“Without question,” said Dr. Rosenwaks, a former director of the Jones Institute for Reproductive Medicine, “identifying a viable embryo is one of the greatest challenges for IVF in the future.”
Dr. Edwards, who had lamented in 2001 that, “something must be fundamentally flawed with a reproductive system that allows only 20% of embryos to implant,” would likely agree (Nature Medicine 2001;7:1091-4).
Still, other leaders say they’re optimistic. “I think there will be more breakthroughs with this,” said Dr. Van Voorhis, who was in medical school when Louise Brown was born. (He said he was swayed into the specialty of ob.gyn. and then reproductive endocrinology, by the early IVF successes.)
There were high hopes that preimplantation genetics diagnosis would serve as a useful tool in identifying healthy embryos, but so far there is little data that PGD improves outcomes. “None of the methods utilized thus far have been able to predict implantation 100%,” Dr. Rosenwaks said. “At best, the ability to predict implantation is between 70% and 80%, even in the most optimistic and enthusiastic circles.”
The long-term health outcomes for children who were conceived through IVF are still an open question, moreover.
“What remains to be seen are things like, will they be more prone to cancer? Are there epigenetic changes that might manifest themselves in the future?” Dr. Van Voorhis said.
Epidemiologic studies have suggested that IVF babies are more likely to have certain birth defects than are babies conceived naturally (it is unclear whether the increase is a treatment effect or brought about by characteristics of the underlying population), but so far, longer-term developmental and neurologic outcomes are encouraging.
Indeed, Nobel Prize committee member Dr. Höög said the committee was influenced by “several [recently reported] long-term studies of the children,” as well as the fact that some of the IVF children have had healthy children themselves. The time seemed right, he said, because of “all these things coming together.”
More than 30 years have passed since Louise Brown was born, but the milestone in 1978 was the culmination of many more prior decades of painstaking research. Research on animal embryos goes back to the last century. In 1959, Dr. Min-Chueh Chang, an embryologist working at Harvard Medical School, Boston, reported the first successful in vitro fertilization in the rabbit. And in 1966, Dr. Edwards, who had begun his work in the 1950s, performed the first fertilization of a human egg in vitro.
“In terms of the development of IVF, many of the things that have come about were not particularly surprising because, early on [in their collaboration], Edwards and Steptoe had predicted many of the things that IVF would allow us to learn about, many of the things that have come to be,” said Dr. Rosenwaks, a past president of the SART and the Society for Reproductive Endocrinology and Infertility.
“They’d predicted, for example, that one would be able to do egg donation and that one would be able to do genetic testing on embryos,” and they knew that the types of ethical controversies they faced early on would continue and that new controversial advances, such as cloning, would evolve, he said.
Dr. Rosenwaks recalls following the IVF developments and anticipating the first successful birth as he pursued his fellowship from 1976 to 1978. “We began treating women who traditionally would have had their gonads removed for cancer, or whatever reason, more conservatively, leaving the uterus in. We definitely considered the coming of IVF in our deliberations. We knew that someday soon, they’d be able to try to conceive with IVF and egg donation.”