Introduction Pregnant women with polycystic ovary syndrome (PCOS) have an increased risk of gestational diabetes mellitus (GDM), preeclampsia and preterm birth, and their offspring are more likely to have an abnormal birth weight and require hospitalization. Current preventive strategies to reduce the rate of pregnancy complications associated with PCOS have ineffective. Myo-inositol supplementation has shown promising clinical benefit in preventing adverse outcomes in individuals with obesity and PCOS-related disorders. Recent randomized controlled trials using daily supplementation with 4 grams of myo-inositol during pregnancy estimated a relative reduction of up to 65% for GDM and preterm delivery.(1–7) These studies included both obese patients and patients with normal body weight. From these trials, post-hoc analysis suggested similar, or even greater, reductions in the sub group of women with PCOS.(8) However, no randomized controlled trials have been conducted to evaluate the potential benefit of myo-inositol supplementation in preventing pregnancy complications in these women.

Methods and analysis This is a prospective, multicenter, double-blind, randomized controlled trial to study the clinical effectiveness and cost-effectiveness of myo-inositol supplementation to prevent pregnancy among women with PCOS. Recruitment will set out to include 464 individuals with PCOS between 8+0 and 16+0 weeks of pregnancy, who are then randomized in a 1:1 ratio to either the intervention group that will receive 4 grams myo-inositol added a standard recommended dose of folic acid, divided over two daily sachets of sugary powder throughout pregnancy; or into the control group that will receive similar looking sachets containing no supplement other than the routinely recommended dose of folic acid. Regular multivitamin use (without inositols) will be allowed for both groups. The primary endpoint is the incidence of the composite outcome of either GDM, preeclampsia and/or preterm birth.

Secondary endpoints include indicators of maternal physical and mental well-being, maternal health-related quality of life, neonatal outcomes, breastfeeding practices and breastmilk composition. Trial results will be analysed according to the intention-to-treat principle. A full economic evaluation will be performed.

Ethics and dissemination The study protocol has been approved by the Medical Ethics Committee of the Erasmus MC University Medical Centre Rotterdam. Approval by the boards of management for all participating hospitals will be obtained. Trial results will be submitted to peer-reviewed journals.

Trial registration number NTR-NL7799

Strengths and limitations of this study

This will be the first prospective randomized controlled trial, aimed specifically at women with polycystic ovary syndrome (PCOS), to estimate the potential of myo-inositol supplementation in preventing common pregnancy complications associated with PCOS.

The double-blinded randomized multicenter design enables unbiased interpretation and generalisability of results.

This study will provide novel recommendations on myo-inositol supplementation as a safe nutritional intervention aimed to improve pregnancy outcomes among women with PCOS.

Inclusion of individuals of diverse ethnic backgrounds may prove a limitation given the relative homogeneous population of the Netherlands; the estimated effect sizes, compared with previous studies upon which our power calculations were based, may also vary across sub populations e.g. women with obesity and different PCOS phenotypes.

Recruitment and compliance in this patient group may lead to self-selection of participants with higher educational, or socio-economic backgrounds. This needs to be taken into account to estimate the impact of implementation.

The authors have declared no competing interest.

https://zorgverlener.mypp-trial.nl/documenten-download/

The MYPP-trial is supported by a grant of the Netherlands Organisation for Health Research and Development (ZonMw), grant number 84801 6013. The manufacturer of the supplements (Gideon Richter, Belgium) has no role in the conduct or execution of the trial, apart from manufacturing and delivering the custom-made supplements.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The trial protocol has been approved by the Medical Research Ethics Committee (MREC) of the Erasmus MC University Medical Centre, Rotterdam under the number MEC-2019-000. Approval by the Board of Directors will be obtained for all participating hospitals. The trial is registered in the public Dutch Trial Registry (NTR) under the number NTR-NL7799 in June 2019. MYPP is also registered online at ClinicalTrials.gov under the number NCT05524259 in September 2022.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

All data produced in the present study are available upon reasonable request to the authors