FRI417 An Interdisciplinary Program Promoting The Adoption Of A Healthy Lifestyle Increases Insulin Sensitivity In Women With Obesity And Infertility
Authors: Forget-Renaud Aurelie , Belan Matea , Jean-Denis Farrah , Pesant Marie-Helene , Baillargeon Jean-Patrice 
Published: October 2023

Disclosure: A. Forget-Renaud: None. M. Belan: None. F. Jean-Denis: None. M. Pesant: None. J. Baillargeon: Grant Recipient; Self; Ferring Pharmaceuticals, JPB received an unrestricted investigator-initiated grant from Ferring Canada, which was not for the reported study.

Introduction Obesity increases the risk of ovulatory and anovulatory infertility in women, mainly through the development of polycystic ovary syndrome (PCOS). Insulin resistance contributes to the pathogenesis of PCOS and may play a role in the infertility of PCOS and non-PCOS women with overweight or obesity. Lifestyle modifications are recommended as a first-line therapy in women with PCOS or those with obesity and infertility, as it was associated with improvement in menstrual pattern and fertility outcomes. We therefore hypothesized that a lifestyle intervention may increase insulin sensitivity in women with obesity and infertility. Methods Women with obesity and infertility were randomly allocated to usual fertility care (control group, CG) or to an interdisciplinary intervention promoting the adoption of a healthy lifestyle (LSG) alone for 6 months and then combined with usual care. Insulin resistance was estimated during fasting (HOMA-IR) and a 75-g oral glucose test (Matsuda Insulin Sensitivity Index, ISI(M)), and β-cell function was estimated using the Insulin Secretion-Sensitivity Index (ISSI-2) in women not taking medication affecting insulin sensitivity (except metformin). Data were collected at baseline, 6, 12 and 18 months, and as soon as possible when the participant knew she was pregnant. We estimated the integrated change in insulin sensitivity during follow-up using the incremental area-under-the-curve of ISI(M) divided by time (iAUC-ISI(M)/time). Results Among 130 randomized participants, 105 had available data (LSG=51, CG=54). PCOS was diagnosed using the Rotterdam criteria in 63.2% of participants, equally distributed between the groups. As compared to CG, women in the LSG improved significantly more their ISI(M) after 6 months (+0.24 [IQR: -0.48 - +0.94] vs 0.16 [-1.32 - +0.53], p=0.039, n=90), as well as their iAUC-ISI(M)/time during follow-up (+0.18±0.84 vs -0.21±0,93, p=0.035, n=104). All these results remained statistically significant after correction for baseline BMI, age and use of folic acid. Increases in iAUC-ISI(M)/time in the intervention vs control groups were significantly more important (p for interaction=0.045) in participants with baseline ISI(M) above the median (LSG: +0.10±1.13, n=24, vs CG: -0.62±1.13, n=27, p=0.028) than in those below the median (LSG: +0.26±0.48, n=27, vs CG: +0.21±0.35, n=26, p=0.71). Interactions with PCOS status and other subgroups were not statistically significant. There was no impact on HOMA-IR or ISSI-2. Conclusion An interdisciplinary program promoting the adoption of a healthy lifestyle significantly increases whole-body insulin sensitivity in women with infertility and obesity, mainly in those with higher baseline insulin sensitivity. It may be explained in part by the weight loss associated with the intervention and may have a role in improving fertility in this population.

Presentation: Friday, June 16, 2023