Advocating hormonal treatment to prevent adult in-fertility in patients diagnosed with congenital un-descended testes.

In 2007 the Nordic group came to the following unanimous conclusions: In general, hormonal treatment is not recommended, considering the poor immediate results and the possible long-term adverse effects on spermatogenesis. Thus, surgery is to be preferred. However, 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 extent of alteration in the unilateral undescended testis correlate with the contralateral descended testis, indicating that unilateral cryptorchidism is a bilateral disease. Idiopathic central hypogonadism explains the phenomenon of defective mini puberty in otherwise healthy cryptorchid boys. We therefore recommend hormonal treatment for cryptorchid boys with defective mini puberty. Gonadotropin releasing hormone agonist (GnRHa) treatment following surgery to correct cryptorchidism restores mini puberty via endocrinological and transcriptional effects and prevents adult infertility in most cases. Several genes are important for central hypogonadotropic hypogonadism in mammals, including many that are transcribed in both the brain and testis. At the molecular level, there is no convincing evidence that heat shock is responsible for the observed pathological testicular changes. Thus, impaired transformation of gonocytes is not the result of temperature stress but rather a hormonal imbalance. Cryptorchidism should therefore be considered a serious andrological problem that cannot be successfully treated by early orchidopexy alone.

16 years follow-up evaluation of immediate vs delayed vs. combined hormonal therapy on fertility of patients with cryptorchidism: results of a longitudinal cohort study.

BACKGROUND: To investigate in a longitudinal cohort study, the best treatment to preserve fertility in cryptorchid subjects. Patients treated with immediate hormonal vs. delayed vs. combined (hormone plus surgery) therapy consecutively enrolled during the period 1987-1997, were evaluated. METHODS: Two hundred fifty-five subjects were enrolled and 192 patients completed the follow-upt. One hundred fifty-six patients and 36 out 192 had monolateral and bilateral cryptorchidism, respectively. Twenty-nine out of 192 were previously treated by surgery alone (Group A), 93/192 by hormone therapy alone (Group B), 51/192 received sequential combined hormone therapy plus surgery (Group C) whilst 19/192 refused any type of treatment (Group D). The other 63 patients were considered lost to follow-up. All the patients underwent medical consultation, scrotal ultrasound scan, sperm analysis and Inhibin B, Follicular Stimulating Hormone (FSH) and Testosterone (T) serum level determination. RESULTS: Testicular volume was found decreased in the Group D patients whilst hormone serum levels were comparable in all groups. Statistically significant differences for sperm characteristics were found in patients treated with hormonal therapy alone or combined with surgery (Groups B and C). These two groups reported better semen quality than patients who received surgery alone or no treatment. No differences were observed between monolateral and bilateral cryptorchidism patients. CONCLUSIONS: Early prolonged hormonal therapy is advisable in all patients with cryptorchidism independently from the surgical option of promoting testicular descent to the scrotum. Hormonal therapy provides in our study better chance to obtain adequate sperm quality in adult life.

The effect of curcumin on NRF2/Keap1 signalling pathway in the epididymis of mouse experimental cryptorchidism.

Nrf2/Keap1 pathway, which prevents cellular damage against reactive oxygen species production, is disrupted in epididymis following cryptorchidism. In this study, we aimed to use curcumin (Cur) as an activator of Nrf2 to decrease the effects of disruption in this pathway caused by cryptorchidism. In this study, animals were randomly divided into following groups: control, sham-surgery, sham-vehicle, sham-Cur50, sham-Cur100 , cryptorchidism, cryptorchidism-vehicle, cryptorchidism-Cur50 and cryptorchidism-Cur100 . For cryptorchidism induction, the left testicle was removed from the scrotum and sutured to the abdominal wall. Two weeks after surgery, Cur was given orally to animals. After 1 month, sperm parameters and testis histopathology were analysed. The expression of Nrf2, NQO1, HO1, and Keap1 genes was evaluated by real-time polymerase chain reaction. Our data showed that Cur, especially at high doses, could improve sperm parameters and testis histopathology, which were damaged following cryptorchidism induction. The expression of HO1, NQO1, and Nrf2 genes, which had decreased in the cryptorchidism group, showed a significant increase after administration of Cur in a dose-dependent manner. Cur, by inducing the expression of genes involved in the Nrf2/Keap1 pathway, could reduce the adverse effects of cryptorchidism and might be used as adjuvant therapy for decreasing cryptorchidism complications before surgery.

A pilot clinical trial with losartan in Myhre syndrome.

