'Mild' IVF Reduces Multiple Pregnancies

UTRECHT, The Netherlands, March 2 -- IVF rates for term live births after "mild" ovarian stimulation, with single-embryo transfer, equaled the rates for standard stimulation with two-embryo transfer, Dutch researchers reported.

In addition, mild stimulation protocols for IVF with a single embryo transfer reduced multiple pregnancies and overall costs, Bart Fauser, M.D., of University Medical Centre here, and colleagues, reported in the March 3 issue of the Lancet.

Mild, or so-called soft ovarian stimulation, involves shorter stimulation protocols, such as gonadotropin-releasing hormone antagonist cotreatment and low-dose gonadotropins, and transfer of a single embryo.

Shorter stimulation protocols and transfer of a single embryo could allow more IVF cycles in the same period as conventional treatment, the researchers said.

The traditional standard ovarian stimulation involved stimulation with the GnRH agonist long protocol, and transfer of two embryos, a more costly, less pleasant, and riskier procedure.

In a randomized, non-inferiority effectiveness trial of 404 patients, the proportion of cumulative pregnancies at one year was 43.4% for those with mild treatment and 44.7% for those given standard treatment (absolute number of patients was 86 for both groups), the researchers reported.

Patients, younger than 38 were recruited from two academic medical centers in Rotterdam and Utrecht from 2002 to 2004.

The proportion of couples with multiple pregnancy outcomes was 0.5% with mild IVF treatment versus 13.1% (P

These findings were for women younger than age 38. However, if mild IVF is to be widely implemented, IVF outcomes should be redefined in broader terms that encompass the interests of the couple, the child, and the providers of health care, the researchers said.

In conclusion, the investigators wrote, these findings should encourage more widespread use of mild ovarian stimulation and single-embryo transfer in clinical practice.

However, they added, "adoption of our mild IVF treatment strategy would need to be supported by counseling of both patients and health-care providers to redefine IVF success and explain the risks associated with multiple pregnancies and by institution of reimbursement systems that encourage, rather than penalize, the practice of single embryo transfer."

In an accompanying comment, William Ledger, M.D., of the University of Sheffield in England wrote that in an adequately powered randomized trial, the Dutch findings provide "robust evidence" for the efficacy and patients' acceptability of one version of soft IVF.

"While 75% of IVF treatment in the United Kingdom continues to be paid for by patients themselves. . . many couples will opt for double embryo transfer because it is much less costly."

Dr. Ledger suggested that governments should recognize the long-term benefits to patients and the public purse of implementing a policy of single-embryo transfer and by encouraging adoption of the policy with increased funding.