Adiposity Alters Follicle Dynamics in Women of Reproductive Age With Regular Menstrual Cycles

Abstract

Obesity increases a woman’s likelihood of experiencing adverse reproductive health outcomes, including menstrual cycle irregularity, anovulation, and luteal phase dysfunction. Despite a heightened risk of reproductive dysfunction some women with obesity display ovulatory cyclicity. The degree to which adiposity affects menstrual cycle characteristics in this population is limited to endocrine assessments; evidence supports decreased luteinizing hormone pulse amplitude and reduced luteal phase progesterone. However, these endocrine disruptions have not been linked to alterations in follicular events. The objectives of the present analysis were to evaluate longitudinal changes in follicle size populations and growth kinetics of selectable follicles (6-9mm) and identify endocrine abnormalities associated with obesity in regular cycles. 14 non-obese women (BMI <30 kg/m2) and 15 obese women (BMI≥ 30 kg/m2) with regular cycles were evaluated by serial ovarian transvaginal ultrasonography and venipuncture every-other-day for one complete inter-ovulatory interval (IOI). The number and diameters of all follicles ≥2 mm at each visit were documented offline using the grid method. Growth profiles of individual follicles which grew to >7mm were assessed using the Identity Method. Diagnostic, morphologic, and endocrine features were compared across groups using parametric and non-parametric t-tests (i.e. cross-sectional features) and mixed models (i.e. longitudinal features). Non-obese and obese women with regular cycles showed similar IOI, follicular phase, and luteal phase lengths. The mean number of recruitment events, maximum dominant follicle diameter, and the growth rates of ovulatory follicles over time did not differ between groups, despite confirmation of compromised mean luteal progesterone production (8.23 ng/mL vs. 14.75 ng/mL, p=0.047) and decreased mean luteal FSH levels in women with obesity (2.33 mIU/mL vs. 5.83 mIU/mL, p=0.040). Over the IOI women with obesity showed an increased proportion of 2-5 mm follicles (β=5.3%; p<0.05) and a decreased proportion of 6-9mm follicles (β=-5.0%; p=0.05) versus non-obese women consistent with fewer follicles transitioning from the 2-5 mm pool to the selectable stage. This is the first comparison of follicle dynamics between non-obese and obese women with regular ovulatory cycles. These data suggest that a smaller pool of selectable follicles is present in women with obesity and may result in suboptimal follicle development luteal function. Future studies are needed to understand the impact of altered follicle populations and luteal hormone dynamics on endometrial receptivity and fertility/fecundity.