ACCURATE prediction of sperm retrieval outcomes using a simple, non-invasive seminal plasma assay in men with non-obstructive azoospermia (NOA), according to new data presented at the 42nd Annual Meeting of the European Society of Human Reproduction and Embryology (ESHRE) in London, UK.
Men with NOA have severely impaired sperm production, meaning that surgical sperm retrieval by microdissection testicular sperm extraction (micro-TESE) often represents their only opportunity to father a biological child. However, sperm retrieval succeeds in only around 60% of cases, leaving many patients to undergo an invasive procedure without benefit.
Non-Obstructive Azoospermia Assay May Improve Patient Selection
Researchers evaluated whether a multi-omics analysis of seminal plasma could predict residual spermatogenesis before micro-TESE in 42 men with idiopathic non-obstructive azoospermia (NOA). Patients with Klinefelter syndrome, Y chromosome microdeletions, or previous chemotherapy or radiotherapy were excluded.
RNA sequencing, DNA sequencing, and proteomic profiling identified two biomarkers, TPTE2 and NEU1, that consistently distinguished patients. Nineteen men showed overexpression of both genes, while 23 had under expression. Following micro-TESE, spermatozoa were successfully retrieved from every patient with gene overexpression, whereas none of those with under expression had successful sperm retrieval.
Notably, conventional predictors, including testicular volume and serum follicle-stimulating hormone levels, did not differ between groups. Among men with successful retrieval, fertilisation was achieved in around 51% of injected oocytes, leading to a 45% clinical pregnancy rate and eight live births. Preliminary results also suggested that a rapid RNA fluorescence in situ hybridisation assay could deliver comparable findings within days rather than weeks.
Further Validation Needed Before Clinical Adoption
The author concluded: “The multi-omics approach is feasible to predict the TESE outcome. It is paramount for patient counselling to portray expectations. It is relatively inexpensive in comparison to TESE. And if our findings are verified, it would help to minimise the surgical and anaesthesia risk, as well as the procedural sequelae.”
The investigators acknowledged that validation in an independent patient cohort remains necessary and that it is not yet clear whether TPTE2 and NEU1 directly regulate spermatogenesis or simply act as biomarkers. If confirmed in larger prospective studies, the assay could offer a precision medicine approach to selecting patients for micro-TESE while avoiding unnecessary surgery.
Reference
Ng L et al. A simple assay to spare azoospermic men from an unnecessary testicular biopsy. Presentation L26-O-180. ESHRE Congress, 5–8 July, 2026.
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