INTRODUCTION: Myhre syndrome (MS) is an ultra-rare disorder due to pathogenic variants in the SMAD4 gene that encodes a protein regulating the TGF-ß pathway and extra-cellular matrix (ECM) homeostasis. Main clinical features of MS include thickening of skin and joint stiffness. Previous studies showed that losartan improved ECM deposition in MS fibroblasts. MATERIALS AND METHODS: Four molecularly confirmed MS subjects (mean age 23.8 ± 17 years) were evaluated for: (a) skin thickness by Rodnan score, (b) joint range of motion (ROM) by goniometry, and (c) speckle-tracking echocardiogram. Following baseline evaluations, three MS individuals received losartan for 12 months and pre-defined endpoints were monitored after 6 and 12 months of treatment. RESULTS: At baseline, Rodnan scores were increased, joint ROM was reduced, and speckle-tracking echocardiogram revealed reduced myocardial strain. In three MS subjects, improvements in skin thickness, joint ROM and to a lesser extent of myocardial strain, were observed after 6 and 12 months of losartan treatment. CONCLUSIONS: Although further long-term controlled clinical trials with a larger number of affected individuals are needed, the present study suggests that losartan might improve skin, joint and heart abnormalities of MS.

Metabolomics analysis reveals metabolic changes associated with trans-resveratrol treatment in experimental cryptorchidism mice.

This study aimed to analyse global metabolomic changes associated with trans-resveratrol (RSV) treatment in mice with cryptorchidism using untargeted metabolomics. Cryptorchidism was established surgically in Kunming mice, which were then treated with 20µg g-1 day-1, s.c., RSV for 35 consecutive days. Typical manifestations of spermatogenesis arrest were seen in mice with cryptorchidism, and RSV treatment for 35 days restored spermatogenesis. Liquid chromatography-tandem mass spectrometry was used to profile the metabolome of testes from mice in the control (non-cryptorchid, untreated), cryptorchid and RSV-treated cryptorchid groups. In all, 1386 and 179 differential metabolites were detected in the positive and negative modes respectively. Seven and six potential biomarkers were screened for spermatogenesis arrest and restoration respectively. Pathway analysis showed changes in 197 metabolic pathways. The hexosamine biosynthesis pathway was inhibited in the cryptorchid group, which probably resulted in a decrease in the end product, uridine diphosphate N-acetylglucosamine (UDP-GlcNAc). Immunoblot analysis showed that total testicular protein O-linked ß-N-acetylglucosamine glycosylation was related to spermatogenesis arrest, further indicating a decrease in UDP-GlcNAc in the cryptorchid group. Thus, untargeted metabolomics revealed the biochemical pathways associated with the restoration of metabolic status in the cryptorchid group following RSV treatment and the findings could be used to monitor the response to RSV treatment. This study provides a meaningful foundation for the future clinical application of RSV in the treatment of spermatogenesis dysfunction.

Antagonistic Effect of Cuscuta chinensis on a Rat Model with Unilateral Cryptorchidism.

BACKGROUND The aim of this study was to investigate the effect of Cuscuta chinensis Lam. on germ cell apoptosis in a rat model of unilateral cryptorchidism. MATERIAL AND METHODS Thirty male SD rats were randomly and equally divided into a control group, a model group, and a Cuscuta group (5.0 g/kg/d) (n=10). The rat model of unilateral cryptorchidism in the model and Cuscuta groups was established by removal of the right gubernaculum, while rats in the control group received no treatment. After modeling, rats in the Cuscuta chinensis group were intragastrically administered Cuscuta chinensis extract (5.0 g/kg/d), while rats in the control group and model group were administered an equal volume of normal saline. After 90 days, all the rats were sacrificed and the testicles were separated and weighed, followed by TUNEL staining to detect germ cell apoptosis, flow cytometry to measure JC-1, ROS, and MDA, and Western blot analysis to evaluate the expression of Bax, Bcl-2, and cleaved caspase3. RESULTS Ninety days after the operation, Cuscuta chinensis Lam significantly minimized the damage caused by modeling by increasing weight of testis, reducing the germ cell apoptosis, and enhancing the mitochondrial membrane potential of testicles, as shown by levels of JC-1, ROS, and MDA, as well as elevating the level of Bcl-2/Bax and reducing the level of cleaved caspase3 (P<0.05). CONCLUSIONS Treatment with Cuscuta chinensis Lam reduced the germ cell apoptosis in rats with unilateral cryptorchidism, which provides new insight for the development of cryptorchidism therapy in the future.

