PCOS in Pregnant Women With Diabetes Linked to High Insulin Requirements, Weight Gain

A study comparing pregnancy outcomes in women with type 2 diabetes (T2D) and polycystic ovary syndrome (PCOS) and those without PCOS found no significant differences in neonatal outcomes. However, PCOS in pregnant women with T2D was linked to high insulin requirements and excess weight gain, with metformin treatment in this patient group associated with an increase in extremely large-for-gestational-age infants and an increase in worsened pre-existing maternal hypertension.

“We hypothesized that the additional presence of PCOS would be associated with an increase in adverse maternal and fetal outcomes, in the setting of T2D in pregnancy,” wrote the researchers of the study. “Secondly, we hypothesized that given the high insulin resistance present in women with PCOS, metformin treatment may be less effective in preventing these adverse maternal and fetal outcomes in individuals with PCOS as compared to those without PCOS in the setting of T2D in pregnancy.”

This retrospective cohort study is published in Diabetes Metabolism Research and Review.

Diabetes

The study analyzed data from a cohort of women with T2D in pregnancy who were treated with metformin. In this study, 502 women were randomized to receive either metformin or a placebo in addition to their usual insulin therapy. Women were eligible for enrollment if they were between ages 18 to 45 years, were diagnosed with T2D before pregnancy or before 20 weeks’ gestation, were receiving insulin, had a live fetus confirmed by ultrasound, and were between 6 and 22 weeks plus 6 days’ gestation.

Furthermore, the diagnosis of PCOS was obtained through a self-reported questionnaire on baseline characteristics.

Using this data, the researchers were able to compare differences in maternal and neonatal outcomes in patients with and without PCOS using linear and logistic regression to adjust for potential confounders. Furthermore, the researchers were able to examine any relative differences in the effect of metformin on pregnancy outcomes among these patients.

The study showed that PCOS was significantly associated with higher excess gestational weight gain (unadjusted 12 vs 11.4 kg, adjusted mean [SD] difference of 2.1 kg [0.3, 3.9]; P = .021) and higher total insulin dose at 34 to 36 weeks (unadjusted 172 vs 124 units per day, unadjusted mean [SD] difference of 44 units [15, 73]; P = .004). However, no differences were seen in neonatal outcomes between patients with and without PCOS.

Furthermore, metformin treatment in the PCOS subgroup was associated with an increase in extremely large-for-gestational-age infants (28.6% vs 14%; P = .008) for interaction and an increase in worsened pre-existing maternal hypertension (16.7% vs 4.5%; P = .046) for interaction.

The researchers acknowledged some limitations to the study, including the diagnosis of PCOS was self-reported, the dataset did not include information on the use of assisted reproductive technology, and not being able to detect rare adverse neonatal outcomes.

Despite these limitations, the researchers believe the study shows how PCOS in women with T2D in pregnancy is associated with adverse outcomes of high insulin requirement and excess weight gain.

“Reassuringly, the presence of PCOS was not associated with an increase in adverse neonatal outcomes,” wrote the researchers of the study. “Furthermore, clinicians should be aware that metformin may be less protective against maternal weight gain and macrosomia than anticipated in this population.”

Reference

Atkins P, Tomlinson G, Feig DS; MiTy Collaborative Group. The presence of polycystic ovary syndrome increases the risk of maternal but not neonatal complications in women with type 2 diabetes in pregnancy. Published online September 7, 2023. Diabetes Metab Res Rev. 2023;e3713. doi:10.1002/dmrr.3713