Comment on “Myo-inositol Supplementation to Prevent Pregnancy Complications in Polycystic Ovary Syndrome: A Randomized Clinical Trial”

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive-age women, and is associated with increased risk of pregnancy complications such as gestational diabetes, preeclampsia, and preterm birth. Insulin resistance, a central feature of PCOS, is thought to be one of the core mediators of these risks. Current preventive strategies, including lifestyle changes and metformin use, have not consistently improved outcomes. Myo-inositol, a naturally occurring sugar involved in insulin signaling, has been shown to improve insulin sensitivity and metabolic function in individuals with PCOS and is considered safe for use during pregnancy. Prior studies in other populations at risk for gestational diabetes suggest that myo-inositol supplementation may reduce adverse pregnancy outcomes, but adequately powered randomized trials in pregnant individuals with PCOS are lacking. This study evaluates whether myo-inositol supplementation reduces pregnancy complications in individuals with PCOS. This multicenter, randomized clinical trial enrolled pregnant individuals with polycystic ovary syndrome from 13 hospitals in the Netherlands between 2019 and 2023. Participants were eligible if they were at least 18 years old, had a singleton pregnancy between 8 and 16 weeks’ gestation, and had a prior diagnosis of PCOS based on Rotterdam criteria. Individuals were excluded if they had preexisting diabetes, kidney failure, or use of medications affecting glucose metabolism. Participants were randomized in a 1:1 ratio to receive either myo-inositol supplementation (4 g daily with folic acid) or placebo (folic acid only) from enrollment until delivery. The primary outcome was a composite of gestational diabetes, preeclampsia, or preterm birth before 37 weeks’ gestation, and secondary outcomes included individual maternal and neonatal complications, supplement adherence, and adverse effects. Analyses used intention-to-treat principles and were applied across predefined and exploratory subgroups. A total of 464 participants were enrolled, with 230 assigned to the myo-inositol group and 234 to the placebo. Primary outcome data were available for over 97% of participants in both groups. Baseline characteristics were similar, with a mean age of 31.5 years and a median pre-pregnancy BMI of 24.7. The primary composite outcome of gestational diabetes (RR: 1.07; 95% CI: 0.71-1.63, P =0.74), preeclampsia (RR: 0.46; 95% CI: 0.16-1.32, P =0.14), or preterm birth (RR: 0.82; 95% CI: 0.44 -1.51, P =0.53) occurred in 25.0% of the myo-inositol group and 26.8% of the placebo group, with no significant difference between groups (relative risk, 0.93 95% CI, 0.68-1.28; P = 0.67). Rates of cesarean delivery, maternal complications, and neonatal outcomes were also similar. Glycated hemoglobin levels remained stable throughout pregnancy in both groups. Planned cesarean delivery occurred less frequently in the myo-inositol group. Adherence and adverse effects did not differ significantly, and subgroup analyses showed no variation in treatment effect by BMI or hyperandrogenism status. The results indicate that myo-inositol supplementation during pregnancy in individuals with PCOS did not reduce the risk of gestational diabetes, preeclampsia, preterm birth, or other maternal and neonatal adverse outcomes compared with placebo. This stands in contrast with prior smaller trials of other high-risk populations, but is consistent with more recent systematic reviews. Strengths of the study include its large sample size, multicenter randomized double-blind design, while limitations were baseline differences in hyperandrogenism, low outcome event rates, and moderate adherence to supplementation. Overall, these findings do not support routine myo-inositol supplementation during pregnancy to prevent complications in individuals with PCOS. (Summarized from van der Wel AWT, Frank CMC, Bout-Rebel R, et al. Myo-inositol supplementation to prevent pregnancy complications in polycystic ovary syndrome. JAMA. 2025;334:1151-1159. doi: 10.1001/jama.2025.13668)