The couple wanted a baby boy, but the male embryo they had chosen — the only one available after an expensive round of in vitro fertilization — received a troubling test result.
A handful of cells from the five-day-old embryo were deemed abnormal, apparently missing Chromosome 21, an absence that can lead to developmental defects.
Many couples having IVF would have reconsidered their choices. But the two women, aged 48 and 45, had the embryo implanted anyway. And despite the initial test findings, their baby was born healthy in 2014.
“The whole pregnancy was an emotional roller coaster,” said one of the mothers. (The women were granted anonymity because no one knows the child is not biologically related to either one, and they would like to explain it to him once he is older.)
“Even when the baby was born, it took me a good five to 10 minutes to even look at him,” she said. “Finally I peeked over, and he looked normal.”
The test used on their embryo is called preimplantation genetic screening, or P.G.S., a biopsy performed by plucking a few cells from the developing embryo. Just a few years ago, P.G.S. was precise enough only to ascertain whether an embryo was normal or abnormal.
Now high-resolution, next-generation sequencing has sharpened the view, and researchers are finding something surprising: About 20 percent of embryos have both normal and abnormal cells, and the percentage increases with maternal age. These so-called mosaic embryos have long been known, but they have been detectable during an active IVF cycle only in the last year.
At least some of these embryos seem to mature into healthy children. The women’s son is one of 10 healthy infants recently born from mosaic embryos, as reported by separate research groups in New York and Italy, representing a success rate of roughly 40 percent.
The births are now provoking controversy among fertility experts about what to do if mosaics are the only viable embryos a couple has left after IVF. Should would-be parents discard them because they contain abnormalities? Or transfer them in the hopes of achieving a normal pregnancy?
“Every research program is fearful of throwing away a healthy embryo, but on the other hand, mosaicism is not always a benign thing,” said Richard Scott, founder and laboratory director at Reproductive Medicine Associates of New Jersey. “Now we are paying attention to these mosaics, but we don’t know exactly what to do with them.”
As an embryo rapidly divides after fertilization, mistakes in cell division sometimes produce abnormal cell lines. If those cells die off and the embryo manages to self-correct, or if the abnormal cells wind up segregated in the placenta, the embryo may develop into a normal baby.
But if abnormal cells proliferate in the embryo, it will probably fail to implant, result in a miscarriage or, more rarely, the birth of a child with serious defects.
Dr. Norbert Gleicher, the director of the Center for Human Reproduction in New York, decided to transfer seemingly abnormal embryos in an experiment after growing doubtful about P.G.S. He questioned whether a biopsy that examines five to 10 random cells from the outer shell of a 200-cell embryo can reliably represent the inner cell mass, the crucial core from which the fetus develops.
“I think the biological hypothesis that you can, from a single biopsy, determine whether an embryo is normal or chromosomally abnormal — that is flawed,” he said.
During last fall’s annual meeting of the American Society for Reproductive Medicine, Dr. Gleicher reported three normal births after the transfer of embryos with both normal and abnormal cells. He has since reported one more normal birth and a normal current pregnancy.
But many IVF doctors are reluctant to implant these embryos and stand by the reliability of P.G.S. A study from the New York University School of Medicine, yet to be released, has found that the error rate in detecting normal embryos is just 1 percent.
And at least three randomized, controlled studies have concluded that P.G.S. is an effective way to improve pregnancy rates and reduce the frequency of miscarriages.
“I can tell you I have not seen a medical test that has had more of an impact on clinical outcomes in reproductive medicine than this,” said Mark Hughes, a clinical scientist who has performed pioneering research on the genetics of embryonic development.
What experts do not yet know is where in the embryo abnormal cells may end up; there is no way to track them as they proliferate. Until more data emerges, many fertility doctors remain unwilling to transfer mosaics.
“We are not reassured that a small subset of normal, as characterized in babies — not children, not adults — warrants a complete change in policy and standard of practice,” said Dr. Mark Sauer, the chief of reproductive endocrinology and infertility at Columbia University Medical Center.
Others, like Dr. James Grifo, the director of the Langone Fertility Center at New York University and an author of the new study on P.G.S.’s accuracy, are cautiously willing to transfer mosaic embryos if a patient has no normal embryos and has genetic counseling first.
“A mosaic embryo does have potential for reproduction,” he said, “but it could be anywhere on the spectrum from a healthy to a damaged baby, and we don’t know where.”
Dr. Santiago Munné, director of Reprogenetics, a P.G.S. lab, applauded the advanced technology for discerning mosaicism even as it raises clinical quandaries.
“I think it’s a good thing we know now there is a third category, so we’re not going to discard any embryo that has even a little chance of implanting,” he said.
For the couple who took a chance on an abnormal embryo, a healthy boy is a joyous — if sobering — reminder of the complexities of early human development.
Now 17 months old, he is “happy, healthy, outgoing, constantly laughing,” said one of his mothers. “Had we not used that embryo, it either would have been discarded or donated to science. The boy we have now wouldn’t have been.”
Image via Flickr
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