Fertility outcomes and predictors for successful sperm retrieval and pregnancy in 327 azoospermic men with a history of cryptorchidism who underwent microdissection testicular sperm extraction

Cryptorchidism is one of the most frequent causes of nonobstructive azoospermia (NOA) in adulthood. Although it is well known that spermatogenesis is more impaired in bilateral than in unilateral cryptorchidism, previous studies have only described small cohorts or inhomogeneous population. Consequently, we analyzed a cohort of 225 men with only a history of cryptorchidism as sole etiopathogenetic factor for NOA, and compared testicular sperm extraction (TESE) outcomes between men with bilateral versus unilateral cryptorchidism. Our results show no difference in follicle-stimulating hormone (FSH) levels and testicular volumes between men with a history of bilateral cryptorchidism compared to unilateral cryptorchidism (median: 21.3 IU l−1 vs 19.3 IU l−1, P = 0.306; and 7.2 ml vs 7.9 ml, P = 0.543, respectively). In addition, sperm retrieval rates were similar (66.2% vs 60.0%, P = 0.353). Using multivariate analysis, we have found that only a low inhibin B level (above the assay's detection limit) was positively associated with successful sperm retrieval (P < 0.05). Regarding intracytoplasmic sperm injection outcomes, we found that cumulative pregnancy rate and live birth rate per cycle were not statistically different between the two groups (17.4% vs 27.8%, P = 0.070; and 16.1% vs 26.4%, P = 0.067, respectively). Unexpectedly, there was no significant difference in hormonal profiles (FSH, luteinizing hormone [LH], testosterone, and inhibin B levels) and TESE outcomes between unilateral versus bilateral cryptorchidism. This suggests that a history of unilateral cryptorchidism could reflect a bilateral testicular impairment. Interestingly, inhibin B level might be a predictor of successful TESE.

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 (octamer-binding transcription factor 3/4 [OCT3/4], 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 months. Germ cell numbers and distributions were evaluated in cross sections of seminiferous tubules, with and without immunostaining. OCT3/4, D2-40, and LIN28 were generally expressed in the early stages of germ cell development, as shown 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.