Preimplantation Genetic Screening (PGS) Using Microarray Technique: Method to Select the Embryo With the Greatest Chance for Successful Implantation During in Vitro Fertilization in Couples With a History of Unsuccessful IVF Attempts

Background In vitro fertilization (IVF) is the most important method to remedy infertility, whether the cause is the male or the female, or when the cause is unknown. Treatment usually involves the transfer to the uterus of a fertilized egg (embryo) that has been cultured for 2-5 days. To select the embryo with the best chance of successful implantation into the endometrium, microscopic evaluation is currently used to grade embryonic cell division, cellular appearance, and other factors. But this method is incomplete because it cannot determine the functional properties of the embryo, or whether it is genetically normal. It is known that couples with a history of multiple unsuccessful IVF treatments produce a large number of embryos that have an abnormal number of chromosomes (aneuploidy), which is also common in women over age 38.

This project intends to use preimplantation genetic screening (PGS) with the microarray technique to determine the chromosome composition of fertilized eggs, so that only chromosomally normal embryos are transferred during IVF. The purpose is to increase the probability of pregnancy and childbirth among couples with a history of repeated unsuccessful IVF attempts. We have previously conducted a prospective randomized study with a similar question (Ö 612-02) on a target group of older women (>38 years) using sampling (biopsy) of the embryo on day 3 of culture, followed by analysis of seven chromosome pairs using the FISH technique. The results of the study showed no improvement in pregnancy outcome . The reasons are probably 1) to begin with, normal eggs are infrequent in this target group; 2) the biopsy was performed on day 3 when the embryo is at a sensitive stage; and 3) only 7 out of a total of 23 chromosome pairs could be analyzed.

Methodological developments in the field have been rapid, and current technology allows for better identification of normal embryos compared with the previous study.

• We know that the embryo is less sensitive when a biopsy is carried out on day 5 (of the blastocyst stage) instead of day 3.
• In blastocyst biopsy, more cells are removed for diagnosis than on a day 3 biopsy (thereby increasing the reliability of the analysis).
• Blastocyst biopsy involves removal of fewer cells on a percentage basis (3-5%) from the total cell mass of the blastocyst compared with the previously used day 3 biopsy, which involved removal of up to 25% of the total number of cells.
• Blastocysts have a higher implantation rate than day 3 embryos.
• Array Comparative Genomic Hybridization (aCGH) can now be used with great precision to analyze all chromosomes using commercial quality-controlled kits.
• Cryopreservation with vitrification of blastocysts is currently a highly successful technique that allows the analysis to be conducted without being pressed for time.

In addition, we will turn to a patient group consisting of women with a proven normal-good ovarian reserve. In the previous study involving women >38 years, the ovarian reserve was generally poor.