Growth and Reproductive Health of Children Born to Mothers With Premature Ovarian Insufficiency

Background: Premature ovarian insufficiency (POI) caused severe disruption to the female reproductive endocrine system. Previous studies suggested that endocrine changes during pregnancy were associated with adverse effects on the development and reproductive health of the offspring in their postnatal life. We aimed to investigate the growth and reproductive health of offspring born to mothers with POI. Methods: This prospective, observational cohort study was done at a reproductive center between January 2011 and March 2019. Using generalized estimating equation models, we assessed growth and reproductive health among children under 3 years of age: one group was born to mothers with POI (n = 69), and the comparison group was born to mothers without POI (n = 134). We further stratified the POI offspring into two groups according to oocyte origin, namely, autologous and donor oocyte group. Findings: We provided evidence of adverse reproductive health effects in the offspring of mothers with POI. Children born to mothers with POI were more prone to changes in hormonal profiles that are similar to those seen in their mothers. Offspring born to mothers with POI who used autologous oocytes to conceive had significant differences in their hormonal profiles, including lower dehydroepiandrosterone sulfate (DHEA-S; β -33·37 [95% CI -46·58, -20·16]) in boys and higher follicle stimulating hormone (FSH; β 4·79 [95% CI 0·58, 9·01]) and lower anti-Mullerian hormone (AMH; β -6·66 [95% CI -10·11, -3·2]) in girls, compared with children born to mothers without POI. Sons of mothers with POI who used donor oocytes had smaller penises and testicles than those born to mothers without POI (penile length, β -0·54 [95% CI -0·97, -0·11]; mean testicular volume, β -0·22 [95% CI -0·45, -0·01]). Interpretation: Adverse reproductive health risks in the offspring of women with POI should be taken seriously. Funding Information: The National Key Research and Development Program of China (2018YFC1004301). Declaration of Interests: All authors declare no competing interests. Ethics Approval Statement: The study was approved by the appropriate institutional review boards. Written informed consents were obtained from all parents.