Skip to main content
Journal of Assisted Reproduction and Genetics logoLink to Journal of Assisted Reproduction and Genetics
. 2005 Feb;22(2):65–74. doi: 10.1007/s10815-005-1495-3

Single and Repeated GnRH Agonist Stimulation Tests Compared With Basal Markers of Ovarian Reserve in the Prediction of Outcome in IVF

D J Hendriks 1,, F J Broekmans 1, L F J M M Bancsi 1, C W N Looman 2, F H de Jong 3, E R te Velde 1
PMCID: PMC3455479  PMID: 15844731

Abstract

Purpose: To study the value of a single or repeated GnRH agonist stimulation test (GAST) in predicting outcome in IVF compared to basal ovarian reserve tests.

Methods: A total of 57 women was included. In a cycle prior to the IVF treatment, on day 3, an antral follicle count (AFC) was performed and blood taken for basal FSH, inhibin B and E2 measurements, followed by a subcutaneous injection of 100 μg triptorelin for the purpose of the GAST. Twenty-four hours later blood sampling was repeated. All the tests were repeated in a subsequent cycle. From the GAST E2 and inhibin B response were used as test parameters. The outcome measures were poor ovarian response and ongoing pregnancy. Group comparisons were done using the Mann– Whitney or chi-square test. Univariate and multivariate logistic regression was applied to assess which test revealed the highest predictive accuracy as expressed in the area under receiver-operating characteristic curve (ROCAUC). Clinical value was compared by calculating classical test characteristics for the best logistic models.

Results: All the basal and GAST variables were significantly different in the poor responders (n = 19) compared to normal responders (n = 38). In the univariate analysis on cycle 1 tests the AFC was the best predictor for poor ovarian response, while in cycle 2 the E2 response in the GAST performed best (ROCAUC of 0.91 for both). Multivariate analysis of the basal variables led to the selection of AFC and inhibin B in cycle 1, yielding a ROCAUC of 0.96. Mean E2 response was selected in a multivariate analysis of the repeated GAST variables (ROCAUC 0.91). At a specificity level of ∼0.90, several logistic models including GAST variables appeared to have a sensitivity (∼0.80), positive predictive value (∼0.82) and false positive rate (∼0.18), comparable to a logistic model containing AFC and inhibin B. None of the test variables showed a significant relation with ongoing pregnancy.

Conclusions: The GAST has a rather good ability to predict poor response in IVF. However, comparing the predictive accuracy and clinical value of the GAST with a day 3 AFC and inhibin B, it appeared that neither a single nor a repeated GAST performed better. In addition, the predictive ability towards ongoing pregnancy is poor. Therefore, the use of the GAST as a predictor of outcome in IVF should not be advocated.

Key words: Antral follicle count, GnRH agonist stimulation test, inhibin B, in vitro fertilization, ovarian reserve

Full Text

The Full Text of this article is available as a PDF (110.1 KB).

