Skip to main content
Top
Published in: Journal of Assisted Reproduction and Genetics 1/2013

01-01-2013 | ASSISTED REPRODUCTION TECHNOLOGIES

Starting and resulting testosterone levels after androgen supplementation determine at all ages in vitro fertilization (IVF) pregnancy rates in women with diminished ovarian reserve (DOR)

Authors: Norbert Gleicher, Ann Kim, Andrea Weghofer, Aya Shohat-Tal, Emanuela Lazzaroni, Ho-Joon Lee, David H. Barad

Published in: Journal of Assisted Reproduction and Genetics | Issue 1/2013

Login to get access

Abstract

Purpose

To investigate whether androgen conversion rates after supplementation with dehydroepiandrosterone (DHEA) differ, and whether differences between patients with diminished ovarian reserve (DOR) are predictive of pregnancy chances in association with in vitro fertilization (IVF).

Methods

In a prospective cohort study we investigated 213 women with DOR, stratified for age (≤38 or >38 years) and ovarian FMR1 genotypes/sub-genotypes. All women were for at least 6 weeks supplemented with 75 mg of DHEA daily prior to IVF, between initial presentation and start of 1st IVF cycles. Levels of DHEA, DHEA-sulfate (DHEAS), total T (TT) and free T (FT) at baseline (BL) and IVF cycle start (CS) were then compared between conception and non-conception cycles.

Results

Mean age for the study population was 41.5 ± 4.4 years. Forty-seven IVF cycles (22.1 %) resulted in clinical pregnancy. Benefits of DHEA on pregnancy rates were statistically associated with efficiency of androgen conversion from DHEA to T and amplitude of T gain. Younger women converted significantly more efficiently than older females, and selected FMR1 genotypes/sub-genotypes converted better than others. FSH/androgen and AMH/androgen ratios represent promising new predictors of IVF pregnancy chances in women with DOR.

