IVF Hits 40-Year Mark, But Challenges Remain

Kerry Dooley Young

July 27, 2018

The 40th birthday of the world's first so-called test-tube baby finds the field of assisted reproductive technology both notably advanced in terms of technique and fragmented in terms of access and affordability.

"What's remarkable is how fast the field has moved from its early days to becoming a mainstream practice," Vitaly A. Kushnir, MD, of the Center for Human Reproduction in New York City, told Medscape Medical News. "It's really changed the way that our species reproduces."

Louise Joy Brown. Source: Getty Images

The birth of Louise Joy Brown in England on July 25, 1978, marked the initial success with in vitro fertilization (IVF). Brown now finds herself in the company of an estimated 6 to 8 million children born through advanced fertility techniques, a point she made in an article she wrote recently for a British newspaper, The Independent.

"Heartbreakingly things don't work out for everyone. The moral debate about how far science should go in genetics rages on," Brown wrote. "IVF is now a multibillion-pound worldwide industry and it depends on where you live as to what help is available — and at what cost."

Physicians interviewed by Medscape Medical News cited a lack of access as a major concern with IVF, even as new approaches emerge to try to boost the chances for creating successful pregnancies. These include improved techniques for extracting sperm, genetic screening, and a move toward implanting a single embryo.

IVF costs can start around $3000 to $5000 and rise to $30,000 if a donated egg is involved, Kushnir said.

Yet in England, people with infertility face what's called a " postcode lottery " for IVF with varying levels of the service covered in different regions of the country. The decision on IVF rests there with individual National Health Service clinical commissioning groups.

In the United States, there's a patchwork of regulations on coverage. For example, this year Delaware enacted a law requiring insurers to cover a comprehensive list of infertility treatments, including IVF. The American Society for Reproductive Medicine said 16 of the 50 US states now have laws regarding infertility coverage.

Physicians have been advocating on behalf of their patients for expanded insurance payments for IVF and other reproductive assistance, but the cause hasn't attracted broad public sympathy, Richard J. Paulson, MD, past president of the American Society for Reproductive Medicine, told Medscape Medical News.

"To this day, it is absolutely shocking to me how the fertile population is not sympathetic to the infertile population," said Paulson, who is chief of the division of reproductive endocrinology and infertility at the Keck School of Medicine at the University of Southern California, Los Angeles. Infertility "is extremely painful to the people who experience it. It brings into question your own sense of self."

Kushnir said many people who need IVF are unable to access it because of the high cost. In some cases, people have delayed attempts to start a family because of misconceptions about how much can be done to help older women become pregnant.

"People underappreciate just how rapidly fertility declines in women who are in their late 30s or early 40s,"  Kushnir said.

New Approaches

Several tech companies, such as Apple, made headline news when they started covering the cost of egg freezing  for employees who wish to delay starting families. Yet researchers at the University of California, San Francisco (UCSF) have urged continued monitoring of the effects of this procedure, known as elective oocyte cryopreservation. As reported recently, they have already found a significant number of women expressing some regret about the procedure.

In an interview with UCSF News,  Eleni Greenwood, MD, MSc, a clinical fellow in obstetrics, gynecology, and reproductive sciences, said more research will be needed to understand this reaction. "What is clear is that egg freezing is more than just your standard insurance transaction for many women," Greenwood said.

There's long been a watchful approach to assisted reproductive technologies in general, with new developments often greeted with apprehension.

Robert Edwards, PhD, who eventually won a Nobel Prize for the development of IVF, faced objections early on from some religious leaders and even fellow scientists for his research into ways to fertilize eggs outside of the body. After the UK's Medical Research Council decided not to fund continuation of a project, a private donation allowed Edwards and colleagues to advance the work that would pay off in the 1978 birth of Louise Brown.

Since then, there's been continued monitoring of children conceived through IVF for signs of health problems, said Craig Niederberger, MD, co-editor of the journal Fertility and Sterility. Researchers have followed cohorts of children, comparing their medical histories to those of children born to mothers of similar ages.

"We in the field are very, very concerned about what we do," Niederberger told Medscape Medical News. "So far, it looks like IVF is safe."

There's similar monitoring underway for children conceived with the aid of a somewhat newer technique in which a sperm is injected directly into an egg, said Niederberger, who also is a professor of urology at the University of Illinois at Chicago.

Dating to the 1990s, intracytoplasmic sperm injection (ICSI) aids men who may have too few sperm for artificial insemination or IVF. ICSI is also used in cases where sperm may not move in a normal fashion or may have trouble attaching to the egg.

In taking this route, physicians can aid men who otherwise might not be able to father children. But they do so by eliminating the fierce competition that sperm face even in IVF procedures, Niederberger said. Typically, 50,000 or more swimming sperm are placed next to the egg in a laboratory dish for traditional IVF, with one then succeeding in fertilization.

"At least, nature is choosing a sperm with IVF” even if there's a shortcut provided by placing the sperm in the same place as the egg, he said. “It's reproduction the old fashioned way."

"We've completely stepped in for nature when we do [ICSI]", with technicians choosing the sperm to put in the eggs, Niederberger added. "It's very important than that we follow up about those children and we are doing that."

There also have been concerns over the years about potential cancer risks to women from the repeated exposures to high levels of hormones used in assisted reproduction. Research published in the BMJ earlier this month suggested that women who receive assisted reproductive technology, such as IVF, have no increased risk of invasive breast or uterine cancer.

In recent years, there has also been a push to transfer fewer embryos in IVF resulting in safer outcomes for the resulting pregnancies, J. Ryan Martin, MD, told Medscape Medical News. Pregnancies with twins and triplets may pose more risk of complications for both the mother and the babies, said Martin, who practices at Shady Grove Fertility in Warrington, Pennsylvania.

Improved freezing and thawing techniques for embryos have helped in these efforts, which result in fewer cases of multiple births. Research presented at the American Society for Reproductive Medicine 2017 Scientific Congress found single-embryo transfers were more likely than multiple-embryo transfers to end in a healthy birth, irrespective of whether fresh or frozen oocytes are used.

"It's a big deal from a patient safety standpoint," Martin said. "Our goal is not just to help people get pregnant, but for them to deliver safely."

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