Skip to main content
Top
Published in: Journal of Ovarian Research 1/2014

Open Access 01-12-2014 | Research

Dehydroepiandrosterone improves follicular fluid bone morphogenetic protein-15 and accumulated embryo score of infertility patients with diminished ovarian reserve undergoing in vitro fertilization: a randomized controlled trial

Authors: Huan H Zhang, Ping Y Xu, Juan Wu, Wei W Zou, Xia M Xu, Xia Y Cao, Lian Z Wei

Published in: Journal of Ovarian Research | Issue 1/2014

Login to get access

Abstract

Objective

To evaluate the effect of dehydroepiandrosterone (DHEA) on infertility patients with diminished ovarian reserve undergoing in vitro fertilization.

Methods

This is a prospective study. Ninety-five patients with diminished ovarian reserve were included in this study. Of them, 42 patients were randomly allocated to the DHEA group, who received DHEA 75 mg daily for three consecutive menstrual cycles prior to IVF cycles, and 53 patients were allocated to the control group, who entered IVF cycles directly. All patients were treated with the same ovarian stimulation protocol. Follicular fluid samples from both groups were collected for bone morphogenetic protein-15 (BMP-15) and growth differentiation factor-9 (GDF-9). Fluid from the first aspirated follicle without any visible blood contamination was carefully collected. In addition, day 3 Blood samples were collected pre- and post-treatment of DHEA for serum anti-Mullerian hormone (AMH), follicle stimulating hormone (FSH) and estradiol (E2) in the DHEA group.

Results

The level of BMP-15 in follicular fluid samples from the DHEA group was significantly higher than that of the control samples (P=.000). Patients after DHEA treatment demonstrated a significantly higher level of AMH and a significantly lower level of FSH, E2 compared to themselves prior to DHEA therapy (P=.015; P=.036; P=.002; respectively). Moreover, the accumulated score of embryos was significantly higher in the DHEA group (P=.033).

Conclusions

These observations confirm the beneficial effect of DHEA for infertility patients with diminished ovarian reserve.

