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Jerusalem's Shaare Zedek Medical Center is apparently the first in the world to produce by pre-implantation genetic diagnosis (PGD) and in-vitro fertilization (IVF) a normal baby to a dwarf mother suffering from the genetic disease achondroplasia, The Jerusalem Post has learned.
Prof. Ephrat Levy-Lahad, head of the hospital's medical genetics unit, told the Post that in 2003, a French fertility center tried to accomplish the same thing but failed and said in an article published in Human Reproduction that PGD and IVF may have to be abandoned in treating such women.
Achondroplasia, the most common cause of dwarfism, is caused by a dominant gene found in one in 10,000 people. Only one parent having it is enough to produce a dwarf baby in 50 percent of all cases. People with achondroplasia reach a final height of 1.20 meters (women) to 1.30 meters (men.) They have normal intelligence and do not have impaired fertility, but women don't respond well to hormonal stimulation to produce ripe ova, and they have difficulty carrying and delivering babies normally because of their narrow pelvises.
Achondroplasia results from a mutation in the fibroblast growth factor receptor gene 3 (FGFR3), which causes an abnormality of cartilage formation and has a negative regulatory effect on bone growth. People with achondroplasia have one normal copy of the fibroblast growth factor receptor 3 gene and one mutant copy. Two copies of the mutant gene are invariably fatal before or shortly after birth. Only one copy of the gene needs to be present for the disorder to occur.
The 39-year-old Jerusalemite mother, who gave birth to a healthy boy at Shaare Zedek two weeks ago, underwent a surgical procedure to gradually lengthen her bones; her husband does not suffer from achondroplasia. "The couple came to me before they married, about eight or nine years ago. We explained that they could go abroad for PGD, which was not yet available here," Levy-Lahad said. "But after they married and wanted children, they said they had a normal life and would have babies without intervention. Their first child has achondroplasia. They decided that before a second pregnancy, they would undergo PGD, which became available here, at Shaare Zedek."
The woman underwent two fertility cycles, the first of which produced six eggs and four embryos, but they could not be implanted. The second cycle succeeded, using a special technique to retrieve the ripe ova despite the woman's narrow pelvis and minimal number of ripe eggs. Dr. Talia Geva of the hospital's IVF unit then performed PGD - in which one or two cells are removed from young embryos produced by IVF and their genes examined to see if they have an inherited disease or are healthy - and found two healthy ova not affected by dwarfism. The molecular diagnosis was done by Dr. Gheona Altarescu and Dr. Paul Renbaum, who heads the molecular lab.
The embryos were implanted, and the woman became pregnant with one fetus. She delivered by Cesarean section due to her narrow pelvis.
"We never thought she would want another child, but soon after her Cesarean, she asked us when we could produce another baby," Levy-Lahad recalled with surprise.
Why was Shaare Zedek successful, when the French hospital was not with the same type of case? Levy-Lahad said the answer may be that "our IVF people figured out how to do it, even though it was more complicated. We can't rule out the possibility that it worked because our IVF team sampled 'polar bodies' attached to the embryos rather than two cells taken from the embryo itself. We didn't touch the embryo, but only the polar bodies."
There have been many previous cases of achondroplastic women having healthy babies by chance (1 in 2) or by having a prenatal diagnosis with DNA tests after becoming pregnant and then aborting the fetus if it turned out to be affected by the gene.
"But there are ethical problems, as the children are not mentally retarded or sick. They are just very short, have a large head and short fingers and can suffer ridicule," said Levy-Lahad. "Using PGD, healthy embryos can be selected before implantation."