Effect of inter-cycle interval on oocyte production in humans in the presence of the weak androgen DHEA and follicle stimulating hormone: a case-control study

Reproductive Biology and Endocrinology

Norbert Gleicher²  Emanuela Lazzaroni¹  Ho-Joon Lee¹  Vitaly A Kushnir¹  David H Barad² 

[1] The Center for Human Reproduction, 21 East 69th St, New York, New York, USA;Foundation for Reproductive Medicine, New York, New York, USA

关键词: Anti-Müllerian hormone (AMH);    Gonadotropin s;    Follicle stimulating hormone (FSH);    Oocyte yield;    Diminished ovarian reserve (DOR);    In vitro fertilization (IVF);    Dehydroepiandrosterone (DHEA);   

Others  :  1139787
DOI  :  10.1186/1477-7827-12-68

 received in 2014-04-15, accepted in 2014-06-27,  发布年份 2014

【 摘 要 】

Background

In various animal models androgens have been demonstrated to enhance follicle stimulating hormone (FSH) activity on granulosa cells during small growing follicle stages. To assess whether similar synergism may also exist in humans we investigated women on androgen (dehydroepiandrosterone, DHEA) supplementation with varying concomitant FSH exposure.

Methods

In a case controlled cohort study we determine if time interval between IVF cycles of IVF treatment with FSH had an effect on ovarian response to ovulation induction in women supplemented with DHEA. Among 85 women with known low functional ovarian reserve (LFOR), supplemented with DHEA, and undergoing at least 3 consecutive IVF cycles, 68 demonstrated short (<120 days) intervals between repeated cycles (Group 1) and were, therefore, considered to have consistent FSH exposure. In contrast 17 women (Group 2) demonstrated long (> = 120 days) intervals between repeated cycles and, therefore, were considered to demonstrate inconsistent FSH exposure. Trends in oocyte yields were compared between these groups, utilizing mixed model repeated measures ANOVA, adjusted for initial age and FSH dose.

Results

Only women in Group I demonstrated a linear increase in oocyte yields across their three cycles of treatments (F = 7.92; df 1, 68.6; p = 0.017). Moreover, the analysis revealed a significant interaction between the two patient groups and cycle number for retrieved oocytes (F = 6.32, df = 2, 85.9, p = 0.003).

Conclusions

This study offers preliminary confirmatory evidence that repeated short interval exposure to androgens in combination with FSH improves human FOR. A higher level of evidence will require prospectively randomized studies.