References

  • 1.te Velde ER, Pearson PL. The variability of female reproductive ageing. Hum Reprod Update. 2002;8:141–154. doi: 10.1093/humupd/8.2.141. [DOI] [PubMed] [Google Scholar]
  • 2.Toner JP, Philput CB, Jones GS, Muasher SJ. Basal follicle-stimulating hormone level is a better predictor of in vitro fertilization performance than age. Fertil Steril. 1991;55:784–791. doi: 10.1016/s0015-0282(16)54249-6. [DOI] [PubMed] [Google Scholar]
  • 3.Bancsi LF, Huijs AM, den Ouden CT, Broekmans FJ, Looman CW, Blankenstein MA, te Velde ER. Basal follicle-stimulating hormone levels are of limited value in predicting ongoing pregnancy rates after in vitro fertilization. Fertil Steril. 2000;73:552–557. doi: 10.1016/s0015-0282(99)00552-x. [DOI] [PubMed] [Google Scholar]
  • 4.Bancsi LF, Broekmans FJ, Mol BW, Habbema JD, te Velde ER. Performance of basal follicle-stimulating hormone in the prediction of poor ovarian response and failure to become pregnant after in vitro fertilization: a meta-analysis. Fertil Steril. 2003;79:1091–1100. doi: 10.1016/s0015-0282(03)00078-5. [DOI] [PubMed] [Google Scholar]
  • 5.Loumaye E, Billion JM, Mine JM, Psalti I, Pensis M, Thomas K. Prediction of individual response to controlled ovarian hyperstimulation by means of a clomiphene citrate challenge test. Fertil Steril. 1990;53:295–301. doi: 10.1016/s0015-0282(16)53284-1. [DOI] [PubMed] [Google Scholar]
  • 6.Navot D, Rosenwaks Z, Margalioth EJ. Prognostic assessment of female fecundity. Lancet. 1987;2:645–647. doi: 10.1016/S0140-6736(87)92439-1. [DOI] [PubMed] [Google Scholar]
  • 7.Scott RT, Leonardi MR, Hofmann GE, Illions EH, Neal GS, Navot D. A prospective evaluation of clomiphene citrate challenge test screening of the general infertility population. Obstet Gynecol. 1993;82:539–544. [PubMed] [Google Scholar]
  • 8.Winslow KL, Toner JP, Brzyski RG, Oehninger SC, Acosta AA, Muasher SJ. The gonadotropin-releasing hormone agonist stimulation test— A sensitive predictor of performance in the flare-up in vitro fertilization cycle. Fertil Steril. 1991;56:711–717. doi: 10.1016/s0015-0282(16)54604-4. [DOI] [PubMed] [Google Scholar]
  • 9.Fanchin R, deZiegler D, Olivennes F, Taieb J, Dzik A, Frydman R. Exogenous follicle stimulating hormone ovarian reserve test (EFORT): A simple and reliable screening test for detecting ‘poor responders’ in in-vitro fertilization. Hum Reprod. 1994;9:1607–1611. doi: 10.1093/oxfordjournals.humrep.a138760. [DOI] [PubMed] [Google Scholar]
  • 10.Hall JE, Welt CK, Cramer DW. Inhibin A and inhibin B reflect ovarian function in assisted reproduction but are less useful at predicting outcome. Hum Reprod. 1999;14:409–415. doi: 10.1093/humrep/14.2.409. [DOI] [PubMed] [Google Scholar]
  • 11.Seifer DB, MacLaughlin DT, Christian BP, Feng B, Shelden RM. Early follicular serum mullerian-inhibiting substance levels are associated with ovarian response during assisted reproductive technology cycles. Fertil Steril. 2002;77:468–471. doi: 10.1016/s0015-0282(01)03201-0. [DOI] [PubMed] [Google Scholar]
  • 12.Van Rooij IA, Broekmans FJ, te Velde ER, Fauser BC, Bancsi LF, de Jong FH, Themmen AP. Serum anti-Mullerian hormone levels: a novel measure of ovarian reserve. Hum Reprod. 2002;17:3065–3071. doi: 10.1093/humrep/17.12.3065. [DOI] [PubMed] [Google Scholar]
  • 13.Chang MY, Chiang CH, Hsieh TT, Soong Yk, Hsu KH. Use of the antral follicle count to predict the outcome of assisted reproductive technologies. Fertil Steril. 1998;69:505–510. doi: 10.1016/S0015-0282(97)00557-8. [DOI] [PubMed] [Google Scholar]
  • 14.Tomas C, Nuojua-Huttunen S, Martikainen H. Pretreatment transvaginal ultrasound examination predicts ovarian responsiveness to gonadotrophins in in-vitro fertilization. Hum Reprod. 1997;12:220–223. doi: 10.1093/humrep/12.2.220. [DOI] [PubMed] [Google Scholar]
