Introduction. This prospective study investigated the efficacy of a gonadotropin-releasing hormone agonist (LH-RHa) in restoring defective mini-puberty. Materials and Methods. Boys with isolated bilateral cryptorchidism and defective mini-puberty were randomly divided into two groups. The “surgery only” group underwent a second orchidopexy without hormonal treatment (control). The “LH-RHa” group received LH-RHa therapy followed by a second orchidopexy. The number of Ad spermatogonia and the total germ cell count per tubule (S/T) were analyzed. Results. Five boys were included in each arm. In the LH-RHa group, the median S/T increased from 0.11 to 0.42, p=0.04. In the surgery only group, the median S/T did not change. In the surgery only group, none of the testes had Ad spermatogonia. In contrast, in the LH-RHa group, all testes completed the transition from gonocytes to Ad spermatogonia (p=0.008). Conclusions. Treatment with LH-RHa was effective in rescuing defective mini-puberty in boys with bilateral cryptorchidism.

Defective mini-puberty results in insufficient testosterone secretion that impairs the differentiation of gonocytes into dark-type (Ad) spermatogonia. The differentiation of gonocytes into Ad spermatogonia can be induced by administration of the gonadotropin-releasing hormone agonist, GnRHa (Buserelin, INN)). Nothing is known about the mechanism that underlies successful GnRHa treatment in the germ cells. Using RNA-sequencing of testicular biopsies, we recently examined RNA profiles of testes with and without GnRHa treatment. Here, we focused on the expression patterns of known gene markers for gonocytes and spermatogonia, and found that DMRTC2, PAX7, BRACHYURY/T, and TERT were associated with defective mini-puberty and were responsive to GnRHa. These results indicate novel testosterone-dependent genes and provide valuable insight into the transcriptional response to both defective mini-puberty and curative GnRHa treatment, which prevents infertility in man with one or both undescended (cryptorchid) testes.

Defective mini-puberty inducing insufficient gonadotropin secretion is one of the most common causes of nonobstructive azoospermia in men suffering from congenital isolated unilateral or bilateral cryptorchidism. The aim of our study was to determine the risk for azoospermia by histologic criteria in a cohort of unilateral cryptorchid boys undergoing orchidopexy and bilateral testicular biopsy. We performed a retrospective analysis of data available in the library of the Cryptorchidism Research Institute, Liestal, Switzerland. Complete histological evaluations were available for 319 boys operated on for unilateral cryptorchidism with simultaneous biopsy of the contralateral descended testicle. The median age was 39 (5–192) months and 58 patients were <18 months of age. Forty-eight percent of undescended testis (UDT) and 21% of contralateral testis had no A dark (Ad) spermatogonia. Furthermore, in 11% of boys Ad spermatogonia were lacking in both testes. Positive correlation was found between the spermatogonia/tubule ratio of the UDT and contralateral testis (Spearman rank order correlation is 0.16, P = .003). The extent of alteration in the UDT correlated with the contralateral descended testis, indicating that unilateral cryptorchidism is a bilateral disease. Observed impaired transition from gonocytes into Ad spermatogonia indicates defective mini-puberty, providing one of explanations for azoospermia and infertility development in unilateral cryptorchid men.

Background: Cryptorchidism is a frequent endocrinopathy in boys that has been associated with an increased risk of developing testicular cancer and infertility. The condition is curable by combined surgery and hormonal treatment during early pre-pubertal stages using gonadotropin releasing hormone agonist (GnRHa). However, whether the treatment also alters the expression of testicular long non-coding RNAs (lncRNAs) is unknown. To gain insight into the effect of GnRHa on testicular lncRNA levels, we re-analyzed an expression dataset generated from testicular biopsies obtained during orchidopexy for bilateral cryptorchidism. Results: We identified EGFR-AS1, Linc-ROR, LINC00221, LINC00261, LINC00282, LINC00293, LINC00303, LINC00898, LINC00994, LINC01121, LINC01553, and MTOR-AS1 as potentially relevant for the stimulation of cell proliferation mediated by GnRHa based on their direct or indirect association with rapidly dividing cells in normal and pathological tissues. Surgery alone failed to alter the expression of these transcripts. Conclusion: Given that lncRNAs can cooperate with chromatin-modifying enzymes to promote epigenetic regulation of genes, GnRHa treatment may act as a surrogate for mini-puberty by triggering the differentiation of Ad spermatogonia via lncRNA-mediated epigenetic effects. Our work provides additional molecular evidence that infertility and azoospermia in cryptorchidism, resulting from defective mini-puberty cannot be cured with successful orchidopexy alone.

Infantile hemangiomas (IHs) are benign lesions found in infants. Predicting the cosmetic outcome of these lesions is very difficult. Therefore, in this prospective study, we assessed whether using an infrared thermometer (IRT) to measure the surface temperature of IHs would help to predict their proliferative potential. Between January 2012 and March 2014, we prospectively investigated 103 children up to 6 months of age with a diagnosis of IH. None of them required immediate treatment. Two projection plain photographs of the IHs were obtained and the temperature of the IH surface was measured with the IRT at each visit. The IHs in these patients were divided into three groups: stable, slightly growing and growing IHs. We analyzed temperature differences between the groups, relative operating characteristic (ROC) curves, and possible application of this method to clinical practice. The median initial temperatures in the groups were 36.7°C for the stable group, 37°C for the slightly growing group, and 37.4°C for the growing group (P<0.01). The area under the ROC curve for the temperature values to predict growth was 0.929. Temperatures at or above 37.4°C showed a specificity of 95%, a sensitivity of 75%, a positive predictive value 81%, and a negative predictive value of 95%. IRT is a time and cost effective tool, and is easy to learn. The surface temperature of IH reflects its remaining growth potential and could be used in the outpatient setting for the evaluation and follow-up of IH.