Exploratory analysis of serum concentrations of oocyte biomarkers growth differentiation factor 9 and bone morphogenetic protein 15 in ovulatory women across the menstrual cycle

Serum concentrations of oocyte-secreted factors growth differentiation factor 9 and bone morphogenetic protein 15 showed minimal changes across the menstrual cycle in ovulatory women from young to advanced reproductive ages.

VOLUME 116, ISSUE 2, P546-557


Angelique H. Riepsamen, Ph.D., Mark W. Donoghoe, Ph.D., Angela Baerwald, M.D., Ph.D., Michael W. Pankhurst, Ph.D., Shelly Lien, B.Sc., Yih Harng Chong, Ph.D., David M. Robertson, Ph.D., William L. Ledger, M.D., Ph.D., Robert B. Gilchrist, D.Sc.



To characterize and evaluate the variation in serum concentrations of oocyte-secreted growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) throughout the menstrual cycle in women from young to advanced reproductive ages.


Cross-sectional, observational, and exploratory study.


Multicenter university-based clinical practices and laboratories.


Serum was collected every 1–3 days throughout the menstrual cycle from 3 cohorts of healthy, ovulatory women: menses to late luteal phase (21–29 years of age; n = 16; University of Otago) and across one interovulatory interval (18-35 years of age; n = 10; and 45–50 years of age; n = 15; University of Saskatchewan).



Main Outcome Measure(s)

To detect the changes in serum GDF9 and BMP15 across the cycle, mean concentration and variance were statistically modeled using a generalized additive model of location, shape and scale (GAMLSS). Follicle-stimulating hormone, luteinizing hormone, estradiol, progesterone, and anti-Müllerian hormone were also assessed.


GDF9 and BMP15 were detectable in 54% and 73% of women and varied 236-fold and 52-fold between women, respectively. Across the menstrual cycle, there were minimal changes in GDF9 or BMP15 within a woman for all cohorts, with no significant differences detected in the modeled mean concentrations. However, modeled variances were highest in the luteal phases of all women for BMP15 immediately after ovulation, regardless of age.


Serial changes in GDF9 or BMP15 concentrations across the cycle were not statistically detected and are likewise similar across the reproductive lifespan. Further research is required to fully elucidate the utility of these oocyte biomarkers at diagnosing fertility potential and/or disease.