Polycystic ovary syndrome (PCOS) is a polyendocrine disorder and the most common endocrinopathy in women of reproductive age. Affected women have an elevated prevalence of being overweight and obese. Our study sought to determine how weight loss associated with lifestyle changes affects the endometrium specific proteome, endocrine-metabolic characteristics, and motor capabilities of obese women with PCOS and infertility. A group of 12 infertile women under the age of 38 with PCOS and BMI ≥30 kg/m²were included in the study. An evaluation was performed by a gynecologist and an endocrinologist. The weight-loss program lasted 8 weeks under the guidance of a professional trainer. Endometrial sampling during a period of implantation window for proteome determination was performed before and after weight loss. In endometrial samples at the end of the study increased protein abundance was recorded for Legumain, Insulin-like growth factor-binding protein 7, Hepatocyte growth factor receptor, Keratin, type II cytoskeletal 7, and Cystatin-B, while the B-lymphocyte antigen CD20 protein abundance decreased. Our results also indicate significantly lowered fasting blood glucose level and free testosterone concentration and significant improvements in body composition and physical capacity. This study may open up the venues for investigating important biomarkers that may affect endometrial receptivity.Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT04989244?term=NCT04989244&draw=2&rank=1, identifier: NCT04989244.

Obesity is an increasing worldwide problem, and it is common in women with polycystic ovaries syndrome (PCOS). It is well known that women with PCOS have lower chances of spontaneous conception as well as lower success with IVF procedures. The mechanisms by which obesity causes lower fertility are not yet fully understood. The aim of the present study was to determine the effect of a lifestyle intervention weight loss program on the expression of the endometrial genes during the window of implantation (WOI). For this purpose, 15 infertile women with obesity and PCOS were included in the study. Endometrial samples were taken during the WOI before and at the end of the program, and RNASeq analysis was performed. There were no significantly differentially expressed genes before and after the weight loss program. We then compared the results of our study with previously published studies on markers of endometrial receptivity. The biomarker genes that were found to be down-regulated during the WOI in previous studies were more down-regulated after the weight loss program in the present study. Furthermore, 25% of the women who achieved the desired 5% or more weight reduction conceived spontaneously. Our study shows that weight loss might positively impact endometrial receptivity. which may lead towards the improved fertility of obese women with PCOS.