  • 15.Bancsi LF, Broekmans FJ, Eijkemans MJ, de Jong FH, Habbema JD, te Veld ER. Predictors of poor ovarian response in in vitro fertilization: A prospective study comparing basal markers of ovarian reserve. Fertil Steril. 2002;77:328–336. doi: 10.1016/S0015-0282(01)02983-1. [DOI] [PubMed] [Google Scholar]
  • 16.Avrech OM, Royburt M, Sabah G, Zukerman Z, Pinkas H, Amit S, Ovadia J, Fisch B. The initial flare-up induced by gonadotropin releasing hormone agonist may serve as a predictor of ovarian response in the current IVF-ET treatment cycle in normogonadotropic women aged 40– 48 years. J Assist Reprod Genet. 1996;13:395–400. doi: 10.1007/BF02066171. [DOI] [PubMed] [Google Scholar]
  • 17.Dzik A, Lambert-Messerlian G, Izzo VM, Soares JB, Pinotti JA, Seifer DB. 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. doi: 10.1016/s0015-0282(00)01627-7. [DOI] [PubMed] [Google Scholar]
  • 18.Eldar-Geva T, Margalioth EJ, Ben Chetrit A, Gal M, Robertson DM, Healy DL, Diamant YZ, Spitz IM. Serum inhibin B levels measured early during FSH administration for IVF may be of value in predicting the number of oocytes to be retrieved in normal and low responders. Hum Reprod. 2002;17:2331–2337. doi: 10.1093/humrep/17.9.2331. [DOI] [PubMed] [Google Scholar]
  • 19.Elting MW, Kwee J, Schats R, Rekers-Mombarg LT, Schoemaker J. The rise of estradiol and inhibin B after acute stimulation with follicle-stimulating hormone predict the follicle cohort size in women with polycystic ovary syndrome, regularly menstruating women with polycystic ovaries, and regularly menstruating women with normal ovaries. J Clin Endocrinol Metab. 2001;86:1589–1595. doi: 10.1210/jcem.86.4.7396. [DOI] [PubMed] [Google Scholar]
  • 20.Galtier-Dereure F, De Bouard V, Picto MC, Vergnes C, Humeau C, Bringer J, Hedon B. Ovarian reserve test with the gonadotrophin-releasing hormone agonist buserelin: Correlation with in-vitro fertilization outcome. Hum Reprod. 1996;11:1393–1398. doi: 10.1093/oxfordjournals.humrep.a019406. [DOI] [PubMed] [Google Scholar]
  • 21.Ranieri DM, Quinn F, Makhlouf A, Khadum I, Ghutmi W, McGarrigle H, Davies M, Serhal P. Simultaneous evaluation of basal follicle-stimulating hormone and 17 beta-estradiol response to gonadotropin-releasing hormone analogue stimulation: an improved predictor of ovarian reserve. Fertil Steril. 1998;70:227–233. doi: 10.1016/s0015-0282(98)00159-9. [DOI] [PubMed] [Google Scholar]
  • 22.Ravhon A, Lavery S, Michael S, Donaldson M, Margara R, Trew G, Winston R. Dynamic assays of inhibin B and oestradiol following buserelin acetate administration as predictors of ovarian response in IVF. Hum Reprod. 2000;15:2297–2301. doi: 10.1093/humrep/15.11.2297. [DOI] [PubMed] [Google Scholar]
  • 23.Padilla SL, Bayati J, Garcia JE. Prognostic value of the early serum estradiol response to leuprolide acetate in in vitro fertilization. Fertil Steril. 1990;53:288–294. doi: 10.1016/s0015-0282(16)53283-x. [DOI] [PubMed] [Google Scholar]
  • 24.Bukman A, Heineman MJ. Ovarian reserve testing and the use of prognostic models in patients with subfertility. Hum Reprod Update. 2001;7:581–590. doi: 10.1093/humupd/7.6.581. [DOI] [PubMed] [Google Scholar]
  • 25.Broekmans FJ, Bernardus RE, Broeders A, Berkhout G, Schoemaker J. Pituitary responsiveness after administration of a GnRH agonist depot formulation: Decapeptyl CR. Clin Endocrinol (Oxf) 1993;38:579–587. doi: 10.1111/j.1365-2265.1993.tb02138.x. [DOI] [PubMed] [Google Scholar]
  • 26.Groome NP, Illingworth PJ, O’Brien M, Pai R, Rodger FE, Mather JP, McNeilly AS. Measurement of dimeric inhibin B throughout the human menstrual cycle. J Clin Endocrinol Metab. 1996;81:1401–1405. doi: 10.1210/jcem.81.4.8636341. [DOI] [PubMed] [Google Scholar]
