Testis tissue cryopreservation may be considered in boys with cryptorchidism

This study assessed the feasibility of testis tissue cryopreservation (TTC) for fertility preservation in prepubescent boys with cryptorchidism. From January 2014 to December 2022, the University Hospital of Copenhagen (Rigshospitalet, Copenhagen, Denmark) implemented TTC for 56 boys with cryptorchidism to preserve their reproductive potential. Testis tissue samples were collected during orchiopexy (32 cases) or at subsequent follow-up procedures (24 cases), necessitated by an increased risk of infertility as indicated by hormonal assessments and/or findings from initial surgical biopsies. Testis samples were procured for TTC and pathological analysis. The cohort had an average age of 1.3 (range: 0.3–3.8) years at the time of orchiopexy, with 91.1% presenting bilateral cryptorchidism. The study revealed a median germ cell count of 0.39 (range: 0–2.88) per seminiferous tubule, with germ cells detected in 98.0% of the bilateral biopsies and 100% of the unilateral, indicating a substantial potential for fertility in these immature tissues. A dark spermatogonia (Ad) was detected in 37 out of 56 patients evaluated, with a median Ad spermatogonia count of 0.027 (range: 0.002–0.158) per seminiferous tubule. A total of 30.2% of the samples lacked Ad spermatogonia, indicative of potential gonadotrophin insufficiency. The median hormone levels measured were as follows: follicle-stimulating hormone (FSH) at 0.69 (range: 0.16–2.5) U l−1, luteinizing hormone (LH) at 0.21 (range: 0.05–3.86) U l−1, and inhibin B at 126 (range: 17–300) pg ml−1. Despite early orchiopexy, 20%–25% of boys with cryptorchidism remain at risk for future infertility, substantiating the necessity of TTC as a precaution. The study highlights the need for refined predictive techniques to identify boys at higher risk of future infertility.

Postnatal germ cell development in cryptorchid boys

Cryptorchidism is associated with infertility in adulthood.Early orchiopexy is suggested to reduce the risk.Information is lacking on the potential link between infant germ cell maturation and the risk of future infertility.The objective of the study was to evaluate age-related germ cell development in cryptorchidism.Immunostaining for markers of germ cell development(octamerbinding transcription factor 3/4[0CT3/4],placental alkaline phosphatase[PLAP],KIT proto-oncogene[C-KIT],podoplanin[D2-40],Lin-28 homolog A[LIN28],and G antigen 7[GAGE-7])was performed in testicular biopsies from 40 cryptorchid boys aged 4-35 mon ths.Germ cell nu mbers and distributi ons were evaluated in cross sectio ns of semi niferous tubules,with and without immuno staini ng.OCT3/4,D2-40,and LIN 28 were gen erally expressed in the early stages of germ cell development,as show n by positive expression in germ cells in the central region of seminiferous tubules・In contrast,PLAP and GAGE-7 were expressed in both central and peripheral parts of the tubules in the early stages of development and expressed mainly in a peripheral position with advancing age.Germ cell maturation was delayed in this study population as compared with that observed in our previous study on germ cell markers in a healthy population.The number of GAGE-7-positive germ cells per tubular cross section obtained by immunostaining was significantly higher than that obtained by standard hematoxylin and eosin staining.Double immunostaining revealed heterogeneity in germ cell development in cryptorchid testes.These results shed light on the pathophysiology of germ cell development in boys with cryptorchidism.