Testicular hypertrophy as predictor of contralateral nonpalpable testis among Chinese boys: An 18-year retrospective study.

OBJECTIVE: To assess the accuracy of contralateral testis hypertrophy for predicting the fate of nonpalpable testis in Chinese boys at different ages. METHODS: The data of patients who presented with unilateral impalpable testis and who underwent laparoscopy at the Children's Hospital of Chongqing Medical University between January 1, 2000 and January 1, 2018 were reviewed. The boys were divided into four groups: age-matched volunteers with no testicular abnormalities represented the control group (group I), boys with palpable undescended testis (group II), boys with nonpalpable testis (NPT)/viable testis (VT) (group III), and boys with NPT/non-viable testis (NVT) group (group IV). Scrotal testes were prospectively measured by ultrasonography for volume and size, and diagnostic laparoscopy was performed to determine the state of the cryptorchid testis. RESULTS: The mean contralateral testicular volume and length in the boys with an absent testis was 0.78mL and 17mm compared with 0.67mL and 15mm in the boys with a testis present and 0.63mL and 15mm in the controls, respectively (P<0.05). The predictive accuracy, sensitivity, and specificity for an absent testis were 64.9%, 75%, and 49%, respectively, for volume and 64.2%, 56.3%, and 76.4%, respectively for length at the optimal cutoff value of 0.65mL volume and 16.55mm length. Contralateral testis volume was the most accurate in predicting monorchism in 0-2-year-olds (sensitivity: 75%, specificity: 70%, accuracy: 73.1%) and the contralateral testicular length was most accurate for 4-6-years-old (sensitivity: 68.6%; specificity: 77.8%; accuracy: 72.2%). We also included 29 patients with bilateral undescended testis (UDT) and with unilateral nonpalpable. Cutoff values for testicular volume and length were 0.6mL (sensitivity: 81.8%, specificity: 88.9%, accuracy: 86.2%) and 13.5mm (sensitivity: 63.6%, specificity: 77.8%, accuracy: 77.8%). CONCLUSION: The present results exclusively obtained from laparoscopic exploration suggest that a testis volume of>0.65mL or a testis length of>16.55mm could predict monarchism with an accuracy of about 65%. In younger patients aged 0-2 years and 4-6 years, the overall predictive accuracy increases to about 73% but laparoscopic exploration is still required.

Placental Weight and Risk of Cryptorchidism and Hypospadias in the Collaborative Perinatal Project.

Cryptorchidism and hypospadias are the most common congenital anomalies of the genitourinary tract in males, but their etiology remains unclear. Placental insufficiency has been suggested to be linked to both conditions. Placental weight is a commonly used proxy measure for placental insufficiency; thus, we examined placental weight and other placental characteristics in relation to cryptorchidism and hypospadias in the Collaborative Perinatal Project, a US mother-child cohort study. Pregnant women were recruited between 1959 and 1965. The analysis contrasted boys with cryptorchidism (n = 413) and boys with hypospadias (n = 145) with boys without cryptorchidism (n = 23,799) and boys without hypospadias (n = 22,326). Odds ratios and 95% confidence intervals were calculated using unconditional logistic regression. In categorical analyses in which the middle tertile was the referent, cryptorchidism was inversely associated with placental weight (odds ratio = 0.66, 95% confidence interval: 0.46, 0.95) among white boys and positively associated with the lowest tertile of placental weight among black boys (odds ratio = 1.70, 95% confidence interval: 1.11, 2.59). We conclude that lower placental weight may be related to risk of cryptorchidism. Further investigation of placental functioning may offer insights into the etiology of cryptorchidism.

Molecular analysis of SNP12 in estrogen receptor α gene in hypospadiac or cryptorchid patients from Northwestern China.

OBJECTIVE: To investigate the single nucleotide polymorphism 12 (SNP12) in the estrogen receptor α (ESR1) gene in hypospadiac or cryptorchid patients from Northwestern China. METHODS: 103 patients and 40 controls were analyzed for SNP12 to verify whether this genetic variant was associated with hypospadias or cryptorchidism. RESULTS: The frequencies of the A allele and homozygote individuals for the A allele of SNP12 in the hypospadiac group were higher than in the control group, respectively (p = 0.011, p = 0.005). The frequency of the A allele of SNP12 in the cryptorchid group was higher than in the control group (p = 0.038). However, no significant difference was observed between the cryptorchid group and control group of homozygote individuals for the A allele of SNP12 (p = 0.070). CONCLUSIONS: Our results suggested that the A allele of SNP12 may increase the risk of hypospadias or cryptorchidism.

