Does hormonal contraception prior to in vitro fertilization (IVF) negatively affect oocyte yields? - A pilot study

Reproductive Biology and Endocrinology

Norbert Gleicher²  Andrea Weghofer³  Hala Kubba¹  Ann Kim¹  David H Barad² 

[1] Center for Human Reproduction, New York, NY, USA;Foundation for Reproductive Medicine, New York, NY, USA;Department of Gynecologic Endocrinology and Reproductive Medicine, Medical University Vienna, Vienna, Austria

关键词: Androgens;    Ovarian reserve;    Oocyte yield;    In vitro fertilization (IVF);    Hormonal contraception;    Oral contraceptives;   

Others  :  812347
DOI  :  10.1186/1477-7827-11-28

 received in 2013-01-31, accepted in 2013-03-13,  发布年份 2013

【 摘 要 】

Background

As oral contraceptives (OCs) suppress anti-Müllerian hormone (AMH), and hormonal contraceptives (HCs), likely, suppress functional ovarian reserve, this study was initiated to determine whether HC affect oocyte yields.

Methods

We investigated in a retrospective cohort study 43 oocyte donors in 71 in vitro fertilization (IVF) cycles, evaluating anti-Müllerian hormone (AMH) and oocyte yields as reflections of functional ovarian reserve (OR). In 25 IVF cycles egg donors were on HC within one month prior to IVF, and in 46 cycles they were not. Donors, based on their HCs, were further subdivided into 12 with less, and 13 with more androgenic progestins.

Results

While the three groups did not differ in age, age at menarche, BMI and AMH, oocyte yields among donors who utilized estrane- and gonane-derived (higher androgenic) HCs were lower 11.3 (95% CI 8.3 – 14.3) than either donors using no HCs 16.6 (95% CI 14.7 -18.4) (P < 0.05) or those using anti-androgenic HCs 19.0 (95% CI 12.2-25.8) (P< 0.01). Significance was maintained after adjustments for the donor age and total FSH dose used in ovulation induction.

Conclusions

Even in young oocyte donors, high androgenic OC exposure appears to suppress functional ovarian reserve and oocyte yields. Since OCs are often routinely used in preparation for IVF, such practice may require reevaluation. Especially in women with diminished ovarian reserve OCs, and especially high androgenic progestin HCs, should, likely, be avoided.

