Ovulatory Recovery following weight loss in women with polycystic ovary syndrome and obesity: a post hoc analysis of the BAMBINI randomised controlled trial.

study questionWhat is the frequency of ovulatory recovery (OvR) after different degrees of total weight loss (TWL) in women with polycystic ovary syndrome (PCOS) and obesity, and can an excessive degree of TWL be identified that is harmful to the chance of OvR? SUMMARY ANSWER: Any degree of TWL was associated with a higher likelihood of OvR, and no upper threshold of TWL associated with reduced OvR was identified. WHAT IS KNOWN ALREADY: Modest weight loss (5-10%) improves reproductive function in women with PCOS. However, the relationship between greater degrees of TWL and OvR remains uncertain. STUDY DESIGN, SIZE, DURATION: Secondary post hoc analysis of a multicentre, open-label, randomised controlled trial (BAMBINI) conducted in the UK between February 2020 and April 2023. Eighty women were randomised (1:1) to standard medical care or vertical sleeve gastrectomy. Seventy-five were included in this analysis and followed up for 52 weeks. PARTICIPANTS/MATERIALS, SETTING,

methodsParticipants had PCOS, a BMI of 35 kg/m2 or higher, and oligomenorrhea/amenorrhoea. OvR was defined as two consecutive biochemically confirmed ovulatory events (serum progesterone 16.0 nmol/l or higher), occurring 3-5 weeks apart within the 52 week follow up period. Associations between TWL, reproductive hormones, and OvR were analysed using logistic regression. Analyses were exploratory and not prespecified. MAIN RESULTS AND THE ROLE OF CHANCE: At 52 weeks, 50.8% (38/75) achieved OvR. OvR occurred in 19% of participants without weight loss and in >50% of those who lost weight. Each 1% reduction in body weight was associated with a 5.6% increase in the odds of OvR (OR 0.944, 95% CI 0.900-0.990). Higher baseline serum anti-Müllerian hormone (OR 0.963, 95% CI [0.938-0.988]; P = 0.004) and higher plasma total testosterone (OR 0.324, 95% CI [0.142-0.742]; P = 0.008) were associated with lower odds of OvR. Greater TWL following bariatric surgery was associated with increased sex hormone-binding globulin and reduced free androgen index. LIMITATIONS, REASONS FOR CAUTION: This was an exploratory post hoc analysis not designed to define optimal or upper TWL thresholds. The study was not powered to detect potential adverse reproductive effects at higher degrees of TWL. WIDER IMPLICATIONS OF THE

findingsThese findings suggest that OvR in women with PCOS and obesity improves progressively with increasing TWL, supporting weight loss strategies including bariatric surgery in appropriately selected women not seeking imminent pregnancy. STUDY FUNDING/COMPETING INTEREST(S): The Jon Moulton Charity Trust funded the BAMBINI trial. This work was supported by grants from the National Institute of Health Research (NIHR), the NIHR/Wellcome Trust Imperial Clinical Research Facility, and the NIHR Imperial Biomedical Research Centre. The Section of Endocrinology and Investigative Medicine was funded by grants from the Medical Research Council (MRC), Biotechnology and Biological Sciences Research Council (BBSRC), and the NIHR, and was supported by the NIHR Biomedical Research Centre Funding Scheme. The views expressed are those of the author(s) and not necessarily those of the MRC, the NHS, the NIHR, or the Department of Health. S.N.S.S. was supported by an Imperial post-doctoral post-CCT Fellowship. A.A. was supported by an NIHR Clinician Scientist Award CS-2018-18-ST2-002. All authors acknowledge infrastructure support for this research from the NIHR Imperial Biomedical Research Centre (BRC).A.D.M. has received research funding from the Medical Research Council (MRC), National Institute for Health and Care Research (NIHR), Jon Moulton Charitable Foundation, PEACEPLUS programme (EU and UK government), Anabio, Fractyl, Boehringer Ingelheim, Eli Lilly, Gila, Randox, and Novo Nordisk. A.D.M. has received honoraria for lectures and presentations from Novo Nordisk, AstraZeneca, Currax Pharmaceuticals, Boehringer Ingelheim, Screen Health, GI Dynamics, Algorithm, Eli Lilly, Ethicon, and Medtronic. A.D.M. is a shareholder in the Beyond BMI clinic, which provides clinical obesity care. H.R. is on the advisory board for Novo Nordisk and is the national lead for the REDEFINE 3 trial. TRIAL REGISTRATION NUMBER: N/A.