Screening Embryos for Chromosomal Errors

A twenty-nine-year-old woman got pregnant four times over two and a half years and miscarried each time. She appeared to be fertile but “just couldn’t hold” her pregnancy. On two of those occasions, the miscarried fetuses were chromosomally tested. One was monosomy X (only one X chromosome), and the other was a trisomy 17 and 18 (three copies of both chromosome 17 and 18). Clearly, this was a woman with a propensity for ovulating aneuploid eggs. After the pain and suffering of four consecutive miscarriages, she feared ever becoming pregnant again. So we decided to do IVF with PGD. We were able to stimulate her sufficiently to get seventeen eggs, fifteen of which fertilized. She made many beautiful-appearing embryos, but only two of them were chromosomally normal, and they were both 46XX girls. We replaced these two embryos into her uterus, she became pregnant, and delivered a healthy baby girl nine months later.

A thirty-two-year-old woman had a history of five previous miscarriages in her twenties, and despite her young age, she was simply afraid ever to get pregnant again. Out of thirty-seven embryos we obtained during IVF (administered not because she couldn’t get pregnant, but rather to avoid miscarriage), only three were normal, two normal females and one normal male. After all these miscarriages and fear of ever getting pregnant again, she now had a healthy twin pregnancy, a normal boy and a normal girl.

A thirty-three-year-old woman with a history of cancer of the uterus wanted desperately to have a child. She was treated with high-dose progesterone, and her cancer was cured. It was important for her to have a child as soon as possible because of the risk of a recurrence of this uterine cancer, which would require a hysterectomy. In fact, she did become pregnant with her first IVF cycle, but this pregnancy resulted in miscarriage because of the usual problem of chromosomal abnormality. Despite a history of uterine cancer, the problem was not with her uterus, but with her embryos. In the next IVF cycle we performed PGD, and of twenty-three embryos only three were chromosomally normal. All three were boys. She became pregnant and delivered a healthy baby boy nine months later.

You might wonder why it would be that not all of those chromosomally normal embryos resulted in a pregnancy. For example, in the last patient discussed, we transferred three normal male embryos, but only one implanted and survived. One reason for this is that we cannot test for all of the chromosomes. We have to pick the chromosomes that are most commonly abnormal in miscarriage. This generally means the smaller chromosomes: 13, 15, 16, 18, 21, and 22, along with, of course, X and Y. Thus, when our testing shows that an embryo is normal chromosomally, there may still be larger chromosomes that we could not test (i.e., chromosomes 1 through 12) that are abnormal, and which would prevent implantation altogether.

Furthermore, there can be errors in the FISH interpretation, where one signal looks like two or two signals overlap and look like one. Most confusing is when the embryo has some cells that are normal and some that are not. Testing only one cell, or even two, in such cases can be misleading. Thus, PGD does not increase the pregnancy rate, but it may reduce the risk of miscarriage in women who are otherwise highly predisposed to miscarriage.

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