title: Ovarian reserve assessment in users of oral contraception seeking fertility advice on their reproductive lifespan.
abstract: OBJECTIVE
  To what extent does oral contraception (OC) impair ovarian reserve parameters in women who seek fertility assessment and counselling to get advice on whether their remaining reproductive lifespan is reduced?
  
  
  CONCLUSIONS
  Ovarian reserve parameters defined by anti-Müllerian hormone (AMH), antral follicle count (AFC) and ovarian volume were found to be significantly decreased by 19% (95% CI 9.1-29.3%), 18% (95% CI 11.2-24.8%) and 50% (95% CI 45.1-53.7%) among OC users compared with non-users.
  
  
  BACKGROUND
  AMH and AFC have proved to be reliable predictors of ovarian ageing. In women, AMH declines with age and data suggest a relationship with remaining reproductive lifespan and age at menopause. OC may alter parameters related to ovarian reserve assessment but the extent of the reduction is uncertain.
  
  
  METHODS
  A cross-sectional study of 887 women aged 19-46 attending the Fertility Assessment and Counselling Clinic (FACC) from 2011 to 2014 comparing ovarian reserve parameters in OC users with non-OC users.
  
  
  METHODS
  The FAC Clinic was initiated to provide individual fertility assessment and counselling. All women were examined on a random cycle day by a fertility specialist. Consultation included; transvaginal ultrasound (AFC, ovarian volume, pathology), a full reproductive history and AMH measurement. Women were grouped into non-users and users of OC (all combinations of estrogen-progestin products and the contraceptive vaginal ring). Non-users included women with an intrauterine device (IUD) or no hormonal contraception.
  
  
  RESULTS
  Of the 887 women, 244 (27.5%) used OC. In a linear regression analyses adjusted for age, ovarian volume was 50% lower (95% CI 45.1-53.7%), AMH was 19% lower (95% CI 9.1-29.3%), and AFC was 18% lower (95% CI 11.2-24.8%) in OC users compared with non-users. Comparison of AMH at values of <10 pmol/l OC was found to have a significant negative influence on AMH (OR 1.6, 95% CI 1.1; 2.4, P = 0.03). Furthermore, we found a significant decrease in antral follicles sized 5-7 mm (P < 0.001) and antral follicles sized 8-10 mm (P < 0.001) but an increase in antral follicles sized 2-4 mm (P = 0.008) among OC users. The two groups (OC users versus non-users) were comparable regarding age, BMI, smoking and maternal age at menopause.
  
  
  CONCLUSIONS
  The study population comprised women attending the FAC Clinic. Recruitment was based on self-referral, which could imply a potential selection bias. Ovarian reserve was examined at a random cycle day. However, both AMH and AFC can be assessed independently of the menstrual cycle. The accuracy in predicting residual reproductive lifespan is still needed in both users and non-users of OC.
  
  
  CONCLUSIONS
  OC has a major impact on the ovarian volume, and a moderate impact on AFC and AMH with a shift towards the smaller sized antral follicle subclasses. The most evident reduction occurs in the antral follicles of 5-7 and 8-10 mm with the highest number of AMH secreting granulosa cells. It is essential to be aware of the impact of OC use on ovarian reserve parameters when guiding OC users on their fertility status and reproductive lifespan.
  
  
  BACKGROUND
  The FAC Clinic was established in 2011 as part of the ReproHigh collaboration. This study received funding through the Capital Region Research Fund and by EU-regional funding. There are no competing interests.
  
  
  BACKGROUND
  The biobank connected to FAC Clinic is approved by the Scientific Ethical Committee (H-1-2011-081).
authors: Fertility Clinic, Copenhagen University Hospital, Blegdamsvej 9, DK-2100 Copenhagen, Denmark kbirch@dadlnet.dk.
authors: K
authors: K
authors: Birch Petersen
authors: Fertility Clinic, Copenhagen University Hospital, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
authors: H W
authors: HW
authors: Hvidman
authors: The Department of Biostatistics, Copenhagen University, 1014 Copenhagen, Denmark.
authors: J L
authors: JL
authors: Forman
authors: Department of Gynecology/Obstetrics, Copenhagen University Hospital Hvidovre Hospital, Kettegård Alle 30, 2650 Hvidovre, Copenhagen, Denmark.
authors: A
authors: A
authors: Pinborg
authors: Fertility Clinic, Copenhagen University Hospital, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
authors: E C
authors: EC
authors: Larsen
authors: Fertility Clinic, Copenhagen University Hospital, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
authors: K T
authors: KT
authors: Macklon
authors: Fertility Clinic, Copenhagen University Hospital, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
authors: R
authors: R
authors: Sylvest
authors: Fertility Clinic, Copenhagen University Hospital, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
authors: A Nyboe
authors: AN
authors: Andersen
mesh_terms: D000328:Adult; D000375:Aging; D054304:Anti-Mullerian Hormone / Q000378:metabolism; D003267:Contraception; D003276:Contraceptives, Oral / Q000627:therapeutic use*; D003430:Cross-Sectional Studies; D005260:Female; D005298:Fertility / Q000187:drug effects*; D006801:Humans; D016014:Linear Models; D008875:Middle Aged; D006080:Ovarian Follicle / Q000473:pathology*; D065851:Ovarian Reserve / Q000187:drug effects*; D010053:Ovary / Q000187:drug effects* / Q000502:physiology; D011446:Prospective Studies; D012098:Reproduction; D011795:Surveys and Questionnaires; D055815:Young Adult
chemical_list: D003276:Contraceptives, Oral; D054304:Anti-Mullerian Hormone
keywords: AFC; AMH; oral contraception; ovarian reserve assessment; ovarian volume