title: The M-OVIN study: does switching treatment to FSH and / or IUI lead to higher pregnancy rates in a subset of women with world health organization type II anovulation not conceiving after six ovulatory cycles with clomiphene citrate - a randomised controlled trial.
abstract: BACKGROUND
  Clomiphene citrate (CC) is first line treatment in women with World Health Organization (WHO) type II anovulation and polycystic ovary syndrome (PCOS). Whereas 60% to 85% of these women will ovulate on CC, only about one half will have conceived after six cycles. If women do not conceive, treatment can be continued with gonadotropins or intra-uterine insemination (IUI). At present, it is unclear for how many cycles ovulation induction with CC should be repeated, and when to switch to ovulation induction with gonadotropins and/or IUI.
  
  
  METHODS
  We started a multicenter randomised controlled trial in the Netherlands comparing six cycles of CC plus intercourse or six cycles of gonadotrophins plus intercourse or six cycles of CC plus IUI or six cycles of gonadotrophins plus IUI.Women with WHO type II anovulation who ovulate but did not conceive after six ovulatory cycles of CC with a maximum of 150 mg daily for five days will be included.Our primary outcome is birth of a healthy child resulting from a pregnancy that was established in the first eight months after randomisation. Secondary outcomes are clinical pregnancy, miscarriage, multiple pregnancy and treatment costs. The analysis will be performed according to the intention to treat principle. Two comparisons will be made, one in which CC is compared to gonadotrophins and one in which the addition of IUI is compared to ovulation induction only. Assuming a live birth rate of 40% after CC, 55% after addition of IUI and 55% after ovulation induction with gonadotrophins, with an alpha of 5% and a power of 80%, we need to recruit 200 women per arm (800 women in total).An independent Data and Safety Monitoring Committee has criticized the data of the first 150 women and concluded that a sample size re-estimation should be performed after including 320 patients (i.e. 80 per arm).
  
  
  CONCLUSIONS
  The trial will provide evidence on the most effective, safest and most cost effective treatment in women with WHO type II anovulation who do not conceive after six ovulatory cycles with CC with a maximum of 150 mg daily for five days. This evidence could imply the need for changing our guidelines, which may cause a shift in large practice variation to evidence based primary treatment for these women.
  
  
  BACKGROUND
  Netherlands Trial register NTR1449.
authors.affiliation: Department of Obstetrics and Gynaecology, Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands. m.nahuis@vumc.nl.
authors.forename: Marleen J
authors.initials: MJ
authors.lastname: Nahuis
authors.forename: Nienke S
authors.initials: NS
authors.lastname: Weiss
authors.forename: Fulco
authors.initials: F
authors.lastname: van der Veen
authors.forename: Ben Willem J
authors.initials: BW
authors.lastname: Mol
authors.forename: Peter G
authors.initials: PG
authors.lastname: Hompes
authors.forename: Jur
authors.initials: J
authors.lastname: Oosterhuis
authors.forename: Nils B
authors.initials: NB
authors.lastname: Lambalk
authors.forename: Jesper M J
authors.initials: JM
authors.lastname: Smeenk
authors.forename: Carolien A M
authors.initials: CA
authors.lastname: Koks
authors.forename: Ron J T
authors.initials: RJ
authors.lastname: van Golde
authors.forename: Joop S E
authors.initials: JS
authors.lastname: Laven
authors.forename: Ben J
authors.initials: BJ
authors.lastname: Cohlen
authors.forename: Kathrin
authors.initials: K
authors.lastname: Fleischer
authors.forename: Angelique J
authors.initials: AJ
authors.lastname: Goverde
authors.forename: Marie H
authors.initials: MH
authors.lastname: Gerards
authors.forename: Nicole F
authors.initials: NF
authors.lastname: Klijn
authors.forename: Lizka C M
authors.initials: LC
authors.lastname: Nekrui
authors.forename: Ilse A J
authors.initials: IA
authors.lastname: van Rooij
authors.forename: Diederik A
authors.initials: DA
authors.lastname: Hoozemans
authors.forename: Madelon
authors.initials: M
authors.lastname: van Wely
mesh_terms: D000858:Anovulation / Q000150:complications / Q000628:therapy*; D002996:Clomiphene; D005260:Female; D005640:Follicle Stimulating Hormone / Q000627:therapeutic use*; D006062:Gonadotropins / Q000627:therapeutic use*; D006801:Humans; D007247:Infertility, Female / Q000209:etiology / Q000628:therapy*; D007315:Insemination, Artificial / Q000379:methods; D009426:Netherlands; D010062:Ovulation Induction / Q000379:methods*; D011085:Polycystic Ovary Syndrome / Q000150:complications / Q000628:therapy*; D011247:Pregnancy; D018873:Pregnancy Rate; D061685:Time-to-Pregnancy; D016896:Treatment Outcome
chemical_list: D006062:Gonadotropins; D002996:Clomiphene; D005640:Follicle Stimulating Hormone