Polycystic ovarian syndrome is characterized by elevated androgens and is a well-known
risk factor for the occurrence of gestational diabetes mellitus. Androgens (particularly
dehydroepiandrosterone-sulfate) are crucial for the development and characteristics
of the male reproductive tract during fetal life, and fetal dehydroepiandrosterone-sulfate
enters the placenta where it is metabolized and functions as an estrogen substrate.
Given this unique sex-specific relationship in androgens and the association of serum
dehydroepiandrosterone-sulfate with insulin resistance, we hypothesized that metabolic
comorbidities in pregnancy might differ by fetal sex in gravidae with polycystic ovarian
syndrome, notably those with infertility.
Our objective was to employ a large population-based database to explore if fetal
sex was significantly associated with gestational diabetes mellitus in infertile gravidae
with polycystic ovarian syndrome, after controlling for confounders.
This study was designed to evaluate the risk of occurrence and rates of gestational
diabetes mellitus among infertile gravidae with a history of polycystic ovarian syndrome.
We used a 2-hospital, single academic institution database comprised of over 30,000
subjects enrolled from September 2011 to June 2021 to identify all gravidae with diagnoses
of infertility and polycystic ovarian syndrome at time of delivery and compare them
with gravidae that lacked these co-morbidities. Data on covariates, including but
not limited to maternal age, body mass index, fetal sex, race, ethnicity, presence
or absence of hypertensive disease, and presence or absence of gestational diabetes
were identified. Unadjusted and adjusted odds rations were calculated.
We found a statistically significant association between fetal female sex and the
development of gestational diabetes mellitus in gravidae with polycystic ovarian syndrome
[odds ratio for female versus male 2.13 (95% confidence interval, 1.06-4.32), p =0.03].
After adjusting for potential confounders identified in our univariate analyses, there
continued to be a statistically significant association between female fetuses and
the development of gestational diabetes mellitus [adjusted odds ratio for female versus
male 2.10 (95% confidence interval 1.04-4.41), p =0.04]. In contrast, there was no
significant association between fetal sex and the development of gestational diabetes
mellitus in our similar analysis of gravidae without infertility and polycystic ovarian
While gestational diabetes mellitus is of multifactorial origin, we found that fetal
female sex is associated with gestational diabetes mellitus in infertile gravidae
with polycystic ovarian syndrome but not their comparative controls. Further research
on the molecular mechanisms driving the association between female fetuses and development
of gestational diabetes mellitus in the context of maternal polycystic ovarian syndrome
Publication stageIn Press Accepted Manuscript
Disclosure statement: The authors report no conflict of interest.
Financial Support: Components of this work were supported by the National Institute of Health including NIDDK (1R01 DK128187-01A1, 6R01DK089201 both to KA) and NICHD Women's Reproductive Health Research (WRHR) (K12 HD103087) of which Dr. Sassin is a scholar.
The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
This work was presented as abstract 1213 at the 42nd Annual Pregnancy Meeting, Society for Maternal-Fetal Medicine, Orlando, Florida -Virtual, January 31-February 5, 2022.
Condensation sentence: Infertile gravidae with polycystic ovarian syndrome were 2x more likely to develop gestational diabetes mellitus when carrying a female fetus compared to a male fetus.
AJOG-MFM at a Glance
A. Why was this study conducted?
This retrospective cohort study was conducted to explore the significance of the relationship between fetal sex and occurrence of GDM in gravidae with PCOS and a history of infertility.
B. What are the key findings?
After adjusting for potential confounders, gravidae with polycystic ovarian syndrome and infertility were at a significantly higher risk for the occurrence of gestational diabetes mellitus when carrying a female fetus compared to carrying a male fetus.
C. What does this study add to what is already known?
Recent studies suggest that there is the potential for maternal-fetal interactions in the occurrence of dysregulated glucose metabolism (such as gestational diabetes), presumptively due to androgen differences between male and female fetuses. While the precise mechanism is unknown and our study cannot directly address, our findings suggest that future lines of investigation may benefit from considering sex-specific alterations to the placental function and feto-hormonal milieu.
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