Oral Virtual Presentation (Virtual only) ESA-SRB-ANZBMS 2021

Oocyte-secreted GDF9 and BMP15 as serum biomarkers of ovarian function in healthy women and women with PCOS (#83)

Angelique H Riepsamen 1 , Inthrani R Indran 2 3 , Mark W Donoghoe 4 , Shelly Lien 1 , Leah Hechtman 1 , David M Robertson 1 , William L Ledger 1 , Robert B Gilchrist 1 , Eu Leong Yong 2
  1. Fertility and Research Centre, School of Women’s and Children’s Health, University of New South Wales, Sydney, NSW, Australia
  2. Department of Obstetrics & Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
  3. Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
  4. Stats Central, Mark Wainwright Analytical Centre, University of New South Wales, Sydney, NSW, Australia

Oocyte-secreted growth differentiation factor-9 (GDF9) and bone morphogenetic protein-15 (BMP15) are critical paracrine regulators of female fertility and are predominantly expressed by oocytes. However, it is unknown if serum concentrations reflect changes in ovarian function and/or reproductive endocrine disorders. This study aimed to determine if serum GDF9/BMP15 are associated with ovarian and endocrine parameters, and the ovarian pathology PCOS.

 

Women aged 21-45 years (n=381) were included from a cross-sectional study at the National University Hospital, Singapore. Participants were volunteers and cases with possible PCOS. Anthropometric measurements, transvaginal ultrasound scans and blood tests were performed, and a questionnaire completed. Serum GDF9 and BMP15 concentrations were determined and analyzed relative to ovarian (cycle regularity, ovarian volume, AFC, AMH), pituitary (FSH, LH, prolactin), estrogenic (estrone, estradiol), androgenic (testosterone, DHT, androstenedione, DHEAS, SHBG, mFG score), and metabolic (BMI, waist-to-hip ratio, insulin, glucose, triglycerides, cholesterol, HDL, LDL, HOMA-IR) characteristics in asymptomatic, PCOM and PCOS women. Statistical analyses used censored regression models and Kendall’s tau correlation appropriate for data containing values below the limit of detection. 

 

Serum GDF9 and BMP15 were detectable in 40% and 41% of women, respectively. Serum GDF9 positively correlated with ovarian volume (p=0.02), AFC (p=0.004), and weakly with AMH (p=0.05). Furthermore, irregular menstrual cycles were associated with high GDF9 (p=0.005), and similar, although non-significant associations were seen for BMP15. When stratified into PCOS (n=130), PCOM (n=59), and control (n=192), GDF9 and BMP15 were not different between these groups, and were not associated with the majority of androgenic features of PCOS. However, the relationship between GDF9 and AFC was significantly different between PCOM, PCOS and control women (p=0.02).

 

These results suggest that serum GDF9 and BMP15 concentrations reflect ovarian but not androgenic characteristics of PCOS, and that the relationships between GDF9 and AFC may be aberrant in women with PCOM/PCOS.