Associations between congenital cryptorchidism in newborn boys and levels of dioxins and PCBs in placenta

In animal studies, exposure to dioxins has been associated with disrupted development of the male reproductive system, including testicular maldescent. Some polychlorinated biphenyls (PCBs) have also dioxin-like effects. In addition, one previous case-control study has reported an association between congenital cryptorchidism and colostrum PCB levels. We performed a case-control study to evaluate whether congenital cryptorchidism in boys was associated with increased levels of dioxins or PCBs in placenta reflecting foetal exposure. In addition, associations between placenta levels of these chemicals and reproductive hormone levels in boys at 3 months were studied. Placentas were collected in a Danish-Finnish joint prospective cohort study on cryptorchidism (1997-2001). The boys were examined for cryptorchidism at birth and at 3 months. Altogether, 280 placentas [112 Finnish (56 cases, 56 controls) and 168 Danish (39 cases, 129 controls)] were analysed for 17 toxic polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and 37 PCBs (including 12 dioxin-like PCBs). Infant serum samples taken at 3 months were analysed for reproductive hormones. No significant differences between cases and controls were observed in either country in dioxin WHO-TEq levels (median 9.78 vs. 8.47 pg/g fat, respectively, in Finland, and 11.75 vs. 10.88 pg/g fat in Denmark) or PCB WHO-TEq levels (median 2.12 vs. 2.15 pg/g fat in Finland, 2.34 vs. 2.10 pg/g fat in Denmark) or total-TEq levels (median 11.66 vs. 10.58 pg/g fat in Finland, 13.94 vs. 13.00 pg/g fat in Denmark). Placenta WHO-TEq levels of dioxins were not associated with infant reproductive hormone levels at 3 months. In Finland, PCB WHO-TEq levels in placenta associated positively with infant LH levels. WHO-TEq levels of dioxins and PCBs and total-TEq levels were higher in Danish than Finnish samples. In conclusion, no association between placenta levels of dioxins or PCBs and congenital cryptorchidism was found. Significant country differences in chemical levels were observed.     

Acquired cryptorchidism is frequent in infancy and childhood

Accurate prevalence data for acquired cryptorchidism are currently sparse and systematic prospective studies have not yet been reported. Our aim was to determine the prevalence of testicular ascent in childhood. In a prospective longitudinal population-based child cohort from Copenhagen, Denmark (1997–2007), testicular position was examined according to a standardised protocol in a total of 1072 boys, at birth ( n  = 1051), at 3 months ( n  = 983), 18 months ( n  = 888), 36 months ( n  = 790) and again once between 4½ and 10 years of age ( n  = 509). Ascensus testis was defined as ascent of the testis into a cryptorchid position after normal scrotal position at birth. A congenital cryptorchid testis with spontaneous postnatal descent followed by recurrence of cryptorchidism was named recurrent cryptorchidism. Ascensus testis occurred in 0.2%, 0.6% and 0.6% of boys at 3, 18 and 36 months of age respectively. When including recurrent cryptorchidism the prevalence was 0.2%, 1.2% and 0.8% respectively. Ascensus testis accounts for 58% of all cases of cryptorchidism (congenital and acquired) at 18 months, 71% at 36 months and thereafter 69%. Ascensus testis accounts for more than half of cryptorchid testes seen in childhood and occurs in both previously scrotal and cryptorchid testes. We therefore recommend that all boys should have testis position checked regularly during childhood, at least up to 3 years of age.     

Cryptorchidism: seasonal variations in Greece do not support the theory of light

To examine seasonal trends of cryptorchidism in Greece, 583 males with true isolated cryptorchidism were analyzed. All 208 912 live-born boys born during the same period were used as a comparison group. Seasonality by month of birth was evaluated using both Edwards' model with adjusted frequencies and exact theta(i), and Walter-Elwood method with exact theta(i). Both tests resulted in consistent findings. The incidence of cryptorchid births in Greece follows a documented cyclic pattern of simple harmonic type with spring being the season of statistical predominance (peak in March with a second, almost equivalent, peak in May). In contrast, in autumn the incidence of cryptorchid births was considerably lower (trough in September). Given the fact that no significant differences in daylight length are found among seasons in Greece, the detection of a significant seasonal variation suggests that factors other than light are involved in the pathogenesis of cryptorchidism. Low environmental temperature is proposed as a causative factor negatively influencing the maternal hCG profiles and the inguinoscrotal phase of testicular descent. This is further supported by: (i) the similarity of our results to those reported by other European countries of different longitude and geographical width and (ii) our data showing significantly smaller maternal hCG profiles at the 26th week of gestation during winter compared with summer.     

