Indications for Preimplantation Genetic Screening (PGS)

PGS has been performed for several indications:

• routine screening of embryos looking for age-related chromosomal abnormalities
• recurrent miscarriage
• repeated IVF failure

For each of these indications, studies of IVF with PGS relying on day 3 biopsy of a blastomere and FISH analysis have now been completed. Most have concluded that the end result, birth of a healthy infant, is not increased with PGS. The implantation rates are not significantly better, the pregnancy rates are not significantly better. Some studies have shown a decrease in miscarriage, but other studies have not.

Technical limitations of PGS with FISH

• 10 percent of the cells biopsied do not yield a result
• 6 percent of the time a transfer is not done because of a false positive result (the test result indicated the embryo was abnormal, but when retested it was normal)
• 9 percent of the embryos are mosaic. It appears that some embryos that are mosaic will develop normally, with the normal cells dominating the future growth and development of the embryo. However, these embryos are not transferred.
• The implantation rate (the chance that an embryo transferred will develop into a fetus) is not statistically higher with PGS than with an embryo that is transferred at the day 5 stage. Implied in this are two considerations:

1. that the day 3 biopsy impairs implantation and
2. that allowing the embryos develop to the blastocyst stage itself is a fairly a good screen for abnormalities.

• Miscarriage rates and live birth rates are not significantly different with PGS versus traditional IVF.

For these reasons, IVF with PGS has not significantly increased the chance of pregnancy over IVF alone. PGS did reduce the risk of facing a decision for genetic termination. The American Society for Reproductive Medicine published a Committee Opinion in 2008, stating that the routine use of PGS with FISH and a day 3 biopsy did not improve the live-birth rates in patients with advance maternal age, previous implantation failure ore recurrent miscarriage.

There are still individual situations in which PGS may be appropriate. It is important to discuss your particular case with your physician.

RSC’s Recommendation

Now, the new question is whether a day 5 biopsy with either CGH or SNP assays will yield better results. Because of the evolving information about PGS, RSC’s recommendation is to perform the biopsy on day 5 and perform either CGH or SNP. This requires cryopreservation of the embryo until the genetic report is available, delaying a transfer by 4 weeks. RSC has had excellent pregnancy rates with frozen thawed blastocyst embryos and clinical trials from other centers performing day 5 biopsy with freeze then thaw of embryos have reported pregnancy rates comparable to a fresh transfer.