Protocol of the Fit-For-Fertility study: a multicentre randomised controlled trial assessing a lifestyle programme targeting women with obesity and infertility.

INTRODUCTION: Women with obesity are at a higher risk of infertility as well as gestational and neonatal complications. Lifestyle changes are universally recommended for women with obesity seeking fertility treatments, but such intervention has only been assessed in very few robust studies. This study's objectives are therefore to assess the clinical outcomes and cost-effectiveness of an interdisciplinary lifestyle intervention (the Fit-For-Fertility Programme; FFFP) targeting women with obesity and subfertility in a diverse population. METHODS AND ANALYSIS: This pragmatic multicentre randomised controlled trial (RCT) will include 616 women with obesity (body mass index ≥30 kg/m2 or ≥27 kg/m2 with polycystic ovary syndrome or at-risk ethnicities) who are evaluated at a Canadian fertility clinic for subfertility. Women will be randomised either to (1) the FFFP (experimental arm) alone for 6 months, and then in combination with usual care for infertility if not pregnant; or (2) directly to usual fertility care (control arm). Women in the intervention group benefit from the programme up to 18 months or, if pregnant, up to 24 months or the end of the pregnancy (whichever comes first). Women from both groups are evaluated every 6 months for a maximum of 18 months. The primary outcome is live birth rate at 24 months. Secondary outcomes include fertility, pregnancy and neonatal outcomes; lifestyle and anthropometric measures; and cost-effectiveness. Qualitative data collected from focus groups of participants and professionals will also be analysed. ETHICS AND DISSEMINATION: This research study has been approved by the Research Ethics Board (REB) of Centre intégré universtaire de santé et des services sociaux de l'Estrie-CHUS (research coordinating centre) on 10 December 2018 and has been or will be approved successively by each participating centres' REB. This pragmatic RCT will inform decision-makers on improving care trajectories and policies regarding fertility treatments for women with obesity and subfertility. TRIAL REGISTRATION NUMBER: NCT03908099. PROTOCOL VERSION: 1.1, 13 April 2019.

Alanine Aminotransferase Is a Marker of Lipotoxicity Consequences and Hyperandrogenemia in Women with Polycystic Ovary Syndrome.

BACKGROUND: Several studies have reported higher levels of Alanine aminotransferase (ALT) in women with polycystic ovary syndrome (PCOS) compared with control subjects. Plasma ALT levels are considered a marker of hepatic lipotoxicity because of their significant associations with different hepatic metabolic dysfunctions, such as hepatic steatosis and hepatic insulin resistance. METHODS: Retrospective chart review aiming to assess, in PCOS women, the relationship between ALT levels and measures of lipotoxicity consequences that are available clinically, both during fasting and using the oral glucose tolerance test. RESULTS: Women (n = 132) with PCOS, were in average 27.9 years of age, with a mean body mass index of 34.1 kg/m2 and 49% had a metabolic syndrome (MetS). ALT levels were significantly correlated with homeostatic model assessment for insulin resistance (r = 0.42, P < 0.001), HDL-C (r = -0.31, P < 0.001), Matsuda index (-0.45, P < 0.001), insulin secretion-sensitivity index-2 (-0.26, P = 0.043), and free testosterone (0.38, P < 0.001), but not with fasting glucose and triglyceride levels. ALT cutoff ≥24 IU/L was associated with all these parameters, including fasting glucose (P = 0.021) and triglyceride levels (P = 0.041), and detected more women with the MetS (59.2% vs. 36.1%, P = 0.008) and whole-body insulin resistance (Matsuda index <12.3 L2·10/mmol2, 85.3% vs. 51.9%, P = 0.004). CONCLUSIONS: Plasma ALT levels seem to be a strong predictor not only of liver lipotoxicity but also of systemic lipotoxic consequences and hyperandrogenemia in women with PCOS. Although it requires validation in another study, an ALT cutoff of ≥24 IU/L may help clinicians identify women with increased metabolic risks.

The Obesity-Fertility Protocol: a randomized controlled trial assessing clinical outcomes and costs of a transferable interdisciplinary lifestyle intervention, before and during pregnancy, in obese infertile women.

BACKGROUND: Obesity in infertile women increases the costs of fertility treatments, reduces their effectiveness and increases significantly the risks of many complications of pregnancy and for the newborn. Studies suggest that even a modest loss of 5-10 % of body weight can restore ovulation. However, there are gaps in knowledge regarding the benefits and cost-effectiveness of a lifestyle modification program targeting obese infertile women and integrated into the fertility clinics. This study will evaluate clinical outcomes and costs of a transferable interdisciplinary lifestyle intervention, before and during pregnancy, in obese infertile women. We hypothesize that the intervention will: 1) improve fertility, efficacy of fertility treatments, and health of mothers and their children; and 2) reduce the cost per live birth, including costs of fertility treatments and pregnancy outcomes. METHODS/DESIGN: Obese infertile women (age: 18-40 years; BMI ≥30 kg/m(2) or ≥27 kg/m(2) with polycystic ovary syndrome) will be randomised to either a lifestyle intervention followed by standard fertility treatments after 6 months if no conception has been achieved (intervention group) or standard fertility treatments only (control group). The intervention and/or follow-up will last for a maximum of 18 months or up to the end of pregnancy. Evaluation visits will be planned every 6 months where different outcome measures will be assessed. The primary outcome will be live-birth rates at 18 months. The secondary outcomes will be sub-divided into four categories: lifestyle and anthropometric, fertility, pregnancy complications, and neonatal outcomes. Outcomes and costs will be also compared to similar women seen in three fertility clinics across Canada. Qualitative data will also be collected from both professionals and obese infertile women. DISCUSSION: This study will generate new knowledge about the implementation, impacts and costs of a lifestyle management program in obese infertile women. This information will be relevant for decision-makers and health care professionals, and should be generalizable to North American fertility clinics. TRIAL REGISTRATION: ClinicalTrials.gov NCT01483612. Registered 25 November 2011.