Risk factors for cryptorchidism and hypospadias

PURPOSE: We studied risk factors for cryptorchidism and hypospadias. MATERIALS AND METHODS: We performed a register based, case control study of 6,177 boys with cryptorchidism, 1,345 with hypospadias and 23,273 male controls born live in Denmark from 1983 to 1992 to determine the effects of cryptorchidism and hypospadias on the presence of the other abnormality in an individual, the presence of the abnormalities in an older brother, birth weight, weeks of gestation, maternal history of stillbirth, parity, twin birth, parental age, nationality and professional status. Unconditional logistic regression analysis was used to estimate odds ratios. RESULTS: In an individual simultaneous cryptorchidism and hypospadias were more common than expected. There was an increased risk of both entities when the same abnormality was present in an older brother. The risk of cryptorchidism and hypospadias increased with decreasing birth weight independent of weeks of gestation. Twins were at lower risk than singletons for both entities in all lower birth weight groups. An increased risk of hypospadias was noted in the sons of women who had had a previous stillbirth. The risk of cryptorchidism and hypospadias slightly increased with decreasing parity. CONCLUSIONS: Birth weight was the principal determinant of cryptorchidism and hypospadias. Twins were at lower risk for both abnormalities than singletons in the same birth weight classes. There are indications of separate genetic as well as common environmental causes of cryptorchidism and hypospadias.     

Does citrate prevent nephrocalcinosis in preterm neonates?

Nephrocalcinosis (NC) occurs frequently in preterm neonates. A high U-calcium/citrate is one of the contributing factors to the development of NC. In stone-forming children and adults citrate supplementation is a successful preventive therapy. In this randomized controlled trial the effect of citrate therapy was studied on the development of NC in preterm neonates with a gestational age <32 weeks. Thirty-eight preterm neonates (mean gestational age 29.8 weeks (SD 1.6), mean birth weight 1,300 g (SD 351) were treated with sodium citrate (0.52 mmol/kg/day in four doses) from day 8 of life until at term and 36 preterm neonates (mean gestational age 29.6 weeks (SD 1.6), mean birth weight 1,282 g (SD 256) were not treated. U-calcium, U-creatinine, U-citrate and U-pH were measured at day 7, 14, 21, 28 of life and at term. Renal ultrasonography (US) was performed at term. U-citrate/creatinine and U-pH were significantly higher and U-calcium/citrate was significantly lower in the citrate group at day 14, 21 and 28 compared with the control group (P<0.05). Complications of citrate administration were not encountered, however the incidence of NC was not significantly different in the treated (34%) compared with the control group (44%), P=0.37. Preterm neonates treated with citrate in the first months of life have higher U-citrate/creatinine and lower U-calcium/citrate compared with controls. Sodium citrate therapy in a dosage of 0.52 mmol/kg/day is safe but does not prevent NC. Whether a higher dose or potassium citrate decreases the incidence of NC should be evaluated in further studies.     

Hodenhochstand und Infertilit?t unter besonderer Ber��cksichtigung der interdisziplin?ren Leitlinie

Cryptorchidism is the most common genital disorder in boys. Early-born boys are affected in up to one third of the cases, while about 2-5% of full-term newborns suffer from at least one undescended testicle. As a result of short-term endogenous testosterone secretion after birth the prevalence decreases to 1-2% after 3 months. According to most studies, watchful waiting after 6 months is not justified because after this time spontaneous testicular descent only very rarely occurs. Even though the effects of testicular development and fertility in undescended testis have been extensively examined, the only fact that remains certain is that approximately 90% of untreated men with bilateral cryptorchidism develop azoospermia. The remaining scenarios of cryptorchidism (unilateral, ectopic, inguinal, treated or not treated) exhibit unpredictable fertility and likelihood of fatherhood.     

Seasonal variation in children with developmental dysplasia of the hip

Background

It has been postulated that developmental dysplasia of the hip (DDH) is more frequent in infants born in the winter months. It was the purpose of this study to ascertain if there was any seasonal variation in DDH at the author’s institution and compare/contrast our results with those in the literature using rigorous mathematical fitting.

Methods

All children with DDH treated at the author’s institution from 1993 to 2012 were identified. The month of birth was recorded and temporal variation was analyzed using cosinor analysis. Similar data from the literature was analyzed.

