Theory and practice of preimplantation genetic screening (PGS). 2019

Andreas G Schmutzler
University Women's Hospital, Christian-Albrechts-University, Kiel, Germany; gyn-medicum, Center for Reproductive Medicine, Goettingen, Germany. Electronic address: schmutzler@email.uni-kiel.de.

OBJECTIVE 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. CONCLUSIONS 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. CONCLUSIONS 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. CONCLUSIONS 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.

UI MeSH Term Description Entries
D011247 Pregnancy The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH. Gestation,Pregnancies
D001755 Blastocyst A post-MORULA preimplantation mammalian embryo that develops from a 32-cell stage into a fluid-filled hollow ball of over a hundred cells. A blastocyst has two distinctive tissues. The outer layer of trophoblasts gives rise to extra-embryonic tissues. The inner cell mass gives rise to the embryonic disc and eventual embryo proper. Embryo, Preimplantation,Blastocysts,Embryos, Preimplantation,Preimplantation Embryo,Preimplantation Embryos
D004624 Embryo Transfer The transfer of mammalian embryos from an in vivo or in vitro environment to a suitable host to improve pregnancy or gestational outcome in human or animal. In human fertility treatment programs, preimplantation embryos ranging from the 4-cell stage to the blastocyst stage are transferred to the uterine cavity between 3-5 days after FERTILIZATION IN VITRO. Blastocyst Transfer,Tubal Embryo Transfer,Tubal Embryo Stage Transfer,Embryo Transfers,Transfer, Embryo,Transfers, Embryo
D005260 Female Females
D005307 Fertilization in Vitro An assisted reproductive technique that includes the direct handling and manipulation of oocytes and sperm to achieve fertilization in vitro. Test-Tube Fertilization,Fertilizations in Vitro,In Vitro Fertilization,Test-Tube Babies,Babies, Test-Tube,Baby, Test-Tube,Fertilization, Test-Tube,Fertilizations, Test-Tube,In Vitro Fertilizations,Test Tube Babies,Test Tube Fertilization,Test-Tube Baby,Test-Tube Fertilizations
D005820 Genetic Testing Detection of a MUTATION; GENOTYPE; KARYOTYPE; or specific ALLELES associated with genetic traits, heritable diseases, or predisposition to a disease, or that may lead to the disease in descendants. It includes prenatal genetic testing. Genetic Predisposition Testing,Genetic Screening,Predictive Genetic Testing,Predictive Testing, Genetic,Testing, Genetic Predisposition,Genetic Predictive Testing,Genetic Screenings,Genetic Testing, Predictive,Predisposition Testing, Genetic,Screening, Genetic,Screenings, Genetic,Testing, Genetic,Testing, Genetic Predictive,Testing, Predictive Genetic
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000782 Aneuploidy The chromosomal constitution of cells which deviate from the normal by the addition or subtraction of CHROMOSOMES, chromosome pairs, or chromosome fragments. In a normally diploid cell (DIPLOIDY) the loss of a chromosome pair is termed nullisomy (symbol: 2N-2), the loss of a single chromosome is MONOSOMY (symbol: 2N-1), the addition of a chromosome pair is tetrasomy (symbol: 2N+2), the addition of a single chromosome is TRISOMY (symbol: 2N+1). Aneuploid,Aneuploid Cell,Aneuploid Cells,Aneuploidies,Aneuploids,Cell, Aneuploid,Cells, Aneuploid
D019836 Preimplantation Diagnosis Determination of the nature of a pathological condition or disease in the OVUM; ZYGOTE; or BLASTOCYST prior to implantation. CYTOGENETIC ANALYSIS is performed to determine the presence or absence of genetic disease. Diagnosis, Preimplantation,Preimplantation Genetic Diagnosis,Diagnosis, Preimplantation Genetic,Preimplantation Screening,Diagnoses, Preimplantation,Diagnoses, Preimplantation Genetic,Genetic Diagnoses, Preimplantation,Genetic Diagnosis, Preimplantation,Preimplantation Diagnoses,Preimplantation Genetic Diagnoses,Preimplantation Screenings,Screening, Preimplantation,Screenings, Preimplantation
D020554 Sperm Injections, Intracytoplasmic An assisted fertilization technique consisting of the microinjection of a single viable sperm into an extracted ovum. It is used principally to overcome low sperm count, low sperm motility, inability of sperm to penetrate the egg, or other conditions related to male infertility (INFERTILITY, MALE). ICSI,Injections, Sperm, Intracytoplasmic,Intracytoplasmic Sperm Injections,Injection, Intracytoplasmic Sperm,Injections, Intracytoplasmic Sperm,Intracytoplasmic Sperm Injection,Sperm Injection, Intracytoplasmic

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