【 授权许可】

   
2014 Barad et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]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.
• [2]Rice S, Ojha K, Whitehead S, Mason H: Stage-specific expression of androgen receptor, follicle-stimulating hormone receptor, and anti-Mullerian hormone type II receptor in single, isolated, human preantral follicles: relevance to polycystic ovaries. J Clin Endocrinol Metab 2007, 92(3):1034-1040.
• [3]Sen A, Hammes SR: Granulosa cell-specific androgen receptors are critical regulators of ovarian development and function. Mol Endocrinol 2010, 24(7):1393-1403.
• [4]Harlow CR, Shaw HJ, Hillier SG, Hodges JK: Factors influencing follicle-stimulating hormone-responsive steroidogenesis in marmoset granulosa cells: effects of androgens and the stage of follicular maturity. Endocrinology 1988, 122(6):2780-2787.
• [5]Nielsen ME, Rasmussen IA, Kristensen SG, Christensen ST, Mollgard 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(1):63-70.
• [6]Lisi F, Caserta D, Montanino M, Berlinghieri V, Bielli W, Carfagna P, Carra MC, Costantino A, Lisi R, Poverini R, Ciardo F, Rago R, Marci R, Moscarini M: Recombinant luteinizing hormone priming in multiple follicular stimulation for in-vitro fertilization in downregulated patients. Gynecol Endocrinol 2012, 28(9):674-677.
• [7]Gleicher N, Barad DH: Dehydroepiandrosterone (DHEA) supplementation in diminished ovarian reserve (DOR). Reprod Biol Endocrinol 2011, 9:67.
• [8]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(12):629-634.
• [9]Weghofer A, Kim A, Barad DH, Gleicher N: The impact of androgen metabolism and FMR1 genotypes on pregnancy potential in women with dehydroepiandrosterone (DHEA) supplementation. Hum Reprod 2012, 27(11):3287-3293.
• [10]Gougeon A: Dynamics of follicular growth in the human: a model from preliminary results. Hum Reprod 1986, 1(2):81-87.
• [11]Gleicher N, Weghofer A, Barad DH: Anti-Mullerian hormone (AMH) defines, independent of age, low versus good live-birth chances in women with severely diminished ovarian reserve. Fertil Steril 2010, 94(7):2824-2827.
• [12]te Velde ER, Scheffer GJ, Dorland M, Broekmans FJ, Fauser BC: Developmental and endocrine aspects of normal ovarian aging. Mol Cell Endocrinol 1998, 145(1–2):67-73.
• [13]Gobert B, Barbarino-Monnier P, Guillet-May F, Bene MC, Faure GC: Anti-ovary antibodies after attempts at human in vitro fertilization induced by follicular puncture rather than hormonal stimulation. J Reprod Fertil 1992, 96(1):213-218.
• [14]Reichman DE, Chung P, Meyer L, Greenwood E, Davis O, Rosenwaks Z: Consecutive gonadotropin-releasing hormone-antagonist in vitro fertilization cycles: does the elapsed time interval between successive treatments affect outcomes? Fertil Steril 2013, 99(5):1277-1282.
• [15]Luk J, Arici A: Does the ovarian reserve decrease from repeated ovulation stimulations? Curr Opin Obstet Gynecol 2010, 22(3):177-182.
• [16]Barad DH, Gleicher N: Increased oocyte production after treatment with dehydroepiandrosterone. Fertil Steril 2005, 84(3):756.
• [17]Khairy M, Clough A, El-Toukhy T, Coomarasamy A, Khalaf Y: Antral follicle count at down-regulation and prediction of poor ovarian response. Reprod Biomed Online 2008, 17(4):508-514.
• [18]Elter K, Kavak ZN, Gokaslan H, Pekin T: Antral follicle assessment after down-regulation may be a useful tool for predicting pregnancy loss in vitro fertilization pregnancies. Gynecol Endocrinol 2005, 21(1):33-37.
• [19]Klinkert ER, Broekmans FJ, Looman CW, Habbema JD, te Velde ER: The antral follicle count is a better marker than basal follicle-stimulating hormone for the selection of older patients with acceptable pregnancy prospects after in vitro fertilization. Fertil Steril 2005, 83(3):811-814.
• [20]Barad DH, Weghofer A, Gleicher N: Age-specific levels for basal follicle-stimulating hormone assessment of ovarian function. Obstet Gynecol 2007, 109(6):1404-1410.
• [21]Barad DH, Weghofer A, Gleicher N: Utility of age-specific serum anti-Mullerian hormone concentrations. Reprod Biomed Online 2011, 22(3):284-291.
• [22]Lee RK, Wu FS, Lin MH, Lin SY, Hwu YM: The predictability of serum anti-Mullerian level in IVF/ICSI outcomes for patients of advanced reproductive age. Reprod Biol Endocrinol 2011, 9:115.
• [23]Weghofer A, Dietrich W, Barad DH, Gleicher N: Live birth chances in women with extremely low-serum anti-Mullerian hormone levels. Hum Reprod 2011, 26(7):1905-1909.
• [24]Broer SL, Mol BW, Hendriks D, Broekmans FJ: The role of antimullerian hormone in prediction of outcome after IVF: comparison with the antral follicle count. Fertil Steril 2009, 91(3):705-714.
• [25]Gnoth C, Schuring AN, Friol K, Tigges J, Mallmann P, Godehardt E: Relevance of anti-Mullerian hormone measurement in a routine IVF program. Hum Reprod 2008, 23(6):1359-1365.
• [26]Buyuk E, Seifer DB, Younger J, Grazi RV, Lieman H: Random anti-Mullerian hormone (AMH) is a predictor of ovarian response in women with elevated baseline early follicular follicle-stimulating hormone levels. Fertil Steril 2011, 95(7):2369-2372.
• [27]Irez T, Ocal P, Guralp O, Cetin M, Aydogan B, Sahmay S: Different serum anti-Mullerian hormone concentrations are associated with oocyte quality, embryo development parameters and IVF-ICSI outcomes. Arch Gynecol Obstet 2011, 284(5):1295-1301.
• [28]La Marca A, Giulini S, Tirelli A, Bertucci E, Marsella T, Xella S, Volpe A: Anti-Mullerian hormone measurement on any day of the menstrual cycle strongly predicts ovarian response in assisted reproductive technology. Hum Reprod 2007, 22(3):766-771.
• [29]Eppsteiner EE, Sparks AE, Liu D, Van Voorhis BJ: Change in oocyte yield in repeated in vitro fertilization cycles: effect of ovarian reserve. Fertil Steril 2014, 101(2):399-402.
• [30]Kolibianakis EM, Devroey P: No decrease occurs in the number of COCs retrieved with repeated IVF cycles. Hum Reprod 2004, 19(8):1927-1928.
• [31]Kolibianakis E, Osmanagaoglu K, Camus M, Tournaye H, Van Steirteghem A, Devroey P: Effect of repeated assisted reproductive technology cycles on ovarian response. Fertil Steril 2002, 77(5):967-970.
• [32]de Boer EJ, Den Tonkelaar I, Burger CW, Looman CW, van Leeuwen FE, te Velde ER: The number of retrieved oocytes does not decrease during consecutive gonadotrophin-stimulated IVF cycles. Hum Reprod 2004, 19(4):899-904.