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

Richard S. Legro, Allen R. Kunselman, Robert G. Brzyski, Peter R. Casson, Michael Peter Diamond, William D. Schlaff, Gregory M. Christman, Christos Coutifaris, Hugh S. Taylor, Esther Eisenberg, Nanette Santoro, Heping Zhang

Research output: Contribution to journalArticle

42 Citations (Scopus)

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 50. mg every day for 5. days (days 3-7 of cycle), or B) letrozole 2.5. mg 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 7.5. mg 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.

Original languageEnglish (US)
Pages (from-to)470-481
Number of pages12
JournalContemporary Clinical Trials
Volume33
Issue number3
DOIs
StatePublished - May 1 2012
Externally publishedYes

Fingerprint

letrozole
Clomiphene
Polycystic Ovary Syndrome
Infertility
Pregnancy
Live Birth
Random Allocation
Female Infertility
Selective Estrogen Receptor Modulators
Therapeutics
Multiple Pregnancy
Aromatase Inhibitors
Birth Rate
Progestins
Pregnancy Rate
Clinical Trials
Safety

Keywords

  • Clomiphene citrate
  • Hyperandrogenism
  • Infertility
  • Letrozole
  • Ovulation induction
  • Polycystic Ovary Syndrome

ASJC Scopus subject areas

  • Pharmacology (medical)

Cite this

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. / Legro, Richard S.; Kunselman, Allen R.; Brzyski, Robert G.; Casson, Peter R.; Diamond, Michael Peter; Schlaff, William D.; Christman, Gregory M.; Coutifaris, Christos; Taylor, Hugh S.; Eisenberg, Esther; Santoro, Nanette; Zhang, Heping.

In: Contemporary Clinical Trials, Vol. 33, No. 3, 01.05.2012, p. 470-481.

Research output: Contribution to journalArticle

Legro, Richard S. ; Kunselman, Allen R. ; Brzyski, Robert G. ; Casson, Peter R. ; Diamond, Michael Peter ; Schlaff, William D. ; Christman, Gregory M. ; Coutifaris, Christos ; Taylor, Hugh S. ; Eisenberg, Esther ; Santoro, Nanette ; Zhang, Heping. / 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. In: Contemporary Clinical Trials. 2012 ; Vol. 33, No. 3. pp. 470-481.
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