Prospective Observational Case Series in Infertile Women with Overweight or Obesity Treated with a Very-Low Calorie Ketogenic Diet (VLCKD) Prior to an In Vitro Fertilization (IVF) Treatment.

Background: Elevated BMI in women is linked to metabolic and endocrine imbalances that impair fertility and increase pregnancy risks. While >10% weight loss before an Assisted reproductive technology (ART) treatment may improve outcomes, sustained results through conventional diets are challenging. A very-low calorie ketogenic diet (VLCKD) promotes rapid fat loss while preserving lean mass and may offer long-term benefits. This study evaluated the efficacy (≥10% weight loss without lean mass reduction), adherence, metabolic effects, and pregnancy outcomes of a meal replacement VLCKD in women with overweight or obesity scheduled for ART. Methods: This monocentric, prospective case-series was conducted at the Obesity and Work Center, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan (September 2019-September 2023). Eligible women underwent a three-phase dietary program: a 3-month VLCKD (<800 kcal/day), a 6-month transition with gradual carbohydrate reintroduction, and a Mediterranean-style maintenance diet. Participants were monitored for safety, body composition, adherence, and biochemical changes. Results: Of 52 women enrolled, 40 initiated the VLCKD; 27 (68%) achieved ≥10% weight loss while preserving lean mass. Eleven conceived naturally during or after the diet; 22 underwent ART, with 12 additional pregnancies. This corresponds to a 58% pregnancy rate among those who began the VLCKD. Significant improvements were observed in body mass index (BMI), fat mass, waist circumference, glucose metabolism, lipid profile, and liver function. No adverse events were reported. Conclusions: A meal replacement VLCKD protocol is feasible, well-tolerated, and associated with significant improvements in weight, especially in body composition, metabolic health, and potentially outcomes in women with overweight or obesity awaiting ART.