Article| Volume 25, ISSUE 6, P612-619, December 2012

Ovarian reserve parameters: a comparison between users and non-users of hormonal contraception

Published:September 17, 2012DOI:


      It remains controversial whether anti-Müllerian hormone (AMH) concentration is influenced by hormonal contraception. This study quantified the effect of hormonal contraception on both endocrine and sonographic ovarian reserve markers in 228 users and 504 non-users of hormonal contraception. On day 2–5 of the menstrual cycle or during withdrawal bleeding, blood sampling and transvaginal sonography was performed. After adjusting for age, ovarian reserve parameters were lower among users than among non-users of hormonal contraception: serum AMH concentration by 29.8% (95% CI 19.9 to 38.5%), antral follicle count (AFC) by 30.4% (95% CI 23.6 to 36.7%) and ovarian volume by 42.2% (95% CI 37.8 to 46.3%). AFC in all follicle size categories (small, 2–4 mm; intermediate, 5–7 mm; large, 8–10 mm) was lower in users than in non-users of hormonal contraception. A negatively linear association was observed between duration of hormonal-contraception use and ovarian reserve parameters. No dose–response relation was found between the dose of ethinyloestradiol and AMH or AFC. This study indicates that ovarian reserve markers are lower in women using sex steroids for contraception. Thus, AMH concentration and AFC may not retain their accuracy as predictors of ovarian reserve in women using hormonal contraception.
      Serum anti-Müllerian hormone (AMH) concentration is an indirect marker of the number of small follicles in the ovary and thereby the ovarian reserve. The AMH concentration is now widely used as one of the markers of the ovarian reserve in ovarian hormonal stimulation regimens. Hence the AMH concentration in a patient is used to decide the dose of the ovarian hormonal stimulation prior to IVF treatment. In some infertile patients, hormonal contraception is used prior to ovarian hormonal stimulation and therefore it is important to clarify whether serum AMH concentration is influenced by the use of sex steroids. The aim of this study was to quantify the potential effect of hormonal contraception on the ovarian function by hormonal analyses and ovarian ultrasound examination. Examinations were performed in the early phase of the menstrual cycle or the hormone-free interval of hormonal contraception. We compared the AMH concentration, the antral follicle count (AFC) and the ovarian volume in 228 users versus 504 non-users of hormonal contraception. Users of hormonal contraception had 29.8% lower AMH concentration, 30.4% lower AFC and 42.2% lower ovarian volume than non-users. These findings were more pronounced with increasing duration of hormonal contraception. No dose–response relation was found between the dose of ethinylestradiol and the impact on serum AMH and AFC. The study indicates that ovarian reserve markers are lower in women using sex steroids for contraception. Thus, serum AMH concentration and AFC may not retain their accuracy as predictors of the ovarian reserve in women using hormonal contraception.


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        • Andersen A.N.
        • Witjes H.
        • Gordon K.
        • Mannaerts B.
        Predictive factors of ovarian response and clinical outcome after IVF/ICSI following a rFSH/GnRH antagonist protocol with or without oral contraceptive pre-treatment.
        Hum. Reprod. 2011; 26: 3413-3423
        • Arbo E.
        • Vetori D.V.
        • Jimenez M.F.
        • Freitas F.M.
        • Lemos N.
        • Cunha-Filho J.S.
        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
        • Bancsi L.F.
        • Broekmans F.J.
        • Eijkemans M.J.
        • de Jong F.H.
        • Habbema J.D.
        • te Velde E.R.
        Predictors of poor ovarian response in in vitro fertilization: a prospective study comparing basal markers of ovarian reserve.
        Fertil. Steril. 2002; 77: 328-336
        • Broekmans F.J.
        • Kwee J.
        • Hendriks D.J.
        • Mol B.W.
        • Lambalk C.B.
        A systematic review of tests predicting ovarian reserve and IVF outcome.
        Hum. Reprod. Update. 2006; 12: 685-718
        • Broer S.L.
        • Eijkemans M.J.
        • Scheffer G.J.
        • van Rooij I.
        • de Vet A.
        • Themmen A.P.
        • Laven J.S.
        • de Jong F.H.
        • te Velde E.R.
        • Fauser B.C.
        • et al.
        Anti-mullerian hormone predicts menopause: a long-term follow-up study in normoovulatory women.
        J. Clin. Endocrinol. Metab. 2011; 96: 2532-2539
        • Bromberger J.T.
        • Matthews K.A.
        • Kuller L.H.
        • Wing R.R.
        • Meilahn E.N.
        • Plantinga P.
