Pre-implantation Genetic Testing

In vitro fertilization is the process of transferring the female and male reproductive cells out of the body and fertilising them in laboratory environment and transferring the embryo to the mother-to-be’s uterus. As couples who apply for IVF treatment are naturally unable to obtain pregnancy, there is a problem with the woman, man, or both that prevents pregnancy. Thus, before the decision of IVF treatment is taken, men and women are subjected to detailed tests, analyses and examinations. Depending on the obtained data from these processes, the IVF treatment begins. As the parents-to-be’s own reproductive cells are utilised, complications such as miscarriages, premature birth, maternal infant deaths and Down Syndrome might also occur in the IVF treatment if the problem is genetic, chromosomal. Today, however, thanks to the IVF treatment, sperms and eggs, and then the obtained embryo can be examined genetically. As we can examine reproductive cells and embryo through genetic tests, existing or probable problems can be detected and precautions can be taken accordingly.

*Genetic procedures in IVF, namely PGT (Preimplantation Genetic Testing) is consisted of 2 main investigations:

  1. Pre-implantation genetic diagnosis (for genetically inherited disease)
  2. Pre-implantation genetic screening for aneuploidies (PGT-A)

PGD (Preimplantation Genetic Diagnosis)

Embryos are observed and examined for nearly 5 days after the fertilization of eggs from the mother-to-be and sperms from the-father-to-be. Between the 2nd and 5th day of this period, 1-2 of the healthiest, most quality, most viable embryos are selected and transferred to the mother-to-be’s uterus. Even if the treatment is completed successfully and the embryo seen as the most suitable for pregnancy is selected, miscarriages and uncomfortable pregnancies might sometimes occur. For this reason, the need for genetic investigation of reproductive cells arises. In this context, PGD helps identify and isolate embryos that are genetically problematic and unproblematic. Quantitative chromosomal defects in the embryo are eliminated through PGD. Thanks to PGD recommended for approximately 10% of the patients receiving IVF treatment, normal and healthy embryos can be transferred to the uterus and thus, the success rate of the treatment can be increased. PGD, which increases treatment success rate and significantly reduces the number of miscarriages, is planned to be applied to a larger number of IVF patients in the future.

Who is PGD applied to?

PGD is not considered to be applied to all patients who receive IVF treatment. Since, it is a fact that chromosomal defects seen in embryos may disappear themselves later and embryos can heal themselves. PGD is primarily and especially used in recurrent miscarriages and also on patients whose parents have chromosomal mosaicism. In addition, PGD should also be applied to individuals who have previously given birth to a child with a single gene disorder, and to anyone of the couple if he/she has single gene disorder which is likely to pass on to the child.

PGT-A (Preimplantation Genetic Testing for Aneuploidies)

This technique is consisted of blastocyst biopsy and NGS investigation of trophoblastic cells to reveal the chromosomal number of an embryo. Frozen embryo transfer is prerequisite for PGT-A.

Main indications are:

  1. Older woman age (>40)
  2. Elective single embryo transfer
  3. Recurrent miscarriages (>3)
  4. Repeated implantation failure (>3)
  5. Severe male infertility

 

Pros and cons are present for PGT-A examination:

Pros:

Defining genetic status of embryo

Selecting the embryo with implantation potential.

Cons:

Cycle cancellations due to embryonic developmental problems

Aneuploid results

CGH (Comparative Genomic Hybridization)

CGH is the process of identifying the genetic and chromosomal problems that occur in eggs by examining eggs one by one, and selecting and freezing the normal ones. Since CGH allows the IVF treatment to be carried out with genetically and chromosomally normal eggs, the success rate of the treatment is increased by nearly 80% compared to the conventional IVF treatment. Furthermore, the infant is prevented from having a chromosomal disorder such as Down Syndrome. Since CGH allows healthy eggs to be selected and frozen, a healthy pregnancy can be achieved by thawing frozen eggs at any time. CGH, which has been in use for 1-2 years in European countries and has just started to be recognized in our country, allows us to examine eggs in a more detailed way compared to PGD. In the CGH process, all chromosomes of all embryos are examined and a single most healthy embryo is transferred to the uterus. Thus, being some of the risks of IVF, multiple pregnancies and miscarriages due to unhealthy embryos can be avoided.

Who is CGH applied to?

CGH should be applied to determine genetic and chromosomal problems when the couple goes through the IVF treatment twice in a row, but a pregnancy or a healthy birth cannot be achieved. CGH should be applied if one embryo has been obtained through PGD but the treatment is unsuccessful, if the woman is over 38 years old, if there is no sperm in the semen of the father-to-be (azoospermia).

NGS (Next Generation Sequencing)

New generation sequencing (NGS) and intense parallel or deep sequencing are terms that define a DNA sequencing technology that revolutionizes genetic research. Through NGS, an entire human genome can be sequenced in a single day. In contrast, it took ten years to present the final draft in the previous Sanger sequencing technology, which was used to decipher the human genome. In genomic studies, NGS has not yet been transformed into a routine clinical practice, although it has mostly replaced conventional Sanger sequencing. The NGS method is, in short, a very comprehensive chromosomal scan used to evaluate and examine 24 chromosomes. Therefore, the success rate of in vitro fertilization and having healthy babies increases.

Who is NGS applied to?

Next Generation Sequencing (NGS) has been developed for the same purposes as CGH due to its current status and it is a technique, like CGH, which deals with quantitative and some structural abnormalities in all chromosomes. Now one of the major advantages compared to CGH and expected to bring to PGD is the reduction of costs. In addition, NGS is the foreground in that it will allow the evaluation of both chromosomal and gene-based diseases at the same time in the future. The application areas of this method are the same as CGH, but because of its advantages, NGS is gradually replacing CGH.

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