Successful treatment of unilateral cryptorchid boys risking infertility with LH-RH analogue

INTRODUCTION: Infertility is the primary concern for boys with uni- or bilateral undescended testes. An early and seemingly successful orchiopexy does not improve fertility in a substantial number of cryptorchid males. We confirmed that LH-RH analogue (LH-RHa) treatment induces an increase in and maturation of the germ cells; however, it was uncertain if treatment would improve the chance of fertility later in life. MATERIALS AND METHODS: Thirty unilateral cryptorchid boys, with an average age of 3 years at the time of surgery, were included in the study. Testicular biopsy showed that they had impaired testicular maturation and were therefore at high risk for infertility. Fifteen of the 30 unilateral cryptorchid boys were treated with 10 µg LH-RHa (Buserelin) nasal spray, administered on alternate days for a period of 6 months, following orchiopexy. The control group consisted of 15 cryptorchid boys who had been treated by Schoemakers type of orchiopexy, alone. After puberty, the ejaculates of both groups were analyzed. RESULTS: All males in the untreated group were severely oligospermic, with 20 percent being azoospermic. In contrast, 86 percent of the treated ex-cryptorchid males had a sperm concentration within the normal range; this was significantly different from the sperm concentration found in the untreated group (p = 0.000008). CONCLUSION: For the first time, we demonstrate that infertility in cryptorchidism can be successfully corrected when suitably treated with a LH-RHa. Sperm parameters normalized following therapy in the majority of cryptorchid males who, untreated, would have remained infertile. This innovative hormonal treatment will have a profound effect on the current recommended surgical treatment of boys with undescended testes.

Insulin 3-like hormone and its role in epididymo-testicular descent

PURPOSE: The role of insulin 3-like (Insl3) hormone signaling in the testicular descent process has been demonstrated. The purpose of the present study was to evaluate epididymal development in Insl3-deficient mice. MATERIALS AND METHODS: Heterozygous and homozygous Insl3 mutants of a mixed CD1 X 129/Sv genetic background were generated by breeding Insl3-/- females with Insl3+/- males, and their genotypes were determined by polymerase chain reaction. On the first postnatal day, newborn males were sacrificed, embedded in paraffin, and cut in 4 µm sections. Sections were stained with hematoxylin/eosin and immunoreacted with anti-± actin antibody. RESULTS: An analysis of stained sections indicated an arrest in the development of the epididymis in all homozygous mice. The cauda and corpus of the epididymis were undersized. Compared to the heterozygous epididymis, the homozygous epididymis had fewer peritubular layers and dwarfish musculature. We confirmed this with immunostaining with monoclonal antibodies against ± -smooth muscle actin. CONCLUSION: Defective development of the smooth musculature in the epididymis of Insl3 homozygous mutant mice, combined with its high intraabdominal undescended position, supports previous observations regarding the importance of intact epididymis morphology and function for descent of the epididymo-testicular unit.

Early successful orchidopexy does not prevent from developing azoospermia

INTRODUCTION: The incidence of Ad spermatogonia (stem cells for fertility) was assessed in 20 cryptorchid patients, all of whom had a successful orchidopexy in childhood but developed azoospermia following puberty. MATERIALS AND METHODS: From a cohort of 231 patients who had a semen analysis following successful orchidopexy 20 patients (9 percent) had azoospermia. The patients were classified into 2 groups according to the time of surgery: A = < 21 months of age (n = 5, mean = 10.7 ± 8.6 months) and B = during childhood (n = 15, mean = 10.1 ± 3 years). Nine of the 20 patients (45 percent) had bilateral cryptorchidism: A = 1 and B = 8. Testicular biopsies were performed during orchidopexy and analyzed with semi-thin technique. The number of Ad spermatogonia and entire number of germ cells was determined. The patients' semen analyses were evaluated at least twice; FSH and testosterone plasma values were estimated. RESULTS: In group A, all patients had germ cells at the time of surgery (mean = 1.04 ± 1.4 germ cells per tubular cross section); only 6 patients in group B (40 percent) had no germ cells (mean = 0.17 ± 0.4); A vs. B, p = 0.0133. Importantly, Ad spermatogonia were absent in the entire study population. The plasma FSH of 16 patients (80 percent) was abnormal [median = 16.35 IU/L (Interquartile range of sample - IQR 9.075-27.85 95 percent CI, 3-53)] while the plasma testosterone of all the patients was normal. CONCLUSIONS: The most severe cause of infertility in cryptorchid patients cannot be mitigated by an early successful surgery alone.