NGS Based Male and Female Infertility Panels

Since NGS technology s tepped in molecular genetic applications,it has become quite easy to incorporate exome and genome-scale technologies into our routine practice.In today's technology, we have been using Next Generation Sequencing(NGS) based infertility panels, markers for azospermiacases, sperm DNA damage/ apoptosis tes ts for the evaluationof male infertility. NGS based infertility panels, Immunologicalfactors, endometrial receptivity tes ts are mainly used for theevaluation of female infertility.The genetic causes of male infertility are quite complex. Geneticfactors are responsible for ۱۵% of male infertility. A largenumber (at leas t ۲۰۰۰) of genes is thought to be responsible forspermatogenesis. With the highes t frequency of known geneticfactors contributing to men, spermatogenic numerical defectscons titute ۲۵%. Until now, a limited number of tes ts were usedin the evaluation of male infertility. However molecular geneticsand flow cytometric tes ts have been implemented for comprehensiveinfertility analysis. In this context by using NGSbased infertility panels we can detect Kalman Syndrome, genesrelated to spermatogenic failures. Additionally novel genes relatedto male infertility can be evaluated. We designed targetedNGS based male infertility tes t panel (۴۰ genes) for the genesrelated to spermatogenic failure/sperm maturation, hormones/receptors, congential bilateral absence of vas deference and motility/ fertilization failure. There are increasing the number ofpublications about infertility genetics. Novel genes have beendiscovered especially related with spermatogenic failure . Inthis context it wont be easy to dedicate a targeted small NGSpanel for infertility diagnosis.The inability of limited gene panels to detect novel variants hasled us to apply exome based comprehensive panels. Same scenariois also valid for female infertility. We were performingNGS based female infertility tes t panel (۳۸ genes) for the genesrelated with primary ovarian insufficiency, sex reversal syndromes,hypogonadotrophic hypogonadism and oocyte maturationdefects. Since NGS technology is not compatible to detectrepeat expansion type mutations, a specific method like TPPCRhas been performed to detect Fragile X Syndrome. Sinces tudies on infertility-related genes are very recent, the clinicalrelevance of many variants has not been fully demons trated.Mos t of the variants we have been predicting are class۳ variants.We call these variants as variants of unknown significancedue to lack of clinical correlation between the gene and the infertility.As association s tudies increase, variant classificationknowledge will also be improved and the specificity of theseNGS-based tes ts will also become s tronger. Although rapiddevelopments have been occuring in wet laboratory s tages ofexome-based tes ts, variant classification and clinical data associations tudies are not progressing at the same level. For thispurpose, we have been using high technology bioinformatic solutionswhich give chance to achieve daily updated literatureinformation for infertility related genes.The importance of gene panels in male and female infertilitydiagnosis consis ts of the following matters;• This tes t panel is a screening tes t to identify the etiology ofmale infertility• It is aimed to reveal the cause of infertility and to receive specificand correct treatment for the infertile patients• The inheritance of these mutations to the next generations canbe prevented via Preimplantation Genetic Tes ts.Developments in the field of molecular Genetics lead to importantimprovements in Reproductive Medicine. Knowing theexact cause of infertility allows for better diagnos tic decisionsand enables enhanced counseling for couples.