The frequency of undescended testis from birth to adulthood: a review.

We performed a systematic review and critique of the literature on the frequency of undescended testis (UDT) among boys from birth to adolescence. Special attention was given to whether previous testicular position was taken into account to distinguish between congenital and acquired UDT. We searched Medline, Embase, Cinahl and the Cochrane Library. Any study reporting on the frequency of UDT was included. Study population age, number of boys studied, period of examination, primary examiner, area of study, study design, ethnicity, definitions used and previous testicular position were analysed. A total of 46 studies met the inclusion criteria. Twenty-three of the 46 (50%) studies involved newborns. Definitions were described in half of the studies; however, the definitions used were heterogeneous. Previous testis position was described in 11% (5/46) of the studies. At birth, in term and/or birth weight >2.5 kg infants, the UDT rate ranged from 1.0 to 4.6%, and in premature and/or birth weight <2.5 kg infants from 1.1 to 45.3%. At the age of 1 year UDT in term and/or birth weight >2.5 kg infants was seen in 1.0-1.5%, at 6 years in 0.0-2.6%, at 11 years in 0.0-6.6% and at 15 years in 1.6-2.2% of boys. The frequency of UDT shows variable figures in the literature. The actual frequency of acquired UDT essentially remains unclear because of the shortage of studies performed at an older age, and of studies reporting on previous testicular position.

Maternal smoking, alcohol consumption, and caffeine consumption during pregnancy in relation to a son's risk of persistent cryptorchidism: a prospective study in the Child Health and Development Studies cohort, 1959-1967.

The Child Health and Development Studies is a > or =40-year follow-up of 20,754 pregnancies occurring between 1959 and 1967 in California. There were 84 cases of undescended testes at birth persisting to at least age 2 years among 7,574 liveborn sons whose mothers were interviewed in early pregnancy. Cases were matched to three controls on birth year and race. Compared with mothers of controls, mothers of cryptorchid boys consumed more caffeine during pregnancy (odds ratio = 1.4, 95% confidence interval: 1.1, 1.9 for an interquartile range equivalent to three cups of coffee per day) but were not more likely to smoke or drink alcohol when all behaviors were considered together. Other maternal and perinatal risk factors were not significantly associated with persistent cryptorchidism and did not confound the association with caffeine.

Risk factors for cryptorchism among populations at differing risks of testicular cancer.

BACKGROUND: Cryptorchism is strongly associated with the development of testicular germ cell tumours (TGCTs), possibly owing to a common aetiology. However, while TGCT incidence varies greatly between white and black men, little variability has been reported between the two groups in cryptorchism prevalence. This may suggest that cryptorchism risk factors differ by ethnicity. METHODS: To examine this hypothesis, a prospective analysis was conducted among black and white participants in the US Collaborative Perinatal Project. White participants included 238 cryptorchid sons and 12,296 non-cryptorchid sons, while black participants included 188 cryptorchid sons and 11,942 non-cryptorchid sons. RESULTS: While cryptorchism was significantly more common among white sons (1.90% vs 1.55%; P = 0.04), the difference was incompatible with the 5-fold difference in TGCT rates. The principal maternal risk factors among white sons were age (P = 0.03), hypertension/proteinuria (P = 0.006), and length of time to become pregnant (P = 0.055), while major maternal risk factors among black sons were age (P = 0.06), height (P = 0.007), weight (P = 0.06), and radiation exposure (P = 0.02). Only maternal height, however, had a different relationship with risk among black and white sons. Neonatal associations with risk (shorter gestational age, lower birthweight, shorter length) were similar in the two groups. CONCLUSIONS: These results do not support the hypothesis that the risk factors for cryptorchism vary dramatically by ethnicity but may suggest that cryptorchism is not as closely linked to TGCT among black men as among white men.

