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Docs Assess Three Therapy Approaches for Poor IVF Responders

After testing three different treatment approaches for poor responders to in vitro fertilization (IVF), a team of researchers has concluded that one approach may generate more successful results than the other two for these difficult-to-treat patients.

Their study appears in the November issue of the journal Fertility and Sterility.1

Why Are Some Unsuccessful?
Women who respond poorly to IVF do so for a number of reasons, wrote Michael Thomas, MD, and a team of reproductive endocrinologists in the Center for Reproductive Health at the University of Cincinnati Medical Center. They include older women who produce fewer, high quality eggs.

"Other factors, such as advanced endometriosis, as well as previous ovarian surgery, can lead to a poor reproductive response," they wrote. In any case, women who don't respond initially tend to cancel future IVF cycles.

Treatment Approaches Debated
As a result, different approaches to improve the odds for these women have been developed over the years, Thomas and his colleagues wrote. One of these includes the use of medications that fall in a class of fertility drugs known as gonadotropin releasing hormone agonists (GnRH agonists), which help prevent the premature release of natural hormones resulting, in turn, in premature ovulation. This, instead, allows doctors to time, and better control, ovulation by using fertility drugs.

Doctors have debated which GnRH agonist regimens should be used to improve the odds of success for women who've responded poorly to IVF. For one, it's still uncertain which approach leads to improved ovarian stimulation, Thomas and his cohorts pointed out.

This study, therefore, was an attempt to determine which of three approaches might offer the best results.

Scrutinizing a Trio of Protocols for Poor Responders
The researchers evaluated the records of 48 women who had arrived at their fertility clinic between 1999 and 2004. All of them had been poor responders initially to IVF, either due to older age, previous poor response to ovarian hyperstimulation using fertility drugs, increased levels of follicle-stimulating hormone (FSH), or previously cancelled IVF cycles.

Each of the patients had undergone one of three treatment protocols. The so-called stop protocol at the clinic involved the use of Lupron (leuprolide acetate), a GnRH agonist given during the mid-luteal phase of the patient's cycle—which occurs about a week before menstruation—until the beginning of menstruation. This is followed by the use of gonadotropins (hormone drugs) from day 2 of the cycle until a drug known as human chorionic gonadotropin (hCG) is given to induce ovulation.

The microdose flare protocol involves the use of oral contraceptives started during the previous menstrual period, followed by twice-daily doses of a GnRH agonist, then gonadotropin doses on day 2 of the stimulation cycle until the day hCG is administered.

The regular dose flare protocol includes the use of gonadotropins given in combination with a GnRH agonist from cycle day 2 until hCG is given.

The doses of gonadotropins given varied depending on the number of developing follicles observed, as well as estrogen levels in each patient. Anywhere from two to four embryos were transferred to each patient to begin pregnancy.

The researchers reviewed the numbers of successful embryo implantations, clinical pregnancies, and deliveries for each patient.

A total of 61 IVF cycles, some involving the use of intracytoplasmic sperm injection (ICSI), were performed during the study period. (ICSI involves the injection of a single sperm into an egg in the laboratory. It is often used in cases in which infertility is due to some male factor).

One Approach Offered Better Results
The numbers of successful implantations, pregnancies, and deliveries were higher in those patients using the microdose flare protocol, according to Thomas and his fellow investigators. Nearly a third of the women using that approach had successful embryo implantations. That compares to about eight percent and approximately 16 percent of those using the stop protocol and regular dose flare protocol, respectively.

Half of the women given the microdose flare protocol became pregnant, compared to about one-fifth of those using the stop protocol, and 28 percent of those using the regular dose flare protocol.

Of those, 40 percent using the microdose flare protocol delivered healthy infants, compared to about a fifth of those using the stop protocol, and 11 percent of those who underwent the regular dose flare protocol.

Applicable to the 'Real World'?
Despite the apparent positive findings, the investigators admitted that the results may not be reproducible in the wider population of women who don't respond favorably to IVF, and could have occurred by chance alone. (P=.061). Still, Thomas and his team wrote that if larger numbers of patients could be studied, more closely representing the larger population, the results may be different.

"A prospective, randomized study, possibly involving more than one center, would be necessary to determine whether the microdose protocol confirms its trend toward a higher percentage of clinical and completed pregnancies," they wrote.

1. Detti L, Williams DB, Robins JC, Maxwell RA, Thomas MA. A comparison of three downregulation approaches for poor responders undergoing in vitro fertilization. Fertil Steril 2005 Nov;84(5):1401-5.

John Martin is a long-time health journalist and an editor for CuraScript. His credits include overseeing health news coverage for the website of Fox Television's The Health Network, and articles for the New York Post and other consumer and trade publications.

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