原发性卵巢功能不全（POI）妇女的子女数量与对照妇女在其生殖寿命期间相比如何？大约有14%较少的POI妇女会生育子女，但对于能够生育子女的人来说，中位数数量比同龄对照组少1个。POI妇女经常在寻求生育治疗时被发现，但是一些已经有子女的POI妇女在诊断后仍然有很低的怀孕机会。此外，POI具有遗传性，但不确定与POI妇女的亲属在家族规模方面是否比对照组的亲属较小。本研究是一项回顾性病例对照研究，研究对象为1995年至2021年间被诊断为POI的妇女（n = 393）和年龄相配对的对照组（n = 393）。POI妇女是通过电子病历中的ICD9和10代码（1995-2021年）从犹他州两个主要医疗系统中识别出来的，并进行准确性审核。病例与犹他人口数据库中的谱系信息互相关联。所有POI病例（n = 393）必须至少有三代祖先的谱系信息可用。确定了两组女性对照组：一组根据出生地（犹他州或其他地方）和5年出生队列进行匹配，另一组还根据生育状况（有子女）进行匹配。出生证明（可从1915年至2020年）用于确定研究对象、对照组和其亲属的子女数量和母亲年龄。比较使用Mann-Whitney U检验。对POI妇女和对照组至少生育一子女的妇女以及达到45岁的妇女进行子集分析。在393名POI妇女和对照组中，有211名POI妇女（53.7%）和266名对照组妇女（67.7%）至少有一个子女。与对照组相比，POI妇女生育的子女较少（中位数（四分位范围）为1（0-2）与2（0-3）；P = 3.33 × 10-6）。POI和原发性闭经或在诊断前25岁的妇女没有生育子女。在分析至少有一个子女的妇女时，POI妇女与对照组相比生育的子女较少（2（1-3）与2（2-4）；P = 0.017），并且在分析达到45岁的妇女时（2（1-3）与3（2-4）；P = 0.0073）。在已知供者卵子妊娠除外的情况下，7.1％的POI妇女在诊断后生育子女。与POI妇女相关的亲属的子女数量没有差异，包括那些有家族性POI的亲属。数据的限制在于无法确定妇女在整个生育寿命中是尝试怀孕还是使用避孕措施。基于对使用供者卵子的不完整数据，诊断POI后自然生育的情况可能被稍微高估。结果可能不适用于晚育或出生率较低的国家或地区。大约一半的POI妇女将在诊断前生育子女。尽管POI妇女的子女较对照组少，但每位妇女子女的差异为1个。数据表明，对于25岁或更晚被诊断为POI且有继发闭经的妇女，在POI诊断之前的能力可能不会受到损害。然而，在诊断后的怀孕率较低，我们确认了<10％的出生率。在以群体为单位进行检查时，较少数量的子女并未扩展到亲属，这表明通过家族史来预测POI可能很困难。本文的研究工作受到R56HD090159和R01HD099487（C.K.W.）的支持。我们还要感谢美国国家癌症研究所的拨款P30 CA2014部分支持犹他人口数据库。内容完全由作者负责，并不一定代表美国国立卫生研究院的官方观点。作者声明没有利益冲突。无。©2023作者（有）出版，由牛津大学出版社代表欧洲人类生殖与胚胎学学会出版。版权所有，禁止复制。欲获取权限，请通过电子邮件联系：journals.permissions@oup.com。

How does the number of children in women with primary ovarian insufficiency (POI) compare to the number for control women across their reproductive lifespans?Approximately 14% fewer women with POI will have children, but for those able to have children the median number is 1 less than for age-matched controls.Women with POI are often identified when presenting for fertility treatment, but some women with POI already have children and there remains a low chance for pregnancy after the diagnosis. Further, POI is heritable, but it is not known whether relatives of women with POI have a smaller family size than relatives of controls.The study was a retrospective case-control study of women with POI diagnosed from 1995 to 2021 (n = 393) and age-matched controls (n = 393).Women with POI were identified using ICD9 and 10 codes in electronic medical records (1995-2021) from two major healthcare systems in Utah and reviewed for accuracy. Cases were linked to genealogy information in the Utah Population Database. All POI cases (n = 393) were required to have genealogy information available for at least three generations of ancestors. Two sets of female controls were identified: one matched for birthplace (Utah or elsewhere) and 5-year birth cohort, and a second also matched for fertility status (children present). The number of children born and maternal age at each birth were ascertained by birth certificates (available from 1915 to 2020) for probands, controls, and their relatives. The Mann-Whitney U test was used for comparisons. A subset analysis was performed on women with POI and controls who delivered at least one child and on women who reached 45 years to capture reproductive lifespan.Of the 393 women with POI and controls, 211 women with POI (53.7%), and 266 controls (67.7%) had at least one child. There were fewer children born to women with POI versus controls (median (interquartile range) 1 (0-2) versus 2 (0-3); P = 3.33 × 10-6). There were no children born to women with POI and primary amenorrhea or those <25 years old before their diagnosis. When analyzing women with at least one child, women with POI had fewer children compared to controls overall (2 (1-3) versus 2 (2-4); P = 0.017) and when analyzing women who reached 45 years old (2 (1-3) versus 3 (2-4); P = 0.0073). Excluding known donor oocyte pregnancies, 7.1% of women with POI had children born after their diagnosis. There were no differences in the number of children born to relatives of women with POI, including those with familial POI.The data are limited based on inability to determine whether women were trying for pregnancy throughout their reproductive lifespan or were using contraception. Unassisted births after the diagnosis of POI may be slightly over-estimated based on incomplete data regarding use of donor oocytes. The results may not be generalizable to countries or states with late first births or lower birth rates.Approximately half of women with POI will bear children before diagnosis. Although women with POI had fewer children than age matched controls, the difference in number of children is one child per woman. The data suggest that fertility may not be compromised leading up to the diagnosis of POI for women diagnosed at 25 years or later and with secondary amenorrhea. However, the rate of pregnancy after the diagnosis is low and we confirm a birth rate of <10%. The smaller number of children did not extend to relatives when examined as a group, suggesting that it may be difficult to predict POI based on family history.The work in this publication was supported by R56HD090159 and R01HD099487 (C.K.W.). We also acknowledge partial support for the Utah Population Database through grant P30 CA2014 from the National Cancer Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors have no conflicts of interest.N/A.© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.