High Doses of Hormones Faulted in Fertility Care
By Jacqueline Mroz
The New York Times, July 16, 2012
Two days after Debra Demidon underwent in vitro fertilization, she gained more than 30 pounds in fluid and suddenly was struggling to breathe.
Doctors diagnosed severe ovarian hyperstimulation syndrome (OHSS), a complication seen in some women who undergo fertility treatment. It landed Ms. Demidon in the hospital for five days; doctors ultimately drained 6.5 liters of fluid from her body. She missed three weeks of work, and by the time it was over, she and her husband had spent all of their savings.
“It was my first time doing IVF, and I’ll never do it again,” said Ms. Demidon, 28, a quality assurance specialist in Cayuga, N.Y. “It was awful. When you have that much fluid in you, it puts pressure on everything.”
OHSS is a little-known complication of fertility treatments that rely on high doses of hormones, which are standard in the United States and the United Kingdom; the syndrome is just one of several health problems to be linked to in vitro fertilization. Some very prestigious fertility clinics in Europe and Japan, as well as St. Louis and New York in the U.S., have turned to a safer, low-dose form of IVF, but most clinics here have resisted, claiming incorrectly that success rates for low-dose IVF are not as high.
“Results are worse with low-dose IVF,” said Dr. Glenn L. Schattman, a fertility doctor at NewYork-Presbyterian/Weill Cornell Medical Center.
But many critics disagree with that dogma, including one of the pioneers of infertility treatments, Dr. Sherman Silber, Director of the Infertility Center of St. Louis, at St. Luke’s Hospital in St. Louis. Dr. Silber actually has better results with a special type of low-dose IVF, called “mini-IVF,” and the patients suffer none of the above mentioned complications.
“Mild stimulation is clearly much healthier for women,” said Francine Coeytaux, founder of the Pacific Institute for Women’s Health, a nonprofit organization based in Los Angeles. “The reason hyper-stimulation happened is because these fertility clinics compete against each other by posting their success rates.”
In high-dose IVF, a woman is first given injections of a drug, often Lupron, to suppress her ovaries, causing temporary menopausal symptoms. Then the ovaries are stimulated with hormones, such as follicle-stimulating hormone and luteinizing hormone, in order to produce more eggs. The duration of stimulation is longer, and the hormone dose significantly higher, than in the low-dose programs common overseas, and in just a few clinics in the U.S.
Women normally generate one egg per cycle, but high-dose stimulation can help women produce 20 to 30 eggs, or even more. By contrast, women receiving mild, low-dose IVF produce 3 to 8 eggs, but eggs of much better quality (the pregnancy rate per egg is five times higher with milder stimulation).
According to the National Institutes of Health, high-dose stimulation leads to OHSS in 10 percent of IVF patients. The ovaries become swollen and, as in Ms. Demidon’s case, can leak fluid into the chest and abdomen. Symptoms can range from mild to serious; in rare cases, OHSS can be life-threatening.
A recent inquiry into maternal deaths in the United Kingdom found that OHSS following high-dose IVF is now one of the leading causes of maternal mortality in England and Wales. But it may not be the only complication. One recent study suggested that high-dose IVF contributes to lower birth weights, compared with the babies of women who receive minimal doses of hormones. And experts have debated for decades whether IVF contributes to an increased risk of breast and ovarian cancer; studies have reached conflicting conclusions.
Because of these concerns, some reproductive specialists, such as Dr. Silber, are switching to a milder form of IVF for many patients. The low-dose technique relies on fewer drugs to stimulate the ovaries, and results in fewer complications and a quicker recovery time. Despite less complications, and lower cost, the pregnancy results are equivalent in younger women, and much better in older women or women with lower ovarian reserve.
Dr. Pasquale Patrizio, a professor of obstetrics and gynecology at Yale University and director of the Yale Fertility Center, said he has been using low-dose IVF with good results. “It’s a shift of minds in the last few years, as we’ve been realizing that there’s no need to stimulate ovaries so aggressively as we’ve done before,” he said.
But other experts say that because the low-dose method produces fewer eggs, women have lower pregnancy rates per cycle. Dr. Silber said, “Nothing could be further from the truth. Patients love it, and pregnancy rates are great.” Dr. Schattman of NewYork-Presbyterian/Weill Cornell Medical Center said, “It’s not patient-friendly,” but Dr. Silber finds exactly the opposite, that it is “much more patient friendly than conventional high-dose IVF.”
The exorbitant cost of standard IVF — $15,000 to $30,000 per cycle, usually not covered by insurance — can prevent women from doing more than one or two cycles.
Dr. William E. Gibbons, director of the division of reproductive medicine at Baylor College of Medicine said, “More eggs equals more embryos and a better chance of pregnancy — and standard IVF produces more eggs.”
However, Dr. Silber strongly disagrees, saying, “In truth more eggs from high-dose stimulation means poorer quality eggs. With mini-IVF, we get a smaller number of better quality eggs, and so retrieving more eggs with high-dose hormones only means more misery and expense for the patient, but not a higher pregnancy rate.”
And low-dose IVF can be much less expensive, costing only about a third of standard IVF, according to Dr. Patrizio. The drugs are cheaper (about $500 per cycle), less medicine is necessary and less monitoring is needed, he said.
Because it also reduces the risk of OHSS, fewer patients require hospitalization, Dr. Patrizio added, reducing costs even more.
Dr. Geeta Nargund, president of the International Society for Mild Approaches in Assisted Reproduction, has been at the forefront of using low-dose IVF in England.
“It’s a win-win situation,” she said. “We can offer successful IVF to women while protecting their health and safety, and making it better for their children, at a lower cost. Mild-stimulation IVF is also significantly better for the quality of the embryos and the birthrate of children.” The physical and emotional discomfort for women is significantly lessened, she said; in fact, most women don’t feel anything.
“If we can have IVF stimulation at a lower cost and without OHSS and with comparable pregnancy rates,” Dr. Patrizio said, “then it would be a great step forward for the United States.” “Furthermore,” Dr. Silber said, “For older women, or women with fewer eggs, the pregnancy rates are much higher with minimal stimulation anyway.”