Efficacy and safety of human chorionic gonadotropin for treatment of cryptorchidism: A meta-analysis of randomised controlled trials.

AIM: Although human chorionic gonadotropin (hCG) has long been employed in the management of cryptorchidism, its safety and efficacy is still controversial. Hence, in the present study, we conducted a meta-analysis of the treatment of cryptorchidism using hCG. METHODS: We searched the Medline, Embase, CINAHL, EBSCO, The Cochrane Library, China National Knowledge Infrastructure and WanFang databases. Data were extracted by two reviewers using the designed extraction form. Data up to July 2015 were obtained using the terms 'cryptorchidism', 'chorionic gonadotropin' and 'randomised controlled trials'. All the publications were downloaded, and the respective authors were contacted for any further details and clarifications, if deemed necessary. The data analysis included randomised controlled trials that compared hCG with other hormone treatments offered to prepubescent males presenting with cryptorchidism. Testicular descent rate was used as the final positive outcome of the treatments offered. The software Review Manager (RevMan 5.3, The Cochrane Collaboration, London, UK) was used to review the management and data analysis. Risk ratios (RRs) with 95% confidence intervals (CIs) were pooled with a fixed effect model if no heterogeneity was present. RESULTS: A total of seven trials satisfied the selection criteria. The overall quality of the studies downloaded from various databases was low. Data from these seven studies were divided into three subgroups depending on the design of the trials: Two studies compared hCG with a placebo, and three studies compared hCG with gonadotropin-releasing hormone (GnRH) in unilateral cryptorchidism, whereas two other studies compared hCG with GnRH in bilateral cryptorchidism. Analysis of these trials revealed no significant differences between the effectiveness of hCG treatment and GnRH treatment in bilateral (RR 0.05, 95% CI (-0.29-0.40), two trials, n = 104, P = 0.76) as well as unilateral cryptorchidism (RR 0.04, 95% CI (-0.12, 0.21), three trials, n = 81, P = 0.61). A meta-analysis of these studies showed that hCG treatment is not superior to placebo (RR 7.74, 95% CI (0.14-425.72), two trials, n = 31, P = 0.32). CONCLUSION: A meta-analysis of the seven studies led us to conclude that hCG treatment is no more effective than placebo, and there were no significant differences in the effectiveness of hCG versus GnRH treatment.

Genes Involved in Long-Term Memory Are Expressed in Testis of Cryptorchid Boys and Respond to GnRHa Treatment.

It has been known for many years that boys with unilateral or bilateral undescended testis (cryptorchidism) tend to have a low IQ, and those who belong to the high infertility risk (HIR) group perform less well at school than low infertility risk (LIR) patients. However, the molecular biological processes underlying this phenomenon are not understood. In this study, we report the outcome of testicular RNA profiling for genes involved in long-term memory formation. We analyzed the histology and the transcriptome of testicular biopsies from bilateral HIR cryptorchid boys, comparing those who received GnRHa treatment for 6 months after the first surgery with those who did not receive GnRHa before the second surgery. We found that GnRHa treatment alters the testicular mRNA levels of neuronal genes that are involved in long-term memory and testosterone synthesis. These data highlight a possible molecular link between cryptorchidism, impaired mini-puberty, and diminished cognitive functions. Our results are consistent with the hypothesis that hypogonadotropic hypogonadism in cryptorchid boys with altered mini-puberty may affect neuronal genes important for memory and learning, which could help explaining the negative correlation between cryptorchidism and intellectual abilities.

The Effectiveness of hCG and LHRH in Boys with Cryptorchidism: A Meta-Analysis of Randomized Controlled Trials.

To systematically review the efficacy of hCG and LHRH on testicular descent in boys with cryptorchidism, comprehensive search was performed to identify randomized controlled trials (RCTs) in PubMed, EMBASE, the Cochrane Library, Wanfang Database, and China National Knowledge Infrastructure (CNKI) up to March 2014. Outcomes included testicular complete descent rate (TCDR) and cure rate of patients. Study quality was evaluated using the Jadad scale. Meta-analysis was performed using Review Manager software. Finally, 13 studies were included. hCG and LHRH increased TCDR comparing with control group. The success rate of hCG and LHRH was 24 and 19%, respectively. Further, hCG and LHRH had significant effect on bilateral cryptorchidism, but not on unilateral cryptorchidism. All side effects were transitory and not severe, but if they have long-term harms were not clear. hCG and LHRH can effectively increase TCDR and there was no significant difference between them. However, the hormones cannot be recommended for everyone because of their low success rates and potential long-term harms. Further studies are needed to determine the efficacy of hormonal treatment for subtypes of cryptorchidism.

