Association of bioavailable inhibin B and oocyte yield in controlled ovarian stimulation

Rachel B Danis, Intira Sriprasert, Jacqueline R Ho, Lynda K McGinnis, Ajay Kumar, Frank Z Stanczyk, Rachel B Danis, Intira Sriprasert, Jacqueline R Ho, Lynda K McGinnis, Ajay Kumar, Frank Z Stanczyk

Abstract

Objective: To determine if the biologically active or bioavailable inhibin B (bio-inhB) correlated with the oocyte yield in controlled ovarian stimulation (COS).

Design: Cross-sectional study.

Setting: Academic center.

Patients: Women undergoing oocyte cryopreservation.

Interventions: None.

Main outcome measures: Serum of women were sampled to measure bio-inhB at three points: baseline ("start"); middle ("mid"); and end of COS. A validated, highly specific enzyme-linked immunosorbent assay (Ansh Labs, Webster, TX) measured bio-inhB. The Spearman tests analyzed correlations between bio-inhB and other ovarian reserve markers, including age, follicle-stimulating hormone (FSH), antral follicle count (AFC), and antimüllerian hormone (AMH), and correlations between these markers and oocyte yield.

Results: A total of 144 women were included. Bioavailable inhibin B at the mid and end of COS, plus its delta, were strongly correlated with other ovarian reserve markers. As the bio-inhB concentration increased, the AFC and AMH levels also increased, whereas the FSH concentration and age decreased. Bioavailable inhibin B values, except at the start of COS, were more strongly correlated with oocyte yield than the FSH concentration (r = 0.72-0.82 vs. r = -0.44) and correlated similarly to the AFC and AMH concentration (r = 0.79 and 0.81, respectively). These correlations strengthened in those with diminished ovarian reserve, specifically age ≥35 years or AMH concentration <2 ng/mL (r = 0.71-0.86 vs. r = 0.49-0.67).

Conclusions: Predicting COS outcome is imperfect. When using a highly specific enzyme-linked immunosorbent assay, bio-inhB correlated with the oocyte yield similar to or more strongly than traditionally used ovarian reserve markers. These correlations strengthened in cases of diminished ovarian reserve. Bioavailable inhibin B provides physicians with an additional clinical tool for estimating COS outcome.

Keywords: Inhibin B; controlled ovarian stimulation; oocyte yield; ovarian reserve.

© 2021 The Author(s).

Figures

Figure 1
Figure 1
Trend of bioavailable inhibin B (bio-inhB) during controlled ovarian stimulation. Median concentration of bio-inhB at the start, middle, and end of stimulation; error bars indicate interquartile range. ∗n = 141; ∗∗n = 143.

