November 17, 2014 (New York, NY) – There is substantial evidence that women with low functional ovarian reserve (LFOR) should be supplemented with androgens in order to improve intraovarian testosterone levels and maximize pregnancy chances with in vitro fertilization (IVF), according to a new OPINION commentary issued by the Center for Human Reproduction (CHR).
Clinically introduced approximately a decade ago by CHR investigators, the use of androgen supplementation—particularly with dehydroepiandrosterone (DHEA)—has greatly increased in women with LFOR worldwide in recent years. Skeptics have argued that without randomized, prospectively controlled trials (RCTs) of adequate size, the evidence for supplementation is not sufficient. In the just published OPINION piece, CHR argues that, despite the absence of properly powered RCTs, accumulated evidence overwhelmingly supports androgen supplementation in women with LFOR.
“Timely RCTs are sometimes impossible to conduct for a variety of reasons in clinical medicine,” explains Norbert Gleicher, MD, Medical Director, and Chief Scientist at CHR. “In such cases, sufficient evidence must be developed through other means.”
The OPINION notes that women with LFOR are aware that they are short on time and are thus hesitant to participate in RCTs in which they have a 50% chance of receiving a placebo. Consequently, it has been difficult to produce an RCT of appropriate size. A number of RCTs concerning DHEA supplementation—including two sponsored by CHR—were abandoned because patients refused to participate. To date, only four underpowered RCTs have been published worldwide, further confirming the hesitancy of patients to participate in these types of studies.
In the published OPINION, CHR explains how lower-level evidence studies have strongly supported the efficacy of androgen treatments in improving IVF outcomes. Animal studies have provided a comprehensive molecular understanding that supports androgen supplementation. Additionally, human clinical studies of lower levels of evidence, such as cohort or case-control studies, have established adequate evidence to support androgen supplementation for women with LFOR.
“In clinical situations like this, the scientific community faces a choice: either we accept human studies of lower evidence levels as adequate to introduce new therapeutic modalities, supported by appropriately designed animal experiments, or, we simply do nothing and continue preaching about the necessity of unlikely to be performed RCTs,” says Dr. Gleicher in the piece.
About Center for Human Reproduction
The Center for Human Reproduction (CHR), located in New York City, is a leading clinical and research center in reproductive medicine and infertility. Independently vocal on issues impacting fertility patients, CHR has become known nationally and internationally as a center of independent thinking in the profession. Dr. Gleicher is available for additional comments.
Last Updated: November 17, 2014