The Use of Medical Genetics in the Reproductive Medicine

Overview

Reproductive genetics (RG) is another new field of medical genetics, integrated with reproductive medicine,assisted reproduction and developmental genetic. RG is closely linked to the periconceptional prevention, perinato-logy, ultrasound and biochemical screening in the end of the first and beginning of the second trimesters. RG is basedon the system of specialized genetic counseling, clinical cytogenetics, molecular cytogenetics and molecular geneticsto provide prefertilization, preimplantation and classical prenatal diagnosis in the Ist to IIIrd trimesters. Thus, RGis part of the fetal medicine and therapy. The six years experience with RG is summarized. A system of the specializedhealth care, organized, if possible in one integrated center of RG and reproductive medicine (RM) is presented.Reproductive medicine provides all necessary clinical gynecological and andrological surveillance, with assistedreproduction and further obstetrical ultrasound examinations, including nuchal translucency measurements and 2D,3D ultrasound, echokardiography examinations, if indicated, as well as the invasive method of prenatal diagnosisand perinatology care. Specialized genetic counseling and cytogenetic analysis, if indicated, should be offered to allpartners with reproductive disorders as well as to oocyte donors. Chromosome anomalies are disclosed in 6% ofmen with abnormal sperm analysis as well as in women with severe reproductive disorders. In males with severe oligo, azoospermia, the sperm aneuploidy analysis by molecular cytogenetic methods is recommended. Adviced isalso the molecular genetic detection of Y chromosome microdeletions, which is detected in 9% of our azoospermicmen with deletions in AZFb region. CFTR gene mutations and intron 8 and 10 polymorphism examination is providednot only in men with obstructive azoospermia (CBAVD), but also if severe oligospermy with less than 1x106sperm/mlis detected. Molecular genetic analysis of thrombophilic mutations of factor II., V. (Leiden) and MTHFR gene inunexplained recurrent abortions and in cases with unsuccessful IVF is part of the diagnostic strategy. The populationfrequencies of carriers of mutation of factor II. (2.3%), factor V.-Leiden (5.7%) and MTHFR gene (38%) weredetermined. The laser biopsy of the first polar body and of blastomeres was introduced for FISH analysis ofchromosome aneuploidies. Quantitative fluorescent PCR (QFPCR) detection is used for testing of the most frequentdelta F508 CFTR gene mutation and the most frequent aneuploidies of chromosome 13, 18, 21, X and Y. QFPCRwas successfully tested for male fetal sex examination from partially purified fetal cells in the maternal blood. Thefirst trimester ultrasound and biochemical screening is recommended to all successful pregnancies after differentIVF methods. If borderline levels of first trimester biochemical screening of PAPP-A protein and bhCG are detectedwithout pathological ultrasound findings, classical triple test of biochemical screening in 16th week of gestation isrecommended. If pathological results of ultrasound and biochemical screening are disclosed, invasive prenatal geneticdiagnosis is indicated as well as in pregnancies after ICSL, if there is not any obstetrical contraindication.

Key words:
reproductive genetics, reproductive medicine, preimplantation prenatal diagnosis, ultrasound andbiochemical screening, CFTR and thrombofilic mutations, Y chromosome microdeletions, genetic counseling.