Skip to main content
SpringerLink
Log in

Dynamic measurements of serum inhibin B and estradiol: apredictive evaluation of ovarian response to gonadotrophin stimulation in the early stage of IVF treatment

  • Published:
Journal of Zhejiang University SCIENCE B Aims and scope Submit manuscript

Abstract

Objective

We dynamically measured serum inhibin B and estradiol in the early stage of hormonal stimulation to predict the ovarian response in in vitro fertilization (IVF) treatment.

Methods

A total of 57 patients (<40 years of age) who underwent the first cycle of long protocol IVF or introcytoplasmic sperm injection (ICSI) treatment were included. Serum inhibin B, estradiol, follicle stimulating hormone (FSH) and luteinizing hormone (LH) levels were measured four times: (1) on Day 3 of the menstrual cycle (basal); (2) on the day before the first administration of gonadotrophin (Gn) (Day 0); (3) on Day 1 of Gn therapy; and (4) on Day 5 of Gn therapy. Comparisons of these measurements with ovarian responses and pregnancy outcomes were made and analyzed statistically.

Results

(1) On Day 1 and Day 5 of recombinant FSH (rFSH) stimulation, ovarian response, i.e., numbers of follicles, oocytes, fertilized oocytes, and embryos, had a positive correlation (r s=0.46∼0.61, P=0.000) with raised inhibin B and estradiol concentrations, but a negative correlation (r s=−0.67∼−0.38, P=0.000 or P<0.01) with total rFSH dose and total days of rFSH stimulation. (2) No significant variation (P>0.05) between the pregnant and non-pregnant groups on the basis of mean age or on all hormone concentrations at four times of the IVF cycle was observed. However, all the seven patients aged >35 years did not reach pregnancy.

Conclusions

(1) Serum inhibin B and estradiol concentrations obtained shortly after Gn therapy may offer an accurate and early prediction of ovarian response; (2) Low levels of serum inhibin B and estradiol obtained shortly after Gn stimulation indicate the need for a longer period of Gn treatment and a higher daily dosage; (3) No obvious pregnancy difference among patients of age <35 years was found; however, IVF pregnancy outcome is significantly lower in women of age >35 years.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Balasch, J., Creus, M., Fábregues, F., Carmona, F., Casamitjana, R., Ascaso, C., Vanrell, J.A., 1996. Inhibin, folliclestimulating hormone, and age as predictors of ovarian response in in vitro fertilization cycles stimulated with gonadotropin-releasing hormone agonist-gonadotropin treatment. Am. J. Obstet. Gynecol., 175(5):1226–1230. [doi:10.1016/S0002-9378(96)70032-7]

    Article  PubMed  CAS  Google Scholar 

  • Bancsi, L.F., Broekmans, F.J., Eijkemans, M.J., Jong, F., Habbema, J.D., Velde, E.R., 2002. Predictors of poor ovarian response in vitro fertilization: a prospective study comparing basal markers of ovarian reserve. Fertil. Steril., 77(2):328–336. [doi:10.1016/S0015-0282(01)02983-1]

    Article  PubMed  Google Scholar 

  • Cahill, D.J., Prosser, C.J., Wardle, P.G., Ford, W.C., Hull, M.G., 1994. Relative influence of serum follicle stimulating hormone, age and other factors on ovarian response to gonadotrophin stimulation. Br. J. Obstet., 101(11):999–1002.

    CAS  Google Scholar 

  • Corson, S.L., Gutmann, J., Batzer, F.R., Wallace, H., Klein, N., Soules, M.R., 1999. Inhibin B as a test of ovarian reserve for infertile woman. Hum. Reprod., 14(11):2818–2824. [doi:10.1093/humrep/14.11.2818]

    Article  PubMed  CAS  Google Scholar 

  • Danforth, D.R., Arbogast, L.K., Mrouch, J., Kim, M.H., Kennard, E.A., Seifer, D.B., Friendman, C.I., 1998. Dimeric inhibin: a direct marker of ovarian aging. Fertil. Steril., 70(1):119–124. [doi:10.1016/S0015-0282(98)00127-7]