Conclusions

DOR at all ages appears to represent an androgen-deficient state, benefitting from androgen supplementation. Efficacy of androgen supplementation with DHEA, however, varies depending on female age and FMR1 genotype/sub-genotype. Further clarification of FMR1 effects should lead to better individualization of androgen supplementation, whether via DHEA or other androgenic compounds.
Literature
1.
go back to reference Gleicher N, Weghofer A, Barad DH. The role of androgens in follicle maturation and ovulation induction: friend or foe of infertility treatment? Reprod Biol Endocrinol. 2011;9:116.PubMedCrossRef Gleicher N, Weghofer A, Barad DH. The role of androgens in follicle maturation and ovulation induction: friend or foe of infertility treatment? Reprod Biol Endocrinol. 2011;9:116.PubMedCrossRef
2.
go back to reference Sen A, Hammes SR. Granulosa-cell specific androgen receptors are critical regulators of ovarian development and function. Mol Endorcinol. 2010;24:1393–403.CrossRef Sen A, Hammes SR. Granulosa-cell specific androgen receptors are critical regulators of ovarian development and function. Mol Endorcinol. 2010;24:1393–403.CrossRef
3.
go back to reference Barad DH, Gleicher N. Increased oocyte production after treatment with dehydroepiandrosterone. Fertil Steril. 2005;84(756):e1–3. Barad DH, Gleicher N. Increased oocyte production after treatment with dehydroepiandrosterone. Fertil Steril. 2005;84(756):e1–3.
4.
go back to reference Mahajan DK. Polycystic ovarian disease: animal models. Endocrinol Metab Clin North Am. 1988;17:705–32.PubMed Mahajan DK. Polycystic ovarian disease: animal models. Endocrinol Metab Clin North Am. 1988;17:705–32.PubMed
5.
go back to reference Luchetti CG, Solano ME, Sander V, Arcos ML, Gonzales C, et al. Effects of dehydroepiandrosterone on ovarian cystogenesis and immune function. J Reprod Immunol. 2004;64:59–74.PubMedCrossRef Luchetti CG, Solano ME, Sander V, Arcos ML, Gonzales C, et al. Effects of dehydroepiandrosterone on ovarian cystogenesis and immune function. J Reprod Immunol. 2004;64:59–74.PubMedCrossRef
6.
go back to reference Gleicher N, Barad DH. Dehydroepiandrosterone (DHEA) supplementation in diminished ovarian reserve. Reprod Biol Endocrinol. 2011;9:67.PubMedCrossRef Gleicher N, Barad DH. Dehydroepiandrosterone (DHEA) supplementation in diminished ovarian reserve. Reprod Biol Endocrinol. 2011;9:67.PubMedCrossRef
7.
go back to reference Buster JE, Casson PR, Straughn AB, Dale D, Umstot ES, et al. Postmenopausal steroid replacement with micronized dehydroepiandrosterone : preliminary oral bioavailability and dose proportionality studies Am J Obstet Gynecol. 1992;66:1163–8. Buster JE, Casson PR, Straughn AB, Dale D, Umstot ES, et al. Postmenopausal steroid replacement with micronized dehydroepiandrosterone : preliminary oral bioavailability and dose proportionality studies Am J Obstet Gynecol. 1992;66:1163–8.
8.
go back to reference Barad DH, Brill H, Gleicher N. Update on the use of dehydroepiandrosterone supplementation among women with diminished ovarian function. J Assist Reprod Genet. 2007;24:629–34.PubMedCrossRef Barad DH, Brill H, Gleicher N. Update on the use of dehydroepiandrosterone supplementation among women with diminished ovarian function. J Assist Reprod Genet. 2007;24:629–34.PubMedCrossRef
9.
go back to reference Weghofer A, Kim A, Barad DH, Gleicher N. (2012) The impact of androgens on pregnancy potential in women with diminished ovarian reserve. Hum Reprod. In press. Weghofer A, Kim A, Barad DH, Gleicher N. (2012) The impact of androgens on pregnancy potential in women with diminished ovarian reserve. Hum Reprod. In press.
10.
go back to reference Eldar-Geva T, Margalioth EJ, Gal M, Ben-Chetrit A, Algur N, et al. Serum anti-Mullerian hormone levels during controlled ovarian stimulation in women with polycystic ovaries with and without hyperandrogenism. Hum Reprod. 2005;20:1814–9.PubMedCrossRef Eldar-Geva T, Margalioth EJ, Gal M, Ben-Chetrit A, Algur N, et al. Serum anti-Mullerian hormone levels during controlled ovarian stimulation in women with polycystic ovaries with and without hyperandrogenism. Hum Reprod. 2005;20:1814–9.PubMedCrossRef
