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

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

Amsterdam UMC - University of Amsterdam
Amsterdam UMC
Utrecht University
Erasmus University Rotterdam
Clinical Trials Unit of the Netherlands Society for Obstetrics and Gynaecology
Maastricht University
Maasstad Hospital
Diakonessenhuis Utrecht
Catharina Hospital
Jeroen Bosch Ziekenhuis
Franciscus Gasthuis and Vlietland
Albert Schweitzer Ziekenhuis
Centre for Reproductive Medicine
Medisch Spectrum Twente
St. Antonius Ziekenhuis
Zuyderland
Maxima Medical Centre
Eindhoven University of Technology

Research output: Contribution to journal › Article › Academic › peer-review

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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.

Original language	English
Pages (from-to)	1151-1159
Number of pages	9
Journal	JAMA
Volume	334
Issue number	13
DOIs	https://doi.org/10.1001/jama.2025.13668
Publication status	Published - 7 Oct 2025

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Myo-inositol-supplementation-to-prevent-pregnancy-complications-in-polycystic-ovary-syndrome.pdfFinal published version, 430 KBLicence: Taverne

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van der Wel, A. W. T., Frank, C. M. C., Bout-Rebel, R., Duijnhoven, R. G., van Bree, B. E., Valkenburg, O., Al-Nasiry, S., van Oppenraaij, R. H. F., Vogelvang, T. E., Westerhuis, M. E. M. H., van de Nieuwenhof, H. P., Gielen, S. C. J. P., Bandell, M. L., Bekker, M. N., Wouters, M. G. A. J., Mijatovic, V., Franx, A., Lambalk, C. B., Broekmans, F. J. M., ... van Rijn, B. B. (2025). Myo-inositol Supplementation to Prevent Pregnancy Complications in Polycystic Ovary Syndrome: A Randomized Clinical Trial. JAMA, 334(13), 1151-1159. https://doi.org/10.1001/jama.2025.13668

@article{304cc2b428dc48bc97b22de869056845,

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

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.",

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

note = "Publisher Copyright: {\textcopyright} 2025 American Medical Association.",

year = "2025",

month = oct,

day = "7",

doi = "10.1001/jama.2025.13668",

language = "English",

volume = "334",

pages = "1151--1159",

journal = "JAMA",

issn = "0098-7484",

publisher = "American Medical Association",

number = "13",

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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 2025, 'Myo-inositol Supplementation to Prevent Pregnancy Complications in Polycystic Ovary Syndrome: A Randomized Clinical Trial', JAMA, vol. 334, no. 13, pp. 1151-1159. https://doi.org/10.1001/jama.2025.13668

TY - JOUR

T1 - Myo-inositol Supplementation to Prevent Pregnancy Complications in Polycystic Ovary Syndrome

T2 - A Randomized Clinical Trial

AU - van der Wel, Anne W. T.

AU - Frank, Chryselle M. C.

AU - Bout-Rebel, Rebekka

AU - Duijnhoven, Ruben G.

AU - van Bree, Bo E.

AU - Valkenburg, Olivier

AU - Al-Nasiry, Salwan

AU - van Oppenraaij, Robbert H. F.

AU - Vogelvang, Tatjana E.

AU - Westerhuis, Michelle E. M. H.

AU - van de Nieuwenhof, Hedwig P.

AU - Gielen, Susanne C. J. P.

AU - Bandell, Myrthe L.

AU - Bekker, Mireille N.

AU - Wouters, Maurice G. A. J.

AU - Mijatovic, Velja

AU - Franx, Arie

AU - Lambalk, Cornelis B.

AU - Broekmans, Frank J. M.

AU - de Weerd, Sabina

AU - Gerards, Jet M. H.

AU - Baalman, Jelle H.

AU - van Disseldorp, Jeroen

AU - Langenveld, Josje

AU - Gunning, Marlise N.

AU - Frederix, Geert W. J.

AU - Painter, Rebecca C.

AU - Fauser, Bart C. J. M.

AU - Laven, Joop S. E.

AU - van Rijn, Bas B.

PY - 2025/10/7

Y1 - 2025/10/7

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/105018021204

U2 - 10.1001/jama.2025.13668

DO - 10.1001/jama.2025.13668

M3 - Article

C2 - 40920401

SN - 0098-7484

VL - 334

SP - 1151

EP - 1159

JO - JAMA

JF - JAMA

IS - 13

ER -

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

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