Results

There were 424 children (363 girls, 61 boys). An additional 22,936 children were added from the literature for a total of 23,360. Pearson’s Chi-square test demonstrated a non-uniform distribution in the month of birth for both our 424 children as well as the combined literature series in both the Northern and Southern hemispheres. Cosinor analysis of the 424 children demonstrated double peaks in mid-March and mid-October. For the entire 23,360 children, no seasonal variation was observed in 2,205 (9.4 %), a single winter peak in 16,425 (70.3 %), a single summer peak in 1,280 (5.5 %), and double peaks in the spring and autumn in 3,450 (14.8 %).

Conclusions

This study partly supports the hypothesis of tight clothing/cold temperature as one factor in the etiology of DDH with the tighter clothing/swaddling increasing the risk of DDH. However ~20 % of the DDH births demonstrated a non-winter peak. The single summer and double spring/autumn peaks, as well as in those series where no seasonal variation was noted, refutes the cold winter clothing hypothesis. Perhaps these different patterns in seasonal variation represent the heterogeneity of the genetic factors in DDH interacting with external factors (temperature and clothing) and internal factors (metabolic). Further study will be required to understand these different patterns in DDH seasonal variation.

Level of evidence

IV—case series.     

Congenital abnormalities and growth patterns among cryptorchidic boys

Congenital abnormalities, birth weight and approximate gestational age among 165 boys operated upon for cryptorchidism were registered. Their growth and sexual development was recorded on the basis of a follow-up questionnaire. We found a high incidence of congenital abnormalities, a slightly reduced birth weight and a high incidence of prematurely born boys. The patients seemed to be somewhat taller and more slender during the prepubertal period than their brothers who served as reference material. This trend seemed to disappear at the onset of puberty. The final height and weight did not differ from the final height and weight among the patients' brothers and fathers. The observed data may indicate that the prepubertal growth of cryptorchidic boys follows a hypogonadic pattern. The incidence of familial occurrence of undescended testes was also registered, 3.9% of the father and 6.5% of the brothers were reported to have undescended testes.     

Rates of orchiopexies in Sweden: 1977-1991

Cryptorchidism is a known risk factor for testicular cancer and the secular increase in testicular cancer incidence might have been paralleled by a similar increase in cryptorchidism. Data on trends in prevalence of cryptorchidism are however conflicting and decreases have recently been reported. To analyse Swedish trends in rates of orchiopexy, we used the Swedish Hospital Discharge Register to identify all cases of orchiopexy carried out for cryptorchidism between 1977 and 1991, that is, before the era of outpatient orchiopexies in Sweden. Observed trends were analysed in 5-year age groups. The estimated average annual per cent changes (EAPCs) and the years in which the EAPC significantly changed were estimated using Joinpoint Regression. Finally, we estimated the cumulative incidence of orchiopexy by birth cohort. Among boys aged less than 10, the orchiopexy rate started to decrease in the early 1980s. EAPCs were −2.88 (95% confidence interval (CI): −5.48, −0.21) among boys aged 5–9 and −6.63 among those aged 0–4 (95% CI: −8.84, −4.37). Among subjects aged at least 10, the rate decreased over the whole study period. Although the use of orchiopexy rates to measure prevalence of cryptorchidism has limitations, our findings may suggest that cryptorchidism prevalence decreased in Sweden starting from the early 1980s.     

The Epidemiology of Congenital Cryptorchidism,Testicular Ascent and Orchiopexy

PurposeThe frequency, significance and possible etiology of testicular ascent (acquired cryptorchidism) are characterized in light of the known incidence and natural history of congenital cryptorchidism, and data provided by longitudinal and epidemiological studies of ascended testes and orchiopexy rates.Materials and MethodsWe comprehensively reviewed the literature addressing the epidemiology of congenital and acquired cryptorchidism and orchiopexy.ResultsThe incidence of congenital cryptorchidism in full-term males at birth (2% to 4%) and at age 1 year (approximately 1%) has not increased in the last few decades. The risk of ascent may be as high as 50% in cases where 1 testis is significantly retractile. Ascended testes are typically unilateral (77%), identified in mid childhood and located distal to the inguinal canal (77%). Ascended and significantly retractile testes may be prone to the same germ cell maldevelopment seen in congenital cryptorchidism. Cumulative orchiopexy rates in defined populations are 2% to 4%, and mean age at orchiopexy remains higher than expected (greater than 4 years), despite a long held standard of care that includes recommendation for surgery by age 2. These data suggest that cryptorchidism may be acquired in a significant subset of cases.ConclusionsWith close monitoring of young boys spontaneous ascent of testes from a scrotal to a suprascrotal position may be observed with time, due to either true or apparent testicular ascent, with possible adverse effects on germ cell development and fertility potential. Patients with significant testicular retractility appear to be at highest risk for acquired cryptorchidism, and should be followed closely at yearly intervals until puberty.     

