The status of ovarian reserve markers during hormonal contraception (HC) remains uncertain with conflicting literature data. The purpose of this study was to assess the impact of HC on circulating anti-Müllerian hormone (AMH) and other ovarian reserve markers.
Materials and Methods:
A systematic review was conducted, including all cohort, cross-sectional, and randomized controlled studies assessing serum anti Müllerian hormone concentration in women using HC. Data sources included MEDLINE, EMBASE, DynaMed Plus, ScienceDirect, TRIP database, ClinicalTrials.gov, and the Cochrane Library from January 2000 to October 2018.
Results:
A total of 366 studies were identified, of which 15 were eligible, including 3280 women, mostly using combined HC (CHC). Articles were divided according to duration of HC into short- (2–3 weeks), medium- (2–6 months), long- (>1 year), and varied-term studies. Two study designs were identified, including studies comparing AMH before and during/after CHC and studies comparing CHC users versus nonusers. Short- and medium-term studies (n = 284) reported no change in circulating AMH in women using cyclical CHC for one to six cycles. Apart from one study, all long- and varied-term studies (six studies, n = 1601) consistently showed a marked decline in AMH, antral follicle count, and ovarian volume. Three long-term studies (n = 1324) provided evidence of AMH recovery after discontinuation of HC.
Conclusion:
Circulating AMH seems to remain unchanged in women using cyclical CHC for up to 6 months, but appears to markedly decline in long-term users with recovery after discontinuation.
Get full access to this article
View all access options for this article.
References
1.
MillsM, RindfussRR, McDonaldP, Te VeldeE. Why do people postpone parenthood? Reasons and social policy incentives. Hum Reprod Update, 2011; 17:848–860.
2.
TremellenK, SavulescuJ. Ovarian reserve screening: A scientific and ethical analysis. Hum Reprod, 2014; 29:2606–2614.
3.
HvidmanHW, PetersenKB, LarsenEC, MacklonKT, PinborgA, Nyboe AndersenA. Individual fertility assessment and pro-fertility counselling; should this be offered to women and men of reproductive age?. Hum Reprod, 2014; 30:9–15.
4.
La MarcaA, SighinolfiG, GiuliniS, et al.Normal serum concentrations of anti-Müllerian hormone in women with regular menstrual cycles. Reprod Biomed Online, 2010; 21:463–469.
5.
ESHRE Capri Workshop Group. Ovarian and endometrial function during hormonal contraception. Hum Reprod, 2001; 16:1527–1535.
6.
SchlaffWD, LynchAM, HughesHD, CedarsMI, SmithDL. Manipulation of the pill-free interval in oral contraceptive pill users: The effect on follicular suppression. Am J Obstet Gynecol, 2004; 190:943–951.
7.
FanchinR, SchonäuerLM, RighiniC, GuibourdencheJ, FrydmanR, TaiebJ. Serum anti-Müllerian 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.
8.
La MarcaA, StabileG, ArtenisioAC, VolpeA. Serum anti-Mullerian hormone throughout the human menstrual cycle. Hum Reprod, 2006; 21:3103–3107.
9.
HehenkampWJ, LoomanCW, ThemmenAP, de JongFH, Te VeldeER, BroekmansFJ. Anti-Mullerian hormone levels in the spontaneous menstrual cycle do not show substantial fluctuation. J Clin Endocrinol Metab, 2006; 91:4057–4063.
10.
TsepelidisS, DevrekerF, DemeestereI, FlahautA, GervyC, EnglertY. Stable serum levels of anti-Müllerian hormone during the menstrual cycle: A prospective study in normo-ovulatory women. Hum Reprod, 2007; 22:1837–1840.
11.
van DisseldorpJ, LambalkCB, KweeJ, et al.Comparison of inter-and intra-cycle variability of anti-Müllerian hormone and antral follicle counts. Hum Reprod, 2009; 25:221–227.
12.