Trial registration

Appendix
Available only for authorised users
Literature
1.
go back to reference Frattarelli JL, Hill MJ, McWilliams GD, Miller KA, Bergh PA, Scott RT Jr: A luteal estradiol protocol for expected poor-responders improves embryo number and quality. Fertil Steril 2008, 89: 1118–1122. 10.1016/j.fertnstert.2007.05.025CrossRefPubMed Frattarelli JL, Hill MJ, McWilliams GD, Miller KA, Bergh PA, Scott RT Jr: A luteal estradiol protocol for expected poor-responders improves embryo number and quality. Fertil Steril 2008, 89: 1118–1122. 10.1016/j.fertnstert.2007.05.025CrossRefPubMed
2.
go back to reference Ulug U, Ben-Shlomo I, Turan E, Erden HF, Akman MA, Bahceci M: Conception rates following assisted reproduction in poor responder patients: a retrospective study in 300 consecutive cycles. Reprod Biomed Online 2003, 6: 439–443. 10.1016/S1472-6483(10)62164-5CrossRefPubMed Ulug U, Ben-Shlomo I, Turan E, Erden HF, Akman MA, Bahceci M: Conception rates following assisted reproduction in poor responder patients: a retrospective study in 300 consecutive cycles. Reprod Biomed Online 2003, 6: 439–443. 10.1016/S1472-6483(10)62164-5CrossRefPubMed
3.
go back to reference Casson PR, Lindsay MS, Pisarska MD, Carson SA, Buster JE: Dehydroepiandrosterone supplementation augments ovarian stimulation in poor responders: a case series. Hum Reprod 2000, 15: 2129–2132. 10.1093/humrep/15.10.2129CrossRefPubMed Casson PR, Lindsay MS, Pisarska MD, Carson SA, Buster JE: Dehydroepiandrosterone supplementation augments ovarian stimulation in poor responders: a case series. Hum Reprod 2000, 15: 2129–2132. 10.1093/humrep/15.10.2129CrossRefPubMed
4.
go back to reference Barad GN: Effect of dehydroepiandrosterone on oocyte and embryo yields, embryo grade and cell number in IVF. Hum Reprod 2006, 21: 2845–2849. 10.1093/humrep/del254CrossRefPubMed Barad GN: Effect of dehydroepiandrosterone on oocyte and embryo yields, embryo grade and cell number in IVF. Hum Reprod 2006, 21: 2845–2849. 10.1093/humrep/del254CrossRefPubMed
5.
go back to reference Barad D, Brill H, Gleicher N: Update on the use of dehydroepiandrosterone supplementation among women with diminished ovarian function. J Assist Reprod Genet 2007, 24: 629–634. 10.1007/s10815-007-9178-xPubMedCentralCrossRefPubMed Barad D, Brill H, Gleicher N: Update on the use of dehydroepiandrosterone supplementation among women with diminished ovarian function. J Assist Reprod Genet 2007, 24: 629–634. 10.1007/s10815-007-9178-xPubMedCentralCrossRefPubMed
6.
go back to reference Gleicher N, Ryan E, Weghofer A, Blanco-Mejia S, Barad DH: Miscarriage rates after dehydroepiandrosterone (DHEA) supplementation in women with diminished ovarian reserve: a case control study. Reprod Biol Endocrinol 2009, 7: 108. 10.1186/1477-7827-7-108PubMedCentralCrossRefPubMed Gleicher N, Ryan E, Weghofer A, Blanco-Mejia S, Barad DH: Miscarriage rates after dehydroepiandrosterone (DHEA) supplementation in women with diminished ovarian reserve: a case control study. Reprod Biol Endocrinol 2009, 7: 108. 10.1186/1477-7827-7-108PubMedCentralCrossRefPubMed
7.
go back to reference Gleicher N, Barad DH: Androgen priming before ovarian stimulation for IVF. Hum Reprod 2008, 23: 2868–2870. 10.1093/humrep/den319CrossRefPubMed Gleicher N, Barad DH: Androgen priming before ovarian stimulation for IVF. Hum Reprod 2008, 23: 2868–2870. 10.1093/humrep/den319CrossRefPubMed
8.
go back to reference Barad D, Weghofer A, Gleicher N: Dehydroepiandrosterone treatment of ovarian failure. Fertil Steril 2009, 91: e14. 10.1016/j.fertnstert.2008.12.134CrossRefPubMed Barad D, Weghofer A, Gleicher N: Dehydroepiandrosterone treatment of ovarian failure. Fertil Steril 2009, 91: e14. 10.1016/j.fertnstert.2008.12.134CrossRefPubMed
