Couple's necessity was the mother of invention

CAROLYN ABRAHAM

From Saturday's Globe and Mail

In what is being billed as a world first, a Canadian couple has given birth to a little girl who was conceived through a two-step, test-tube method that could herald the next revolution in baby making.

Researchers at the McGill Reproductive Centre in Montreal say Noorfatima Khan, now a healthy 10-month-old, is the first baby in the world known to be born of an egg that had not only been frozen, but that had never ripened inside of a woman. The process allowed Kiran Wasi, the mother, to undergo in vitro fertilization without taking standard fertility drugs.

Scientists say the birth, which is to be announced at the World IVF Congress in September, is a triumph in the expanding international efforts to pioneer fertility treatments that rely on fewer drugs and will be safer, easier and cheaper for the women and couples who need them.

Standard IVF treatments require a woman to pump herself with powerful, pricey hormones to produce multiple mature eggs at the same time, instead of the one egg a month that ovaries normally release. Only mature eggs can be successfully fertilized with a man's sperm.

But as part of a continuing clinical trial, McGill researchers collected immature eggs from Ms. Wasi's ovaries, matured them in the lab, froze them for two months and in September of 2005, thawed and fertilized them in a lab dish with the sperm of her husband, Amir Khan.

McGill researchers in 1999 reported Canada's first birth with a lab-ripened egg, a technique known as IVM, or in vitro maturation. In 2005, they announced the country's first birth with a frozen egg. But they say that this is the first time anyone anywhere has achieved a live birth using both technologies together and the combination could have several significant applications.

Women undergoing cancer treatments that could leave them sterile often have no time to take the fertility drugs needed to produce mature eggs that can be frozen before chemotherapy starts. Potential egg donors and women trying to preserve their fertility beyond the natural childbearing years may be more inclined to donate or to freeze their eggs for future use if egg collections were less expensive and less invasive.

Ultimately, however, the researchers hope the procedure might one day be an option for any woman who lacks either the money or desire to undergo standard cycles of IVF.

“If we can do IVM with egg freezing, it will be easier, and clinically more accessible in many cases,” said Seang Lin Tan, director of the McGill Centre. “It's cheaper and there are fewer possible side effects for the woman.”

So far, 20 women have undergone the experimental procedure at McGill and four, Ms. Wasi included, have become pregnant.

“My idea is to do this natural cycle and IVM for all women,” said Ri-Cheng Chian, the McGill scientist who has pioneered technology in the area. “The drug companies don't like me any more … they don't invite me anywhere.”

Where there's a will … Ms. Wasi and Mr. Khan prayed for a child from the day they were married. Family and friends were puzzled, “What is it?” they asked as the years passed, “Why no children?” The devout Muslim couple wondered the same thing. Everyday they beseeched God to send them a baby, until finally they decided to put a little faith in science too.

Ms. Wasi had suffered two miscarriages after their marriage in Pakistan seven years ago. Doctors there discovered she had a punctured Fallopian tube and she underwent surgery to repair it. But the couple could not conceive and their sorrow, Mr. Khan explained, was only made worse by the shame.

“It was everything for us to have a child,” he said on a recent Sunday afternoon in his Montreal home. “We all come from big families, everyone has three or four or five kids. In my culture, it's a pretty shameful thing, especially for a woman, not to have a baby.”In January of 2003, after the couple had settled in Montreal, their family doctor referred them to Dr. Tan, the chief obstetrician and gynecologist of the McGill Centre. Dr. Tan told them that IVF could help them to become pregnant and laid out details of the procedure and its price tag.

A single cycle of standard IVF with the hormone drugs needed to stimulate the ovaries to produce several mature eggs can run upward of $7,000.

“We were not ready for this,” Mr. Khan said. “For us that was really expensive, and I did not have the money at that time.”

Mr. Khan, a 40-year-old electrical engineer by training, had been unable to get a job in his field since emigrating from Pakistan to Canada in 1998. He has since made his living working odd jobs, pumping gas and most recently as a truck driver.

So, for two years, Mr. Khan and his wife scrimped and saved and in 2005, they returned to the clinic perched high on the slopes of Mount Royal. But this time, Dr. Tan had an option for the couple, an experimental procedure that could be safer, and certainly save them some of their hard-earned money.