    Article  PubMed  CAS  Google Scholar 

  • Dzik, A., Lambert, M.G., Lzzo, V.M., Soares, J.B., Pinotti, J.A., Seifer, D.B., 2000. Ihibin B response to EFORT is associated with the outcome of oocyte retrieval in the subsequent in vitro fertilization cycle. Fertil. Steril., 74(6):1114–1117. [doi:10.1016/S0015-0282(00)01627-7]

    Article  PubMed  CAS  Google Scholar 

  • Fábregues, F., Balasch, J., Creus, M., Carmona, F., Puerto, B., Quinto, L., Casamitjana, R., Vanrell, J.A., 2000. Ovarian reserve test with human menopausal gonadotropin as a predictor of in vitro fertilization outcome. J. Assist. Reprod. Genet., 17(1):13–19. [doi:10.1023/A:1009441812247]

    Article  PubMed  Google Scholar 

  • Farhi, J., Homburg, R., Ferber, A., Orvieto, R., Ben-Rafael, Z., 1997. Non-response to ovarian stimulation in normogonadotrophic, normogonadal women: a clinical sign of impending onset of ovarian failure pre-empting the rise in the basal follicle stimulating hormone levels. Hum. Reprod., 12(2):241–243. [doi:10.1093/humrep/12.2.241]

    Article  PubMed  CAS  Google Scholar 

  • Frattarelli, J.L., Biergh, P.A., Drews, M.R., Drews, M.R., Sharara, F.I., Scott, J.R., 2000. Evaluation of basal estradiol levels in assisted reproductive technology cycles. Fertil. Steril., 74(3):518–524. [doi:10.1016/S0015-0282(00)00693-2]

    Article  PubMed  CAS  Google Scholar 

  • Galtier-Dereure, F., de Bouard, V., Picot, M.C., Vergnes, C., Humeaus, C., Bringer, J., Hédon, B., 1996. Ovarian reserve test with the Gn-releasing hormone agonist buserelin: correlation with in-vitro fertilization outcome. Hum. Reprod., 11(7):1393–1398.

    PubMed  CAS  Google Scholar 

  • Groome, N.P., Illingworth, P.J., O’Brien, M., Cooke, I., Ganesan, T.S., Baird, D.T., McNeilly, A.S., 1994. Detection of dimeric inhibin throughout the human menstrual cycle by two-site enzyme immunoassay. Clin. Endocrinol. (Oxf), 40(6):717–723. [doi:10.1111/j.1365-2265.1994.tb02504.x]

    Article  CAS  Google Scholar 

  • Groome, N.P., Illingworth, P.J., O’Brien, M., Pai, R., Rodger, F.E., Mather, J.P., McNeilly, A.S., 1996. Measurement of dimeric inhibin-B throughout the human menstrual cycle. J. Clin. Endocrinol. Metab., 81(4):1401–1405. [doi:10.1210/jc.81.4.1401]

    Article  PubMed  CAS  Google Scholar 

  • Hall, J.E., Welt, C.K., Cramer, D.W., 1999. Inhibin A and inhibin B reflect ovarian function in assisted reproduction but are less useful at predicting outcome. Hum. Reprod., 14(2):409–415. [doi:10.1093/humrep/14.2.409]

    Article  PubMed  CAS  Google Scholar 

  • Hofmann, G.E., Danforth, D.R., Seifer, D.B., 1998. Inhibin-B: the physiological basis of the clomiphene citrate challenge test for ovarian reserve screening. Fertil. Steril., 69(3):474–479. [doi:10.1016/S0015-0282(97)00531-1]

    Article  PubMed  CAS  Google Scholar 

  • Hughes, E.G., Robertson, D.M., Handelsman, D.J., Hayward, S., Healy, D.L., de Kretser, D.M., 1990. Inhibin and estradiol response to ovarian hyperstimulation: effects of age and predictive value for in vitro fertilization outcome. J. Clin. Endocrinol. Metab., 70(2):358–364.

