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Hatching Human Eggs, Israeli Style

Dr. Miryam Z. Wahrman

It is no surprise that Israeli clinics are at the cutting edge in infertility research. Children and family life play central roles in Israeli society, so infertile couples are willing to go to great lengths to conceive. In addition, the national health care system covers in vitro fertilization (IVF) for a couple to have two children. The procedures involved in producing two IVF - or so called "test-tube" babies, would cost an American couple tens of thousands of dollars. Those factors have led to the development of more than two dozen state-of-the-art IVF clinics - an extremely high number for a population of 5.9 million.

Some Israeli clinics are working on developing valuable new techniques to help couples conceive. One such breakthrough involves using laser beams to help eggs hatch out of their protective coat, increasing the success rate for couples who fail to conceive after several IVF trials.

In vitro fertilization is used when a man's sperm cannot reach or fertilize his partner's eggs. The difficulty may be due to blocked or damaged Fallopian tubes or reduced numbers or quality of sperm. IVF involves removing eggs from the woman's ovaries and combining them with her partner's sperm in a petri dish in the laboratory. A few days after conception occurs, the developing embryos are returned to the woman's uterus to complete development. The success rate of this technique varies from clinic to clinic, with the average pregnancy rate at 20 - 25 %. For some couples who fail on the first try, repeated attempts increase the chance of success. Other less fortunate couples experience recurrent failures, and until recently there was no way to improve the success rate for that group of patients.

In the past decade, IVF clinics began to experiment with microsurgery of human eggs and embryos - manipulating and treating them with microscopic tools in order to increase the likelihood of pregnancy. Scientists observed that eggs from women who had repeated IVF failures and eggs from older women sometimes looked different because the "zona pellucida", or clear shell surrounding the egg, appeared thicker. Experiments involving the thinning out or rupture of the zona became known as "assisted hatching" since once fertilization occurs the embryo must hatch out of its zona in order to implant into the uterus. The earliest methods to hatch the eggs involved the use of either an acid solution to erode the zona, or a sharp needle which tore a hole in the zona. The latest method - developed by doctors at Hadassah Medical Center - uses laser beams to burn away a part of the zona.

"There is a segment of recurrent patients who produce eggs with a thick zona, or defective embryos with regard to dissolving the zona," reported Professor Neri Laufer, Director of the In Vitro Fertilization program at Hadassah Medical Center on Mount Scopus in Jerusalem. He explained that the problem with mechanically piercing the zona is that frequently the ruptured zona heals, and the embryo cannot emerge. This tearing method also was reported to be associated with an increased frequency of monozygotic, or identical, twinning. And that might indicate that the embryo itself is being disturbed or altered, since formation of identical twins involves cells of the early embryo pulling apart from each other. Artificial twinning is not desirable because implications for the future health of the babies is unknown.

Laufer's team has developed a method to open a window in the zona using laser energy. The group built a prototype of a miniature laser which "acts by photochemistry to dissolve the chemical bonds in the shell," explained Laufer, "You need about ten zaps with the laser to etch a hole big enough for the embryo to hatch." In order to prevent genetic damage the laser is set at a wavelength which will not damage DNA. Laufer described how the machine is similar to the one used in keratoplasty - corrective surgery of the cornea of the eye - so it is approved for use in the United States for that application.

Experiments with laser-assisted hatching of embryos were first performed in mice in the early 1990s. The health of the offspring was monitored for several mouse generations to confrim that normal development occured.

Laser assisted hatching has been used at Hadassah for embryos from two different groups of women. In young women who had suffered recurrent IVF failures, it increased success rates to the typical 18-20% seen in other IVF patients. In another group of patients where the women were older than 38, the technique did not seem to increase the success rate. "They produce eggs that a priori are defective," concluded Laufer.

The prototype of the miniaturized laser device cost about $60,000 to produce, but this cost should be significantly lower when it is produced commercially for use in other IVF clinics.


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