… there's a way

Scientists have long chased the technology to mature the human egg in a petri dish. Unlike sperm, which men produce all their lives, women are born with all the eggs they will ever have, but these remain in a sleepy state of immature hibernation until puberty hits.

These immature eggs are nestled in the follicles, or pouches of a woman's ovaries. Normally, after adolescence, one egg matures every month as a woman ovulates.

Dr. Tan, who in his younger years worked with the same British doctors who produced the world's first test-tube baby in 1978, was keenly aware that perfecting IVM could be a great benefit since it would allow the collection of several eggs without relying on harsh drugs to mature them.

Not long after he took up the helm at the McGill Centre in the mid-90s, Dr. Tan began recruiting adventurous researchers. Several of them had trained in Korea, where more liberal rules around assisted reproduction research had birthed a generation of talented, well-practised fertility scientists.

Dr. Chian was one of those recruited to McGill, where as a basic scientist he began lab and animal experiments to mature human eggs.

On a recent morning in the McGill clinic, Dr. Chian explained that to ripen eggs in a culture dish he concocted a 39-ingredient liquid medium rich in the vitamins and minerals that mimic the fluid found in the ovarian follicles. Marinating in this lab-made bath, most eggs will mature on their own within 24 to 48 hours, he said.

Louise Brown, the world's first test-tube baby, he notes, was born through IVF that did not involve hormone drugs, since doctors simply collected the mature egg available. But by the early 1980s, in an effort to increase the chances of achieving pregnancies, hormone drugs known as a gonadotropins were developed. These stimulating agents shoot a woman's ovaries into overdrive to produce many mature eggs at one time.

“The worldwide average is 10 mature eggs at one time,” said Dr. Chian. “But 50 per cent of the eggs retrieved with standard IVF are abnormal, there is something wrong with the chromosomes.”

Fertilizing multiple eggs has also resulted in the spike of multiple births associated with fertility treatments, which can pose health risks to both mother and babies.

Indeed, McGill's work on IVM is part of a growing international effort to rethink the status-quo of IVF. In the past six months, doctors interested in pursuing milder fertility treatments have held an inaugural meeting in London and have published two major studies on more natural methods of IVF – a position backed by Bob Edwards, who helped to create the first test-tube baby nearly 30 years ago.

From Dr. Chian's perspective, current technology that relies on ultrasounds and new culture to mature eggs simply makes it unnecessary to retrieve several mature eggs.

He noted that in Korea, where natural cycle and IVM have long been pursued, doctors collect one mature egg that has ripened naturally and three to five immature ones that undergo IVM in the lab. “In Korea the [pregnancy] success rates are around 43 per cent,” said Dr. Chian, which is similar to standard IVF rates. “Other clinics in the U.S. are watching the procedures and waiting to see and when the success rates get better then they will adopt them.”

Andrew LaBarbera, scientific director of the American Society for Reproductive Medicine, said the data suggest that babies born of IVM alone (and there have been about 1,000 worldwide) appear to have a birth-defect rate similar to standard IVF, of between 1 and 3 per cent. This is slightly higher than natural births, in which the rate runs between 1 and 2 per cent.

Still, Dr. LaBarbera stressed, the ASRM considers IVM an experimental procedure not because of birth defects or safety concerns, but because the success rates in achieving pregnancies vary so widely that it cannot be routinely offered as a reliable fertility treatment.

The average international pregnancy rate with IVM is around 20 per cent, he said, compared with 50 to 60 per cent with standard IVF.

At the McGill Centre, the pregnancy rate with IVM is about 20 per cent, Dr. Tan said. But he noted that collecting eggs through a more natural cycle could be more successful, cumulatively speaking. The drugs needed to collect mature eggs make it expensive and risky for infertile couples to undergo more than a few cycles of standard IVF. “With a natural cycle, you can do 12 cycles no problem,” he noted. IVM is roughly half the cost of standard IVF.

‘I had a good feeling'Three of Ms. Wasi's 17 eggs survived the IVM and freezing and two, once fertilized, were implanted.

Mr. Khan had a crisis of faith that the procedure might fail. But not his wife. “I had a good feeling, I knew it would work,” she said.

One of the surviving eggs grew into their precious daughter. Noorfatima, whose Arabic name means light of Fatima, has indeed become the sunshine in her parents' life.

“We have no words to describe what she means to us,'' Mr. Khan said.

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