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

Journal of Ovarian Research

Lian Z Wei²  Xia Y Cao²  Xia M Xu¹  Wei W Zou¹  Juan Wu²  Ping Y Xu²  Huan H Zhang² 

[1] Laboratory of the Reproductive Medicine Center, The Affiliated Hospital of Anhui Medical University, Anhui, People’s Republic of China;Department of Reproductive Endocrinology, the Reproductive Medicine Center, The Affiliated Hospital of Anhui Medical University, Anhui, People’s Republic of China

关键词: AMH;    GDF-9;    BMP-15;    Diminished ovarian reserve;    Dehydroepiandrosterone;   

Others  :  1132883
DOI  :  10.1186/s13048-014-0093-3

 received in 2014-08-02, accepted in 2014-09-30,  发布年份 2014

【 摘 要 】

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

ChiCTR-TRC-14005002 webcite

【 授权许可】

   
2014 Zhang et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]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.
• [2]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.
• [3]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.
• [4]Barad GN: Effect of dehydroepiandrosterone on oocyte and embryo yields, embryo grade and cell number in IVF. Hum Reprod 2006, 21:2845-2849.
• [5]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.
• [6]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. BioMed Central Full Text
• [7]Gleicher N, Barad DH: Androgen priming before ovarian stimulation for IVF. Hum Reprod 2008, 23:2868-2870.
• [8]Barad D, Weghofer A, Gleicher N: Dehydroepiandrosterone treatment of ovarian failure. Fertil Steril 2009, 91:e14.
• [9]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]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.
• [11]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.
• [12]Emori C, Sugiura K: Role of oocyte-derived paracrine factors in follicular development. Anim Sci J 2014, 85:627-633.
• [13]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.
• [14]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.
• [15]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.
• [16]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.
• [17]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. BioMed Central Full Text
• [18]Gleicher N, Weghofer A, Barad DH: Improvement in diminished ovarian reserve after dehydroepiandrosterone (DHEA) supplementation. Reprod Biomed Online 2010, 21:360-365.
• [19]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.
• [20]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. BioMed Central Full Text
• [21]Sen A, Hammes SR: Granulosa-cell specific androgen receptors are critical regulators of ovarian development and function. Mol Endocrinol 2010, 24:1393-1403.
• [22]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.
• [23]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.
• [24]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.
• [25]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.
• [26]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.
• [27]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.
• [28]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.
• [29]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.