Abstract
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 (<0.2ng/mL). Of these, 0% had successful sperm retrieval(0-17%: 95% CI) . In contrast, of the 40 men with 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.
Highlights
Of men with infertility, ~ 20% have azoospermia or no sperm in the ejaculate, with the majority (49–93%) of these men having spermatogenic failure (non-obstructive azoospermia (NOA))
In previous work from our laboratory, using liquid chromatography-tandem mass spectrometry (LC-MS/MS), we identified two seminal proteins, epididymis-specific protein ECM1 and germ cell-specific protein TEX101 that were able to differentiate obstructive versus non-obstructive azoospermia with 100% specificity and 81% sensitivity.[22,23,24,25,26,27]
Men who were eligible for the study who were planning on proceeding with sperm retrieval were approached to enter the study
Summary
Of men with infertility, ~ 20% have azoospermia or no sperm in the ejaculate, with the majority (49–93%) of these men having spermatogenic failure (non-obstructive azoospermia (NOA)). The advent of the era of intra-cytoplasmic sperm insertion (ICSI) with the capacity to inject a single sperm into an oocyte opened the door for successful therapies for men with very low sperm counts. This revolutionary therapy for couples with infertility was extended to treat men with azoospermia, with sperm retrieved from the testis/ epididymis/vas deferens being successfully used for ICSI.[6,7,8,9,10] Testicular sperm extraction for men with NOA is used world-wide with reported successful sperm retrieval rates of 30–70% and ICSI pregnancy rates between 19–50%.8,10–16. Results: 20/60 karyotypically normal men with NOA had semen TEX101 < LOD
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