DewaillyD, AndersenCY, BalenA, et al.The physiology and clinical utility of anti-Müllerian hormone in women. Hum Reprod Update, 2014; 20:370–385.
13.
OverbeekA, BroekmansFJ, HehenkampWJ, et al.Intra-cycle fluctuations of anti-Müllerian hormone in normal women with a regular cycle: A re-analysis. Reprod Biomed Online, 2012; 24:664–669.
14.
HadlowN, LonghurstK, McClementsA, NatalwalaJ, BrownSJ, MatsonPL. Variation in antimüllerian hormone concentration during the menstrual cycle may change the clinical classification of the ovarian response. Fertil Steril, 2013; 99:1791–1797.
15.
D'ArpeS, Di FeliciantonioM, CandelieriM, FranceschettiS, PiccioniMG, BastianelliC. Ovarian function during hormonal contraception assessed by endocrine and sonographic markers: A systematic review. Reprod Biomed Online, 2016; 33:436–448.
16.
ArboE, VetoriDV, JimenezMF, FreitasFM, LemosN, Cunha-FilhoJS. Serum anti-müllerian hormone levels and follicular cohort characteristics after pituitary suppression in the late luteal phase with oral contraceptive pills. Hum Reprod, 2007; 22:3192–3196.
17.
FábreguesF, Castelo-BrancoC, CarmonaF, GuimeráM, CasamitjanaR, BalaschJ. The effect of different hormone therapies on anti-müllerian hormone serum levels in anovulatory women of reproductive age. Gynecol Endocrinol, 2011; 27:216–224.
18.
ShawCM, StanczykFZ, EglestonBL, et al.Serum antimüllerian hormone in healthy premenopausal women. Fertil Steril, 2011; 95:2718–2721.
19.
BentzenJG, FormanJL, PinborgA, et al.Ovarian reserve parameters: A comparison between users and non-users of hormonal contraception. Reprod Biomed Online, 2012; 25:612–619.
20.
KristensenSL, Ramlau-HansenCH, AndersenCY, et al.The association between circulating levels of antimüllerian hormone and follicle number, androgens, and menstrual cycle characteristics in young women. Fertil Steril, 2012; 97:779–785.
21.
KallioS, PuurunenJ, RuokonenA, VaskivuoT, PiltonenT, TapanainenJS. Antimüllerian hormone levels decrease in women using combined contraception independently of administration route. Fertil Steril, 2013; 99:1305–1310.
22.
DollemanM, VerschurenWM, EijkemansMJ, et al.Reproductive and lifestyle determinants of anti-Müllerian hormone in a large population-based study. J Clin Endocrinol Meta, 2013; 98:2106–2115.
23.
JohnsonLN, SammelMD, DillonKE, LechtenbergL, SchanneA, GraciaCR. Antimüllerian hormone and antral follicle count are lower in female cancer survivors and healthy women taking hormonal contraception. Fertil Steril, 2014; 102:77–781.
24.
PetersenKB, HvidmanHW, FormanJL, et al.Ovarian reserve assessment in users of oral contraception seeking fertility advice on their reproductive lifespan. Hum Reprod, 2015; 30:2364–2375.
25.
SomunkiranA, YavuzT, YucelO, OzdemirI. Anti-Müllerian hormone levels during hormonal contraception in women with polycystic ovary syndrome. Eur J Obstet Gynecol Reprod Biol, 2007; 134:196–201.
26.
StreuliI, FraisseT, PilletC, IbecheoleV, BischofP, De ZieglerD. Serum antiMüllerian hormone levels remain stable throughout the menstrual cycle and after oral or vaginal administration of synthetic sex steroids. Fertil Steril, 2008; 90:395–400.
27.
LiHW, WongCY, YeungWS, HoPC, NgEH. Serum anti-Müllerian hormone level is not altered in women using hormonal contraceptives. Contraception, 2011; 83:582–585.
28.
