Despite early hopes and smaller studies suggesting benefits, this large trial shows myo-inositol offers no protection against common pregnancy complications in women with PCOS.
Study: Myo-inositol Supplementation to Prevent Pregnancy Complications in Polycystic Ovary Syndrome. Image credit: Prostock-studio/Shutterstock.com
A recent study in JAMA assessed the efficacy of myo-inositol supplementation during pregnancy in terms of lowering the risk of a composite outcome of preeclampsia, gestational diabetes, and preterm birth in women with polycystic ovary syndrome (PCOS).
Pregnancy complications and Myo-inositol
In individuals with PCOS, about a quarter of pregnancies (25-27% in this trial) are complicated by preeclampsia, gestational diabetes, or preterm birth. Although lifestyle interventions and metformin are commonly prescribed to mitigate these risks, these strategies have not been successful in improving pregnancy outcomes.
Myo-inositol is abundant in many healthy foods, including citrus fruits and cantaloupe, beans, nuts, whole grains, and leafy vegetables. It is a carbohydrate with favorable effects on glucose metabolism. In the human body, it is involved in multiple metabolic processes. Research conducted on women with PCOS has shown that supplementation with myo-inositol may raise natural conception rates, metabolic profiles, and insulin sensitivity. Due to myo-inositol’s antiandrogenic effects, it is hypothesized that women with a hyperandrogenic phenotype of PCOS, i.e., in cases where pregnancy complications are particularly prevalent, may benefit from its supplementation. The use of myo-inositol during pregnancy is considered safe and well-tolerated.
Prior studies have suggested reductions in the risk for gestational diabetes in individuals with overweight or obesity or individuals with a family history of type 2 diabetes (T2D). Like PCOS patients, these groups of individuals are prone to abnormal glucose regulation. However, no appropriately sized randomized controlled trials have been conducted to study the potentially beneficial effects of myo-inositol among pregnant individuals with PCOS.
About the study
The Myo-Inositol Supplementation to Prevent Pregnancy Complications in Women with Polycystic Ovary Syndrome (MYPP) was a double-blind, multicenter, placebo-controlled trial in the Netherlands. Adults with a prior diagnosis of PCOS and with a viable singleton pregnancy between 8 and 16 weeks’ gestation were included and randomly assigned to either the intervention or the control group. Exclusion criteria included pre-existing conditions, such as diabetes or kidney failure.
The trial was conducted at 13 hospitals in the Netherlands, with enrolment between June 2019 and March 2023. Coupled with 0.2 mg of folic acid twice daily (0.4 mg/day total), the daily dose of myo-inositol supplementation was 4 g in the treatment group. In contrast, the control group received only the folic acid supplement. Adherence to the intervention was assessed between 24 and 28 weeks’ gestation and at 6 weeks post-partum. The primary outcome was a composite of preeclampsia, gestational diabetes, or preterm birth. Additionally, a wide range of secondary maternal and obstetric outcomes were considered.
Study findings
Between June 2019 and March 2023, 464 participants were enrolled, with 49.6% assigned to the myo-inositol group. The average age was 31.5 years, and the median pre-pregnancy body mass index (BMI) was 24.7. About 86% of the participants were White, 67.5% conceived through assisted reproductive technology, and 66% were nulliparous.
Primary outcome data were available for 97.4% of the intervention group participants. The proportion was the same for the control group. The baseline characteristics were similar across the groups, with only one exception. The incidence of biochemical hyperandrogenism was higher in the myo-inositol group (29%) compared to 18.5% in the placebo group.
The primary outcome occurred in 25% of the women in the myo-inositol group and 26.8% in the placebo group, with no significant difference. Concerning secondary outcomes, the groups' cesarean delivery rates were similar overall. Planned cesarean delivery was performed in about 6% of participants in the intervention group and 11.6% in the placebo group, a statistically significant difference that the authors caution may be coincidental. For other maternal outcomes, no significant differences were noted across the groups.
Adherence was also similar across the groups, with 80% or higher adherence rates being met by 30.7% in the placebo group and 38.9% in the myo-inositol group. Adherence rates of 60% or higher were noted in almost 70% of the placebo group and 76.0% of the myo-inositol group. Approximately 9% of participants in the placebo group reported adverse effects, compared with approximately 7% in the myo-inositol group.
Glycated hemoglobin did not differ between the groups and was stable throughout pregnancy. Neonatal anthropometric measures, gestational age at birth, neonatal intensive care unit admission, and other outcomes did not differ significantly between the intervention and placebo groups. No significant heterogeneity was noted across different BMI categories.
Conclusions
This study shows that myo-inositol supplementation is not associated with improved pregnancy outcomes and, therefore, it should not be recommended to pregnant individuals with PCOS.
A key limitation of this trial is that the baseline biochemical hyperandrogenism was substantially higher in the intervention group, which could have influenced the results.
The incidence of the primary outcome was lower than anticipated, which the authors attribute to differences in demographic characteristics compared with the referral cohort and to possible effects of trial participation, such as closer monitoring and structured follow-up.
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