Recombinant Human FSH Treatment Outcomes in Five Boys With Severe Congenital Hypogonadotropic Hypogonadism

Context Recombinant human FSH (r-hFSH), given to prepubertal boys with hypogonadotropic hypogonadism (HH), may induce Sertoli cell proliferation and thereby increase sperm-producing capacity later in life. Objective To evaluate the effects of r-hFSH, human chorionic gonadotropin (hCG), and testosterone (T) in such patients. Design and Setting Retrospective review in three tertiary centers in Finland between 2006 and 2016. Patients Five boys: ANOS1 mutation in two, homozygous PROKR2 mutation in one, FGFR1 mutation in one, and homozygous GNRHR mutation in one. Prepubertal testicular volume (TV) varied between 0.3 and 2.3 mL; three boys had micropenis, three had undergone orchidopexy. Interventions Two boys received r-hFSH (6 to 7 months) followed by r-hFSH plus hCG (33 to 34 months); one received T (6 months), then r-hFSH plus T (29 months) followed by hCG (25 months); two received T (3 months) followed by r-hFSH (7 months) or r-hFSH plus T (8 months). Main Outcome Measures TV, inhibin B, anti-Müllerian hormone, T, puberty, sperm count. Results r-hFSH doubled TV (from a mean ± SD of 0.9 ± 0.9 mL to 1.9 ± 1.7 mL; P < 0.05) and increased serum inhibin B (from 15 ± 5 ng/L to 85 ± 40 ng/L; P < 0.05). hCG further increased TV (from 2.1 ± 2.3 mL to 8.6 ± 1.7 mL). Two boys with initially extremely small testis size (0.3 mL) developed sperm (maximal sperm count range, 2.8 to 13.8 million/mL), which was cryopreserved. Conclusions Spermatogenesis can be induced with gonadotropins even in boys with HH who have extremely small testes, and despite low-dose T treatment given in early puberty. Induction of puberty with gonadotropins allows preservation of fertility.

Variation in testis weight of the Tibetan toad Scutiger boulengeri along a narrow altitudinal gradient

Life-history theory predicts that organisms inhabiting harsh environments such as high altitudes should invest less in reproduction and more in survival. Testis size is associated with the intensity of male-male competition for mating and thus may be treated as an indicator of male reproductive investment. Hence, it may be expected that organisms will reduce their testis size with increasingly harsh environments. Here we test this prediction in a toad species, Scutiger boulengeri, endemic to the Tibetan plateau using data from three populations located at altitudes of 4078, 4276, and 4387 m. Consistent with the prediction, male toads exhibited smaller testes at higher altitudes, despite the relatively narrow altitudinal span. It is likely that cold climates and strong seasonality constrain the ability of high-altitude male toads to allocate more energy into reproduction, thereby leading to small testis size. In addition, the left testis was significantly heavier than the right one and the degree of size asymmetry was unrelated to either altitude or body condition.

Testicular sparing surgery in small testis masses: A multinstitutional experience

Introduction: The incidence of benign testicular tumors is increasing in particular in small lesion incidentally found at scrotal ultrasonography. Primary aim of this study was to perform radical surgery in malignant tumor. Secondary aim was to verify the efficacy of the diagnostic-therapeutic pathway recently adopted in management of small masses with testis sparing surgery in benign lesions. Materials and methods: In this multicenter study, we reviewed all patients with single testis lesion less than 15 mm at ultrasound as main diameter. We applied the diagnostic-therapeutic pathway described by Sbrollini et al. (Arch Ital Urol Androl 2014; 86:397) which comprises: 1) testicular tumor markers, 2) repeated scrotal ultrasound at the tertiary center, 3) surgical exploration with inguinal approach, intraoperative ultrasound, and intraoperative pathological examination. Definitive histology was reviewed by a dedicated uro-pathologist. Results: Twenty-eight patients completed this clinical flowchart. The mean lesion size was 9.3 mm (range 2.5-15). Testicular tumor markers were normal except in a case. Intraoperative ultrasound was necessary in 8/28 cases. We treated 11/28 (39.3%) with immediate radical orchiectomy and 17/28 (60.7%) with testis-sparing surgery. Definitive pathological results were: malignant tumor in 6 cases (seminoma), benign tumor in 10 cases (5 Leydig tumors, 2 Sertoli tumors, 1 epidermoid cyst, 1 adenomatoid tumor, 1 angiofibroma), benign disease in 11 (8 inflammation with haemorragic infiltration, 2 tubular atrophy, 1 fibrosis), and normal parenchyma in 1 case. We observed a good concordance between frozen section examination and definitive histology. Any malignant tumor was treated conservatively. Any delayed orchiectomy was necessary based on definitive histology. Conclusions: The incidence of benign lesions in 60% of small testis lesions with normal tumor markers makes orchiectomy an overtreatment. Testicular sparing surgery of single testicular nodules below 15 mm is a safe option, but requires a standardized pathway in diagnosis. Our pathway has shown good reliability and security profile to be applied in a multicenter management for small scrotal masses. Our study has shown the reliability of the diagnostic-therapeutic pathway in the management of single testicular masses. The higher incidence of benign lesions in 60% of patients makes often orchiectomy an overtreatment.

Diagnostic-therapeutic pathway for small lesions of the testis

Objective of our study was to define a diagnostic-therapeutic pathway for proper treatment of not-palpable testicular masses, that may be benign in 38% of cases. Since the intraoperative diagnosis is difficult to reach in particular in small lesion (< 8 mm) and the risk of tissue loss in frozen section analysis occurs frequently, we propose a diagnostic flow chart for the best management of small testis lesions. This proposed protocol has to be shown in details to physicians and patients, who must understand the clinical implications and the risk to undergo a second radical surgery.

Novel DMRT1 3'UTR+11insT mutation associated to XY partial gonadal dysgenesis

The Y-chromosome-located SRY gene encodes a small testis-specific protein containing a DNA-binding motif known as the HMG (high mobility group) box. However, mutations in SRY are not frequent especially in cases of 46,XY partial gonadal dysgenesis. Several sex-determining genes direct the fate of the bipotential gonad to either testis or ovary. In addition, heterozygous small deletions in 9p can cause complete and partial XY gonadal dysgenesis without other symptoms. Human DMRT1 gene, which is located at 9p24.3, is expressed in testis and ovary and has been considered, among others, a candidate autosomal gene responsible for gonadal dysgenesis. In this report we describe a nucleotide insertion in DMRT1 3'UTR in a patient of XY partial gonadal dygenesis. The 3'UTR+11insT is located within a conserved motif important for mRNA stabilization.