Semen biomarker TEX101 predicts sperm retrieval success for men with testicular failure

Background:  Azoospermia could be due to either obstruction (obstructive azoospermia: OA) or spermatogenic failure (non-obstructive azoospermia: NOA). Close to 50% of men with NOA have small pockets of sperm in the testis which could be retrieved surgically and then injected into oocytes in a program of intra-cytoplasmic sperm insertion. Presently, there are no accepted non-invasive tests allowing clinicians to predict the success rates of sperm retrieval. Previously, we have identified a germ cell-specific protein TEX101 in semen found in the primary spermatocytes and more mature sperm forms, but not in spermatogonia, Sertoli or Leydig cells. We hypothesized that the semen concentration of TEX101 could be used to predict sperm production in men with NOA.  Methods:  This was a prospective cohort study on men with NOA being treated at a male infertility centre.   Men with NOA planning sperm retrieval provided 1–3 semen samples prior to surgery.  Semen TEX101 concentrations were measured by an in-house-developed ELISA assay and compared with the results of the surgery to retrieve sperm.   Results:  20/60 karyotypically normal men with NOA had semen TEX101 LOD, sperm was found in 50% (34-66%: 95% CI, sig diff. Fisher’s exact test, p<0.05). Conclusions:  Undetectable (<0.2 ng/mL) semen TEX101 is highly predictive of sperm retrieval failure for karyotypically normal men with NOA and is the single strongest non-invasive predictor of sperm retrieval failure reported so far. Semen TEX101 concentration will help couples decide their individual chances of successful sperm retrieval.