    Article  PubMed  CAS  Google Scholar 

  • Kably, A.A., Barron, V.J., Tapia, L.R.C., Krivitsky, S.K., 2000. Effect of blood concentrations of preovulatory estradiol on the quality of eggs and pre-embryos in patients treated with fertilization in vitro. Ginecol. Obstet. Mex., 68(11):435–441.

    Google Scholar 

  • Kim, M.R., 1998. Screening for ovarian reserve. Assist. Reprod. Rev., 8(1):17–22.

    Google Scholar 

  • Kim, Y.K., Wasser, S.K., Fujimoto, V.Y., Klein, N.A., Moore, D.E., Soules, M.R., 1997. Utility of follicle stimulating hormone (FSH), luteinizing hormone ratio (LH), estradiol and FSH: LH ratio in predicting reproductive age in normal women. Hum. Reprod., 12(6):1152–1155. [doi:10.1093/humrep/12.6.1152]

    Article  PubMed  Google Scholar 

  • Laven, J.S., Fauser, B.C., 2004. Inhibins and adult ovarian function. Mol. Cell. Endocrinol., 225(1–2):37–44. [doi:10.1016/j.mce.2004.02.011]

    Article  PubMed  CAS  Google Scholar 

  • Licciardi, F.L., Liu, H.C., Rosenwaks, Z., 1995. Day 3 estradiol serum concentration as prognostic data of ovarian stimulating response and pregnancy outcome in patients undergoing in vitro fertilization. Fertil. Steril., 64(5):991–994.

    PubMed  CAS  Google Scholar 

  • Lockwood, G.M., Muttukrishna, S., Groome, N.P., Knight, P.G., Ledger, W.L., 1996. Circulating inhibins and activin A during GnRH-analogue down-regulation and ovarian hyperstimulation with recombinant FSH for in-vitro fertilization-embryo transfer. Clin. Endocrinol., 45(6):741–748. [doi:10.1046/j.1365-2265.1996.8510861.x]

    Article  CAS  Google Scholar 

  • Maroulis, G.B., 1991. Effect of aging on fertility and pregnancy. Semin. Reprod. Med., 9(3):165–175. [doi:10.1055/s-2007-1019407]

    Article  Google Scholar 

  • Mosher, W.D., Pratt, W.F., 1990. Fecundity and Infertility in the United States, 1965–1988. Advanced Data from Vital and Health Statistics, No. 192, Dec. 4. National Center for Health Statistics, Hyattsville, MD.

    Google Scholar 

  • Mosher, W.D., Pratt, W.F., 1991. Fecundity and infertility in the United States: incidence and trends. Fertil. Steril., 56(2):192–193.

    PubMed  CAS  Google Scholar 

  • Mukherjee, T., Copperman, A.B., Lapinski, R., Sandler, B., Bustillo, M., Grunfeld, L., 1996. An elevated Day 3 follicle stimulating hormone: luteinizing hormone ratio (FSH/LH) in the presence of a normal Day 3 FSH predicts a poor response to controlled ovarian hyperstimulation. Fertil. Steril., 65(3):588–593.

    PubMed  CAS  Google Scholar 

  • Navot, D., Rosenwaks, Z., Margalioth, E.J., 1987. Prognostic assessment of female fecundity. Lancet, 330(8560):645–647. doi:10.1016/S0140-6736(87)92439-1]

    Article  Google Scholar 

  • Navot, D., Bergh, P.A., Laufer, N., 1992. Ovarian hyperstimulation syndrome in novel reproductive technologies: prevention and treatment. Fertil. Steril., 58(2):249–261.

    PubMed  CAS  Google Scholar 

  • Pellicer, A., Valbuena, D., Cano, F., Remohi, J., Simon, C., 1996. Lower implantation rates in high responders: evidence for altered endocrine milieu during the preimplantation period. Fertil. Steril., 65(6):1190–1195.