9.
go back to reference Yilmaz N, Uygur D, Inal H, Gorkem U, Cicek N: Mollamahmutoglu:Dehydroepiandrosterone supplementation improves predictive markers for diminished ovarian reserve: serum AMH, inhibin B and antral follicle count. Eur J Obstet Gynecol Reprod Biol 2013, 169: 257–260. 10.1016/j.ejogrb.2013.04.003CrossRefPubMed Yilmaz N, Uygur D, Inal H, Gorkem U, Cicek N: Mollamahmutoglu:Dehydroepiandrosterone supplementation improves predictive markers for diminished ovarian reserve: serum AMH, inhibin B and antral follicle count. Eur J Obstet Gynecol Reprod Biol 2013, 169: 257–260. 10.1016/j.ejogrb.2013.04.003CrossRefPubMed
10.
go back to reference Yeung TW, Li RH, Lee VC, Ho PC, Ng EH: A Randomized Double-Blinded Placebo-Controlled Trial on the Effect of Dehydroepiandrosterone for 16 Weeks on Ovarian Response Markers in Women with Primary Ovarian Insufficiency. J Clin Endocrinol Metab 2013, 98: 380–388. 10.1210/jc.2012-3071CrossRefPubMed Yeung TW, Li RH, Lee VC, Ho PC, Ng EH: A Randomized Double-Blinded Placebo-Controlled Trial on the Effect of Dehydroepiandrosterone for 16 Weeks on Ovarian Response Markers in Women with Primary Ovarian Insufficiency. J Clin Endocrinol Metab 2013, 98: 380–388. 10.1210/jc.2012-3071CrossRefPubMed
11.
go back to reference Orisaka M, Jiang JY, Orisaka S, Kotsuji F, Tsang BK: Growth Differentiation Factor 9 promotes rat pre-antral follicle growth by up-regulating follicular androgen biosynthesis. Endocrinology 2009, 150: 2740–2748. 10.1210/en.2008-1536CrossRefPubMed Orisaka M, Jiang JY, Orisaka S, Kotsuji F, Tsang BK: Growth Differentiation Factor 9 promotes rat pre-antral follicle growth by up-regulating follicular androgen biosynthesis. Endocrinology 2009, 150: 2740–2748. 10.1210/en.2008-1536CrossRefPubMed
13.
go back to reference Dong J, Albertini DF, Nishimori K, Kumar TR, Lu N, Matzuk MM: Growth differentiation factor-9 is required during early ovarian folliculogenesis. Nature 1996, 383: 531–535. 10.1038/383531a0CrossRefPubMed Dong J, Albertini DF, Nishimori K, Kumar TR, Lu N, Matzuk MM: Growth differentiation factor-9 is required during early ovarian folliculogenesis. Nature 1996, 383: 531–535. 10.1038/383531a0CrossRefPubMed
14.
go back to reference Wu YT, Tang L, Cai J, Lu XE, Xu J, Zhu XM, Luo Q, Huang HF: High bone morphogenetic protein-15 level in follicular fluid is associated with high quality oocyte and subsequent embryonic development. Hum Reprod 2007, 22: 1526–1531. 10.1093/humrep/dem029CrossRefPubMed Wu YT, Tang L, Cai J, Lu XE, Xu J, Zhu XM, Luo Q, Huang HF: High bone morphogenetic protein-15 level in follicular fluid is associated with high quality oocyte and subsequent embryonic development. Hum Reprod 2007, 22: 1526–1531. 10.1093/humrep/dem029CrossRefPubMed
15.
go back to reference Ferraretti AP, La Marca A, Fauser BCJM: ESHRE consensus on the definition of `poor response’to ovarian stimulation for in vitro fertilization: the Bologna criteria. Hum Reprod 2011, 26: 1616–1624. 10.1093/humrep/der092CrossRefPubMed Ferraretti AP, La Marca A, Fauser BCJM: ESHRE consensus on the definition of `poor response’to ovarian stimulation for in vitro fertilization: the Bologna criteria. Hum Reprod 2011, 26: 1616–1624. 10.1093/humrep/der092CrossRefPubMed
16.
go back to reference Wiser A, Gonen O, Ghetler Y: 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: 2496–2500. 10.1093/humrep/deq220CrossRefPubMed Wiser A, Gonen O, Ghetler Y: 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: 2496–2500. 10.1093/humrep/deq220CrossRefPubMed
