Doctors in Scotland yesterday reported the first known birth of a test-tube baby with both male and female sex organs, leading them and others to wonder whether in vitro fertilization techniques increase the odds of a rare and usually subtle genetic condition.
The child, created through standard in vitro fertilization (IVF) techniques, is a "chimeric hermaphrodite," a medical term referring to two of Greek mythology's more fabulous creatures: the Chimera, which was a combination of three different animals, and Hermaphroditus, who was both male and female.
The child is a biological chimera because he is the result of an unintended fusion of two separate embryos, which normally would have developed separately into two babies.
He is a hermaphrodite because the two embryos that fused were of different sexes -- a boy and a girl -- which means that about half the cells in the child's body are genetically male and half are female.
The child, whose identity is being kept a secret, is now a toddler and looks and acts like a normal boy, his doctors said. But he was born with both a testicle and an ovary, and he is being monitored closely to make sure that no complications arise as he develops.
Genetic chimeras have been identified following natural conception, but some scientists suspect that IVF pregnancies may produce them at greater frequency since IVF routinely involves the placement of multiple embryos into a woman's womb.
It's unclear, however, how commonly chimeras occur, said Cheryl Chase, director of the Intersex Society, a San Francisco advocacy group for people born with mixed anatomies. Some of them, Chase said, first learn of their condition after undergoing genetic tests to get into the Olympics. Most chimeras probably go unnoticed, either because they resulted from a fusion of same-sex embryos or because only one of the two cell lines got involved in forming the genitals, where genetic mix-ups can be most apparent, said David C. Page, a Howard Hughes Investigator at the Massachusetts Institute of Technology's Whitehead Institute in Cambridge.
Still, the condition could create problems later in life, experts said, including immune system abnormalities and a mixed blood type, which could lead to complications if an emergency transfusion were needed. Thus chimerism may be a new reason, some said, to limit the number of embryos transferred in IVF procedures.
Currently, because IVF does not work very well, several embryos must be transferred to a woman's womb to provide a reasonable chance of getting even one baby. That has led to high numbers of twins, triplets and other multiple births among IVF mothers -- and all the complications those births bring for mothers and children -- including, perhaps, chimerism.
"The increase in the frequency of dizygotic [fraternal] twins after in vitro fertilization by a factor of approximately 33 implies a similarly increased risk of rare twin-associated anomalies such as chimerism," wrote the University of Edinburgh's Lisa Strain and David T. Bonthron and their colleagues, who describe the new case in today's issue of the New England Journal of Medicine. "The observation of chimerism after in vitro fertilization should therefore be taken seriously."
England recently passed a regulation limiting to three the number of embryos that doctors may transfer during each IVF attempt. In the United States, however, where the fertility industry receives no federal money and so is not subject to the kind of regulation that the government imposes on other areas of research, no such limits exist -- as was evident with the recent birth of septuplets in Iowa.
Nonetheless, the American Society for Reproductive Medicine is poised to release "clinical practice guidelines" that call for a voluntary restriction on the number of embryos transferred. For women under age 35 that number will be three; for women 35 to 40 it will be four; and for women older than 40, up to five. Those recommendations would not be binding or enforceable, but may lead to an accepted standard of care, said Sean Tipton, a spokesman for the organization, the nation's largest for fertility specialists.
The Scottish baby was born to a woman who used sperm from an anonymous donor. The newborn looked like a normal boy, but his left testis was not descended into the scrotum. When that testis remained hidden at 15 months, surgeons intervened and, finding it abnormal, removed it. Examination revealed it to be an ovary attached to a fallopian tube.
Genetic tests showed that some of the boy's cells have two X chromosomes, indicative of a female, while others have an X and a Y, indicative of a male. "More detailed genetic analysis revealed that the origins of the two cell lines were unequivocably two separate embryos," said Mark P.R. Hamilton of the Aberdeen Maternity Hospital, who was involved in the case. Because each embryo was grown in a separate laboratory dish, he said, the fusion must have occurred in the woman's womb.
It's important to note that studies of IVF babies have found no increase in apparent birth defects or sexual uncertainty, said Joe Leigh Simpson, chairman of obstetrics and gynecology and a professor of human genetics at Baylor College of Medicine in Houston. However, he said, "We don't know how many other people are walking around with this condition undiagnosed."
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