PanidisD, GeorgopoulosNA, PioukaA, et al.The impact of oral contraceptives and metformin on anti-Müllerian hormone serum levels in women with polycystic ovary syndrome and biochemical hyperandrogenemia. Gynecol Endocrinol, 2011; 27:587–592.
29.
DebS, CampbellBK, Pincott-AllenC, ClewesJS, CumberpatchG, Raine-FenningNJ. Quantifying effect of combined oral contraceptive pill on functional ovarian reserve as measured by serum anti-Müllerian hormone and small antral follicle count using three-dimensional ultrasound. Ultrasound Obstet Gynecol, 2012; 39:574–580.
30.
LiberatiA, AltmanDG, TetzlaffJ, et al.The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: Explanation and elaboration. PLoS Med, 2009; 6:e1000100.
31.
WellsGA, SheaB, O'ConnellD, et al.The Newcastle–Ottawa Scale (NOS) for assessing the quality of non-randomized studies in meta-analysis. Ottawa Health Research Institute. www.ohri.ca/programs/clinical_epidemiology/oxford.asp Accessed February15, 2019.
32.
RaffiF, MetwallyM, AmerS. The impact of excision of ovarian endometrioma on ovarian reserve: A systematic review and meta-analysis. J Clin Endocrinol Metab, 2012; 97:3146–3154.
33.
MohamedAA, Al-HussainiTK, FathallaMM, El ShamyTT, AbdelaalII, AmerSA. The impact of excision of benign nonendometriotic ovarian cysts on ovarian reserve: A systematic review. Am J Obstet Gynecol, 2016; 215:169–176.
34.
SteinerAZ, StanczykFZ, PatelS, EdelmanA. Antimullerian hormone and obesity: Insights in oral contraceptive users. Contraception, 2010; 81:245–248.
35.
BentzenJG, FormanJL, LarsenEC, et al.Maternal menopause as a predictor of anti-Müllerian hormone level and antral follicle count in daughters during reproductive age. Hum Reprod, 2012; 28:247–255.
36.
AndersenAN, WitjesH, GordonK, MannaertsB. 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.
37.
KuceraR, Ulcova-GallovaZ, TopolcanO. Effect of long-term using of hormonal contraception on anti-Müllerian hormone secretion. Gynecol Endocrinol, 2016; 32:383–385.
38.
Van den BergMH, Van Dulmen-den BroederE, OverbeekA, et al.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.
39.
BarnesRB, NamnoumAB, RosenfieldRL, LaymanLC. The role of LH and FSH in ovarian androgen secretion and ovarian follicular development: Clinical studies in a patient with isolated FSH deficiency and multicystic ovaries: Case report. Hum Reprod, 2002; 17:88–91.
40.
FréourT, MiralliéS, Bach-NgohouK, DenisM, BarrièreP, MassonD. Measurement of serum anti-Müllerian hormone by Beckman Coulter ELISA and DSL ELISA: Comparison and relevance in assisted reproduction technology (ART). Clin Chim Acta, 2007; 375:162–164.
41.
BroerSL, BroekmansFJ, LavenJS, FauserBC. Anti-Müllerian hormone: Ovarian reserve testing and its potential clinical implications. Hum Reprod Update, 2014; 20:688–701.
42.
KumarA, KalraB, PatelA, McDavidL, RoudebushWE. Development of a second generation anti-Müllerian hormone (AMH) ELISA. J Immunol Methods, 2010; 362:51–59.
43.
WallaceAM, FayeSA, FlemingR, NelsonSM. A multicentre evaluation of the new Beckman Coulter anti-Mullerian hormone immunoassay (AMH Gen II). Ann Clin Biochem, 2011; 48:370–373.
44.
Magnusson Å, OlerödG, Thurin-KjellbergA, BerghC. The correlation between AMH assays differs depending on actual AMH levels. Hum Reprod Open, 2017; 2017:1–5.
