Little evidence found for IVF as most effective infertility treatment

In vitro fertilization can improve pregnancy rates among couples with unexplained infertility, but there is little evidence to show whether IVF results in more live births than other treatments, according to a new review of recent studies.

Although expensive and invasive, IVF is a widely used treatment, despite potential complications, including a multiple pregnancy rate of about 25 percent.

According to the analysis by Dr. Zabeena Pandian of the University of Aberdeen, Scotland, and colleagues, the rate of babies born from IVF procedures is not significantly different from the rate of live births from artificial insemination and a procedure called gamete intrafallopian transfer.

The review appears in the April 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.

“There is insufficient evidence at present to suggest that IVF is more effective than the other treatment options available for unexplained infertility,” Pandian and colleagues conclude.

However, pregnancy rates were significantly higher with IVF than with “watchful waiting” and with IVF compared to gamete intrafallopian transfer, or GIFT, the researchers found. In one study comparing IVF with no treatment, 20 of 68 women receiving IVF became pregnant, while only one of 71 women were pregnant after three months of no treatment. In two studies comparing IVF with GIFT treatment, 39 of 84 women became pregnant with IVF, compared with 24 out of 85 women with GIFT.

The researchers note, however, that the studies in the review were small and varied considerably in their quality, definitions of unexplained infertility and follow-up periods.

“Until more evidence is available, IVF may not be the preferred first line of treatment for these [infertile] couples and it might be appropriate to continue with less invasive options,” Pandian says.

IVF is a process in which egg and sperm are joined to produce an embryo in the laboratory before the embryo is implanted in a woman’s uterus. In GIFT, egg and sperm are mixed in the laboratory and inserted in a woman’s fallopian tubes before the formation of an embryo. Artificial insemination involves placing a specially prepared semen sample directly into a woman’s uterus during ovulation.

IVF has become a widely accepted treatment for unexplained infertility even though very few high quality studies comparing infertility treatments exist, according to Pandian.

“IVF is becoming popular when there is no specific explanation for infertility as it may be able to overcome a variety of problems,” she says. “However, it is expensive, complicated and can have many adverse effects, including multiple births.”

The researchers found no significant differences in multiple pregnancy rates between IVF and intrauterine insemination, but there was a higher rate of multiple births in IVF recipients compared to those who received GIFT. In one study, for instance, the rate of twins was 53 percent with IVF, compared with 17 percent with GIFT.

Pandian and colleagues found no studies comparing live birth or pregnancy rates between IVF and treatment with clomiphene citrate, or Clomid, a widely used drug that stimulates ovulation.

The review included six studies with a total of 1,305 women. All patients included in the studies were part of a couple that had tired to conceive for at least one year and who had no detectable fertility abnormalities.

Pandian says that “various national laws governing IVF treatment, as well as the fact that most IVF treatments are privately funded, make it difficult to randomize clinical trials of infertility treatment.” Under these conditions, she explains, researchers have a difficult time assigning women to receive no treatment as a comparison to those receiving IVF, and many women drop out of the “no treatment” groups.

More studies used pregnancy rates as an endpoint rather than live-birth rates, however, Pandian says, “Live-birth rates per patient is the most important outcome to the couple.

A 2004 systematic review sponsored by the American Academy of Pediatrics, the American Society for Reproductive Medicine and the Genetics and Public Policy Center at Johns Hopkins University concluded that children born from IVF were at no higher risk of developing cancer, disabilities or mental disorders than their naturally conceived counterparts.

“This study was enormously valuable because it brought together all the available data and allows it to be viewed as a whole; and what we see so far is that the kids are fine,” says Dr. Robert Rebar, executive director of the American Society for Reproductive Medicine.