Intrafollicular activin-A, inhibin-B, and follistatin are associated with in vitro fertilization outcomes in subfertile women.
TL;DR
Follicular fluid follistatin and inhibin-B were associated with favorable intermediate IVF outcomes, whereas activin-A showed an exploratory inverse association with implantation, clinical pregnancy, and live birth.
Abstract
Purpose
The follicular microenvironment strongly influences oocyte and embryo quality and therefore plays a critical role in assisted reproduction therapy outcomes. This study prospectively evaluated the association between follicular fluid (FF) concentrations of activin-A, follistatin, and inhibin-B and in vitro fertilization (IVF) outcome parameters.
Methods
Couples with primary infertility attending an Assisted Conception Unit in Athens, Greece, were recruited as part of an ongoing prospective cohort study evaluating the impact of dietary and lifestyle patterns on fertility. FF levels of activin-A, follistatin, and inhibin-B were measured in 86 women undergoing IVF/ICSI cycles, along with assessments of oocyte yield and quality, embryo number and quality, implantation success, clinical pregnancy, and live birth rates. FF samples were collected at oocyte retrieval from follicles ≥ 18 mm in diameter and analyzed using the enzyme-linked immunosorbent assay. Associations between FF biomarkers and IVF outcomes were assessed using correlation analyses and multivariable-adjusted regression models.
Results
FF activin-A concentrations were positively correlated with both follistatin and inhibin-B levels (p < 0.001), while FF follistatin and inhibin-B levels were significantly associated with oocyte and embryo number and quality (p < 0.05). Multivariable-adjusted relative risk analyses demonstrated that FF activin-A levels were independently and inversely associated with primary clinical endpoints. Specifically, each 10 pg/mg increase in protein-normalized FF activin-A was independently and inversely associated with successful implantation [RR (95% CI) = 0.82 (0.69-0.96), p = 0.016], clinical pregnancy [RR (95% CI) = 0.76 (0.66-0.86), p < 0.001], and live birth [RR (95% CI) = 0.79 (0.64-0.97), p = 0.023]; however, none of these associations met the Benjamini-Hochberg adjusted significance threshold and all attenuated to marginal non-significance upon adjustment for family subfertility history.
Conclusion
Follicular fluid follistatin and inhibin-B were associated with favorable intermediate IVF outcomes, whereas activin-A showed an exploratory inverse association with implantation, clinical pregnancy, and live birth. These findings warrant prospective validation in larger, independent cohorts before any clinical translation can be considered.