Intrafollicular activin-A, inhibin-B, and follistatin are associated with in vitro fertilization outcomes in subfertile women.
Follistatin and inhibin-B in follicular fluid may correlate with IVF outcomes, but activin-A's inverse association with success needs further validation.
Where it sits
this study against the rest of the follistatin-344 corpusSummary and findings
This study evaluated the association between follicular fluid concentrations of activin-A, follistatin, and inhibin-B and in vitro fertilization outcomes in 86 women undergoing IVF/ICSI cycles. It measured oocyte yield and quality, embryo number and quality, implantation success, clinical pregnancy, and live birth rates. The findings suggest associations but do not establish causation.
Abstract
<h4>Purpose</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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.
Background
This paper addresses the role of the follicular microenvironment in influencing oocyte and embryo quality, which is critical for assisted reproduction therapy outcomes. Prior studies have indicated that various biomarkers in follicular fluid may correlate with IVF success. Understanding these associations could potentially enhance IVF protocols and outcomes.
Methods
The study was a prospective cohort analysis involving 86 women with primary infertility attending an Assisted Conception Unit. Follicular fluid samples were collected at oocyte retrieval from follicles ≥ 18 mm in diameter. The primary outcome measures included oocyte yield and quality, embryo number and quality, implantation success, clinical pregnancy, and live birth rates.
Results
FF activin-A concentrations were positively correlated with follistatin and inhibin-B levels (p<0.001). FF follistatin and inhibin-B levels were significantly associated with oocyte and embryo number and quality (p<0.05). Each 10 pg/mg increase in protein-normalized FF activin-A was 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.
Interpretation
The findings suggest that while activin-A levels may inversely correlate with key IVF outcomes, the effect sizes are not clinically significant as they do not withstand adjustments for confounding factors. Previous literature has shown mixed results regarding the role of these biomarkers in IVF outcomes, indicating a need for further research. The limitations of this study, including the lack of adjusted significance and potential confounding by family history, suggest caution in interpreting these results for clinical practice.
Key findings
- FF activin-A levels were positively correlated with follistatin and inhibin-B levels (p<0.001).
- FF follistatin and inhibin-B levels were significantly associated with oocyte and embryo number and quality (p<0.05).
- Each 10 pg/mg increase in protein-normalized FF activin-A was associated with successful implantation [RR (95% CI) = 0.82 (0.69-0.96), p=0.016].
- Each 10 pg/mg increase in protein-normalized FF activin-A was associated with clinical pregnancy [RR (95% CI) = 0.76 (0.66-0.86), p<0.001].
- Each 10 pg/mg increase in protein-normalized FF activin-A was associated with live birth [RR (95% CI) = 0.79 (0.64-0.97), p=0.023].
- None of these associations met the Benjamini-Hochberg adjusted significance threshold.
Limitations
- small n=86
- associations did not meet adjusted significance threshold
- attenuated upon adjustment for family subfertility history
- prospective cohort study, not randomized
- single-site study