        Prospective study of the determinants of age at menopause.
        Am. J. Epidemiol. 1997; 145: 124-133
        • Cramer D.W.
        • Xu H.
        • Harlow B.L.
        Does ‘incessant’ ovulation increase risk for early menopause?.
        Am. J. Obstet. Gynecol. 1995; 172: 568-573
        • Davison A.C.
        • Hinkley D.
        Bootstrap Methods and their Application.
        Cambridge University Press, Cambridge, UK1997
        • Deb S.
        • Campbell B.K.
        • Pincott-Allen C.
        • Clewes J.S.
        • Cumberpatch G.
        • Raine-Fenning N.J.
        Quantifying the effect of the combined oral contraceptive pill on the functional ovarian reserve as measured by serum anti-Mullerian hormone and the small antral follicle count made using three-dimensional ultrasound.
        Ultrasound Obstet. Gynecol. 2012; 35: 574-580
        • de Vet A.
        • Laven J.S.
        • de Jong F.H.
        • Themmen A.P.
        • Fauser B.C.
        Antimullerian hormone serum levels: a putative marker for ovarian aging.
        Fertil. Steril. 2002; 77: 357-362
        • de Vries E.
        • den Tonkelaar I.
        • van Noord P.A.
        • van der Schouw Y.T.
        • te Velde E.R.
        • Peeters P.H.
        Oral contraceptive use in relation to age at menopause in the DOM cohort.
        Hum. Reprod. 2001; 16: 1657-1662
        • Fanchin R.
        • Schonauer L.M.
        • Righini C.
        • Guibourdenche J.
        • Frydman R.
        • Taieb J.
        Serum anti-Mullerian hormone is more strongly related to ovarian follicular status than serum inhibin B, estradiol, FSH and LH on day 3.
        Hum. Reprod. 2003; 18: 323-327
        • Gougeon A.
        Regulation of ovarian follicular development in primates: facts and hypotheses.
        Endocr. Rev. 1996; 17: 121-155
        • Haadsma M.L.
        • Bukman A.
        • Groen H.
        • Roeloffzen E.M.
        • Groenewoud E.R.
        • Heineman M.J.
        • Hoek A.
        The number of small antral follicles (2–6 mm) determines the outcome of endocrine ovarian reserve tests in a subfertile population.
        Hum. Reprod. 2007; 22: 1925-1931
        • Hansen K.R.
        • Knowlton N.S.
        • Thyer A.C.
        • Charleston J.S.
        • Soules M.R.
        • Klein N.A.
        A new model of reproductive aging: the decline in ovarian non-growing follicle number from birth to menopause.
        Hum. Reprod. 2008; 23: 699-708
        • Hendriks D.J.
        • Kwee J.
        • Mol B.W.
        • te Velde E.R.
        • Broekmans F.J.
        Ultrasonography as a tool for the prediction of outcome in IVF patients: a comparative meta-analysis of ovarian volume and antral follicle count.
        Fertil. Steril. 2007; 87: 764-775
        • Jayaprakasan K.
        • Deb S.
        • Batcha M.
        • Hopkisson J.
        • Johnson I.
        • Campbell B.
        • Raine-Fenning N.
        The cohort of antral follicles measuring 2–6 mm reflects the quantitative status of ovarian reserve as assessed by serum levels of anti-Mullerian hormone and response to controlled ovarian stimulation.
        Fertil. Steril. 2010; 94: 1775-1781
        • Kelsey T.W.
        • Anderson R.A.
        • Wright P.
        • Nelson S.M.
        • Wallace W.H.
        Data-driven assessment of the human ovarian reserve.
        Mol. Hum. Reprod. 2012; 18: 79-87
        • Kristensen S.L.
        • Ramlau-Hansen C.H.
        • Andersen C.Y.
        • Ernst E.
        • Olsen S.F.
        • Bonde J.P.
        • Vested A.
        • Toft G.
        The association between circulating levels of antimullerian hormone and follicle number, androgens, and menstrual cycle characteristics in young women.
        Fertil. Steril. 2012; 97: 779-785
        • La Marca A.
        • Spada E.
        • Sighinolfi G.
        • Argento C.
        • Tirelli A.
        • Giulini S.
        • Milani S.
        • Volpe A.
        Age-specific nomogram for the decline in antral follicle count throughout the reproductive period.
        Fertil. Steril. 2011; 95: 684-688
        • Li H.W.
        • Wong C.Y.
        • Yeung W.S.
        • Ho P.C.
        • Ng E.H.
        Serum anti-mullerian hormone level is not altered in women using hormonal contraceptives.
