EVALUATING THE MALE GAMETE GENOME TO IMPROVE ART OUTCOME

To shed light on various causes of reproductive failure by unravelling the male gamete genome using whole exome sequencing (WES). In a 5-year period, 18 consenting couples, with normal semen parameters, negative female infertility workups, and failed ART cycles, comprised infertile cohort. Ten matched successful outcomes, served as fertile control. DNA was extracted amplified from at least 500 spermatozoa (DNA concentration, 760±486 ng/ul; quality, 1.7±0.1 nm) for copy number variant (CNV) analyses WES. Mutations corresponding to CNV were annotated assessed CLC Genomic Server 9.0. Genes considered duplicated or deleted when their read depth >1.5 <0.5 times median in control, respectively. Gene mutation profiles compared between cohorts, well according reasons failure. All couples (n=28) (maternal age, 38.5±4yrs; paternal 39.5±6yrs) had peripheral karyotypes parameters (concentration 59.2±30x106/mL, 44.8±18% motility, morphology) WHO standards. The control cohort (n=10) underwent 12 ICSI achieving an 82.6% (57/69) fertilization rate 10/12 (83.3%) deliveries. (n=18) 24 61.4% (86/140) 5/12 (41.7%) clinical pregnancies, all resulting pregnancy loss. analysis WES indicated lower sperm aneuploidy (4.0%) versus (8.4%) (P<0.00001). Interestingly, both gene deletions associated sperm–egg fusion (ADAM3A) acrosomal development (SPACA, SPATA) identified, explaining need these couples. then categorized complete absence fertilization, poor early embryo development, implantation failure, Couples (n=3) (PLCZ1, PIWIL1, ATP2B3) indicating sperm-related oocyte-activating deficiency. Those mutations (HAUS1, KIF4A, XRN1) essential centrosome integrity spindle/microtubular stabilization. who achieve (n=7) common (IL9R) related cytokine constituents involved pathway. losses (n=5) placentation (NLRP) (TP53). Unraveling allows identification certain germline genes specific processes. While we attempted maternal cannot exclude confounding factors. helps clarify elusive factors underlying competence may aid devising best treatment options.