Ala/Thr60 variant of the Leydig insulin-like hormone is not associated with cryptorchidism in the Japanese population.

BACKGROUND: Leydig insulin-like hormone (Insl3), a member of the insulin-like superfamily, is specifically expressed in Leydig cells of fetal and postnatal murine testis. Recently, the absence of the Insl3 gene has been reported to result in bilateral cryptorchidism in male mice and it has been suggested that mutations of the INSL3 gene may cause cryptorchidism in humans. METHODS: We sequenced the INSL3 gene from five Japanese patients with sporadic bilateral cryptorchidism. Patients' genome DNA was prepared from blood leukocytes. Two exons of the INSL3 gene were amplified by polymerase chain reaction and were sequenced directly. A restriction fragment length polymorphism assay was performed on 70 control samples for analysis of polymorphism. RESULTS: Three of five cases had a heterozygous single-base change, a G to A transition at position 178 of the INSL3 gene, which predicts an alanine (GCC) to threonine (ACC) change at codon 60 (designated A60T). However, the A60T mutation was also found in the normal Japanese population at an allele frequency of 26%, which suggests that this mutation is a common polymorphism and is not associated with the occurrence of cryptorchidism. CONCLUSIONS: No mutation has been found in the INSL3 gene from Japanese patients with idiopathic cryptorchidism. We did find the A60T polymorphism, which was not associated with the occurrence of cryptorchidism.

Risk factors for cryptorchidism: a nested case-control study.

A nested case-control study of cryptorchidism (i.e. undescended testicles) was undertaken as part of a hospital-based cohort study of 6699 singleton male neonates in New York City. Since some of the cryptorchid infants experienced spontaneous descent of their testes, separate analysis was performed for this third group of 'late descenders' (n=140). Cases (n=63) represented infants whose testes remained undescended at the one year assessment. Controls (n=219) represented the next male infant who was delivered immediately after an infant who was cryptorchid at birth. The only independent risk factors for cryptorchidism were Asian ethnic group (adjusted odds ratio (OR) = 3.90, 95% confidence interval (CI) = 1.22-12.41), swollen legs or feet during pregnancy (adjusted OR = 2.16, 95% CI = 1.15-4.04), a family history of cryptorchidism (adjusted OR = 4.32, 95% CI = 1.91-9.80), low birthweight (adjusted OR = 4.10, 95% CI = 1.39-12.08), and use of analgesics during pregnancy (adjusted OR = 1.93, 95% CI = 1.03-3.62). Multiple logistic regression analysis was also performed to identify those factors that were associated with late testicular descent. In this analysis the independent risk factors were black or Hispanic ethnicity (adjusted OR = 2.05, 95% CI = 1.09-3.83), a family history of cryptorchidism (adjusted OR = 4.25, 95% CI = 1.84-9.78), consumption of cola-containing drinks during the pregnancy (adjusted OR = 2.09, 95% CI = 1.10-3.99), a low birthweight delivery (adjusted OR = 9.78, 95% CI = 3.39-28.20), and preterm birth (adjusted OR = 4.01, 95% CI = 1.66-9.70).

Testicular cancer and cryptorchidism.

The records of 273 patients with germ cell tumours of the testis referred between 1970 and July 1991 were reviewed. There were 25 (9%) black, 40 (14%) mixed race and 214 (77%) white patients. Histology showed seminoma in 53% and non-seminomatous and germ cell tumours in 47% of patients. Maldescent of the testis (MDT) was found in 30 patients--an incidence of 11% overall. MDT was present in 8 of 25 (32%) black, 7 of 40 (18%) mixed race and 15 of 214 (7%) white patients with testicular cancer. The incidence of MDT was statistically significantly higher in both black and mixed race patients compared with white patients. None of the black patients had undergone orchiopexy but 71% of mixed race and 87% of white patients had done so. This resulted in a different pattern of presentation in black compared with mixed race and white patients with MDT and testicular cancer. The mean age was 40 years for black, 32 years for mixed race and 33 years for white patients. Black patients presented with abdominal or inguinal tumours rather than scrotal tumours and they had an increased tendency to present with seminomas.