Beyond Leukocyte-Rich Versus Leukocyte-Poor PRP: A Precision Framework for Male Infertility

Platelet-rich plasma (PRP) is being investigated for direct sperm exposure, cryopreservation, and intratesticular treatment, but nominal concentration does not identify the delivered cellular and plasma product. We critically searched PubMed/MEDLINE from inception to 24 September 2026 and screened 115 records, identifying 18 original human reports: 14 ex vivo direct-contact, cryopreservation, or derivative-product studies and four intratesticular studies. Small split-sample experiments report study-specific signals in motility, viability, redox, mitochondrial, and post-thaw endpoints, whereas one healthy-donor dose-ranging study found no benefit. A 2026 randomized trial in 160 men with oligoasthenoteratozoospermia reported adjusted improvements in several semen and hormonal outcomes after intratesticular PRP but contained reporting inconsistencies and did not assess pregnancy or live birth; an uncontrolled non-obstructive-azoospermia cohort achieved sperm retrieval in 4/25 men after PRP and repeat microdissection testicular sperm extraction. Human sperm–neutrophil experiments support quantifying and minimizing neutrophil carryover during direct-contact research but do not establish a clinical depletion threshold. PBMC-mediated Nrf2, AMPK–PGC-1α, macrophage, Treg, telomere, or DNA-repair effects have not been demonstrated in human sperm under the conditions studied. We therefore propose a hypothesis-generating product vector based on delivered platelet and leukocyte-subset doses, erythrocyte burden, plasma/fibrinogen, activation or lysis, residual particles, physicochemical compatibility, exposure, and washout. This is a research-reporting framework, not a validated classification or clinical algorithm; effectiveness requires outcome-linked validation through cumulative live birth and offspring safety.