Changes in antral follicle dynamics following weight loss in women with polycystic ovary syndrome

Abstract STUDY QUESTION Does weight loss from a hypocaloric dietary intervention improve antral follicle dynamics in women with PCOS? SUMMARY ANSWER During a 3-month hypocaloric dietary intervention, women with PCOS who experienced clinically meaningful weight loss showed more organized antral follicle development including fewer recruitment events, but no change in the overall frequency of selection, dominance, or ovulation. WHAT IS KNOWN ALREADY There is a spectrum of disordered antral follicle development in women with PCOS including excessive follicle recruitment and turnover, decreased frequency of selection and dominance, and failure of ovulation. Lifestyle intervention aimed at weight loss is recommended to improve metabolic health in women with PCOS yet benefits on ovarian follicle development and ovulation are unclear. STUDY DESIGN, SIZE, DURATION This was a prospective, single-arm lifestyle intervention study conducted over 4 months including a 1-month baseline assessment period and 3-month hypocaloric dietary intervention. Twenty women were allocated to the intervention with 0% attrition. PARTICIPANTS/MATERIALS, SETTING, METHODS Females, ages 18–38 years, with PCOS and obesity (BMI 30 kg/m2) underwent every-other-day transvaginal ultrasonography and venipuncture at an academic clinical research unit for 4 months. The number and size of all follicles were evaluated at each study visit, with individual growth profiles plotted retrospectively for follicles that grew to at least 7 mm. Gonadotropin and ovarian steroid hormone concentrations were measured every-other-day. Reproductive, anthropometric, and metabolic status markers were assessed at baseline and at the end of the intervention. MAIN RESULTS AND THE ROLE OF CHANCE Hypocaloric dietary intervention resulted in an average weight loss of 8 ± 3% with significant reductions in all anthropometric markers assessed including BMI, waist circumference, total percent fat, and trunk fat mass (all P 0.05). Of the glucoregulatory and cardiovascular risk markers assessed, only diastolic blood pressure (P = 0.040) and 2-h insulin concentrations following a glucose challenge (P = 0.029) were decreased post-intervention. Antral follicle development appeared more cyclic following the intervention with the frequency of recruitment (P = 0.043), and number of follicles recruited per cohort (P 0.0001), decreasing with weight loss. By contrast, the frequency of selection, dominance, and ovulation did not change with weight loss (all P 0.05). When ovulation occurred during the intervention, the size at selection for ovulatory follicles decreased with weight loss (P 0.0001), whereas maximum luteal progesterone levels increased with weight loss (P = 0.036). Participants (35%) who responded to the intervention with a shortened inter-menstrual interval had lower baseline trunk fat mass (P = 0.048), fasting insulin (P = 0.022), and homeostatic model assessment for insulin resistance (P = 0.017) compared to non-responders. LIMITATIONS, REASONS FOR CAUTION The duration of the intervention may not have been sufficient to capture an impact of weight loss on ovulatory cyclicity. Analyses were limited to the antral stages of follicle development and any impact of hypocaloric dietary intervention on pre-antral folliculogenesis was not evaluated. The small study sample limits statistical power and generalizability of the findings. WIDER IMPLICATIONS OF THE FINDINGS Short-term hypocaloric dietary intervention did not consistently improve ovulation frequency in women with PCOS despite clinically meaningful weight loss. Counseling related to the benefits of short-term hypocaloric dietary intervention on reproductive health outcomes should be tempered as improvements in ovulation are likely only in those with a more favorable metabolic profile at the onset. Improvements in the early stages of antral follicle development with weight loss suggest potential for longer dietary interventions to improve ovulatory cyclicity in women with PCOS. STUDY FUNDING/COMPETING INTEREST(S) This research was supported by funds from the President’s Council of Cornell Women, United States Department of Agriculture (Grant No. 8106), and National Institutes of Health (R01-HD0937848, R56-HD089962). F.E.C., B.Y.J., and H.V.B. were supported by doctoral training awards from the National Institutes of Health (5 T32-HD087137, T32-DK007158) and Canadian Institutes of Health Research (Grant No. 146182), respectively. The authors have no competing interests. TRIAL REGISTRATION NUMBER NCT01785719.