Inguinal hernia repair in the perinatal period and early infancy: clinical considerations

Contemporary neonatal intensive care has resulted in survival of many seriously ill preterm and older infants that frequently present with symptomatic inguinal hernia. Controversy exists concerning timing and safety of early repair in prematures or other neonates, especially those hospitalized with concurrent illness. This study examines this topic by evaluating predisposing factors, presentation, and postoperative complications in 100 recent consecutive hernia repairs in previously hospitalized infants less than 2 months of age. There were 85 boys and 15 girls. Thirty percent were premature (less than 36 wks gestation). Forty-two infants were hospitalized for RDS with assisted ventilation in 16 infants, hydrocephalus and ventriculoperitoneal (VP) shunt in 7 infants, and congenital heart disease (CHD) in 19 infants. Clinical presentation was on the right side in 44 infants, bilateral in 42, and on the left side in 14. Incarceration occurred in 31 cases with nine babies having overt intestinal obstruction. The incidence of cryptorchidism was 12.9%. All (VP) shunt, CHD patients, and incarcerated cases were treated with preoperative antibiotics. Following discharge, 49 preterm or previously ill infants developed a symptomatic hernia at home and were readmitted. Nine full-term infants were treated as outpatients. Bilateral inguinal exploration was performed in 92 cases with second hernia or patent processus found in 81. Seven of eight with unilateral exploration had acute incarceration with obstruction at the time of the procedure. Three subsequently required a second hernia repair. Two infants with incarceration and cryptorchid testis or ovarian slider had gonadal infarction. There were eight postoperative complications.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of inguinal hernia and asymptomatic patent processus vaginalis in term and preterm infants

Introduction

The aim of this study was to evaluate the characteristics of inguinal hernia (IH) and patent processus vaginalis (PPV) in term and preterm infants less than the age of 6 months.

Method

Between January 2004 and December 2012, 246 term and 165 preterm infants underwent laparoscopic herniorrhaphy within the first 6 months of life. Preoperative clinical presentation and intraoperative anatomical findings during the laparoscopic procedure were evaluated. Additionally, initial side of hernia, laterality of IH and PPV were analyzed in term and preterm infants.

Results

In the group of term infants, most infants presented with a primary right-sided IH (58.5%) versus 17.9% left-sided and 23.6% bilateral IH. Babies with primary unilateral IH were found to have a contralateral PPV in 41.0% of cases. A difference between left-sided PPV and right-sided PPV could not be identified.In the group of preterm infants, initial bilateral presentation was predominant (38.8%) versus right-sided (30.3%) and left-sided IH (30.9%). Infants with primary unilateral IH were found to have a contralateral PPV in 56.4%. We identified a slight difference between left-sided PPV (54.0%) and right-sided PPV (58.8%).

Conclusion

IH is predominantly right sided in term infants, whereas preterm infants mostly present with bilateral IH. The incidence of PPV was found to be significantly higher in the preterm group. Regarding the incidence of a contralateral PPV in term and preterm infants, no difference between initial left-sided and right-sided IH could be identified between both groups.     

The cryptorchidism prevalence among infants in the general population of Rotterdam, the Netherlands

Published trends and geographical differences in cryptorchidism rates are almost exclusively derived from hospital-based birth defect registers, which are sensitive to selection bias and incomplete reporting. This study aimed to accurately assess the cryptorchidism prevalence in the general population of Rotterdam. Of 7652 consecutive male live births, 7292 (95%) were examined for cryptorchidism at Child Healthcare Centres around the age of 1 month. In a subgroup of cases, the persistence of cryptorchidism was re-assessed during a follow-up examination by expert specialists. The cryptorchidism rate at the median age of 35 days was 1.2% (89/7292). In the re-examined subgroup (median age 95 days) 69% of the boys (24/35) had persistent cryptorchidism, of which 20 were unilateral and four bilateral. The population rate of 1.2% falls within the range of 0.9-9% reported by others. Differences in case ascertainment and population characteristics probably explain part of the differences between studies. Our cross-sectional design does not allow for analysis of a temporal trend, but provides a baseline for future trend studies. To study cryptorchidism rates, trends, and risk factors, a systematic case ascertainment is warranted.     

