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

Anne W T van der Wel; Chryselle M C Frank; Rebekka Bout-Rebel; Ruben G Duijnhoven; Bo E van Bree; Olivier Valkenburg; Salwan Al-Nasiry; Robbert H F van Oppenraaij; Tatjana E Vogelvang; Michelle E M H Westerhuis; Hedwig P van de Nieuwenhof; Susanne C J P Gielen; Myrthe L Bandell; Mireille N Bekker; Maurice G A J Wouters; Velja Mijatovic; Arie Franx; Cornelis B Lambalk; Frank J M Broekmans; Sabina de Weerd; Jet M H Gerards; Jelle H Baalman; Jeroen van Disseldorp; Josje Langenveld; Marlise N Gunning; Geert W J Frederix; Rebecca C Painter; Bart C J M Fauser; Joop S E Laven; Bas B van Rijn

doi:10.1001/jama.2025.13668

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

van der Wel AWT, Frank CMC, Bout-Rebel R, Duijnhoven RG, van Bree BE, Valkenburg O, Al-Nasiry S, van Oppenraaij RHF, Vogelvang TE, Westerhuis MEMH, van de Nieuwenhof HP, Gielen SCJP, Bandell ML, Bekker MN, Wouters MGAJ, Mijatovic V, Franx A, Lambalk CB, Broekmans FJM, de Weerd S, Gerards JMH, Baalman JH, van Disseldorp J, Langenveld J, Gunning MN, Frederix GWJ, Painter RC, Fauser BCJM, Laven JSE, van Rijn BB

Published October 7, 2025 JAMA

DOI 10.1001/jama.2025.13668 PMID 40920401 PMC PMC12418221

Abstract

Importance

Pregnant individuals with polycystic ovary syndrome (PCOS) present with a higher risk of pregnancy complications, including gestational diabetes, preeclampsia, and preterm birth. Myo-inositol supplementation may reduce these risks.

Objective

To determine whether daily supplementation with myo-inositol during pregnancy among individuals with PCOS reduces the risk of a composite outcome of gestational diabetes, preeclampsia, and preterm birth.

Design, Setting, and Participants

This double-blind, placebo-controlled, randomized trial was conducted at 13 hospitals in the Netherlands. Pregnant individuals with PCOS who were between 8 and 16 weeks' gestation were enrolled between June 2019 and March 2023. Final follow-up was complete on December 27, 2023. Analyses were conducted July 2024.

Interventions

Participants were randomized on a 1:1 basis to receive sachets with either myo-inositol, 2 g, with 0.2 mg of folic acid twice daily (n = 230) or matching placebo with 0.2 mg of folic acid only (n = 234) until delivery.

Main Outcomes and Measures

The primary outcome was a composite of gestational diabetes, preeclampsia, or preterm birth (before 37 weeks' gestation).

Results

Among 464 participants, the mean (SD) age was 31.5 (3.8) years; 18 participants (3.9%) reported Asian race and 395 (86.1%) reported White race. The prevalence of biochemical hyperandrogenism was higher at baseline in the myo-inositol group than the placebo group (29.0% [53 of 180] vs 18.5% [37 of 193]). A primary outcome event occurred in 25.0% (n = 56) of participants in the myo-inositol group and 26.8% (n = 61) in the placebo group (relative risk, 0.93 [95% CI, 0.68-1.28]; P = .67).

Conclusions and Relevance

Myo-inositol supplementation during pregnancy did not reduce the incidence of a composite of gestational diabetes, preeclampsia, or preterm birth in patients with PCOS.

Trial Registration

onderzoekmetmensen.nl Identifier: NL67329.078.18.

Anne W T van der Wel, Chryselle M C Frank, Rebekka Bout-Rebel, Ruben G Duijnhoven, Bo E van Bree, Olivier Valkenburg, Salwan Al-Nasiry, Robbert H F van Oppenraaij, Tatjana E Vogelvang, Michelle E M H Westerhuis, Hedwig P van de Nieuwenhof, Susanne C J P Gielen, Myrthe L Bandell, Mireille N Bekker, Maurice G A J Wouters, Velja Mijatovic, Arie Franx, Cornelis B Lambalk, Frank J M Broekmans, Sabina de Weerd, Jet M H Gerards, Jelle H Baalman, Jeroen van Disseldorp, Josje Langenveld, Marlise N Gunning, Geert W J Frederix, Rebecca C Painter, Bart C J M Fauser, Joop S E Laven, Bas B van Rijn

A Wel, C Frank, R Bout-Rebel, R Duijnhoven, B Bree, O Valkenburg, S Al-Nasiry, R Oppenraaij, T Vogelvang, M Westerhuis, H Nieuwenhof, S Gielen, M Bandell, M Bekker, M Wouters, V Mijatovic, A Franx, C Lambalk, F Broekmans, S Weerd, J Gerards, J Baalman, J Disseldorp, J Langenveld, M Gunning, G Frederix, Becky Painter, R Painter, B Fauser, J Laven, B Rijn

PMID 40920401 40920401 DOI 10.1001/jama.2025.13668 10.1001/jama.2025.13668 van der Wel et al. 2025, van der Wel 2025

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

Abstract

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