There is no clear benefit from a hormone commonly prescribed to enhance the effectiveness of infertility treatments, according to a new review of studies. The steroid hormones called glucocorticoids have potent effects on the body's inflammatory and immune responses, so many fertility specialists prescribe them in hopes of making the lining of the uterus more receptive to embryo implantation. But lead review author Carolien Boomsma says that routine practice should stop. "This meta-analysis shows that empirical use of glucocorticoids is not supported by evidence from studies," she said. "Moreover, we don't know enough about the possible adverse effects of glucocorticoids in early pregnancy. Therefore, at present, glucocorticoids should not be prescribed in this way," said Boomsma, a researcher at the University Medical Centre Utrecht in the Netherlands. The review appears in the most recent issue of The Cochrane Library, a publication of The Cochrane Collaboration, an international organization that evaluates medical research. Systematic reviews draw evidence-based conclusions about medical practice after considering both the content and quality of existing medical trials on a topic.
The review compares success rates between would-be mothers who took glucocorticoids around the time of embryo implantation and those who did not. All of the women underwent one of two types of assisted reproductive technology. In vitro fertilization (IVF) involves removing mature eggs from a woman's ovary, mixing them with sperm in the laboratory, and placing the embryos in the woman's reproductive tract. Intracytoplasmic sperm injection (ICSI) is another in vitro fertilization practice where a single sperm is injected directly into a harvested egg. The meta-analysis pooled data from 13 studies including 1,759 couples. Every study was a randomized controlled trial, which is considered the most reliable form of scientific evidence.
The review found no overall improvement in pregnancy rates when the assisted reproductive technologies were combined with glucocorticoid treatment. However, six of the studies -- of 650 women undergoing IVF -- revealed a slightly higher pregnancy rate among women who took the hormones. The review authors say the difference barely exceeds that which could be attributed to mere chance.
"At present, glucocorticoids should not be offered as a routine procedure in women undergoing ART (assisted reproductive technologies), except in the context of well-designed studies," the reviewers conclude. Glucocorticoids can bring on problems such as infections or premature births. Though the available studies reported no significant increases in these negative outcomes, they were "poorly and inconsistently reported," the review said. Further research is needed to clarify both benefits and harms, Boomsma and colleagues said. Only three of the studies in the review continued long enough to report actual birth rates rather than simply pregnancy rates. "Trials should be of sufficient duration to have live birth as their primary outcome," the authors say. Despite substantial improvements in IVF and ICSI techniques, only 20 percent to 30 percent of couples go home with a healthy baby after each treatment cycle. That tantalizing hint of benefit may nevertheless encourage some practitioners to continue routine use of glucocorticoids for their IVF patients, said Randall Hines, M.D., director of the division of reproductive endocrinology and infertility at the University of Mississippi Medical Center. "When you have a therapy that doesn't have significant risk and doesn't impose significant burden on the patient in terms of cost or inconvenience, it's hard for people to let go of it," said Hines, who was not involved in the review and does not prescribe glucocorticoids routinely in his practice.
The compiled studies included couples who were infertile due to a wide variety of problems in either the woman, man or both partners. Future research may reveal that glucocorticoids do help specific subsets of these patients, the authors say. For example, women with unexplained infertility, endometriosis, recurrent implantation failure or certain immunological issues may benefit from the hormonal effects on uterine receptivity. None of the studies included in the review focused specifically on these patient groups.
Reference: Boomsma CM, Keay SD, Macklon NS. Peri-implantation glucocorticoid administration for assisted reproductive technology cycles (Review). Cochrane Database of Systematic Reviews 2007, Issue 1.
The Cochrane Collaboration is an international nonprofit, independent organization that produces and disseminates systematic reviews of health care interventions and promotes the search for evidence in the form of clinical trials and other studies of interventions. Visit http://www.cochrane.org for more information.
