Preimplantation genetic diagnosis (PGD) is being used increasingly at the Fertility Institutes to dramatically improve the chance of a successful IVF pregnancy in couples where prior IVF failures have remained unexplained. It has been estimated that over half of all IVF failures are not able to be explained by
an apparent problem with embryo "quality". For many couples however, this statistic is quite misleading. Most IVF centers look very closely at the appearance of embryos under the microscope as they attempt to determine a "good" or "high quality" embryo from those of lesser quality.
Generally, embryos are given "good" marks when they demonstrate an appropriate number of cell divisions at a given time in their growth cycle, when the individual cells of the embryo appear to have a uniform size and when there is an absence of cellular "fragments" that may or may not represent problems in the growth progress of the embryo.
IVF Success Following PGD
Single cycle IVF success rates (the chance of becoming pregnant)in our program can be raised significantly* when 2 or 3 embryos known to be chromosomally normal are transferred. The chance of healthy pregnancy may double when known genetically normal embryos are utilized. Implantation rates (the chance of each single embryo becoming a gestation) can also be raised greatly with PGD. To determine whether these embryos are chromosomally normal, a PGD analysis is carried out by our scientists prior to their selection for transfer to the mother. In an genetically normal embryo, there should be 2 (and only 2) chromosomes of each of 22 chromosome types in addition to one set of XX female or one set of the XY male chromosomes.
The Successful Use of PGD for Recurrent IVF Failure
Most couples presenting to us for consideration of PGD have one of the following conditions : -
- Prior unexplained IVF failure
- Recurrent miscarriages
- Maternal age over 38
- Conception of a chromosomally abnormal child or fetus
- Polycystic ovary syndrome
- History of ovarian hyperstimulation syndrome
- Heritable medical condition in either the patient or in a prior child (such as hemophilia)
- Two or more children of the same gender (sex selection for family balancing)
- Multiple birth with desire to transfer just one embryo or a need for donor oocytes due to Turner's syndrome
- Premature ovarian failure or premature menopause
The Accuracy Of PGD In "Genetic" IVF Failure
The accuracy of PGD in determining genetic abnormalities exceeds 98%. Once we have the genetic information about each embryo available, we are able to sit down with each couple prior to the embryo transfer, discuss the genetic health of each embryo, explain how the genetic information has improved the chances for pregnancy success compared to their prior unsuccessful attempts at IVF elsewhere, and make a determination about the return of the now "known to be normal" embryos to the mother to be.
Because PGD so improves the success of IVF, many couples elect, in consultation with us to decrease the total number of embryos placed back in the womb. This also decreases the chance of multiple birth and the chance of prematurity. It also allows for the cryopreservation of extra "normal" embryos for future pregnancies. Our experience has shown that even when far fewer embryos are returned to the uterus, pregnancy success increases following PGD.
The Success Of PGD In Improving Recurrent IVF Failure
Using PGD to select the best embryos is clearly superior to traditional methods of selection. Miscarriage rates following PGD are far less than with standard IVF. Currently more than half of couples with two or more normal embryos and maternal age under 41 will take home a baby on a first IVF-PGD attempt in our program. And these are in couples who have failed multiple prior IVF attempts elsewhere!
Seven per cent of couples presenting having failed multiple IVF attempts at other programs had no normal embryos to transfer after PGD analysis in our program.
PGD and Amniocentesis
Because the most vital, but not all chromosomes have been tested, PGD cannot substitute for mid-trimester genetic ultrasound evaluation and amniocentesis or chorionic villi sampling. We encourage additional genetic testing once a successful pregnancy has been established to confirm the total genetic health of the resulting pregnancy. PGD to Determine Sperm or "Both Partner" Infertility Issues
Another very important issue learned from PGD is the fact that sperm, while much less often involved in IVF failure, clearly have the potential to, in selected instances, cause repeated IVF failure. Although many sperm defects will lead to failure to fertilize or arrest of development before blastocyst formation by the embryo, more subtle microdeletions and sperm chromatin fragmentation may explain why some IVF cycles fail despite several PGD normal embryos to choose from. In response to this new information, we have begun considering sperm chromatin fragmentation and microdeletion testing in select IVF cycles to eliminate the potential for unrecognized sperm defects leading to repeated IVF failure.
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