【 授权许可】

   
2013 Barad et al.; licensee BioMed Central Ltd.

【 参考文献 】

• [1]Ferraretti AP, La Marca A, Fauser BC, Tarlatzis B, Nargund G, Gianaroli L: ESHRE consensus on the definition of 'poor response' to ovarian stimulation for in vitro fertilization: the Bologna criteria. Hum Reprod 2011, 26:1616-1624.
• [2]Surrey ES: Management of the poor responder: the role of GnRH agonists and antagonists. J Assist Reprod Genet 2007, 24:613-619.
• [3]Lindheim SR, Barad DH, Witt B, Ditkoff E, Sauer MV: Short-term gonadotropin suppression with oral contraceptives benefits poor responders prior to controlled ovarian hyperstimulation. J Assist Reprod Genet 1996, 13:745-747.
• [4]Fisch B, Royburt M, Pinkas H, Avrech OM, Goldman GA, Bar J, Tadir Y, Ovadia J: Augmentation of low ovarian response to superovulation before in vitro fertilization following priming with contraceptive pills. Isr J Med Sci 1996, 32:1172-1176.
• [5]Biljan MM, Mahutte NG, Dean N, Hemmings R, Bissonnette F, Tan SL: Pretreatment with an oral contraceptive is effective in reducing the incidence of functional ovarian cyst formation during pituitary suppression by gonadotropin-releasing hormone analogues. J Assist Reprod Genet 1998, 15:599-604.
• [6]Patton PE, Burry KA, Wolf DP, Kiessling AA, Craemer MJ: The use of oral contraceptives to regulate oocyte retrieval. Fertil Steril 1988, 49:716-718.
• [7]Kemeter P, Feichtinger W: A fixed stimulation protocol for in vitro fertilization (IVF) without determinations of hormones in blood. Acta Eur Fertil 1989, 20:63-70.
• [8]Meldrum DR, Scott RT Jr, Levy MJ, Alper MM, Noyes N: Oral contraceptive pretreatment in women undergoing controlled ovarian stimulation in ganirelix acetate cycles may, for a subset of patients, be associated with low serum luteinizing hormone levels, reduced ovarian response to gonadotropins, and early pregnancy loss. Fertil Steril 2009, 91:1963-1965.
• [9]Duvan CI, Berker B, Turhan NO, Satiroglu H: Oral contraceptive pretreatment does not improve outcome in microdose gonadotrophin-releasing hormone agonist protocol among poor responder intracytoplasmic sperm injection patients. J Assist Reprod Genet 2008, 25:89-93.
• [10]Kovacs P, Barg PE, Witt BR: Hypothalamic-pituitary suppression with oral contraceptive pills does not improve outcome in poor responder patients undergoing in vitro fertilization-embryo transfer cycles. J Assist Reprod Genet 2001, 18:391-394.
• [11]Smulders B, van Oirschot SM, Farquhar C, Rombauts L, Kremer JA: Oral contraceptive pill, progestogen or estrogen pre-treatment for ovarian stimulation protocols for women undergoing assisted reproductive techniques. Cochrane Database Syst Rev 2010, 11:CD006109.
• [12]Mishell DR: The effect of contraceptive steroids on hypothalamic-pituitary function. Am J Obstet Gynecol 1977, 128:60-74.
• [13]Dericks-Tan JS: Influence of oral contraceptives on integrated secretion of gonadotropins. Contracept 1992, 46:369-377.
• [14]Sitruk-Ware R, Nath A: The use of newer progestins for contraception. Contracept 2010, 82:410-417.
• [15]Fang H, Tong W, Branham WS, Moland CL, Dial SL, Hong H, Xie Q, Perkins R, Owens W, Sheehan DM: Study of 202 natural, synthetic, and environmental chemicals for binding to the androgen receptor. Chem Res Toxicol 2003, 16:1338-1358.
• [16]Sitruk-Ware R: Pharmacological profile of progestins. Maturitas 2008, 61:151-157.
• [17]Africander D, Verhoog N, Hapgood JP: Molecular mechanisms of steroid receptor-mediated actions by synthetic progestins used in HRT and contraception. Steroids 2011, 76:636-652.
• [18]Elger W, Beier S, Pollow K, Garfield R, Shi SQ, Hillisch A: Conception and pharmacodynamic profile of drospirenone. Steroids 2003, 68:891-905.
• [19]Winneker RC, Bitran D, Zhang Z: The preclinical biology of a new potent and selective progestin: trimegestone. Steroids 2003, 68:915-920.
• [20]Schindler AE, Campagnoli C, Druckmann R, Huber J, Pasqualini JR, Schweppe KW, Thijssen JH: Classification and pharmacology of progestins. Maturitas 2008, 61:171-180.
• [21]Ndefo UA, Mosely N: Estradiol valerate and estradiol valerate/dienogest (natazia) tablets: the first four-phasic oral contraceptive. Pharm Therapeutics 2010, 35:61461-61467.