Circaannual rhythms and interactions of vitamin D metabolites, parathyroid hormone, and biochemical markers of skeletal homeostasis: a prospective study.

Recent studies suggest a circannual pattern of bone turnover. To further investigate the underlying mechanisms, 41 healthy subjects (25-80 years old) living in a southwestern German city were studied prospectively over a period of 18 months. Participants were examined every 4 weeks, and blood and urine samples were obtained on each visit. The following parameters were measured: serum 25-hydroxyvitamin D3 [25(OH)D3], 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], and parathyroid hormone (PTH), as regulators, and serum total alkaline phosphatase (TAP), bone-specific alkaline phosphatase (BAP), urinary total pyridinoline (PYD), deoxypyridinoline (DPD), and the aminoterminal telopeptide of collagen type I (NTX), as biochemical markers of bone turnover. The presence of significant circannual rhythms for the various markers was tested using the Pharmfit method. In the total group, 25(OH)D3, 1,25(OH)2D3, and PTH as well as BAP, PYD, DPD, and NTX showed a significant seasonal variation. 25(OH)D3 revealed the highest amplitude (38.0%) with an acrophase in August. Levels of the biochemical markers and of PTH were highest in winter with amplitudes of up to 17.7% (DPD). Results were most pronounced in premenopausal women, in subjects <50 years of age, and in subjects who did show a significant individual rhythm in 25(OH)D3 levels. No differences were found regarding other anthropometric or life style factors. Correlation analyses revealed strongest associations between the amplitudes of a vitamin D metabolite and a biochemical marker in premenopausal women. We conclude that specific markers of bone turnover show significant circannual rhythms. These changes are related directly to variations in the hormonal regulation of skeletal homeostasis. In postmenopausal women and in men, other effects may superimpose the circannual variation of biomarkers of bone turnover.     

Incidence of congenital clubfoot in Sweden

Background Idiopathic clubfoot is one of the most common congenital orthopedic problems. Nationwide studies of the incidence are scarce. We performed a prospective multicenter study in order to assess the cumulative incidence in Sweden over 2 consecutive years.

Patients and methods 44 clinics identified as treating clubfoot reported new cases prospectively. The medical records of 280 children with clubfoot born during 1995- 1996 were collected and analyzed with special reference to gender, regional distribution and seasonal variation.

Results The average cumulative incidence of clubfoot during the study period was 1.4/10³ (95% CI 1.2- 1.6). Three-quarters of the cases were boys. In half of the cases both feet were affected. There was significant regional heterogeneity, but no seasonal variation in occurrence of clubfoot.

Interpretation The cumulative incidence was higher than in earlier Scandinavian studies. Gender distribution and laterality were similar to those in previous reports. We found significant regional differences in incidence, but the cause of this observation must be investigated in greater depth.     

Demographics of idiopathic clubfoot: is there a seasonal variation?

A seasonal variation in the incidence of idiopathic clubfoot has been reported. The purpose of this study was to determine whether a seasonal variation existed in the authors' population. The medical records of 245 children who presented with idiopathic clubfoot were reviewed. Expected month of birth, month of conception, and season of birth were determined. National Vital Statistics Reports for Births: Final Data for 2001 provided comparison data. The authors' group differed from the national data, with a male predominance and a greater percentage of mothers less than 25 years old at delivery, but was similar in regard to infants born preterm, cesarean delivery, and low birthweight. Analysis failed to identify a monthly or seasonal variation in the authors' population.     

Is contralateral exploration necessary in preterm infants with unilateral inguinal hernia?

Purpose

Contralateral inguinal exploration has been the preferred approach to preterm infants with unilateral inguinal hernia. There is no literature evidence to justify this. The aim of this prospective study is to analyze the incidence and to determine any risk factors for the development of contralateral metachronous hernia (MH) in the preterm when compared with term infants.

Methods

Preterm and term infants with unilateral inguinal hernia younger than 6 months who underwent surgery were included. Those infants who subsequently developed MH were analyzed.

