Theory and practice of preimplantation genetic screening (PGS)

In the context of artificial reproductive technology (ART) treatments with in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI), the purpose of genetic screening of oocytes and embryos in vitro prior to implantation (preimplantation genetic screening, PGS) is highly controversial. Therefore, an analysis of the following theoretical prerequisites is presented: the abstract investigation method and the medical diagnostic decision, indication and ethical acceptability. The first is a scientific task, while the other is a physician's task.

As the new term preimplantation genetic diagnosis for aneuploidies (PGT-A) does not sufficiently take into account probable future developments, PGS is retained here. In clinical practice, PGS refers to the biopsy of polar bodies, blastomeres or trophoblast cells with indication-dependent genetic analysis. Goals include increasing pregnancy rates and reducing abortion rates, multiple birth rates, malformation rates and pointless ART treatments. To improve the pregnancy rate, PGS makes no sense if a stochastic selection advantage is not to be expected. Patients may have to choose between the chance of rapid success with a first fresh embryo transfer of blastocysts and a possibly higher overall cumulative chance of pregnancy from fresh and thawed transfers of four-to eight-cell embryos. It is neither necessary nor useful to make every medical decision dependent on randomized controlled trials (RCTs). The randomization of patients is not indicated if observational studies have not shown a positive result. For a "proof-of-principle study", the numerator and denominator of the cascade of parameters for success must be close to each other and far apart in an "efficacy study". The randomization may only be performed before the biopsy.

Following the introduction of blastocyst biopsy and comprehensive chromosome screening (CCS) with, for example, aCGH and NGS, referred to as "PGS 2.0″, all RCTs since 2012 have found a positive effect.

There is still disagreement about the interpretation of the results of PGS 2.0, but the overwhelming view in opinion publications seems to be that it works. This fits with the increasing global commitment to PGS 2.0.

PGS may be beneficial if used with strict indications, taking into account stochastics and the will of the patient. The task of the physician, similar to counselling in prenatal medicine, is as follows: present all methods of investigation and respect the will of the patient.