17.
go back to reference Wu YT, Wang TT, Chen XJ, Zhu XM, Dong MY, Sheng JZ, Xu CM, Huang HF: Bone morphogenetic protein-15 in follicle fluid combined with age may differentiate between successful and unsuccessful poor ovarian responders. Reprod Biol Endocrinol 2012, 26: 116. 10.1186/1477-7827-10-116CrossRef Wu YT, Wang TT, Chen XJ, Zhu XM, Dong MY, Sheng JZ, Xu CM, Huang HF: Bone morphogenetic protein-15 in follicle fluid combined with age may differentiate between successful and unsuccessful poor ovarian responders. Reprod Biol Endocrinol 2012, 26: 116. 10.1186/1477-7827-10-116CrossRef
18.
go back to reference Gleicher N, Weghofer A, Barad DH: Improvement in diminished ovarian reserve after dehydroepiandrosterone (DHEA) supplementation. Reprod Biomed Online 2010, 21: 360–365. 10.1016/j.rbmo.2010.04.006CrossRefPubMed Gleicher N, Weghofer A, Barad DH: Improvement in diminished ovarian reserve after dehydroepiandrosterone (DHEA) supplementation. Reprod Biomed Online 2010, 21: 360–365. 10.1016/j.rbmo.2010.04.006CrossRefPubMed
19.
go back to reference Moawad A, Shaeer M: Long term androgen priming by use of DHEA improves IVF outcomes in poor responders: A randomized control study. Middle East Fertil Soc J 2012, 17: 268–274. 10.1016/j.mefs.2012.11.002CrossRef Moawad A, Shaeer M: Long term androgen priming by use of DHEA improves IVF outcomes in poor responders: A randomized control study. Middle East Fertil Soc J 2012, 17: 268–274. 10.1016/j.mefs.2012.11.002CrossRef
20.
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. 10.1186/1477-7827-9-116PubMedCentralCrossRefPubMed 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. 10.1186/1477-7827-9-116PubMedCentralCrossRefPubMed
21.
go back to reference Sen A, Hammes SR: Granulosa-cell specific androgen receptors are critical regulators of ovarian development and function. Mol Endocrinol 2010, 24: 1393–1403. 10.1210/me.2010-0006PubMedCentralCrossRefPubMed Sen A, Hammes SR: Granulosa-cell specific androgen receptors are critical regulators of ovarian development and function. Mol Endocrinol 2010, 24: 1393–1403. 10.1210/me.2010-0006PubMedCentralCrossRefPubMed
22.
go back to reference Weil SJ, Vendola K, Zhou J, Adesanya OO, Wang J, Okafor J, Bondy CA: Androgen receptor gene expression in the primate ovary: cellular localization, regulation, and functional correlations. J Clin Endocrinol Metab 1998, 83: 2479–2485. 10.1210/jcem.83.7.4917CrossRefPubMed Weil SJ, Vendola K, Zhou J, Adesanya OO, Wang J, Okafor J, Bondy CA: Androgen receptor gene expression in the primate ovary: cellular localization, regulation, and functional correlations. J Clin Endocrinol Metab 1998, 83: 2479–2485. 10.1210/jcem.83.7.4917CrossRefPubMed
23.
go back to reference ElBeltagy K, Honda K, Ozaki K, Misugi T, Tokuyama O, Kimura M, Kira Y, Ishiko O: In vitro effect of dehydroepiandrosterone sulfate on steroid receptors, aromatase, cyclooxygenase-2 expression, and steroid hormone production in preovulatory human granulosa cells. Fertil Steril 2007,88(Suppl 4):1135–1142. 10.1016/j.fertnstert.2007.01.008CrossRefPubMed ElBeltagy K, Honda K, Ozaki K, Misugi T, Tokuyama O, Kimura M, Kira Y, Ishiko O: In vitro effect of dehydroepiandrosterone sulfate on steroid receptors, aromatase, cyclooxygenase-2 expression, and steroid hormone production in preovulatory human granulosa cells. Fertil Steril 2007,88(Suppl 4):1135–1142. 10.1016/j.fertnstert.2007.01.008CrossRefPubMed
24.
