TY - JOUR
T1 - The Pregnancy in Polycystic Ovary Syndrome II (PPCOS II) trial
T2 - 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
AU - Legro, Richard S.
AU - Kunselman, Allen R.
AU - Brzyski, Robert G.
AU - Casson, Peter R.
AU - Diamond, Michael Peter
AU - Schlaff, William D.
AU - Christman, Gregory M.
AU - Coutifaris, Christos
AU - Taylor, Hugh S.
AU - Eisenberg, Esther
AU - Santoro, Nanette
AU - Zhang, Heping
N1 - Funding Information:
This work was supported by National Institutes of Health (NIH)/Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Grants U10 HD27049 (to C.C.); U10 HD38992 (to R.S.L.); U10HD055925 (to H.Z.); U10 HD39005 (to M.P.D.); U10 HD33172 (to M.P.S.); U10 HD38998 (to W.D.S); U10 HD055936 (to G.M.C.); U10 HD055942 (to R.G.B.); and U10 HD055944 (to P.R.C.); U54-HD29834 (to the University of Virginia Center for Research in Reproduction Ligand Assay and Analysis Core of the Specialized Cooperative Centers Program in Reproduction and Infertility Research); General Clinical Research Center Grants MO1RR10732 and construction grant C06 RR016499 (to Pennsylvania State University). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NICHD or NIH.
Funding Information:
The study is funded through a cooperative agreement by the Eunice Kennedy Shriver National Institutes of Child Health and Human Development (NICHD) and is led by a steering committee consisting of the site PIs of the RMN, the PI of the DCC, an independently-selected chair, and the NIH project scientist. Each of these individuals has one vote. Decisions are reached by majority consensus and formal vote. The steering committee meets four times a year face to face, and monthly via phone conference. Additionally there are subcommittees including a protocol committee, a recruitment committee, a publication committee, a Data and Specimen Committee, etc. Additional sites were added (N = 4), led by investigators who had successfully completed training in a NIH sponsored Clinical Reproductive Endocrinology Scholar's Training program (known as CREST).
PY - 2012/5
Y1 - 2012/5
N2 - 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.
AB - 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.
KW - Clomiphene citrate
KW - Hyperandrogenism
KW - Infertility
KW - Letrozole
KW - Ovulation induction
KW - Polycystic Ovary Syndrome
UR - http://www.scopus.com/inward/record.url?scp=84862832321&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84862832321&partnerID=8YFLogxK
U2 - 10.1016/j.cct.2011.12.005
DO - 10.1016/j.cct.2011.12.005
M3 - Article
C2 - 22265923
AN - SCOPUS:84862832321
SN - 1551-7144
VL - 33
SP - 470
EP - 481
JO - Contemporary Clinical Trials
JF - Contemporary Clinical Trials
IS - 3
ER -