Orchiopexy: one procedure, two diagnoses - different male infertility outcomes.

ABSTRACT: Infertility, affecting one in six couples, is often related to the male partner's congenital and/or environmental conditions or complications postsurgery. This retrospective study examines the link between orchiopexy for undescended testicles (UDT) and testicular torsion (TT) in childhood and adult fertility as assessed through sperm analysis. The study involved the analysis of semen samples from 7743 patients collected at Soroka University Medical Center (Beer Sheva, Israel) between January 2009 and December 2017. Patients were classified into two groups based on sperm concentration: those with concentrations below 5 × 10 6 sperm per ml (AS group) and those above (MN group). Medical records and surgical histories were reviewed, categorizing orchiopexies by surgical approach. Among 140 individuals who had undergone pediatric surgery, 83 (59.3%) were placed in the MN group and 57 (40.7%) in the AS group. A higher likelihood of being in the MN group was observed in Jewish compared to Arab patients (75.9% vs 24.1%, P = 0.006). In cases of childhood UDT, 45 (78.9%) patients exhibited sperm concentrations below 5 × 10 6 sperm per ml ( P < 0.001), and 66 (76.7%) had undergone unilateral and 18 (20.9%) bilateral orchiopexy. Bilateral orchiopexy was significantly associated with lower sperm concentration, total motility, and progressive motility than unilateral cases ( P = 0.014, P = 0.001, and P = 0.031, respectively). Multivariate analysis identified UDT as a weak risk factor for low sperm concentration (odds ratio [OR]: 2.712, P = 0.078), with bilateral UDT further increasing this risk (OR: 6.314, P = 0.012). Jewish ethnicity and TT diagnosis were associated with a reduced risk of sperm concentrations below 5 × 10 6 sperm per ml. The findings indicate that initial diagnosis, surgical approach, and ethnicity markedly influence male fertility outcomes following pediatric orchiopexy.

Pathogenic variations in Germ Cell Nuclear Acidic Peptidase (GCNA) are associated with human male infertility.

Infertility affects one in six couples, half of which are caused by a male factor. Male infertility can be caused by both, qualitative and quantitative defects, leading to Oligo- astheno-terato-zoospermia (OAT; impairment in ejaculate sperm cell concentration, motility and morphology). Azoospermia defined as complete absence of sperm cells in the ejaculation. While hundreds of genes are involved in spermatogenesis the genetic etiology of men's infertility remains incomplete.We identified a hemizygous stop gain pathogenic variation (PV) in the X-linked Germ Cell Nuclear Acidic Peptidase (GCNA), in an Azoospermic patient by exome sequencing. Assessment of the prevalence of pathogenic variations in this gene in infertile males by exome sequence data of 11 additional unrelated patients identified a probable hemizygous causative missense PV in GCNA in a severe OAT patient. Expression of GCNA in the patients' testes biopsies and the stage of spermatogonial developmental arrest were determined by immunofluorescence and immunohistochemistry. The Azoospermic patient presented spermatogenic maturation arrest with an almost complete absence of early and late primary spermatocytes and thus the complete absence of sperm. GCNA is critical for genome integrity and its loss results in genomic instability and infertility in Drosophila, C. elegans, zebrafish, and mouse. PVs in GCNA appear to be incompatible with male fertility in humans as well: A stop-gain PV caused Azoospermia and a missense PV caused severe OAT with very low fertilization rates and no pregnancy in numerous IVF treatments.