go back to reference Nielsen ME, Rasmussen IA, Kristensen SG, Christensen ST, Møllgård K, Wreford Andersen E, Byskov AG, Yding Andersen C: In human granulosa cells from small antral follicles, androgen receptor mRNA and androgen levels in follicular fluid correlate with FSH receptor mRNA. Mol Hum Reprod 2011, 17: 63–70. 10.1093/molehr/gaq073CrossRefPubMed Nielsen ME, Rasmussen IA, Kristensen SG, Christensen ST, Møllgård K, Wreford Andersen E, Byskov AG, Yding Andersen C: In human granulosa cells from small antral follicles, androgen receptor mRNA and androgen levels in follicular fluid correlate with FSH receptor mRNA. Mol Hum Reprod 2011, 17: 63–70. 10.1093/molehr/gaq073CrossRefPubMed
25.
go back to reference Lenie 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: 685–695. 10.1095/biolreprod.107.067280CrossRefPubMed Lenie 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: 685–695. 10.1095/biolreprod.107.067280CrossRefPubMed
26.
go back to reference Sunkara SK, Coomarasamy A, Arlt W, Bhattacharya S: Should androgen supplementation be used for poor ovarian response in IVF. Hum Reprod 2012, 27: 637–640. 10.1093/humrep/der464CrossRefPubMed Sunkara SK, Coomarasamy A, Arlt W, Bhattacharya S: Should androgen supplementation be used for poor ovarian response in IVF. Hum Reprod 2012, 27: 637–640. 10.1093/humrep/der464CrossRefPubMed
27.
go back to reference Hickey TE, Marrocco DL, Amato F, Ritter LJ, Norman RJ, Gilchrist RB, Armstrong DT: Androgens augment the mitogenic effects of oocyte-secreted factors and growth differentiation factor 9 on porcine granulosa cells. Biol Reprod 2005, 73: 825–832. 10.1095/biolreprod.104.039362CrossRefPubMed Hickey TE, Marrocco DL, Amato F, Ritter LJ, Norman RJ, Gilchrist RB, Armstrong DT: Androgens augment the mitogenic effects of oocyte-secreted factors and growth differentiation factor 9 on porcine granulosa cells. Biol Reprod 2005, 73: 825–832. 10.1095/biolreprod.104.039362CrossRefPubMed
28.
go back to reference Ogura-Nose S, Yoshino O, Osuga Y, Shi J, Hiroi H, Yano T, Taketani Y: Anti-Mullerian hormone (AMH) is induced by bone morphogenetic protein (BMP) cytokines in human granulosa cells. Eur J Obstet Gynecol Reprod Biol 2012, 164: 44–47. 10.1016/j.ejogrb.2012.05.017CrossRefPubMed Ogura-Nose S, Yoshino O, Osuga Y, Shi J, Hiroi H, Yano T, Taketani Y: Anti-Mullerian hormone (AMH) is induced by bone morphogenetic protein (BMP) cytokines in human granulosa cells. Eur J Obstet Gynecol Reprod Biol 2012, 164: 44–47. 10.1016/j.ejogrb.2012.05.017CrossRefPubMed
29.
go back to reference Thomas FH, Ethier JF, Shimasaki S, Vanderhyden BC: Follicle-Stimulating Hormone Regulates Oocyte Growth by Modulation of Expression of Oocyte and Granulosa Cell Factors. Endocrinology 2005, 146: 941–949. 10.1210/en.2004-0826CrossRefPubMed Thomas FH, Ethier JF, Shimasaki S, Vanderhyden BC: Follicle-Stimulating Hormone Regulates Oocyte Growth by Modulation of Expression of Oocyte and Granulosa Cell Factors. Endocrinology 2005, 146: 941–949. 10.1210/en.2004-0826CrossRefPubMed
Metadata
Title
Dehydroepiandrosterone improves follicular fluid bone morphogenetic protein-15 and accumulated embryo score of infertility patients with diminished ovarian reserve undergoing in vitro fertilization: a randomized controlled trial
Authors
Huan H Zhang
Ping Y Xu
Juan Wu
Wei W Zou
Xia M Xu
Xia Y Cao
Lian Z Wei
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Journal of Ovarian Research / Issue 1/2014
Electronic ISSN: 1757-2215
DOI
https://doi.org/10.1186/s13048-014-0093-3

Other articles of this Issue 1/2014

Journal of Ovarian Research 1/2014 Go to the issue