Effect of resveratrol on restoring spermatogenesis in experimental cryptorchid mice and analysis of related differentially expressed proteins.

The present study aimed to evaluate the effect of trans-Resveratrol on spermatogenesis. Male Kunming suckling mice (10 days old) were surgically rendered cryptorchid and subcutaneously injected with trans-Resveratrol at doses of 5, 10, 20, and 40 µg/g/day as groups I, II, III, and IV, respectively, for 35 days. Animals in the control group received 10 µL/mouse/day of olive oil. Serum estradiol, testosterone, FSH, and LH levels were measured on day 45. Tissue analysis and sperm morphological abnormalities analysis were done. Results showed that in the control group and group I only spermatogonia and primary spermatocytes were present, whereas spermatogenesis was totally restored in groups II, III, and IV. Sperm counts in groups III and IV were remarkably higher than the control group (P<0.05). The morphological abnormalities in resveratrol-treated groups were higher than the mature mice. Serum estradiol levels in the resveratrol-treated groups were not significantly different from the control group, but were lower than the mature mice (P<0.05). There was no significant difference in serum testosterone levels between the resveratrol-treated groups and mature mice, but the levels in the resveratrol-treated groups was significantly lower than the control group (P<0.05). No significant influence of trans-Resveratrol was observed on serum FSH levels in all cryptorchid mice. Serum LH levels in groups I, II, and III were higher than the control group. These results indicate that trans-Resveratrol restores spermatogenesis in cryptorchid mice. In addition, proteomic analysis between the 20 µg/g/day resveratrol-treated group and the control group was carried out, and five kinds of proteins (BAF250, ZFP261, CHD1L, RBBP9, and SOHLH2) were identified. The expression of SOHLH2 increased, while that of BAF250, ZFP261, CHD1L, and RBBP9 decreased in the 20 µg/g/day resveratrol-treated group, indicating that SOHLH2 may contribute to testicular germ cell differentiation.

Undescended testicle: An update on fertility in cryptorchid men.

Cryptorchidism or undescended testis is one of the most common anomalies encountered in paediatric urology and is estimated to affect 1 to 4 per cent of full term and upto 30 per cent of preterm male neonates. The associated problems of sub-fertility or infertility and malignant transformation have been recognized for long. Fertility is impaired after both unilateral and bilateral cryptorchidism. The reported paternity rates in adults are about two-third for unilateral undescended testis and less than one-third for bilateral disease. Over the last five decades, the concepts related to cryptorchidism have changed dramatically as knowledge about its effects has accrued from research conducted worldwide. The recommended age of orchidopexy has fallen progressively from adolescence to less than one year. The realization that the infantile testes are not in a state of 'suspended animation' and the recognition of the defect in the androgen dependent transformation of gonocytes into adult dark spermatogonia in cryptorchidism have been recognized as the primary cause of sub-fertility in these patients. This has paved the way for hormone therapy in an attempt to simulate the 'post-natal gonadotropin surge' or 'mini-puberty'. This review summarizes the current knowledge about the various factors affecting the fertility status in cryptorchidism with a particular focus on the derangements in the development and maturation of the germ cells and the role of surgery, hormone therapy and antioxidants in reversing these changes.

Cryptorchidism: a clinical perspective.

Incomplete descent of the testes is the most common genital anomaly in newborn boys. The prevalence varies with apparent geographical differences. The etiology of cryptorchidism is considered to be multifactorial (genetic, maternal, and environmental factors), and it occurs most often as an isolated disorder with no obvious cause. Cryptorchidism should not be left untreated, since there is an increased risk of developing testicular cancer and infertility/subfertility. However, the mode and timing of treatment, as well as the risks of subfertility and testicular cancer have long been controversial. There is increasing evidence that treatment should be performed early in life. Randomized volumetric and histological studies have shown that early treatment before the age of one year is beneficial for testicular development and future spermatogenesis compared to later treatment. It remains to be proven that this difference persists into adulthood. Due to the low efficacy rate and the possible adverse effects of hormonal treatment, surgery is preferred. The exact optimal time for orchidopexy is not known, but it should probably be before one year of age, at centers with expertise in pediatric anesthesiology and pediatric surgery/urology. The risk of testicular cancer is also reduced if orchidopexy is performed before puberty; however it remains to be proven if treatment in early infancy reduces the risk even further.

