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Advances in Assisted Reproduction (2014)

The use of genetic testing of embryos continues to grow. Preimplantation Genetic Screening or PGS, is a technique used with In Vitro Fertilization-Embryo Transfer (IVF-ET). It deals with the analysis of chromosomal number in embryos.

Preimplantation Genetic Diagnosis or PGD, deals with chromosomal structure or individual genes of an embryo resulting from IVF.  The goal is to transfer embryos which have been screened for abnormalities, so that the chance of conception is increased, and the resulting pregnancy has the greatest chance of being normal. In addition, some couples use the opportunity to select an embryo based on its gender, to balance their family composition.

The major uses of PGD are diagnoses of single gene defects, either recessive (like cystic fibrosis), dominant (like polycystic kidney) or X-linked (like hemophilia, where only male offspring are affected), and detection of carriers of unbalanced chromosomal structural abnormalities (like translocations or inversions, which usually result in miscarriages).

PGS is used more commonly for aneuploidy screening, looking for either polyploidy (too many copies of all the chromosomes), extra copies (trisomy, such as trisomy 21, which causes Down syndrome) or missing copies (monosomy) of individual chromosomes, or complex abnormalities in number and distribution. Any of these abnormalities may result in the inability to become pregnant at all, miscarriages, or the delivery of an abnormal baby.

The reason a couple would think to use PGD is obviously the personal or family history of someone affected by the disease caused by a single gene defect. It could be the known existence of a balanced translocation or inversion in one of the partners determined from previous pregnancy losses or infertility. Advanced maternal age, which increases the chances of infertility, prior miscarriage or an ongoing pregnancy with an abnormal fetus (terminated or delivered), would be a reason for PGS.

Recurrent miscarriage at any age, where either a chromosomal cause has been determined, or after elimination of non-genetic causes, justifies the use of PGS. A single previously chromosomally abnormal fetus or offspring or family history of the same would be a reason to use PGS. For patients going through infertility treatment, the desire to maximize the chance of a normal pregnancy during infertility treatment could justify PGS, and recurrent IVF failure can often be explained by PGS findings.

This may direct the couple to alternative means of family building, such as donor egg or adoption. Even fertile couples who conceive easily without medical assistance, who are reluctant to do invasive prenatal genetic testing, or would refuse to abort an abnormal fetus would find that PGS reduces the need or risks of these events. The incidence of an abnormal fetus

in a pregnancy arising from IVF with PGS is not eliminated, but markedly reduced by 98%. In general, aneuploid screening detects abnormalities of chromosomes that are responsible for 90% of pregnancy losses, so that the residual loss rate is 10-15% due to non-chromosomal factors. The error in the testing is said to be about 2%.

The ability to culture embryos to the blastocyst stage and perform trophectoderm biopsy on days 5,6 and sometimes 7 analyzes the embryos with the greatest functional potential to implant.  After the required number of days following egg retrieval and microfertilization (ICSI), several cells are removed from the outer layer of the embryo, in essence, the future placenta. Obtaining more DNA alone improves the accuracy of the PGS.

The inner cell mass, which becomes the fetus, is not disturbed. The improved accuracy of testing also is due to the use of advanced genetic testing, including aCGH (array comparative genomic hybridization) and MA (microarray) which test for all 23 pairs of chromosomes. After biopsy, the blastocysts are cryopreserved using a quick freeze technique called vitrification while the results are being obtained.

The transfer of a normal embryo (transferring more than one is not encouraged due to the high twin risk with only a small conception benefit) is then done in a subsequent cycle. The hormonal protocol used mimics an idealized natural cycle, rather than the overstimulated one associated with the retrieval.  Fears that cryopreservation may damage the embryos have been put to rest by our data showing similar implantation rates between fresh and frozen-thawed embryos.

The use of PGS in IVF continues to be more common and more successful, and can provide critical information for a couple, whether or not it actually aids in achieving a pregnancy in the treatment cycle. It can give an explanation for fertility treatment failures, recurrent miscarriages, and either provide closure for the older patient in attempting pregnancy using her own eggs or allow further tries.

It can provide reassurance for the couple who has suffered through losses or the termination or birth of an abnormal fetus. Its goal is to make IVF more efficient, and to encourage the transfer of only a single embryo at a time, while giving the best chance of a normal baby.

Nonetheless, the process of PGS is an invasive one, and it leaves room for improvement and alternative. One extremely new method of selecting embryos, that may take the place of PGS some day, is the use of the Embryoscope. This device, which is a specialized embryo incubator, uses time lapse video to monitor the very early cleavage properties of the fertilized oocyte.

These observations may be used to predict which embryos are likely to become blastocysts without waiting the extra days to make that determination. While blastocyst culture is the gold standard to select embryos for transfer based on their developmental quality, the steps leading to that point are generally not taken into consideration.

There is some concern about the length of time an embryo stays in culture before transfer as well. The ability to choose the best embryos earlier in their laboratory stay may have significant benefits. Studies are underway to assess the cleavage properties of normal and abnormal embryos, which may make for selection of euploid embryos without requiring biopsy and testing. These are projects in the works, and Fertility Centers of Illinois is at the cutting edge of these techniques.

In addition, Fertility Centers of Illinois has been involved in studies that are looking into new forms of fertility drugs that may reduce the number of injections in an IVF cycle, studies using new materials to improve implantation rates in previous IVF failures, and others that continue to improve outcomes for our (and your) patients.