The RMN is a multicenter network of clinical sites that, through a cooperative agreement with the NICHD’s Reproductive Sciences Branch, conduct clinical studies to investigate problems in reproductive medicine, including infertility, reproductive disorders and diseases in men and women that affect fertility, and endocrinological disorders affecting reproduction.

Please see http://grants.nih.gov/grants/guide/rfa-files/RFA-HD-06-008.html for more information about the Network.

The RMN was established in 1990 to carry out large, multicenter clinical trials in the areas of male and female infertility and reproductive diseases and disorders. By testing hypotheses in large numbers of patients enrolled in common protocols at multiple sites, answers are provided more rapidly than by individual sites working alone. The Network currently supports Reproductive Medicine Units (RMUs) at:

• University of Pennsylvania
• University of Colorado Denver,
• Penn State Hershey Medical Center
• Wayne State University
• University of Michigan at Ann Arbor
• University of Texas Health Science Center at San Antonio
• University of Vermont College of Medicine

The RMN also supports a Data Coordinating Center at Yale Collaborative Center for Statistics in Science.

The Principal Investigators of the Network sites, the NICHD research coordinator, and an independent chair comprise the RMN Steering Committee, which makes decisions by consensus regarding topics to be studied, protocol design and execution, and publications.

Two independent groups convened by the NICHD also interact with the Network: a Clinical Trials Advisory Board, which advises the Steering Committee on identifying and prioritizing research topics appropriate for study; and a Data Safety and Monitoring Committee, which is responsible for reviewing the safety of ongoing clinical trials and advises on their conduct.

The RMN recently completed a study comparing medications used to induce ovulation in women with polycystic ovary syndrome (PCOS)—specifically, the study compared clomiphene citrate vs. extended-release metformin vs. both. Clomiphene was found to be superior to metformin in achieving live births in infertile women with PCOS, although multiple births occurred more frequently in the clomiphene group (6%). The conception rate among subjects who ovulated was significantly lower in the metformin group (21.7%) than in either the clomiphene group (39.5%, P=0.002) or the combination-therapy group (46.0%, P<0.001). With the exception of pregnancy complications, adverse-event rates were similar in all groups, though gastrointestinal side effects were more frequent, and vasomotor and ovulatory symptoms less frequent, in the metformin group than in the clomiphene group. Furthermore, in an ancillary study, a polymorphism (change in the genetic sequence) in STK11, a kinase gene expressed in liver and implicated in metformin action, was found to be negatively associated with ovulatory response to treatment with metformin in women with PCOS.

Future studies are planned to investigate:

• The safety and efficacy of letrozole, an aromatase inhibitor, compared to clomiphene citrate in achieving live births in infertile women with PCOS;
• Whether treatment with clomiphene citrate is effective in inducing sufficient sperm production in men with non-obstructive azoospermia to enable attempts at conception through assisted reproductive technologies; and
• Whether simulating the environment of the oviduct or uterus by culture conditions of physiologic oxygen tension compared to atmospheric (20%) oxygen tension improves birthrates in human clinical in vitro fertilization.