title: How long should we continue clomiphene citrate in anovulatory women?
abstract: OBJECTIVE
  What is the effectiveness of continued treatment with clomiphene citrate (CC) in women with World Health Organization (WHO) type II anovulation who have had at least six ovulatory cycles with CC but did not conceive?
  
  
  CONCLUSIONS
  When women continued CC after six treatment cycles, the cumulative incidence rate of the ongoing pregnancy rate was 54% (95% CI 37-78%) for cycles 7-12.
  
  
  BACKGROUND
  If women with WHO type II anovulation fail to conceive with CC within six ovulatory cycles, guidelines advise switching to gonadotrophins, which have a high risk of multiple gestation and are expensive. It is however not clear what success rate could be achieved by continued treatment with CC.
  
  
  METHODS
  We performed a retrospective cohort study of women with WHO II anovulation who visited the fertility clinics of five hospitals in the Netherlands between 1994 and 2010. We included women treated with CC who had had at least six ovulatory cycles without successful conception (n = 114) after which CC was continued using dosages varying from 50 to 150 mg per day for 5 days.
  
  
  METHODS
  Follow-up was a total of 12 treatment cycles. Primary outcome was the cumulative incidence rate of an ongoing pregnancy at the end of treatment.
  
  
  RESULTS
  We recruited 114 women that had ovulated on CC for at least six cycles but had not conceived. Of these 114 women, 35 (31%) had an ongoing pregnancy resulting in a cumulative incidence rate of an ongoing pregnancy of 54% after 7-12 treatment cycles with CC.
  
  
  CONCLUSIONS
  Limitations of our study are its retrospective approach.
  
  
  CONCLUSIONS
  Randomized trials comparing continued treatment with CC with the relatively established second line treatment with gonadotrophins are justified. In the meantime, we suggest to only begin this less convenient and more expensive treatment for women who do not conceive after 12 ovulatory cycles with CC.
  
  
  BACKGROUND
  None.
  
  
  BACKGROUND
  Not applicable.
authors.affiliation: Center for Reproductive Medicine, Academic Medical Center, 1105 AZ Amsterdam, the Netherlands Center for Reproductive Medicine, Free University Medical Center, 1081 HZ Amsterdam, the Netherlands Department of Obstetrics and Gynaecology, Onze Lieve Vrouwe Gasthuis, 1091 AC Amsterdam, the Netherlands.
authors.forename: N S
authors.initials: NS
authors.lastname: Weiss
authors.affiliation: Center for Reproductive Medicine, Academic Medical Center, 1105 AZ Amsterdam, the Netherlands Center for Reproductive Medicine, Jeroen Bosch Hospital, 5223 GZ Den Bosch, the Netherlands.
authors.forename: S
authors.initials: S
authors.lastname: Braam
authors.affiliation: Center for Reproductive Medicine, Free University Medical Center, 1081 HZ Amsterdam, the Netherlands.
authors.forename: T E
authors.initials: TE
authors.lastname: König
authors.affiliation: Center for Reproductive Medicine, Free University Medical Center, 1081 HZ Amsterdam, the Netherlands.
authors.forename: M L
authors.initials: ML
authors.lastname: Hendriks
authors.affiliation: Center for Reproductive Medicine, Jeroen Bosch Hospital, 5223 GZ Den Bosch, the Netherlands.
authors.forename: C J
authors.initials: CJ
authors.lastname: Hamilton
authors.affiliation: Department of Obstetrics and Gynaecology, St Elisabeth Hospital, 5000 LC Tilburg, the Netherlands.
authors.forename: J M J
authors.initials: JM
authors.lastname: Smeenk
authors.affiliation: Department of Obstetrics and Gynaecology, Máxima Medical Center, 5504 DB Veldhoven, the Netherlands.
authors.forename: C A M
authors.initials: CA
authors.lastname: Koks
authors.affiliation: Department of Obstetrics and Gynaecology, Onze Lieve Vrouwe Gasthuis, 1091 AC Amsterdam, the Netherlands.
authors.forename: E M
authors.initials: EM
authors.lastname: Kaaijk
authors.affiliation: Center for Reproductive Medicine, Free University Medical Center, 1081 HZ Amsterdam, the Netherlands.
authors.forename: P G A
authors.initials: PG
authors.lastname: Hompes
authors.affiliation: Center for Reproductive Medicine, Free University Medical Center, 1081 HZ Amsterdam, the Netherlands.
authors.forename: C B
authors.initials: CB
authors.lastname: Lambalk
authors.affiliation: Center for Reproductive Medicine, Academic Medical Center, 1105 AZ Amsterdam, the Netherlands.
authors.forename: F
authors.initials: F
authors.lastname: van der Veen
authors.affiliation: Center for Reproductive Medicine, Academic Medical Center, 1105 AZ Amsterdam, the Netherlands.
authors.forename: B W J
authors.initials: BW
authors.lastname: Mol
authors.affiliation: Center for Reproductive Medicine, Academic Medical Center, 1105 AZ Amsterdam, the Netherlands m.vanwely@amc.uva.nl.
authors.forename: M
authors.initials: M
authors.lastname: van Wely
mesh_terms: D000328:Adult; D002996:Clomiphene / Q000008:administration & dosage / Q000627:therapeutic use*; D016208:Databases, Factual; D004334:Drug Administration Schedule; D005260:Female; D005300:Fertility Agents, Female / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D010062:Ovulation Induction / Q000379:methods*; D011247:Pregnancy; D018873:Pregnancy Rate; D012189:Retrospective Studies
chemical_list: D005300:Fertility Agents, Female; D002996:Clomiphene
keywords: anovulation; clomiphene; polycystic ovary syndrome; pregnancy