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New form of in vitro fertilization stirs debate

by Michele Munz

St. Louis Post-Dispatch
January 26, 2012

The Christian family, left to right, twins Reagan, and Darby, 2, and Fred and Linda play with building blocks in their Belleville home Monday Dec. 26, 2011. The girls were conceived through mini in vitro fertilization, a procedure advocated by St. Louis doctor Sherman Silber which, he says, is safer, cheaper and easier on women while maintaining comparable pregnancy rates.
The Christian family, left to right, twins Reagan, and Darby, 2, and Fred and Linda play with building blocks in their Belleville home Monday Dec. 26, 2011. The girls were conceived through mini in vitro fertilization, a procedure advocated by St. Louis doctor Sherman Silber which, he says, is safer, cheaper and easier on women while maintaining comparable pregnancy rates.

Under names such as low-intensity IVF or even patient-friendly IVF — a technique of in vitro fertilization is increasing in use with promises to be safer, cheaper and easier on patients trying to have a baby.

The technique involves mildly stimulating a woman’s ovaries with less drugs to produce far fewer eggs than routine IVF. After the eggs are fertilized in a laboratory, the resulting embryos are usually frozen and implanted in the uterus a few months later during a woman’s natural menstrual cycle.

It may seem mathematically impossible, but St. Louis area doctor Dr. Sherman Silber says if done right, mild stimulation results in pregnancy rates equal to those with routine IVF. In older women, Silber finds dramatically better rates because the process is easier on their more brittle eggs.

“We get better quality eggs, and almost every single one of these eggs forms into a beautiful embryo,” said Silber, one of the U.S. pioneers of the technique, which he calls mini-IVF. He is one of the few in the country routinely offering mini-IVF at his office, the Infertility Center of St. Louis at St. Luke’s Hospital.

Silber says a high-quality lab and foolproof freezing process are behind his success. His findings were published a year ago in the Reproductive BioMedicine Online journal, adding to mounting questions surrounding the current aggressive method of giving women high doses of costly drugs to produce more than a dozen eggs at a time.

With routine IVF, women have to pay a fortune and can experience intense moods swings and painful, swollen ovaries; or as Silber puts it, “they feel like they swallowed a couple grapefruits whole.” The process requires numerous doctor visits, painful needle sticks and ultrasounds. Risks include hyperstimulation, a life-threatening condition that can cause rapid weight gain, vomiting and shortness of breath.

Some fertility doctors, however, question how a mini-IVF cycle which produces only two to six eggs can be as successful as 14 or 15 or even 20, eggs. When trying to get pregnant, more is always better, they say. A large number of eggs increases the chances that some will develop into healthy embryos, so they say.

“I would rather get as many eggs as I could and transfer them fresh and freeze ones leftover,” said Dr. Randall Odem, chief of the reproductive endocrinology division at Washington University School of Medicine.

Silber, however, argues the technique is not experimental. Silber published his research with Dr. John Zang, the director of New Hope Fertility Center in New York, who between them have done over 4,000 mini-IVF cycles since 2004. Doctors in Japan, where Silber learned the technique, have adopted it far more widely.

A leading IVF researcher, Dr. Suheil Muasher of the Muasher Center for Fertility and IVF in Fairfax, Va., has also called for more fertility clinics to offer minimal stimulation after finding similar pregnancy success rates with his patients. “The aggressive approach is no longer essential and has significant drawbacks in terms of cost, stress and increased complications for some patients,” Muasher wrote in a journal article published in August.

With improvements in freezing and identifying quality embryos, fertility experts have begun to question the need for high doses of costly hormones to produce eggs for in vitro fertilization, which is performed about 35,000 times each year in the U.S. and is the most common form of assisted reproduction.

Twins Darby, left, and Reagan Christian play with drawing toys in their Belleville home Monday Dec. 26, 2011. The girls were conceived by parents Fred and Linda Christian through mini in vitro fertilization, a procedure advocated by St. Louis doctor Sherman Silber which, he says, is safer, cheaper and easier on women while maintaining comparable pregnancy rates.
Twins Darby, left, and Reagan Christian play with drawing toys in their Belleville home Monday Dec. 26, 2011. The girls were conceived by parents Fred and Linda Christian through mini in vitro fertilization, a procedure advocated by St. Louis doctor Sherman Silber which, he says, is safer, cheaper and easier on women while maintaining comparable pregnancy rates.

BRITISH SCIENTIST LAUDS METHOD

Among the experts is the British scientist who started it all, Robert Edwards, who along with a surgeon produced the first baby born by in vitro fertilization in 1978. He wrote in 2007 that “considerable changes are afoot in the process of assisted human conception” and minimal stimulation “may well replace routine IVF.”

In 2007, the International Society for Mild Approaches in Assisted Reproduction was created to promote less expensive methods with lower risks.

Silber is known as a pioneer. He completed the first vasectomy reversal as well as the first ovary transplant. “They called me a cowboy,” he said. “When you come up with something new and innovative, you always have critics.”

Silber said he first learned of mini-IVF in 2002 while working with Japanese fertility doctors on a separate project. The foreign doctors used the decades-old cheap drug, Clomid, to stimulate the production of a few eggs. With Clomid, however, the lining of the uterus is too thin for the transfer of fresh embryos. They had to be frozen.

Freezing embryos conventionally involves very slowly dropping the temperature to prevent damage from crystallization, but many are still lost. The Japanese, instead, perfected a flash-freezing technique called vitrification [technical video]. Using four times the concentration of antifreeze and an extremely cold temperature, vitrification instantly turns the embryos into a glass-like state — a process Silber calls flawless if done correctly. No embryos are damaged, he said.

“I was amazed. I thought the pregnancy rate with frozen must be half that of fresh,” he said. “I couldn’t believe they were doing this. And with Clomid? It was so different than anything in the West.”

Silber made a few adjustments in drug dosages for American women and said he was among the first American doctors to begin offering minimal stimulation six years ago. He now uses mini-IVF for all patients over the age of 38 and in about half of his younger patients. He always uses vitrification to freeze embryos.

Whether his younger patients choose mini-IVF depends on the cause of their infertility, how many children they want, their financial situation and ethical concerns, he said. Some patients do not want to face decisions over what to do with leftover frozen embryos.

Silber said he uses mini-IVF with all his older patients — many of whom would be turned away from other fertility clinics — because with mini-IVF in older women, he gets a pregnancy rate nearly five times higher than conventional IVF for this age group. In patients over the age of 42, a pregnancy rate of approximately 50 percent.

But for these older women, it does require two or three mini-IVF cycles, which can be done a month apart, to store up enough vitrified embryos to warrant thawing and transfer. And more waiting for the uterus to be ready.

It was worth the wait for Silber’s patient Suzanne Gastineau, 46, of O’Fallon, Mo. She had trouble conceiving when she decided she wanted a second child. At the age of 43, she went through two cycles of mini-IVF and got three eggs. Only one good embryo developed. In August 2009, her second son, Alexander, was born. “It was a miracle,” she said.

Belleville residents Linda Christian, 39, and her husband, Fred Christian, 65, had twins two years ago thanks to mini-IVF, which Linda Christian called “nearly painless.” After two cycles, she got six eggs which developed into three embryos that were transferred together.

“You are going on trust to some extent,” Christian said. “The temptation is to say, ‘Lets just stick with traditional IVF,’ but we trusted him.”


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