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Randomized Controlled Trial
. 2025 Oct 7;334(13):1151-1159.
doi: 10.1001/jama.2025.13668.

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

Anne W T van der Wel  1   2 , Chryselle M C Frank  3 , Rebekka Bout-Rebel  4 , Ruben G Duijnhoven  1   5 , Bo E van Bree  6 , Olivier Valkenburg  6 , Salwan Al-Nasiry  6 , Robbert H F van Oppenraaij  7 , Tatjana E Vogelvang  8 , Michelle E M H Westerhuis  9 , Hedwig P van de Nieuwenhof  10 , Susanne C J P Gielen  11 , Myrthe L Bandell  12 , Mireille N Bekker  3 , Maurice G A J Wouters  1   2 , Velja Mijatovic  2   13 , Arie Franx  4 , Cornelis B Lambalk  2   13 , Frank J M Broekmans  14   15 , Sabina de Weerd  12 , Jet M H Gerards  8 , Jelle H Baalman  16 , Jeroen van Disseldorp  17 , Josje Langenveld  18 , Marlise N Gunning  14 , Geert W J Frederix  19 , Rebecca C Painter  2   4 , Bart C J M Fauser  14 , Joop S E Laven  4 , Bas B van Rijn  20   21
Affiliations
Randomized Controlled Trial

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

Anne W T van der Wel et al. JAMA. .

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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Mijatovic reported receiving travel and speaker fees from Guerbet and research grants from Guerbet, Merck, Theramex and Ferring. Dr Broekmans reported receiving personal fees from Merck, Ferring, Abbott, and Cooper Surgical and grants from Besins outside the submitted work. Dr Disseldorp reported receiving personal fees from Ferring and nonfinancial support from Merck outside the submitted work. Dr Painter reported receiving grants from ZonMw outside the submitted work. Dr Fauser reported receiving grants from ZonMw during the conduct of the study and personal fees from Gedeon Richter and fees and/or grant support from Celmatix, Controversies in Obstetrics & Gynecology (COGI), European Society of Human Reproduction and Embryology (ESHRE), Ferring, International Federation of Fertility Societies (IFFS), Myovant/Sumitomo, PregLem/Gideon Richter, Pulsenmore, ReproNovo, Reproductive Biomedicine Online (RBMO), Univfy, UpToDate, and Vortex Imaging outside the submitted work. Dr Laven reported receiving grants from ZonMw during the conduct of the study and grants from Ferring, Roche Diagnostics, Art Pred, and Merck and personal fees from Ferring and Gedeon Richter outside the submitted work. Dr van Rijn reported receiving grants from ZonMw outside the submitted work. No other disclosures were reported.

Comment on

References

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