Results

Two hundred sixty-six patients met the inclusion criteria. One hundred five were preterm and 161 were term. Ten preterm (10.31%) and 9 term infants (5.92%) presented subsequently with MH (P =.18). All but 1 were male. There was no relation between the side of hernia, presentation with incarceration, age at surgery, sex of the patient, and the development of MH. However, a trend toward a higher incidence of MH in very low birth weight and early gestational age preterms was noted.

Conclusion

There is no significant difference between the occurrence of MH in preterm when compared with term infants. Routine contralateral exploration in preterm infants with its associated risks is therefore not justified in unilateral hernia.     

Prevalence and characteristics of cryptorchidism in a Nigerian district

OBJECTIVE: To determine the prevalence and characteristics of cryptorchidism among primary schoolboys in a Nigerian district. SUBJECTS AND METHODS: The district selected had 35 primary schools with 23,342 pupils, consisting of 11,275 girls and 11,967 boys. Using a cluster-sampling technique, five primary schools were visited; 1096 boys (aged 5-13 years) participated in the study, giving a sampling ratio of 1:11. The boys underwent a clinical examination of the groin, scrotum and abdomen. RESULTS: Cryptorchidism was found in nine subjects, giving a prevalence rate of 0.82%. All the undescended testes were unilateral, of which five were right-sided. Eight of the testes were intracanalicular and one was at the external ring. There were no cases of orchidopexy. CONCLUSION: The prevalence of cryptorchidism among primary schoolboys in this district of Nigeria was high, at eight per 1000. Delayed diagnosis and treatment remains a problem because of the prevailing socio-economic factors. However, the incidence of cryptorchidism was similar to that reported in other parts of the world.     

A possible role for the PPARG Pro12Ala polymorphism in preterm birth

The links between preterm birth, low birth weight, and adult vascular/metabolic morbidity remain unclear. Genetic susceptibility of babies related to these three conditions might contribute to this long-term association. We tested whether the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor gamma (PPARG) gene could play a role in birth weight and duration of gestation. We genotyped two independent cross-sectional studies from Northern Ireland (n = 382 and 620). In combined populations, the PPARG Ala12 allele was associated (P = 0.03) with lower birth weight, primarily caused by shorter gestational duration (P = 0.04). The frequency of Ala12 allele carriers was higher (P = 0.027) in the group of individuals born before term (35%, n = 60) than in the group of individuals born at term (22%, n = 942). The odds ratios (95% CI) of preterm birth for Ala12 allele carriers were 1.9 (1.1-3.4), P = 0.022, and 4.2 (1.9-9.7), P = 0.0006 (adjusted for sex, maternal age, and study), when considering 37 or 35 weeks of pregnancy as a threshold for preterm birth, respectively. Interestingly, the same allele was also associated with a moderate decreased risk of miscarriages in mothers. In conclusion, the PPARG Pro12Ala polymorphism might represent a genetic susceptibility factor for preterm birth and constitute a link between preterm birth and metabolic diseases later in life.     

Neoadjuvant gonadotropin-releasing hormone therapy before surgery may improve the fertility index in undescended testes: a prospective randomized trial

PURPOSE: Subfertility is considered the principal consequence of cryptorchidism even after timely orchiopexy. Gonadotropin-releasing hormone (GNRH) treatment appears to improve fertility later in life by inducing germ cell maturation. In a prospectively randomized trial we investigated whether preoperative GNRH therapy improves the fertility index in primary cryptorchidism. MATERIALS AND METHODS: A total of 42 boys 11 to 100 months old (median 33.5) with 63 undescended testes were prospectively assigned to 2 groups during a 6-month period. Patients were randomized to receive either orchiopexy alone (21 patients) or with neoadjuvant GNRH therapy (21) as a nasal spray for 4 weeks at 1.2 mg per day. In both groups testicular biopsies were performed at the time of orchiopexy and histopathological fertility index was determined. RESULTS: Mean fertility index in the group treated with GNRH before surgery was significantly higher (1.05, SD +/- 0.71) compared to the group without hormonal stimulation (0.52, SD +/- 0.39, p <0.05). The subgroup of neoadjuvant stimulated boys younger than 24 months achieved the best results compared to the age matched boys without hormonal treatment. CONCLUSIONS: Neoadjuvant GNRH treatment improves fertility index in prepubertal cryptorchidism. Consequently, preoperative hormone therapy should improve fertility in adulthood. Additionally, the nasal application is well tolerated, safe and already recommended in an adjuvant setting after orchiopexy. Maximum salvage of active germinal tissue is achieved by treating cryptorchidism before the end of the first year of life.