Genetic Testing of Embryos:
Should You or Should You Not?
Adapted from “Preimplantation Genetic Testing: a Committee Opinion” by the American Society for Reproductive Medicine (ASRM)
Preimplantation genetic testing includes:
Preimplantation genetic diagnosis (PGD) is used when one or both genetic parents carry a gene mutation, and testing is performed to determine whether that specific mutation has been transmitted to the embryo.
Preimplantation genetic screening (PGS) describes a procedure involving the removal of one or more nuclei from embryos to test for genetic abnormalities before embryo transfer.
Preimplantation Genetic Diagnosis (PGD)
PGD necessitates prior knowledge of the genetic mutation carried by the genetic parent(s) and searches for that specific mutation in each embryo. It is indicated for couples at risk for transmitting a specific genetic disease or abnormality to their offspring.
There is good scientific evidence to recommend the use of PGD to reduce the risk for conceiving a child with a genetic abnormality carried by one or both parents.
Preimplantation Genetic Screening (PGS)
Genetic abnormality in embryos is the most common cause for early pregnancy failure.
There are no specific indications for PGS since, by definition, it is performed in patients having no known chromosomal anomaly, mutation, or other genetic abnormality.
PGS has been advocated for use in conjunction with IVF in efforts to identify and transfer only genetically normal embryos and thereby improve the likelihood for a successful pregnancy.
PGS has been proposed for patients at risk for having an increased likelihood 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), or severe male factor infertility.
Unfortunately, screening for genetic abnormality in embryos has not been shown to consistently improve clinical outcomes 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% false-positive findings resulting in discarding embryos that may have resulted in a live birth.
Theories proposed to explain the phenomenon include:
Approximately 10% of cells removed for screening yield no results.
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 embryo would be discarded.
Self-correction of the abnormal cell line(s). Again, if the embryo biopsy was carried out before this self-correction, such embryo would be discarded.
The genetic analysis may result in false-positive or incorrect result.
This means that we must accept the reality that with PGS testing 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 for miscarriage and the incidence of genetically abnormal embryos increase with maternal age in both naturally conceived pregnancies and those resulting from IVF.
In theory, PGS 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 PGS for advanced maternal age have not demonstrated this theoretical benefit.
Overall, advanced maternal age patients undergoing PGS 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 large majority of pregnancies that miscarry spontaneously are genetically abnormal.
There is insufficient evidence to recommend the use of PGS for patients with repeated pregnancy loss to improve ongoing pregnancy or live birth rates or decrease miscarriage rates. However, couples in whom recurrent pregnancy loss can be attributed to a genetic abnormality in one or both partners may benefit from specific genetic testing (PGD) to detect 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 PGS as currently performed to improve outcomes in patients with repeated implantation failure.
Embryo Selection in “Good Prognosis” IVF Patients
There is good evidence to recommend against the use of PGS 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 PGS for couples with male factor infertility. There is insufficient evidence to recommend the use of PGS for couples undergoing IVF with intracytoplasmic sperm injection (ICSI) for male-factor indications.
There is good evidence to recommend against the use of PGS as currently performed to improve live birth rates in patients with advanced maternal age.
There is insufficient evidence to support the use of PGS as currently performed to improve live birth rates in patients with recurrent pregnancy loss.
There is insufficient evidence to support the use of PGS as currently performed to improve live birth rates in patients with previous implantation failure.
There is insufficient evidence to support the use of PGS as currently performed in patients with recurrent implantation failure to make decisions concerning future treatment options.
There is good evidence to recommend against the use of PGS as currently performed to select the best embryo to transfer in good prognosis patients.