95% CI, 70%-79%], respectively). Women with high serum FSH values (>10 mIU/mL [n = 83]) did not have a significantly different predicted probability of conceiving after 6 cycles of attempt (63%; 95% CI, 50%-73%) compared with women (n = 654) with normal values (62%; 95% CI, 57%-66%) or after 12 cycles of attempt (82% [95% CI, 70%-89%] vs 75% [95% CI, 70%-78%], respectively). Women with high urinary FSH values (>11.5 mIU/mg creatinine [n = 69]) did not have a significantly different predicted probability of conceiving after 6 cycles of attempt (61%; 95% CI, 46%-74%) compared with women (n = 660) with normal values (62%; 95% CI, 58%-66%) or after 12 cycles of attempt (70% [95% CI, 54%-80%] vs 76% [95% CI, 72%-80%], respectively). Inhibin B levels (n = 737) were not associated with the probability of conceiving in a given cycle (hazard ratio per 1-pg/mL increase, 0.999; 95% CI, 0.997-1.001).

CONCLUSIONS AND RELEVANCE

Among women aged 30 to 44 years without a history of infertility who had been trying to conceive for 3 months or less, biomarkers indicating diminished ovarian reserve compared with normal ovarian reserve were not associated with reduced fertility. These findings do not support the use of urinary or blood follicle-stimulating hormone tests or antimüllerian hormone levels to assess natural fertility for women with these characteristics.

摘要

重要性

尽管缺乏卵巢储备生物标志物效用的证据,但这些标志物仍被作为生殖潜能的潜在指标加以推广。

目的

确定晚育年龄女性的卵巢储备生物标志物与生殖潜能之间的关联。

设计、地点和参与者:对年龄在30至44岁、无不孕史且尝试受孕3个月或更短时间的女性进行前瞻性受孕时间队列研究(2008年至2016年3月最后一次随访日期),这些女性是从北卡罗来纳州罗利 - 达勒姆地区的社区招募的(N = 981)。

暴露因素

卵泡早期血清抗苗勒管激素(AMH)、促卵泡生成素(FSH)和抑制素B水平以及尿FSH水平。

主要结局和测量指标

主要结局是尝试6个周期和12个周期时受孕的累积概率以及相对生育力(给定月经周期受孕的概率)。受孕定义为妊娠试验结果呈阳性。

结果

共有750名女性(平均年龄33.3[标准差3.2]岁;白人占77%;超重或肥胖者占36%)提供了血液和尿液样本并纳入分析。在调整年龄、体重指数、种族、当前吸烟状况和近期激素避孕药使用情况后,AMH值低(<0.7 ng/mL[n = 84])的女性与AMH值正常的女性(n = 579)相比,尝试6个周期时预测的受孕概率(65%;95%CI,50% - 75%)无显著差异,尝试12个周期时的受孕概率分别为84%(95%CI,70% - 91%)和75%(95%CI,70% - 79%)。血清FSH值高(>10 mIU/mL[n = 83])的女性与FSH值正常的女性(n = 654)相比,尝试6个周期时预测的受孕概率(63%;95%CI,50% - 73%)无显著差异,尝试12个周期时的受孕概率分别为82%(95%CI,70% - 89%)和75%(95%CI,70% - 78%)。尿FSH值高(>11.5 mIU/mg肌酐[n = 69])的女性与尿FSH值正常的女性(n = 660)相比,尝试6个周期时预测的受孕概率(61%;95%CI,46% - 74%)无显著差异,尝试12个周期时的受孕概率分别为70%(95%CI,54% - 80%)和76%(95%CI,72% - 80%)。抑制素B水平(n = 737)与给定周期受孕概率无关(每增加1 pg/mL的风险比为0.999;95%CI,0.997 - 1.001)。

结论与相关性

在年龄30至44岁、无不孕史且尝试受孕3个月或更短时间的女性中,与正常卵巢储备相比,表明卵巢储备减少的生物标志物与生育力降低无关。这些发现不支持使用尿或血促卵泡生成素检测或抗苗勒管激素水平来评估具有这些特征女性的自然生育力。

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