11.
go back to reference Kristensen SL, Ramlau-Bansen CH, Anderson CY, Ernst E, Olsen SF, et al. The association between circulating levels of antimüllerian hormone and follicle number, androgens, and menstrual cycle characteristics in young women. Fertil Steril. 2012;97:779–85.PubMedCrossRef Kristensen SL, Ramlau-Bansen CH, Anderson CY, Ernst E, Olsen SF, et al. The association between circulating levels of antimüllerian hormone and follicle number, androgens, and menstrual cycle characteristics in young women. Fertil Steril. 2012;97:779–85.PubMedCrossRef
12.
go back to reference Frattarelli JL, Peterson EH. Effect of androgen levels on in vitro fertilization cycles. Fertil Steril. 2004;81:1713–4.PubMedCrossRef Frattarelli JL, Peterson EH. Effect of androgen levels on in vitro fertilization cycles. Fertil Steril. 2004;81:1713–4.PubMedCrossRef
13.
go back to reference Frattarelli JL, Gerber MD. Basal and cycle androgen levels correlate with in vitro stimulation parameters but do not predict pregnancy outcome. Fertil Steril. 2006;86:51–7.PubMedCrossRef Frattarelli JL, Gerber MD. Basal and cycle androgen levels correlate with in vitro stimulation parameters but do not predict pregnancy outcome. Fertil Steril. 2006;86:51–7.PubMedCrossRef
14.
go back to reference Gleicher N, Weghofer A, Barad DH. Ovarian reserve determinations suggest new function of FMR1 (fragile X gene) in regulating ovarian aging. Reprod Biomed Online. 2010;20:768–75.PubMedCrossRef Gleicher N, Weghofer A, Barad DH. Ovarian reserve determinations suggest new function of FMR1 (fragile X gene) in regulating ovarian aging. Reprod Biomed Online. 2010;20:768–75.PubMedCrossRef
15.
go back to reference Gleicher N, Weghofer A, Lee IH, Barad DH. FMR1 genotype with autoimmunity-associated polycystic ovary-like phenotype and decreased pregnancy chance. PLoS One. 2010;5:e15303.PubMedCrossRef Gleicher N, Weghofer A, Lee IH, Barad DH. FMR1 genotype with autoimmunity-associated polycystic ovary-like phenotype and decreased pregnancy chance. PLoS One. 2010;5:e15303.PubMedCrossRef
16.
go back to reference Gleicher N, Weghofer A, Lee I, Barad DH. Association of FMR1 genotypes with in vitro fertilization (IVF) outcomes based on ethnicity/race. PLoS One. 2011;6:e18781.PubMedCrossRef Gleicher N, Weghofer A, Lee I, Barad DH. Association of FMR1 genotypes with in vitro fertilization (IVF) outcomes based on ethnicity/race. PLoS One. 2011;6:e18781.PubMedCrossRef
17.
go back to reference Barad DH, Weghofer A, Gleicher N. Age-specific levels of basal follicle-stimulating hormone assessment of ovarian function. Obstet Gynecol. 2007;109:1404–10.PubMedCrossRef Barad DH, Weghofer A, Gleicher N. Age-specific levels of basal follicle-stimulating hormone assessment of ovarian function. Obstet Gynecol. 2007;109:1404–10.PubMedCrossRef
18.
go back to reference Barad DH, Weghofer A, Gleicher N. Utility of age-specific serum anti-Müllerian hormone concentrations. Reprod Biomed Online. 2011;22:284–91.PubMedCrossRef Barad DH, Weghofer A, Gleicher N. Utility of age-specific serum anti-Müllerian hormone concentrations. Reprod Biomed Online. 2011;22:284–91.PubMedCrossRef
19.
go back to reference Gleicher N, Weghofer A, Barad DH. Defining ovarian reserve to better understand ovarian aging. Reprod Biol Endocrinol. 2011;9:23.PubMedCrossRef Gleicher N, Weghofer A, Barad DH. Defining ovarian reserve to better understand ovarian aging. Reprod Biol Endocrinol. 2011;9:23.PubMedCrossRef
20.
go back to reference Lennie S, Smitz J. Functional Ar signaling is evident in an in vitro mouse follicle culture bioassay that encompasses most stages of folliculogenesis. Biol Reprod. 2009;80:685–95.CrossRef Lennie S, Smitz J. Functional Ar signaling is evident in an in vitro mouse follicle culture bioassay that encompasses most stages of folliculogenesis. Biol Reprod. 2009;80:685–95.CrossRef
21.
go back to reference Gleicher N, Weghofer A, Barad DH. Improvement in diminished ovarian reserve after dehydroepiandrosterone supplementation. Reprod Biomed Online. 2010;21:360–5.PubMedCrossRef Gleicher N, Weghofer A, Barad DH. Improvement in diminished ovarian reserve after dehydroepiandrosterone supplementation. Reprod Biomed Online. 2010;21:360–5.PubMedCrossRef