Recurrent pericarditis in Myhre syndrome.

Myhre syndrome is a rare disorder characterized by pre- and postnatal short stature, brachydactyly, facial dysmorphism (short palpebral fissures, maxillary hypoplasia, prognathism and short philtrum), thick skin, muscular-appearing body build, decreased joint mobility, mixed hearing loss, and cleft lip and palate. Other clinical features include skeletal dysplasia, developmental delay with intellectual disability and/or behavioral disturbance, cardiac defects, cryptorchidism, and bone anomalies. The disease is caused by recently identified SMAD4 mutations. Here we describe a 7-year-old boy with a molecularly proven Myhre syndrome who presented life-threatening recurrent pericarditis and systemic inflammatory symptoms that required treatment with steroid and recombinant interleukin-1 receptor antagonist.

The controversy regarding the need for hormonal treatment in boys with unilateral cryptorchidism goes on: a review of the literature.

Hormonal treatment for unilateral undescended testes continues to be recommended in some countries. We reviewed the literature in favor and against this recommendation. Since the paternity rate of men with a history of unilateral undescended testes only treated with surgery is normal, the effectiveness of hormonal treatment to produce testicular descent is low, the cost is considerable, and there are potential adverse effects, hormonal treatment for boys with unilateral undescended testes should no longer be recommended.

Low-dose every-second-day LHRH treatment following bilateral orchidopexy in children with bilateral cryptorchidism may improve their fertility outcome.

INTRODUCTION/BACKGROUND: Currently the standard treatment for bilateral cryptorchidism is bilateral surgical orchidopexy. Whether a hormonal treatment should be routinely administered postoperatively to increase fertility is debatable. Low-dose postoperative luteinizing hormone releasing hormone (LHRH) can increase spermatogonial numbers, but the effect of native LHRH (Kryptocur®) on adult fertility is unclear. OBJECTIVE: To determine if low-dose every-second-day postoperative LHRH administration in children with bilateral cryptorchidism improves fertility in adulthood and if Nistal testicular histological grading could guide the decision to administer LHRH. STUDY DESIGN METHODS: All patients, actually at least 16yr of age, that underwent a bilateral orchidolysis and orchidopexy for bilateral cryptorchidism (surgery between 1997 and 2018) were contacted and offered a clinical exam, hormone levels, sperm analysis, and a scrotal ultrasound. At the original surgery, testicular biopsy was performed (if 60% of the tubuli contain >1 spermatogonia, this is normal = Nistal-1, if 30-60% filled = Nistal-2, if <30% = Nistal-3 and if Sertoli only = Nistal-4) and if in at least one testis impaired. A low dose native LHRH treatment was offered to the patients, as this treatment is known to increase the number of spermatogonia in a short term. Kryptocur® (LHRH, Gonadorelin, Hoechst®) was prescribed and dosed at 200 µg (one spray in one nostril) every other day for 6-8 months. RESULTS AND LIMITATIONS: Forty-two men were eligible for this study. 20/42 accepted the invitation for a clinical and hormonal evaluation. 16/20 men accepted the invitation for an additional sperm analysis. Fourteen of 20 men received low-dose LHRH postoperatively in a nonrandomized manner. Three men had Nistal grade 1, eight grade 2, seven grade 3, and two had grade 4. Inhibin B levels were higher in men with Nistal 1 and 2 compared with Nistal 3 and 4 P ≤ 0.037). Severe oligospermia/azoospermia (<1 × 106/ejaculate) was observed in 33% of the treated group vs 67% of the untreated group (P ≤ 0.036.) DISCUSSION AND CONCLUSIONS: Low-dose every-second-day postoperative LHRH treatment improves fertility outcome in bilateral cryptorchidism. Histological analysis of prepubertal testes according to Nistal grading cannot be used as a predictive diagnostic test for LHRH treatment.

Hormonal therapy is effective and safe for cryptorchidism caused by idiopathic hypogonadotropic hypogonadism in adult males.