        Contraception. 2011; 83: 582-585
        • Nagel G.
        • Altenburg H.P.
        • Nieters A.
        • Boffetta P.
        • Linseisen J.
        Reproductive and dietary determinants of the age at menopause in EPIC-Heidelberg.
        Maturitas. 2005; 52: 337-347
        • Nardo L.G.
        • Gelbaya T.A.
        • Wilkinson H.
        • Roberts S.A.
        • Yates A.
        • Pemberton P.
        • Laing I.
        Circulating basal anti-Mullerian hormone levels as predictor of ovarian response in women undergoing ovarian stimulation for in vitro fertilization.
        Fertil. Steril. 2009; 92: 1586-1593
        • Nelson S.M.
        • Yates R.W.
        • Lyall H.
        • Jamieson M.
        • Traynor I.
        • Gaudoin M.
        • Mitchell P.
        • Ambrose P.
        • Fleming R.
        Anti-Mullerian hormone-based approach to controlled ovarian stimulation for assisted conception.
        Hum. Reprod. 2009; 24: 867-875
        • Pesarin F.
        • Salmaso L.
        Permutation Tests for Complex Data – Theory, Applications, and software.
        John Wiley and sons, Chichester, UK2010
        • Rombauts L.
        • Healy D.
        • Norman R.J.
        A comparative randomized trial to assess the impact of oral contraceptive pretreatment on follicular growth and hormone profiles in GnRH antagonist-treated patients.
        Hum. Reprod. 2006; 21: 95-103
        • Rosen M.P.
        • Sternfeld B.
        • Schuh-Huerta S.M.
        • Reijo Pera R.A.
        • McCulloch C.E.
        • Cedars M.I.
        Antral follicle count: absence of significant midlife decline.
        Fertil. Steril. 2010; 94: 2182-2185
        • Rosendahl M.
        • Ernst E.
        • Rasmussen P.E.
        • Andersen C.Y.
        True ovarian volume is underestimated by two-dimensional transvaginal ultrasound measurement.
        Fertil. Steril. 2010; 93: 995-998
        • Somunkiran A.
        • Yavuz T.
        • Yucel O.
        • Ozdemir I.
        Anti-Mullerian hormone levels during hormonal contraception in women with polycystic ovary syndrome.
        Eur. J. Obstet. Gynecol. Reprod. Biol. 2007; 134: 196-201
        • 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
        • Tehrani F.R.
        • Shakeri N.
        • Solaymani-Dodaran M.
        • Azizi F.
        Predicting age at menopause from serum antimullerian hormone concentration.
        Menopause. 2011; 18: 766-770
        • Torgerson D.J.
        • Avenell A.
        • Russell I.T.
        • Reid D.M.
        Factors associated with onset of menopause in women aged 45–49.
        Maturitas. 1994; 19: 83-92
        • van den Berg M.H.
        • van Dulmen-den B.E.
        • Overbeek A.
        • Twisk J.W.
        • Schats R.
        • van Leeuwen F.E.
        • Kaspers G.J.
        • Lambalk C.B.
        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
        • van Rooij I.A.
        • Broekmans F.J.
        • te Velde E.R.
        • Fauser B.C.
        • Bancsi L.F.
        • de Jong F.H.
        • Themmen A.P.
        Serum anti-Mullerian hormone levels: a novel measure of ovarian reserve.
        Hum. Reprod. 2002; 17: 3065-3071
        • van Rooij I.
        • Broekmans F.J.
        • Scheffer G.J.
        • Looman C.W.
        • Habbema J.D.
        • de Jong F.H.
        • Fauser B.J.
        • Themmen A.P.
        • te Velde E.R.
        Serum antimullerian hormone levels best reflect the reproductive decline with age in normal women with proven fertility: a longitudinal study.
        Fertil. Steril. 2005; 83: 979-987
        • Weenen C.
        • Laven J.S.
        • Von Bergh A.R.
        • Cranfield M.
        • Groome N.P.
        • Visser J.A.
        • Kramer P.
        • Fauser B.C.
        • Themmen A.P.
        Anti-Mullerian hormone expression pattern in the human ovary: potential implications for initial and cyclic follicle recruitment.
        Mol. Hum. Reprod. 2004; 10: 77-83
        • Yates A.P.
        • Rustamov O.
        • Roberts S.A.
        • Lim H.Y.
        • Pemberton P.W.
        • Smith A.
        • Nardo L.G.
        Anti-Mullerian hormone-tailored stimulation protocols improve outcomes whilst reducing adverse effects and costs of IVF.
        Hum. Reprod. 2011; 26: 2353-2362