Antibodies, Miscarriage, and PGD: Fertile Thoughts
Q: What is your protocol for IVF patients with antibody issues and previous miscarriage?
A: Women with a history of more than one miscarriage need a workup to determine, if possible, the reason(s) for each miscarriage, and they may not all be the same. Most, but not all, early pregnancy losses occur for chromosomal reasons. The miscarriage is nature’s way of preventing the birth of an abnormal child. Other reasons for early pregnancy loss (or miscarriage) include systemic disease, abnormalities in the shape of the uterus, hormonal issues, immunologic issues, problems with uterine receptivity, certain abnormalities in the clotting mechanism, and many more. The idea here is to correct as many problems as possible before an IVF cycle to reduce the risk of future miscarriages.
Examples of the types of testing that may be helpful in determining risk factors for miscarriage are thyroid testing (abnormalities in thyroid function may lead to miscarriage); hysterosalpingogram (HSG) or sonohysterogram (SHG) to look for uterine abnormalities like a uterine septum, a submucous fibroid, an endometrial polyp, or Asherman’s syndrome, all of which are treatable reasons for miscarriage; a thrombophilia workup to test for factor V Leiden, prothrombin gene defects, elevated homocystiene levels, protein S, lipoprotein a, MOCHA profile, antiphospholipid antibody levels, and so on. A careful history needs to be taken to determine which of these tests are appropriate.
When other treatable reasons for repeated miscarriage have been ruled out and a woman is planning to do IVF, it is appropriate to consider the option of doing PGD (preimplantation genetic diagnosis) on the embryos for aneuploidy testing to determine which embryos are chromosomally normal. We know that women who have a history of otherwise unexplained repeated early pregnancy losses frequently have a high percentage of chromosomally abnormal embryos. In these women, PGD can lower the likelihood of a future miscarriage by selecting the best embryos for transfer. Occasionally, a woman will produce no normal embryos. In that case, it is appropriate to consider a donor egg.
You have asked about antibody issues, but you didn’t say what antibody issues. I assume you mean antiphospholipid antibodies because those are associated with repeated early pregnancy loss. In the case of repeated elevations (at least two measurements, at least six weeks apart) of antiphospholipid antibodies, it is appropriate to put a patient on anticoagulants when she conceives, or if she is doing IVF, we usually start anticoagulants a few days before embryo transfer. I hope this answers your questions and if your antibody issues are somewhat unique, please feel free to get back in touch.
Q: When PGD is performed to determine any chromosome issues, can it be done on frozen blastocysts before transfer?
A: PGD (preimplantation genetic diagnosis) is best done on cleavage stage embryos (day three, when they are at the six-to-eight cell stage). PGD requires embryo biopsy, which involves the removal of one of the cells of the embryo. This cell is then tested. Usually the testing is done by FISH (fluorescent in situ hybridization) to look for aneuploidy or by PCR (polymerase chain reaction technology) to look for single gene defects.
Microarray technology may be practical at the single cell level soon, but it is not widely available at present. It takes time to do the testing (one to two days actually). That means if embryos are tested on day three, the results are available by day five, so a blastocyst (day five) transfer is done. Embryos need to be transferred by day five in order to get a good outcome in terms of pregnancy rates—if you biopsy a frozen thawed blastocyst that is a day five or day six embryo. If it takes one to two days to get the result of the test, it is then too late to transfer the embryo and expect a pregnancy to result. Embryos do not develop as well in culture for long periods as they do in a woman’s body. As a result, after this long in culture, they are out of synchrony with the endometrium and poorer in quality if they survive at all for that long. Most embryos will actually arrest in their development by then. I hope this helps.
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