• [22]de Vet AR: Antimüllerian hormone serum levels: a putative marker for ovarian aging. Fertil Steril 2002, 77:357-362.
• [23]Singer T, Barad DH, Weghofer A, Gleicher N: Correlation of antimullerian hormone and baseline follicle-stimulating hormone levels. Fertil Steril 2009, 91:2616-2619.
• [24]Gleicher N, Weghofer A, Barad DH: Discordances between follicle stimulating hormone (FSH) and anti-Mullerian hormone (AMH) in female infertility. Reprod Biol Endocrinol 2010, 8:64. BioMed Central Full Text
• [25]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, 94:2824-2827.
• [26]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
• [27]Somunkiran AR: Anti-Müllerian hormone levels during hormonal contraception in women with polycystic ovary syndrome. Eur J Obstet Gynecol Reprod Biol 2007, 134:196-201.
• [28]Venturoli S, Ravaioli B, Bagnoli A, Colombo FM, Macrelli S, Iadarola I, Vianello F, Mancini F, Flamigni C: Contraceptive and therapeutic effectiveness of two low-dose ethinylestradiol and cyproterone acetate regimens in the treatment of hirsute patients. Eur J Contracept Reprod Health Care 1998, 3:29-33.
• [29]De Leo V, Lanzetta D, Morgante G, De Palma P, D'Antona D: Inhibition of ovulation with transdermal estradiol and oral progestogens in perimenopausal women. Contracept 1997, 55:239-243.
• [30]Arbo E, Vetori DV, Jimenez MF, Freitas FM, Lemos N, Cunha-Filho JS: Serum anti-mullerian hormone levels and follicular cohort characteristics after pituitary suppression in the late luteal phase with oral contraceptive pills. Hum Reprod 2007, 22:3192-3196.
• [31]Kerkhof GF, Leunissen RW, Willemsen RH, de Jong FH, Visser JA, Laven JS, Hokken-Koelega AC: Influence of preterm birth and small birth size on serum anti-Mullerian hormone levels in young adult women. Eur J Endocrinol 2010, 163:937-944.
• [32]Streuli I, Fraisse T, Pillet C, Ibecheole V, Bischof P, de Ziegler D: Serum antimullerian hormone levels remain stable throughout the menstrual cycle and after oral or vaginal administration of synthetic sex steroids. Fertil Steril 2008, 90:395-400.
• [33]Steiner AZ, Stanczyk FZ, Patel S, Edelman A: Antimullerian hormone and obesity: insights in oral contraceptive users. Contracept 2010, 81:245-248.
• [34]Petrie KA, Torgal AH, Westhoff CL: Matched-pairs analysis of ovarian suppression during oral vs. vaginal hormonal contraceptive use. Contracept 2011, 84:e1-e4.
• [35]Phillips A, Hahn DW, Klimek S, McGuire JL: A comparison of the potencies and activities of progestogens used in contraceptives. Contracept 1987, 36:181-192.
• [36]Rosenbaum P, Schmidt W, Helmerhorst FM, Wuttke W, Rossmanith W, Freundl F, Thomas K, Grillo M, Wolf A, Heithecker R: Inhibition of ovulation by a novel progestogen (drospirenone) alone or in combination with ethinylestradiol. Eur J Contracept Reprod Health Care 2000, 5:16-24.
• [37]van den Berg MH, van Dulmen-den BE, Overbeek A, Twisk JW, Schats R, van Leeuwen FE, Kaspers GJ, Lambalk CB: Comparison of ovarian function markers in users of hormonal contraceptives during the hormone-free interval and subsequent natural early follicular phases. Hum Reprod 2010, 25:1520-1527.
• [38]Schlaff WD: Manipulation of the pill-free interval in oral contraceptive pill users: the effect on follicular suppression. Am J Obstet Gynecol 2004, 190:943-9451.
• [39]Baerwald AR: Ovarian follicular development is initiated during the hormone-free interval of oral contraceptive use. Contracept 2004, 70:371-377.
• [40]Said S, el Habashy MA, Osman MM, Shams AT, Madwar AY, Nayel SA: Ovarian morphology and histopathology in post pill amenorrhea. Asia Oceania J Obstet Gynaecol 1987, 13:15-19.
• [41]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.
• [42]Barad D, Gleicher N: Effect of dehydroepiandrosterone on oocyte and embryo yields, embryo grade and cell number in IVF. Hum Reprod 2006, 21:2845-2849.
• [43]Barad DH, Gleicher N: Increased oocyte production after treatment with dehydroepiandrosterone. Fertil Steril 2005, 84:756.
• [44]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