  • 27.van Kooij RJ, Looman CW, Habbema JD, Dorland M, te Velde ER. Age-dependent decrease in embryo implantation rate after in vitro fertilization. Fertil Steril. 1996;66:769–775. doi: 10.1016/s0015-0282(16)58634-8. [DOI] [PubMed] [Google Scholar]
  • 28.Surrey ES, Bower J, Hill DM, Ramsey J, Surrey MW. Clinical and endocrine effects of a microdose GnRH agonist flare regimen administered to poor responders who are undergoing in vitro fertilization. Fertil Steril. 1998;69:419–424. doi: 10.1016/s0015-0282(97)00575-x. [DOI] [PubMed] [Google Scholar]
  • 29.Toukhy T El, Khalaf Y, Hart R, Taylor A, Braude P. Young age does not protect against the adverse effects of reduced ovarian reserve— An eight year study. Hum Reprod. 2002;17:1519–1524. doi: 10.1093/humrep/17.6.1519. [DOI] [PubMed] [Google Scholar]
  • 30.Van Rooij IA, Bancsi LF, Broekmans FJ, Looman CW, Habbema JD, te Velde ER. Women older than 40 years of age and those with elevated follicle-stimulating hormone levels differ in poor response rate and embryo quality in in vitro fertilization. Fertil Steril. 2003;79:482–488. doi: 10.1016/s0015-0282(02)04839-2. [DOI] [PubMed] [Google Scholar]
  • 31.Moody Y, editor. Fertility Assessment and Treatment for People With Fertility Problems. Clinical Guideline 11, NHS. London: RCOG Press; 2004. p. 85. [PubMed] [Google Scholar]
  • 32.Bancsi LF, Broekmans FJ, Looman CW, Habbema JD, te Velde ER. Predicting poor ovarian response in IVF: use of repeat basal FSH measurement. J Reprod Med. 2004;49:187–194. [PubMed] [Google Scholar]
  • 33.Bancsi LF, Broekmans FJ, Looman CW, Habbema JD, te Velde ER. Impact of repeated antral follicle counts on the prediction of poor ovarian response in women undergoing in vitro fertilization. Fertil Steril. 2004;81:35–41. doi: 10.1016/j.fertnstert.2003.06.011. [DOI] [PubMed] [Google Scholar]
  • 34.Gulekli B, Bulbul Y, Onvural A, Yorukoglu K, Posaci C, Demir N, Erten O. Accuracy of ovarian reserve tests. Hum Reprod. 1999;14:2822–2826. doi: 10.1093/humrep/14.11.2822. [DOI] [PubMed] [Google Scholar]
  • 35.Ozkaya O, Kaya H, Sezik M, Akyürek, Ozbasar D. The value of laboratory tests and ultrasonography in evaluating ovarian response to ovulation induction treatment with low-dose recombinant follicle-stimulating hormone. Int J Fertil Womens Med. 2004;49:83–87. [PubMed] [Google Scholar]
  • 36.Scheffer GJ, Broekmans FJ, Looman CW, Blankenstein M, Fauser BC, de Jong FH, te Velde ER. The number of antral follicles in normal women with proven fertility is the best reflection of reproductive age. Hum Reprod. 2003;18:700–706. doi: 10.1093/humrep/deg135. [DOI] [PubMed] [Google Scholar]
  • 37.Csemiczky G, Harlin J, Fried G. Predictive power of clomiphene citrate challenge test for failure of in vitro fertilization treatment. Acta Obstet Gynecol Scand. 2002;81:954–961. doi: 10.1034/j.1600-0412.2002.811010.x. [DOI] [PubMed] [Google Scholar]
  • 38.Tanbo T, Dale PO, Lunde O, Norman N, Abyholm T. Prediction of response to controlled ovarian hyperstimulation: A comparison of basal and clomiphene citrate-stimulated follicle-stimulating hormone levels. Fertil Steril. 1992;57:819–824. doi: 10.1016/s0015-0282(16)54965-6. [DOI] [PubMed] [Google Scholar]
  • 39.Lawson R, El Toukhy T, Kassab A, Taylor A, Braude P, Parsons J, Seed P. Poor response to ovulation induction is a stronger predictor of early menopause than elevated basal FSH: a life table analysis. Hum Reprod. 2003;18:527–533. doi: 10.1093/humrep/deg101. [DOI] [PubMed] [Google Scholar]
  • 40.Roest J, van Heusden AM, Mous H, Zeilmaker GH, Verhoeff A. The ovarian response as a predictor for successful in vitro fertilization treatment after the age of 40 years. FertilSteril. 1996;66:969–973. doi: 10.1016/s0015-0282(16)58691-9. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Assisted Reproduction and Genetics are provided here courtesy of Springer Science+Business Media, LLC

RESOURCES