22.
go back to reference Sánchez F, Adriaenssens T, Romero S, Smitz J. Different follicle-stimulating hormone exposure regimens during antral follicle growth alter gene expression in the cumulus-oocyte complex in mice. Biol Reprod. 2010;83:514–24.PubMedCrossRef Sánchez F, Adriaenssens T, Romero S, Smitz J. Different follicle-stimulating hormone exposure regimens during antral follicle growth alter gene expression in the cumulus-oocyte complex in mice. Biol Reprod. 2010;83:514–24.PubMedCrossRef
23.
go back to reference Gleicher N, Kim A, Weghofer A, Barad DH. Towards a better understanding of functional ovarian reserve: AMH (AMHo) and FSH (FSHo) hormone ratios per retrieved oocyte. J Clin Endocrinol Metabol. 2012;97:995–1004.CrossRef Gleicher N, Kim A, Weghofer A, Barad DH. Towards a better understanding of functional ovarian reserve: AMH (AMHo) and FSH (FSHo) hormone ratios per retrieved oocyte. J Clin Endocrinol Metabol. 2012;97:995–1004.CrossRef
24.
go back to reference Gleicher N, Weghofer A, Barad DH. Anti-Müllerian hormone (AMH) defines, independent of age, low versus good live-birth chances in women with severely diminished ovarian reserve. Fertil Steril. 2010;94:2824–7.PubMedCrossRef Gleicher N, Weghofer A, Barad DH. Anti-Müllerian hormone (AMH) defines, independent of age, low versus good live-birth chances in women with severely diminished ovarian reserve. Fertil Steril. 2010;94:2824–7.PubMedCrossRef
25.
go back to reference Gleicher N, Kim A, Weghofer A, Barad DH. (2012) Differences in ovarian aging patterns between races are likely related to ovarian genotypes and sub-genotypes of the FMR1 gene. Reprod Biol Endocrinol. 2012; In press. Gleicher N, Kim A, Weghofer A, Barad DH. (2012) Differences in ovarian aging patterns between races are likely related to ovarian genotypes and sub-genotypes of the FMR1 gene. Reprod Biol Endocrinol. 2012; In press.
26.
go back to reference Yakin K, Urman B. DHEA as a miracle drug in the treatment of poor responders; hype or hope? Hum Reprod. 2011;26:1941–4.PubMedCrossRef Yakin K, Urman B. DHEA as a miracle drug in the treatment of poor responders; hype or hope? Hum Reprod. 2011;26:1941–4.PubMedCrossRef
27.
go back to reference Sunkara SK, Coomarasamy A, Arit W, Bhattacharya S. Should androgen supplementation be used for poor ovarian response in IVF? Hum Reprod. 2012;27:637–40.PubMedCrossRef Sunkara SK, Coomarasamy A, Arit W, Bhattacharya S. Should androgen supplementation be used for poor ovarian response in IVF? Hum Reprod. 2012;27:637–40.PubMedCrossRef
28.
go back to reference Wiser A, Gonen O, Ghetler Y, Shavit T, Berkovitz A, et al. Addition of dehydroepiandrosterone (DHEA) for poor responder patients before and during IVF treatment improves the pregnancy rate: a randomized prospective study. Hum Reprod. 2010;25:2496–500.PubMedCrossRef Wiser A, Gonen O, Ghetler Y, Shavit T, Berkovitz A, et al. Addition of dehydroepiandrosterone (DHEA) for poor responder patients before and during IVF treatment improves the pregnancy rate: a randomized prospective study. Hum Reprod. 2010;25:2496–500.PubMedCrossRef
29.
go back to reference Gleicher N, Weghofer A, Kim A, Barad DH. Comparison of ovarian FMR1 genotypes and sub-genotypes in oocyte donors and infertile women. J Assist Reprod Genet. 2012;29:529–32.PubMedCrossRef Gleicher N, Weghofer A, Kim A, Barad DH. Comparison of ovarian FMR1 genotypes and sub-genotypes in oocyte donors and infertile women. J Assist Reprod Genet. 2012;29:529–32.PubMedCrossRef
Metadata
Title
Starting and resulting testosterone levels after androgen supplementation determine at all ages in vitro fertilization (IVF) pregnancy rates in women with diminished ovarian reserve (DOR)
Authors
Norbert Gleicher
Ann Kim
Andrea Weghofer
Aya Shohat-Tal
Emanuela Lazzaroni
Ho-Joon Lee
David H. Barad
Publication date
01-01-2013
Publisher
Springer US
Published in
Journal of Assisted Reproduction and Genetics / Issue 1/2013
Print ISSN: 1058-0468
Electronic ISSN: 1573-7330
DOI
https://doi.org/10.1007/s10815-012-9890-z

Other articles of this Issue 1/2013

Journal of Assisted Reproduction and Genetics 1/2013 Go to the issue