References

    1. Speroff L., Fritz M. Lippincott Williams & Wilkins; Philadelphia: 2011. Clinical endocrinology and infertility.
    1. Klein N.A., Illingworth P.J., Groome N.P., McNeilly A.S., Battaglia D.E., Soules M.R. Decreased inhibin B secretion is associated with the monotropic FSH rise in older, ovulatory women: a study of serum and follicular fluid levels of dimeric inhibin A and B in spontaneous menstrual cycles. J Clin Endocrinol Metab. 1996;81:2742–2745.
    1. Burger H.G. Inhibin: definition and nomenclature, including related substances. J Endocrinol. 1988;117:159–160.
    1. Randolph J.F., Harlow S.D., Helmuth M.E., Zheng H., McConnell D.S. Updated assays for inhibin B and AMH provide evidence for regular episodic secretion of inhibin B but not AMH in the follicular phase of the normal menstrual cycle. Hum Reprod. 2014;29:592–600.
    1. Groome N.P., Illingworth P.J., O’Brien M., Pai R., Rodger F.E., Mather J.P. Measurement of dimeric inhibin B throughout the human menstrual cycle. J Clin Endocrinol Metab. 1996;81:1401–1405.
    1. Knauff E.A., Eijkemans M.J., Lambalk C.B., ten Kate-Booij M.J., Hoek A., Beerendonk C.C. Anti-Mullerian hormone, inhibin b, and antral follicle count in young women with ovarian failure. J Clin Endocrinol Metab. 2009;94:786–792.
    1. Hee J., MacNaughton J., Bangah M., Burger H.G. Perimenopausal patterns of gonadotrophins, immunoreactive inhibin, oestradiol and progesterone. Maturitas. 1993;18:9–20.
    1. Sowers M.R., Eyvazzadeh A.D., McConnell D., Yosef M., Jannausch M.L., Zhang D. Anti-mullerian hormone and inhibin B in the definition of ovarian aging and the menopause transition. J Clin Endocrinol Metab. 2008;93:3478–3483.
    1. Chen Y., Yu Q., Zhang Y.W., He F.F., Sun Z.Y. Value of serum inhibin B measurement in predicting ovarian response in controlled ovarian hyperstimulation for in vitro fertilization cycle. Zhonghua Fu Chan Ke Za Zhi. 2006;41:368–373.
    1. Hohmann F.P., Laven J.S., de Jong F.H., Fauser B.C. Relationship between inhibin A and B, estradiol and follicle growth dynamics during ovarian stimulation in normo-ovulatory women. Eur J Endocrinol. 2005;152:395–401.
    1. Tehraninejad E.S., Amirchaghmaghi E., Owj M., Rashidi B.H., Jalilian N., Sadeghi M. The role of inhibin B in prediction of in vitro fertilization or intracytoplasmic sperm injection cycles’ outcome. Saudi Med J. 2007;28:1028–1033.
    1. Muttukrishna S., McGarrigle H., Wakim R., Khadum I., Ranieri D.M., Serhal P. Antral follicle count, anti-mullerian hormone and inhibin B: predictors of ovarian response in assisted reproductive technology? BJOG. 2005;112:1384–1390.
    1. Muttukrishna S., Suharjono H., McGarrigle H., Sathanandan M. Inhibin B and anti-Mullerian hormone: markers of ovarian response in IVF/ICSI patients? BJOG. 2004;111:1248–1253.
    1. Eldar-Geva T., Ben-Chetrit A., Spitz I.M., Rabinowitz R., Markowitz E., Mimoni T. Dynamic assays of inhibin B, anti-Mullerian hormone and estradiol following FSH stimulation and ovarian ultrasonography as predictors of IVF outcome. Hum Reprod. 2005;20:3178–3183.
    1. Dzik A., Lambert-Messerlian G., Izzo V.M., Soares J.B., Pinotti J.A., Seifer D.B. Inhibin B response to EFORT is associated with the outcome of oocyte retrieval in the subsequent in vitro fertilization cycle. Fertil Steril. 2000;74:1114–1117.
    1. Kwee J., Elting M.W., Schats R., Bezemer P.D., Lambalk C.B., Schoemaker J. Comparison of endocrine tests with respect to their predictive value on the outcome of ovarian hyperstimulation in IVF treatment: results of a prospective randomized study. Hum Reprod. 2003;18:1422–1427.
    1. Yong P.Y., Baird D.T., Joo Thong K., McNeilly A.S., Anderson R.A. Prospective analysis of the relationships between the ovarian follicle cohort and basal FSH concentration, the inhibin response to exogenous FSH and ovarian follicle number at different stages of the normal menstrual cycle and after pituitary down-regulation. Hum Reprod. 2003;18:35–44.
    1. McIlveen M., Skull J.D., Ledger W.L. Evaluation of the utility of multiple endocrine and ultrasound measures of ovarian reserve in the prediction of cycle cancellation in a high-risk IVF population. Hum Reprod. 2007;22:778–785.
    1. Ludlow H., Muttukrishna S., Hyvönen M., Groome N.P. Development of a new antibody to the human inhibin/activin betaB subunit and its application to improved inhibin B ELISAs. J Immunol Methods. 2008;329:102–111.
    1. Practice Committee of the American Society for Reproductive Medicine Testing and interpreting measures of ovarian reserve: a committee opinion. Fertil Steril. 2015;103:e9–e17.
    1. Kalra B., Kumar A., Patel K., Patel A., Khosravi M.J. Development of a second generation Inhibin B ELISA. J Immunol Methods. 2010;362:22–31.
    1. Lawrenz B., Depret Bixio L., Coughlan C., Andersen C.Y., Melado L., Kalra B. Inhibin A-a promising predictive parameter for determination of final oocyte maturation in ovarian stimulation for IVF/ICSI. Front Endocrinol (Lausanne) 2020;11:307.
    1. Kristensen S.G., Kumar A., Kalra B., Pors S.E., Bøtkjær J.A., Mamsen L.S. Quantitative differences in TGF-β family members measured in small antral follicle fluids from women with or without PCO. J Clin Endocrinol Metab. 2019;104:6371–6384.
    1. Ferraretti A.P., La Marca A., Fauser B.C., Tarlatzis B., Nargund G., Gianaroli L. ESHRE consensus on the definition of ‘poor response’ to ovarian stimulation for in vitro fertilization: the Bologna criteria. Hum Reprod. 2011;26:1616–1624.
    1. Nelson S.M. Biomarkers of ovarian response: current and future applications. Fertil Steril. 2013;99:963–969.
    1. Barnhart K., Osheroff J. Follicle stimulating hormone as a predictor of fertility. Curr Opin Obstet Gynecol. 1998;10:227–232.
    1. Broekmans F.J., Kwee J., Hendriks D.J., Mol B.W., Lambalk C.B. A systematic review of tests predicting ovarian reserve and IVF outcome. Hum Reprod Update. 2006;12:685–718.
    1. Nelson S.M., Klein B.M., Arce J.C. Comparison of antimüllerian hormone levels and antral follicle count as predictor of ovarian response to controlled ovarian stimulation in good-prognosis patients at individual fertility clinics in two multicenter trials. Fertil Steril. 2015;103:923–930.e1.
    1. Seifer D.B., MacLaughlin D.T., Christian B.P., Feng B., Shelden R.M. Early follicular serum müllerian-inhibiting substance levels are associated with ovarian response during assisted reproductive technology cycles. Fertil Steril. 2002;77:468–471.

Source: PubMed

3
Tilaa