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作者

Wanbing Feng Yujia Ren Jiayi Zhou Hanbing Zhu Han Zhao Yingying Qin Jing Li Mingdi Xia Lihong Xu Mei Li Huidan Wang Linlin Cui Zi-Jiang Chen

作者单位

⁵Shandong Provincial Clinical Research Center for Reproductive Health , Jinan, Shandong China ⁶Shandong Key Laboratory of Reproductive Research and Birth Defect Prevention , Jinan, Shandong China ¹¹Department of Reproductive Medicine, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai, China ¹⁰Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics , Shanghai, China ²National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University , Jinan, Shandong China ³Key Laboratory of Reproductive Endocrinology (Shandong University), Ministry of Education , Jinan, Shandong China ⁸Department of Gynaecology and Obstetrics, Shandong Provincial Hospital Affiliated to Shandong First Medical University , Jinan, Shandong China ⁹The Second Hospital, State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University , China ⁷Research Unit of Gametogenesis and Health of ART-Offspring, Chinese Academy of Medical Sciences (No.2021RU001) , Jinan, Shandong China ⁴Shandong Technology Innovation Center for Reproductive Health , Jinan, Shandong China ¹State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University , China

刊名

Human Reproduction Open

关键词

Poor ovarian response offspring health ovarian reserve anti-Müllerian hormone reproductive endocrine POSEIDON criteria

摘要

STUDY QUESTION Do offspring born to mothers with poor ovarian response have alterations in their reproductive endocrine profile at 2 to 6 years of age compared to those born to mothers with normal ovarian response? SUMMARY ANSWER Female offspring born to young mothers with expected POR were more likely to have low serum anti-Müllerian hormone levels in childhood. WHAT IS KNOWN ALREADY POR affects 32-43% of women in infertility clinics. Genetic susceptibility and potentially adverse intra...更多

STUDY QUESTION Do offspring born to mothers with poor ovarian response have alterations in their reproductive endocrine profile at 2 to 6 years of age compared to those born to mothers with normal ovarian response? SUMMARY ANSWER Female offspring born to young mothers with expected POR were more likely to have low serum anti-Müllerian hormone levels in childhood. WHAT IS KNOWN ALREADY POR affects 32-43% of women in infertility clinics. Genetic susceptibility and potentially adverse intrauterine environments pose threats to the next generation. However, there is currently no direct evidence of intergenerational reproductive effects associated with POR. STUDY DESIGN, SIZE, DURATION We conducted a prospective cohort study to investigate the intergenerational effects of maternal POR on reproductive endocrine health of offspring. Data were obtained from “Assisted Reproductive Technology-born KIDs ”, a birth cohort established in 2013 at a tertiary care centre in China. A total of 3,103 offspring, aged 2 to 6, born between 2013 and 2019, were recruited and included in our study until 2021. The exposed offspring conceived by ART were classified into four groups based on their mothers' categorization using the Patient-Oriented Strategies Encompassing IndividualizeD Oocyte Number criteria. The unexposed offspring were born to mothers with normal ovarian response after ART. PARTICIPANTS/MATERIALS, SETTING, METHODS Offspring conceived by ART provided blood samples at 2 to 6 years for the assessment of reproductive endocrine parameters. Mean difference and 95% CI were obtained based on a linear mixed model. The adjusted model accounted for paternal age, maternal age, offspring age, paternal smoking, use of intracytoplasmic sperm injection, and frozen embryo transfer. MAIN RESULTS AND THE ROLE OF CHANCE Female offspring born to young mothers with expected POR had lower AMH and PRL levels in childhood compared to controls . Female offspring born to older mothers with expected POR showed a decreasing trend in AMH levels, though this difference was not statistically significant compared to controls [AMD = -0.60, 95% CI = -1.31, -0.12]. Female offspring born to young mothers with unexpected POR had lower DHEA-S levels than controls [AMD = -1.38, 95% CI = -2.58, -0.17]. In contrast, male offspring born to POR mothers showed similar reproductive endocrine profiles as controls. LIMITATIONS, REASONS FOR CAUTION The offspring were aged 2-6 years, limiting the ability to assess comprehensive reproductive phenotypic changes. Longer follow-up studies are necessary. WIDER IMPLICATIONS OF THE FINDINGS The potential effects of maternal POR on reproductive endocrine profiles of offspring may be primarily linked to ovarian reserve. Genetic susceptibility, hypoandrogenism and other intrauterine environmental factors may be probable explanations for reduction in AMH levels observed in female offspring born to young mothers with expected POR. STUDY FUNDING/COMPETING INTEREST This study was supported by the National Key Research and Development Program of China , CAMS Innovation Fund for Medical Sciences , Shandong Provincial Natural Science Foundation , the Fundamental Research Funds of Shandong University , the National Special Support Program for High-level Talents, Health Science and Technology Innovation Team Construction Project of Shandong Province, and Taishan Scholars Program for Young Experts of Shandong Province . The authors declare that they have no competing interests. TRIAL REGISTRATION NUMBER N/A. WHAT DOES THIS MEAN FOR PATIENTS? Poor Ovarian Response is a condition that affects nearly half of women undergoing fertility treatment and is one of the main obstacles to having successful pregnancies. POR means that a woman’s ovaries don’t respond well to fertility treatments, producing fewer eggs. Studies have suggested that both genetic factors and environmental influences could affect the reproductive health of future generations, regardless of whether they are sons or daughters. This raises concerns about the potential effect of a mother's POR condition on the fertility of her children. This study, conducted in China, focused on mother-child pairs. Over several years, it was found that daughters born to young mothers with low ovarian reserve were likely to have lower levels of a hormone called anti-Müllerian hormone , than daughters of women not suffering from POR. This suggests that a mother’s fertility could affect her daughter’s future fertility, possibly leading to challenges in having children later in life. No significant effects were found in male children. For these patients , these findings suggest that fertility problems might affect future generations, particularly daughters. Further studies are needed to track how their daughters' fertility may change as they grow older.收起

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