Ob.Gyn News Turns 50

Early days of IVF marked by competition, innovation


 

Answering safety questions

Alan H. DeCherney, MD, currently an infertility researcher at the National Institutes of Health, started Yale University’s IVF program at around the same time Dr. Marrs and the Joneses were starting theirs. Yale already had a large infertility practice, and only academic centers had the laboratory resources and skilled staff needed to attempt IVF in those years.

In 1983, when Yale announced the birth of its first IVF baby – the fifth in the United States – Dr. DeCherney was starting to think about measuring outcomes, as there was concern over the potential for congenital anomalies related to IVF. “This was such a change in the way conception occurred, people were afraid that all kinds of crazy things would happen,” he said.

Dr. Alan H. DeCherney

Dr. Alan H. DeCherney

One concern was about ovarian stimulation with fertility drugs or gonadotropins. The earliest efforts – including by Dr. Steptoe and Dr. Edwards – used no drugs, instead trying to pinpoint the moment of natural egg release by measuring a woman’s hormone levels constantly, but these proved disappointing. Use of clomiphene citrate and human menopausal gonadotropin allowed for more control over timing, and for multiple mature eggs to be harvested at once.

But there were still many unanswered questions related to these agents’ safety and dosing, both for women and for babies.

When the NIH refused to fund a study of IVF outcomes, Dr. DeCherney and Dr. Marrs collaborated on a registry funded by a gonadotropin maker. “The drug company didn’t want to be associated with some terrible abnormal outcomes,” Dr. DeCherney recalled, though by then, “there were 10, maybe even 20 babies around the world, and they seemed to be fine,” he said.

The first registry results affirmed no changes in the rate of congenital abnormalities. (Larger, more recent studies have shown a small but significant elevation in birth defect risk associated with IVF.) A few years later, ovarian stimulation was adjusted to correspond with ovarian reserve, reducing the risk of ovarian hyperstimulation syndrome.

But even by the late 1980s, success rates for IVF per attempted cycle were still low overall, leading many critics, even within the profession, to accuse practitioners of misleading couples. Charles E. Miller, MD, an infertility specialist in Chicago, recalled an early investigation by a major newspaper “that looked at all the IVF clinics in Chicago and found the chances of having a baby was under 3%.”

Dr. Charles E. Miller

Dr. Charles E. Miller

It was true, Dr. Miller acknowledged – “the rates were dismal. But remember that IVF at the time was still considered a procedure of last resort.” Complex diagnostic testing to determine the cause of infertility, surgery, and fertility drugs all came first.

Some important innovations would soon change that and turn IVF into a mainstay of infertility treatment that could help women not only with damaged tubes but also with ovarian failure, low ovarian reserve, or dense pelvic adhesions. Even some types of male factor infertility would find an answer in IVF, by way of intracytoplasmic sperm transfer.

Eggs without surgery

Laparoscopic egg retrieval was the norm in the first decade of IVF. “We went through the belly button, allowing us to directly visualize the ovary and see whether ovulation had already occurred or we had to retrieve it by introducing a needle into the follicle,” Dr. Rosenwaks recalled.

“Some of us were doing 6 or even 10 laparoscopies a day, and it was physically quite challenging,” he said. “There were no video screens in those days. You had to bend over the scope.” And it was worse still for patients, who had to endure multiple surgeries.

Though egg and embryo cryopreservation were already being worked on, it would be years before these techniques were optimized, giving women more chances from a single retrieval of oocytes.

Finding a less invasive means of retrieving eggs was crucial.

Maria Bustillo, MD, an infertility specialist in Miami, recalled being criticized by peers when she and her then-colleagues at the Genetics & IVF Institute in Fairfax, Va., began retrieving eggs via a needle placed in the vagina, using abdominal ultrasound as a guide.

While the technique was far less invasive than laparoscopy, “we were doing it semi-blindly, and were told it was dangerous,” Dr. Bustillo said.

Dr. Maria Bustillo

Dr. Maria Bustillo

But these freehand ultrasound retrievals paved the way for what would become a revolutionary advance – the vaginal ultrasound probe, which by the end of the 1980s made nonsurgical extraction of eggs the norm.

Dr. Marrs recalled receiving a prototype of a vaginal ultrasound probe, in the mid-1980s, and finding patients unwilling to use it, except one who relented only because she had an empty bladder. Abdominal ultrasonography required a full bladder to work.

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