IVF Embryo Genetic Testing

The goal of IVF embryo genetic testing (Preimplantation Genetic Testing - PGT) is to increase the probability of a successful treatment outcome by decreasing the likelihood of transferring genetically abnormal embryos.

IVF genetic testing of embryos has been advocated for use in conjunction with In Vitro Fertilization in efforts to identify and transfer only genetically normal embryos and thereby improve the likelihood of a successful pregnancy.

Embryo genetic testing has been proposed for patients at risk for having an increased probability of having genetically abnormal embryos, including women of advanced maternal age (35 or older) and those with a history of repeated early pregnancy loss (three or more), repeated failed IVF cycles despite the transfer of high-quality embryos (three or more transfers), and for severe male factor infertility.

Unfortunately, testing for genetic abnormality in embryos has not been shown to improve clinical outcomes consistently and may, in fact, be detrimental for some of the believed indications.

Using even the latest methods for genetic analysis has been suggested to be associated with up to 16% of false-positive findings resulting in discarding embryos that may have resulted in a live birth.

Theories proposed to explain the phenomenon include:

1. Approximately 10% of cells removed for testing yield no results.

2. Chromosomal segregation errors may lead to embryo mosaicism (an embryo that contains both normal and abnormal cells), in which abnormal cell lines fail to proliferate, and the normal cell line develops into a normal offspring. If the analyzed cell was biopsied from an abnormal cell line, such an embryo would be discarded.

3. Self-correction of the abnormal cell line(s). Again, if the embryo biopsy was carried out before this self-correction, such an embryo would be discarded.

4. The genetic analysis may result in a false-positive or incorrect result.

This means that we must accept the reality that with PGT, we are discarding embryos that may have resulted in a live birth. A recent report describes the birth of healthy babies after the transfer of mosaic “genetically abnormal” embryos.

Advanced Maternal Age (35 and older)
The risk of miscarriage and the incidence of genetically abnormal embryos increase with maternal age in both naturally conceived pregnancies and those resulting from IVF.

In theory, PGT should increase the likelihood that embryos selected for transfer will be genetically normal and thus result in improved implantation, pregnancy, and live birth rates. However, the results achieved with PGT for advanced maternal age have not demonstrated this theoretical benefit.

Overall, advanced maternal age patients undergoing PGT had, in fact, a significantly lower probability of live birth compared to the control group.

Recurrent Pregnancy Loss (three or more)
Miscarriage is very common, and the majority of pregnancies that miscarry spontaneously are genetically abnormal.

Couples in whom recurrent pregnancy loss can be attributed to a genetic abnormality in one or both partners may benefit from specific genetic testing of embryos (PGT-m) to detect an excess or missing genetic material in their embryos.

Repeated Implantation Failure
Repeated implantation failure has been defined by the number of failed IVF attempts (usually three or more) or by the failure of implantation after a specific total number of embryos has been transferred.

There is insufficient evidence to recommend the use of PGT as currently performed to improve outcomes in patients with repeated implantation failure.

Embryo Selection in “Good Prognosis” IVF Patients
There is enough evidence to recommend against the use of PGT as currently performed for embryo selection in good prognosis IVF patients.

Male Factor Infertility
Abnormal chromosomes may be expected in approximately 10-15% of men with no sperm production, in 5% of men with low sperm counts, and in less than 1% of men with normal semen quality.

No studies have been performed to evaluate the clinical utility of PGT for couples with male factor infertility. There is insufficient evidence to recommend the use of PGT for couples undergoing IVF with intracytoplasmic sperm injection (ICSI) for male-factor indications.

PGT Is a Personal Choice
For couples with no history of repeated pregnancy losses, PGT can be used to reduce the probability that their IVF pregnancies will result in a miscarriage.

Ultimately, whether to add PGT to the IVF treatment is more of a personal than a medical choice. Please let us know if you need any help with your decision.

PGT Procedure
Preimplantation Genetic Testing is a complex treatment consisting of the following steps:

1. In Vitro Fertilization to create embryos
2. Extended embryo culture to blastocyst

   By the fifth to seventh day after the egg retrieval, the embryos should reach the blastocyst stage (80 or more cells).

3. Blastocyst trophectoderm (embryonic tissue) biopsy

   An embryo biopsy is performed by creating an opening in the eggshell around the embryo. It is possible to safely remove six to eight cells through this opening using a special microscope with micromanipulators. The cells are taken from the trophectoderm only (future placenta cells, genetically identical to embryonic cells). The “inner mass” cells (embryonic cells) are not removed.

    

   

    

   So far, there is no evidence that embryonic biopsy results in an increased chance of abnormalities in the baby or that the risk of birth defects is higher when compared to conceptions that occur spontaneously without medical assistance (2% to 5%).

4. Blastocyst vitrification (cryopreservation)

   Since it takes several days to carry out the embryo genetic analysis, the blastocysts are cryopreserved immediately after their biopsy and stored in liquid nitrogen in our IVF laboratory.

5. Genetic analysis of the embryonic tissue

   The accuracy of PGT cell analysis of genetically abnormal embryos approaches 100%, but it is not guaranteed. It is possible, even though highly unlikely, that an embryo that has tested as normal may not be genetically perfect.

6. Liquid nitrogen storage of the cryopreserved embryos

   Vitrified embryos can be stored for extended periods of time, but most PGT patients will start an embryo transfer cycle with the onset of the first menstrual period after their IVF treatment.

7. Subsequent Frozen Embryo Transfer

   The endometrial lining is first stimulated with estrogen and progesterone, followed by the thawing of one or two embryos which tested as normal by the PGT analysis, and then transferring them inside the uterus.