The Penn RMU has been part of the RMN since the Network's inception over twenty two years ago and has played a leadership role in the design, implementation, analysis and publication of many of the RMN's studies. Specifically, of the six major studies the RMN has completed to date, three have been the proposed Penn concept protocols, one resulting in two NEJM publications and the second resulting in three Fertility and Sterility publications comprising the centerpiece of a Controversies section of the journal. The third, the first IVF clinical trial performed by the RMN, evaluating the effect of physiologic (5%) oxygen tension on delivery rates, has randomized to date over 750 couples and is projected to close recruitment by the end of the current funding period. It is anticipated that this trial will establish the standard of care for human embryo culture. The present Penn concept protocol proposes to address possibly the most burning problem in the clinical practice of IVF: multiple pregnancy. It is hypothesized that a single blastocyst transfer results in a delivery rate similar to double blastocyst transfer in good prognosis patients. This will be addressed by performing a randomized clinical trial of a single vs. double blastocyst transfer. In addition, we propose to include subsequent frozen/thawed embryo transfer cycles in order to determine cumulative delivery rates. Thus, the proposed design will not only determine the delivery rate of single blastocyst transfer, but will also help establish the optimal transfer algorithm for maximizing delivery rates and minimizing multiple pregnancy rates in good prognosis patients undergoing IVF. As designed, the study does not utilize federal funds for any aspects of the human IVF laboratory work and, as such, is compliant with current federal restrictions. We strongly believe, that upon completion of the proposed study, the impact on current practice will be extremely significant. Given the track record, excellence of the clinical research infrastructure and the proven expertise in the design, recruitment and analysis of multicenter clinical trials, the members of the Penn RMU are looking forward to continue their participation in the Reproductive Medicine Network. It should me mentioned that in the present application, we propose to continue our collaboration with the University of Connecticut Infertility program, which is the largest program in Connecticut and includes a CREST program graduate. Dr. Laurence Engmann. This collaboration, which covers a distinct and separate geographic area, has proven invaluable to the execution of the current RMN IVF clinical trial (PhOx) with the recruitment of the highest number pf subjects for the trial.

Public Health Relevance

Multiple pregnancies are the major complication of in vitro fertilization treatment affecting both mother and her newborns. Decreasing the incidence of multiple births is of high public health importance. The proposed clinical trial aims at markedly decreasing this undesired outcome taking advantage of recent advances that have resulted in embryos of high implantation potential.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Cooperative Clinical Research--Cooperative Agreements (U10)
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Special Emphasis Panel (ZHD1-DSR-L (55))
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De Paolo, Louis V
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University of Pennsylvania
Obstetrics & Gynecology
Schools of Medicine
United States
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