    PubMed  CAS  Google Scholar 

  • Peñarrubia, J., Balasch, J., Fábregues, F., Carmona, F., Casamitjana, R., Moreno, V., Calafell, J.M., Vanrell, J.A., 2000. Day 5 inhibin B serum concentrations as predictors of assisted reproductive technology outcome in cycles stimulated with gonadotrophin-releasing hormone agonistgonadotrophin treatment. Hum. Reprod., 15(7):1499–1504.

    Article  PubMed  Google Scholar 

  • Phelps, J.Y., Levine, A.S., Hickman, T.N., Zacur, H.A., Wallach, E.E., Hinton, E.L., 1998. Day 4 estradiol levels predict pregnancy success in women undergoing controlled ovarian hyperstimulation for IVF. Fertil. Steril., 69(6):1015–1019. [doi:10.1016/S0015-0282(98)00059-4]

    Article  PubMed  CAS  Google Scholar 

  • Porchet, H.C., Cotonnec, J.Y.L., Loumaye, E., 1994. Clinical pharmacology of recombinant human follicle-stimulating hormone. III. Pharmacokinetic-pharmacodynamic modelling after repeated subcutaneous administration. Fertil. Steril., 61(4):687–695.

    PubMed  CAS  Google Scholar 

  • Ranieri, D.M., Phophong, P., Khadum, I., Meo, F., Davis, C., Serhal, P., 2001. Simultaneous evaluation of basal FSH and estradiol response to GnRH analogue (F-G-test) allows effective drug regimen selection for IVF. Hum. Reprod., 16(4):673–675. [doi:10.1093/humrep/16.4.673]

    Article  PubMed  CAS  Google Scholar 

  • Ravhon, A., Lavery, S., Michael, S., Donaldson, M., Margara, R., Trew, G., Winston, R., 2000. Dynamic assays of inhibin B and estradiol following buserelin acetate administration as predictors of ovarian response in IVF. Hum. Reprod., 15(11):2297–2301. [doi:10.1093/humrep/15.11.2297]

    Article  PubMed  CAS  Google Scholar 

  • Roest, J., van Heusden, A.M., Mous, H., Zeilmaker, G.H., Verhoeff, A., 1996. The ovarian response as a predictor for successful in vitro fertilization treatment after the age of 40 years. Fertil. Steril., 66(6):969–973.

    PubMed  CAS  Google Scholar 

  • Rotsztejn, D.A., Asch, R.H., 1991. Effect ofagingon assisted reproductive technologies (ART): experience from oocyte donation. Semin. Reprod. Med., 9(3):272–279. [doi:10.1055/s-2007-1019419]

    Article  Google Scholar 

  • Scott, R.T., Hofmann, G.E., 1995. Prognostic assessment of ovarian reserve. Fertil. Steril., 63(1):1–11.

    PubMed  Google Scholar 

  • Scott, R.T., Toner, J.P., Muasher, S.J., Oehninger, S., Robinson, S., Rosenwaks, Z., 1989. Follicle stimulating hormone levels on cycle Day 3 are predictive of in vitro fertilization outcome. Fertil. Steril., 51(4):651–654.

    PubMed  CAS  Google Scholar 

  • Seifer, D.B., Lambert-Messerlian, G., Hogan, J.W., Gardiner, A.C., Blazar, A.S., Berk, C.A., 1997. Day 3 serum inhibin-B is predictive of assisted reproductive technologies outcome. Fertil. Steril., 67(1):110–114. [doi:10.1016/S0015-0282(97)81865-1]

    Article  PubMed  CAS  Google Scholar 

  • Seifer, D.B., Scott, R.T., Bergh, P.A., Abrogast, L.K., Friedman, C.I., Mack, C.K., Danforth, D.R., 1999. Women with declining ovarian reserve may demonstrate a decrease in Day 3 serum inhibin B before a rise in Day 3 follicle-stimulating hormone. Fertil. Steril., 72(1):63–65. [doi:10.1016/S0015-0282(99)00193-4]

    Article  PubMed  CAS  Google Scholar 

  • Shanthi, M.K., Harris, S., Hugh, M.G., Muttukrishna, S., 2004. Inhibin B and anti-Mullerian hormone: markers of ovarian response in IVF/ICSI patients? Int. J. Obstet. Gynaecol., 111(Suppl.):1248–1253.

