Can PGS improve IVF outcome?

So as we get ready for Halloween and all those cute little goblins and princesses let’s tackle the million dollar question: Does PGS improve IVF outcomes? The lunch debate between Munne and Hughes at the ASRM sought to discuss that issue. Basically, Dr. Munne presented evidence that in their hand IVF outcomes are better and miscarriage rates are lower. However, the improvement was modest and not the amazingly high pregnancy rates that one would predict. Dr. Munne also criticized the recent article from Europe in the New England Journal of Medicine that showed lower delivery rates after PGS. But still the question remains as to whether PGS is the Holy Grail (“I’ll ask him but I don’t think he’ll be very keen…you see he’s already got one”) of IVF.

Dr. Hughes presented data from a recent study of his that was very informative. In this study, Dr. Hughes analyzed embryo biopsies from PGD cases for single gene defects (like cystic fibrosis). All embryos that were biopsied were analyzed for aneuploidy and also DNA fingerprinting was done. The aneuploidy data was blinded so no one knew what it showed. Once a healthy baby was born, DNA fingerprinting allowed Dr. Hughes to go back and identify the exact embryo that resulted in the healthy baby.

So what did his data show…it showed that in 16% of the cases that resulted in a healthy baby, the aneuploidy screen would have suggested that the embryo was abnormal and should NOT be transferred! How is this possible? Read the Question of the Day from 100 Questions about Infertility and find out….Pretty scary thought for Halloween.

74. Can PGS improve outcomes after IVF?

PGS has been promoted as a means to improve the odds of a successful IVF cycle. However, a large-scale, randomized, controlled study performed in women older than age 37 failed to demonstrate an improvement in clinical outcome following its use. Although the use of PGS will likely decrease the rate of miscarriage resulting from aneuploidy (an abnormal number of chromosomes in the embryo), the overall delivery rate per IVF cycle initiated may not be increased with this technology.

For couples in whom the use of prenatal diagnosis and possible pregnancy termination are not an option, PGS may be appropriate. According to an October 2006 monograph produced by the European Society of Human Reproduction and Embryology (ESHRE), “Although widely used, PGS is still considered as an experimental procedure, and its clinical utility is not fully proven.” One limitation of PGS is that many embryos at the 6- to 8- cell stage of development are mosaics, meaning that some of these cells carry a normal complement of chromosomes while other cells are abnormal. During further embryonic development, the abnormal cells presumably end up relegated to the placenta while the normal cells produce a healthy embryo.

The high rate of mosaicism in cleavage-stage embryos raises a real concern about the accuracy of PGS. One respected geneticist has estimated a rate of misdiagnosis to be 20% with PGS. Approximately 17% of the time a normal embryo is incorrectly labeled as abnormal and discarded. Even more concerning is the 3% chance that an abnormal embryo will be labeled normal and then transferred to the uterus.