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Should we test embryos using PGS with IVF treatment routinely?

The short answer to this complex question is “no” but the common and popular current answer is probably in some cases. Preimplantation genetic screening (PGS) or some practitioners as they call it preimplantation genetic diagnosis (PGD) are tests that fertility doctors use to determine whether an embryo is genetically or more so chromosomally normal or not. PGD applies to reproductive practice better because doctors make a decision based on the report (diagnostic test) instead of ordering another confirmatory test (as in a screening test). In a way, PGS is like the “Pap smear” to screen for cancerous cells, whereas a cervical biopsy would be the diagnostic test or like the “PGD” test.

The use of PGS/PGD has increased dramatically over the years and especially with the advent of newer and more reliable technologies such as comparative genomic hybridization (CGH) or the newest technique called next generation sequencing (NGS). Whereas there are many methods to test for chromosomal competence in IVF practice, NGS technology appears to be the most reliable and optimal for the genetics laboratory.

The important question is who should test their embryos and is there an age cut off? There really isn’t, but it is reasonable to assume that genetic abnormalities increase with the increasing reproductive age. Historically, doctors used to offer or at least suggest amniocentesis to all women above the age of 35. Whereas this has changed over time, guidelines updated and better screening tools have been developed, there is still the tendency to advise screening for genetic issues during pregnancy. The advent of the non-invasive prenatal testing (NIPT) certainly changed the way we counsel patients which allows genetic screening and especially for Down’s syndrome with just a blood draw starting at 9-10 weeks. The non-invasive aspect of this screening tool with over 99% accuracy makes the test a desired one and may soon be the standard way of fetal screening in the first trimester.

PGS allows an earlier detection option at the level of the embryo with high accuracy. High accuracy does not mean a guarantee or 100% reliability. It is not unusual to see 1-2 cases a month who have a “PGS-normal” embryo transferred and not become pregnant. This creates confusion as to whether the embryo was abnormal even though the report indicated that it was normal or the embryo was normal “chromosomally” but abnormal “genetically”. Unfortunately, genetic mapping of the entire chromosomes and what it truly means is still unknown. Certain variations occur at the level of the genes which may be normal or abnormal even in the presence of a normal appearing chromosome. Additionally, the failed implantation may also be due to non-embryo related issues such as the uterus or implantation issues.

It is important to have a discussion about the possibility of PGS resulting in imperfect or wrong diagnosis which can certainly affect the outcome. Most geneticists and clinicians believe that the false positive or false negative rates are below 10% with the newest technologies when the embryo biopsy is done at the blastocyst stage (Day 5-6 embryo stage). If the biopsy is done at the blastocyst stage as opposed to the “day 3” or “cleavage stage”, the reliability is much higher and the level of mosaicism is significantly lower. Mosaicism refers to one cell being normal and the other cells being abnormal in the embryo and vice versa.

The risk of discarding an embryo because it is labeled as being abnormal is quite low but a real issue. On the other hand, the risk of having an embryo transferred that may result in a failed cycle, miscarriage, second trimester loss, abortion, frustration, physical/emotional trauma, unnecessary use of hormones until pregnancy is ruled out and related short and long term complications is also real. The best way to approach this issue is to have a detailed discussion prior to making the decision as to whether we should test the embryos or not, and often times may come down to a decision that is a personal one and based on individual needs, perception and preference of the patient.