Progress on Standardized Outcomes for RPL Studies

Background: Medical progress in the second half of the 20^th century has been largely defined by the rise of evidence-based medicine. The use of accepted guidelines for conducting randomized trials, observational studies, systematic reviews and meta-analyses has greatly improved the quality of publications. However, reporting multiple and disparate outcomes makes it difficult for physicians and patients to evaluate and compare the results of studies. The CROWN initiative is specifically aimed at promoting standardized outcomes in obstetrics and gynecology.

Objective: To provide a framework for the organization and promotion of high quality multi-centered randomized clinical trials (RCTs) for more definitive diagnostic and management recommendations for recurrent pregnancy loss (RPL) patients.

Methods: Investigators at the University of Utah and at Oxford University are organizing a Delphi process with RPL physicians and patients to determine by consensus the remaining controversies with RPL to be addressed and to institute agreed upon outcomes. These include: the definition of unexplained RPL, recommended laboratory and imaging workup, agreement on which tests are not warranted, establish what treatments are indicated, which are not, which should only be undertaken under a research protocol, and to agree on primary and secondary outcomes that must be reported in all studies.

Results: The results of the Delphi survey will be presented. The mandatory reported primary outcome should be the live birth rate reported in absolute numbers, comparing the treated and placebo groups, and using an intention to treat format. Secondary outcomes should include unintended maternal or infant adverse events or side effects (harms). Journal editors and reviewers will be encouraged to use these CONSORT-RPL guidelines as criteria for publication.

Conclusions: The goal of this approach is to obtain consensus from all stakeholders on what is required for well-designed RPL trials with standardized outcomes that are clinically meaningful, important to physicians and patients, and that all investigators should follow.