    Google Scholar 

  • Sharara, F.I., McClamrock, H.D., 1999. High estradiol levels and high oocyte yield are not detrimental to in vitro fertilization outcome. Fertil. Steril., 72(3):401–405. [doi:10.1016/S0015-0282(99)00293-9]

    Article  PubMed  CAS  Google Scholar 

  • Simon, C., Cano, F., Valbuena, D., Remohi, J., Pellicer, A., 1995. Clinical evidence for a detrimental effect on uterine receptivity of high serum estradiol levels in high and normal responder patients. Hum. Reprod., 10(9):2432–2437.

    PubMed  CAS  Google Scholar 

  • Simon, C., Garcia, V.J.J., Valbuena, D., Painado, J.A., Moreno, C., Remohí, J., Pellicer, A., 1998. Increasing uterine receptivity by decreasing estradiol levels during the preimplantation period in high responders with the use of a follicle-stimulating hormone step-down regimen. Fertil. Steril., 70(2):234–239. [doi:10.1016/S0015-0282(98)00140-X]

    Article  PubMed  CAS  Google Scholar 

  • Spandorfer, S., Chung, P., Kligman, I., Liu, H.C., Davis, O.K., Rosenwake, Z., 2000. An analysis of the effect of age on implantation rates. J. Assist. Reprod. Genet., 17(6):303–306. [doi:10.1023/A:1009422725434]

    Article  PubMed  CAS  Google Scholar 

  • Toner, J.P., Brzyski, R.G., Oehninger, S., Veeck, L.L., Simonetti, S., Muasher, S.J., 1991a. Combined impact of the number of pre-ovulatory oocytes and cryopreservation on IVF outcome. Hum. Reprod., 14:284–289.

    Google Scholar 

  • Toner, J.P., Philput, C.B., Jones, G.S., Muasher, S.J., 1991b. Basal follicle stimulating hormone level is a better predictor of in vitro fertilization performance than age. Fertil. Steril., 55(4):784–791.

    PubMed  CAS  Google Scholar 

  • Urbancsek, J., Hauzman, E., Klinga, K., Rabe, T., Papp, Z., Strowitzki, T., 2005a. Use of serum inhibin B levels at the start of ovarian stimulation and at oocyte pickup in the prediction of assisted reproduction treatment outcome. Fertil. Steril., 83(2):341–348. [doi:10.1016/j.fertnstert.2004.06.065]

    Article  PubMed  CAS  Google Scholar 

  • Urbancsek, J., Hauzman, E.E., Murber, A., Lagarde, A.R., Rabe, T., Papp, Z., Strowitzki, T., 2005b. Serum CA-125 and inhibin B levels in the prediction of ovarian response to gonadotropin stimulation in in vitro fertilization cycles. Gynecol. Endocrinol., 21(1):38–44. [doi:10.1080/09513590500099438]

    Article  PubMed  CAS  Google Scholar 

  • Watt, A.H., Legedza, A.T., Ginsburg, E.S., Barbieri, R.L., Clarke, R.N., Hornstein, M.D., 2000. The prognostic value of age and follicle-stimulating hormone levels in women over forty years of age undergoing in vitro fertilization. J. Assist. Reprod. Genet., 17(5):264–268. [doi:10.1023/A:1009458332567]

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Reproductive Endocrinology, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, 310006, China

    Ming-fang Miao & He-feng Huang

Authors
  1. Ming-fang Miao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. He-feng Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to He-feng Huang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Miao, Mf., Huang, Hf. Dynamic measurements of serum inhibin B and estradiol: apredictive evaluation of ovarian response to gonadotrophin stimulation in the early stage of IVF treatment. J. Zhejiang Univ. Sci. B 10, 35–45 (2009). https://doi.org/10.1631/jzus.B0820029

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1631/jzus.B0820029

Key words

CLC number

Search

Navigation