title: The Pregnancy in Polycystic Ovary Syndrome II (PPCOS II) trial: rationale and design of a double-blind randomized trial of clomiphene citrate and letrozole for the treatment of infertility in women with polycystic ovary syndrome.
abstract: Polycystic Ovary Syndrome (PCOS) is a common cause of female infertility and first line treatment is currently oral clomiphene citrate, a selective estrogen receptor modulator, which results in both a high nonresponse rate and multiple pregnancy rate. Aromatase inhibitors such as letrozole may have more favorable ovarian and endometrial effects. The goal of the Pregnancy in Polycystic Ovary Syndrome II (PPCOSII) study is to determine the safety and efficacy of clomiphene citrate (CC) compared to letrozole, in achieving live birth in infertile women with PCOS. The population will consist of 750 infertile women with PCOS. Additionally, the couple will have no other major infertility factor. This will be a multi-center, prospective, double-blind clinical trial of CC vs. letrozole for 5 treatment cycles (or approximately up to 25 weeks). The randomization scheme will be coordinated through the central data coordinating center (DCC) and the randomization is stratified by each participating site. After progestin withdrawal as needed, 750 women will be equally randomized to two different treatment arms: A) CC 50mg every day for 5 days (days 3-7 of cycle), or B) letrozole 2.5mg every day for 5 days (days 3-7 of cycle), for a total of 5 cycles or 25 weeks. The dose will be increased in subsequent cycles in both treatment groups for non-response or poor ovulatory response up to a maximum of 150 mg of CC a day (×5 days) or 7.5mg of letrozole a day (×5 days). The primary analysis will use an intent-to-treat approach to examine differences in the live birth rate in the two treatment arms.
authors.affiliation: Department of Obstetrics and Gynecology, Pennsylvania State University, Hershey, PA, United States. rsl1@psu.edu
authors.forename: Richard S
authors.initials: RS
authors.lastname: Legro
authors.forename: Allen R
authors.initials: AR
authors.lastname: Kunselman
authors.forename: Robert G
authors.initials: RG
authors.lastname: Brzyski
authors.forename: Peter R
authors.initials: PR
authors.lastname: Casson
authors.forename: Michael P
authors.initials: MP
authors.lastname: Diamond
authors.forename: William D
authors.initials: WD
authors.lastname: Schlaff
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Christman
authors.forename: Christos
authors.initials: C
authors.lastname: Coutifaris
authors.forename: Hugh S
authors.initials: HS
authors.lastname: Taylor
authors.forename: Esther
authors.initials: E
authors.lastname: Eisenberg
authors.forename: Nanette
authors.initials: N
authors.lastname: Santoro
authors.forename: Heping
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use; D016009:Chi-Square Distribution; D002996:Clomiphene / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D005300:Fertility Agents, Female / Q000627:therapeutic use*; D006305:Health Status Indicators; D006628:Hirsutism / Q000188:drug therapy; D006801:Humans; D017588:Hyperandrogenism / Q000188:drug therapy; D007247:Infertility, Female / Q000188:drug therapy* / Q000209:etiology; D000077289:Letrozole; D008875:Middle Aged; D009570:Nitriles / Q000627:therapeutic use*; D010062:Ovulation Induction / Q000379:methods*; D011085:Polycystic Ovary Syndrome / Q000150:complications / Q000188:drug therapy*; D011247:Pregnancy; D011788:Quality of Life / Q000523:psychology; D012107:Research Design; D014230:Triazoles / Q000627:therapeutic use*; D016387:Women's Health; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D005300:Fertility Agents, Female; D009570:Nitriles; D014230:Triazoles; D002996:Clomiphene; D000077289:Letrozole