Background: Hormonal therapy is a reasonable treatment for cryptorchidism caused by idiopathic hypogonadotropic hypogonadism (IHH). However, the clinical evidence on whether it is effective and safe for the treatment of cryptorchidism caused by IHH is lacking. Aim: To evaluate the effect of hormonal therapy in testicular descent, puberty development, and spermatogenesis in adult males with cryptorchidism caused by IHH. Methods: This retrospective study included 51 patients with cryptorchidism caused by IHH from the Andrology Clinic of University affiliated teaching hospital. Patients were divided into two groups: group A patients received hormonal therapy; group B patients received surgical treatment for cryptorchidism followed by hormonal therapy. Results: The rate of successful testicular descent following hormonal therapy (19/32 in group A) or surgical treatment (11/19 in group B) shows no statistically significant difference. There was also no statistically significant difference in penile length, Tanner stage of pubic hair, testicular volume, and success rate of spermatogenesis between the two groups. Testicular atrophy was seen in a single patient in group B. Conclusions: Hormone therapy in adult males with cryptorchidism caused by IHH is effective and safe regarding testicular descent, puberty development, and spermatogenesis. This study provides new insight into the treatment of cryptorchidism caused by IHH and highlights that hormonal therapy could be an effective, safe, and economic treatment option for cryptorchidism in males caused by IHH.

Current concepts surrounding neonatal hormone therapy for boys with congenital hypogonadotropic hypogonadism.

INTRODUCTION: Congenital hypogonadotropic hypogonadism (CHH) is a genetic disorder of reproduction and development, characterized by deficient gonadotropin-releasing hormone (GnRH) secretion or action, affecting 1-in-4,000-15,000 males. Micropenis and undescended testes are cardinal features of antenatal GnRH deficiency and could indicate absent minipuberty in the first postnatal months. In this review, we outline the pathophysiology and clinical consequences of absent minipuberty and its implications for optimal approaches to the endocrine management of affected boys. AREAS COVERED: Deficient GnRH activity during fetal development and neonatal-infancy phase of minipuberty accounts for the diminished mass of Sertoli cells and seminiferous tubules among CHH males, enduring impairment of reproductive function even during gonadotropin replacement in adult life. In overcoming this obstacle, several clinical studies of neonatal gonadotropin replacement have consistently shown positive results in inducing testicular development and correcting cryptorchidism. EXPERT OPINION: A high index of clinical suspicion, combined with hormonal testing undertaken in the postnatal period of 1-4 months, can reliably confirm or refute the diagnosis of CHH. Timely identification of CHH in affected male infants (having characteristic "red flag' developmental anomalies) opens up the possibility for gonadotropin replacement as a targeted therapy to restore the normal hormonal milieu of minipuberty. Further work is necessary in formulating optimal gonadotropin treatment regimens to be more widely adopted in clinical practice.

The safety of neoadjuvant hormonal treatment in infants with cryptorchidism.

BACKGROUND/PURPOSE: The standard treatment for boys with non-syndromic cryptorchidism is an early orchidopexy. It is unclear if surgical intervention alone is enough for future fertility. Recent studies show benefit of neoadjuvant or adjuvant hormonal treatment with gonadorelin (GnRH) for spermatogonia maturation based on testicular biopsy. The aim of this prospective study was to assess the safety of this treatment in infants with undescended testis at the recommended timing of early gonadorelin administration and timing of orchidopexy. METHODS: Unilateral cryptorchid full term boys were initially examined (including hormonal, physical and ultrasound examination) at the age of 2.5-3.5 months. At 6 months of age, cryptorchidism was confirmed. Those with non-syndromic cryptorchidism and palpable or sonographically detected testis were randomly assigned into two groups: with and without intranasal gonadorelin treatment. Inclusion criteria were met by 36 boys (21 in GNRH and 15 in the control groups). The following orchidopexy was performed before 12 months of age with repeated examination at time of surgery. Penile size and testicular volume (using ultrasound) and basal serum levels of LH, FSH, testosterone, Inhibin B and AMH were recorded at age of 3.0 (mean) months and 11.0 (mean) months (date of surgery). The stimulation hormonal levels were checked during GnRH administration. RESULTS: Between minipuberty (mean 3 months) and time of orchidopexy (mean 11 months of age) the penile size increased significantly and similarly in both groups. There was no significant difference in the change of the volume of descended testis between the groups nor of the volume of undescended testis. In addition, we did not find any significant difference in the change (drop) of hormonal levels of LH, FSH, Testosterone, Inhibin B and AMH (Table 1a) CONCLUSION: The neoadjuvant gonadorelin stimulation in infants with unilateral undescended testis has not shown any specific effect on the development of penile size, testicular volume and hormonal levels at time of orchidopexy in comparison with boys without stimulation, and in the mid-term, this treatment can be considered safe. Further follow-up is necessary to evaluate the long-term effect of this early treatment.