Elevated Anti-Müllerian Hormone Levels in Newborns of Women with Polycystic Ovary Syndrome: a Systematic Review and Meta-analysis Based on Observational Studies

Abstract

We performed this updated systematic review and meta-analysis to evaluate anti-Müllerian hormone levels (AMH) in newborns of mothers with polycystic ovary syndrome (PCOS) compared with healthy controls. A search of the literature was conducted in the PubMed, MEDLINE, EMBASE, Cochrane Library, CBM, CNKI, WANFANG, and VIP for articles to assess AMH levels in offspring of PCOS and non-PCOS mothers irrespective of language. These databases were searched from their inception to December 7, 2020. The quality of studies was assessed using the Newcastle-Ottawa Scale (NOS) scoring system. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were adopted to calculate the overall estimates with random-effects models. A total of 6 studies with 846 participants were included. The pooled analysis found an increased AMH level in the umbilical cord blood in newborns of PCOS mothers (SMD =0.62, 95% CI [0.28, 0.95]). Subgroup analyses revealed an elevation of AMH concentrations in female neonates, neonates born to American and Asian PCOS mothers. In addition, higher AMH levels were also found in studies diagnosed by the National Institute of Health (NIH) criteria, maternal clinical/biochemical hyperandrogenism, or maternal body mass index (BMI) >30 kg/m2. Meta-regression analysis suggested that diagnostic criterion contributed mostly to the high heterogeneity. We demonstrated that AMH levels in neonates born to PCOS mothers were essentially higher, which indicates that AMH may act as an enigmatic role in the pathogenesis of PCOS which inhibits folliculogenesis in the fetal stage.

Endocrine and metabolic interactions in healthy pregnancies and hyperinsulinemic pregnancies affected by polycystic ovary syndrome, diabetes and obesity

“…Anderson et al. ( 73 ) reported decreased E2 levels in female PCOS cord blood samples compared with controls, and lower E2 levels have been noted in cord blood compared to maternal levels ( 22 , 110 ). Few studies report on estrogens in relation with other reproductive and metabolic hormones.…”

“…On the other hand, no significant associations were observed between maternal AMH concentrations and AMH in female offspring (110), whereas AMH was higher in male fetuses, than in the mother (22). This suggests that AMH concentrations in umbilical cord blood might differ from that in maternal serum because there is no passage of AMH from fetus to mother (22,110). Instead, elevated AMH concentrations could be a result of placental passage from the mother and increased AMH production by the fetal compartment.…”

“…Lower E1 concentrations were found in cord blood from girls and women with PCOS compared with controls, but there were no differences in E2 and E3 in these studies (74, 88). Anderson et al (73) reported decreased E2 levels in female PCOS cord blood samples compared with controls, and lower E2 levels have been noted in cord blood compared to maternal levels (22,110). Few studies report on estrogens in relation with other reproductive and metabolic hormones.…”

“…Elevated levels of AMH potentially impact the developing fetus. Studies have found elevated serum AMH levels in the umbilical vein at time of delivery in newborns of women with PCOS compared with healthy controls ( 110 ). Importantly, higher levels of AMH were observed in neonates born from women with PCOS and maternal hyperandrogenism or maternal BMI higher than 30 kg/m 2 ( 110 ).…”

“…Studies have found elevated serum AMH levels in the umbilical vein at time of delivery in newborns of women with PCOS compared with healthy controls ( 110 ). Importantly, higher levels of AMH were observed in neonates born from women with PCOS and maternal hyperandrogenism or maternal BMI higher than 30 kg/m 2 ( 110 ). On the other hand, no significant associations were observed between maternal AMH concentrations and AMH in female offspring ( 110 ), whereas AMH was higher in male fetuses, than in the mother ( 22 ).…”