Men with a history of congenital undescended testes (UDT) have an increased risk of fertility problems. Despite no definitive proof, current guidelines recommend early surgical intervention because this may have a positive effect on future fertility potential by preventing degenerative changes of the testes in early life. Also surgical intervention facilitates observability of the testes in view of possible malignancy. We evaluated testicular function in adult men with previous UDT treated at different ages before puberty. A longterm follow-up study of men with previous UDT was performed. Andrological evaluation included medical history taking, physical examination, scrotal ultrasound, determination of reproductive hormones, and semen analysis. Findings were compared with those of a control group of men with normal testicular descent. The influence of age at orchiopexy on future fertility parameters was evaluated in a multivariate regression analysis. 62 men were included of whom seven had had bilateral UDT. Twenty-four patients had had their orchiopexy before the age of 24 months of whom eight men had it before 12 months of age. Forty-eight men had had unsuccessful luteinizing-hormone-releasing-hormone (LHRH) nasal spray treatment during childhood, whereas 14 of 24 men operated before 24 months of age had not received LHRH treatment before orchiopexy. Fertility potential in men with a history of UDT is compromised in comparison with controls. We could not detect any influence of age at orchiopexy on fertility parameters. However, the number of patients operated before the age of 12 months is limited. This study does not support the assumption that early orchiopexy results in better fertility potential.

Genomic prediction of the extreme forms of adult body height or stature is of practical relevance in several areas such as pediatric endocrinology and forensic investigations. Here, we examine 770 extremely tall cases and 9,591 normal height controls in a population-based Dutch European sample to evaluate the capability of known height-associated DNA variants in predicting tall stature. Among the 180 normal height-associated single nucleotide polymorphisms (SNPs) previously reported by the Genetic Investigation of ANthropocentric Traits (GIANT) genome-wide association study on normal stature, in our data 166 (92.2 %) showed directionally consistent effects and 75 (41.7 %) showed nominally significant association with tall stature, indicating that the 180 GIANT SNPs are informative for tall stature in our Dutch sample. A prediction analysis based on the weighted allele sums method demonstrated a substantially improved potential for predicting tall stature (AUC = 0.75; 95 % CI 0.72-0.79) compared to a previous attempt using 54 height-associated SNPs (AUC = 0.65). The achieved accuracy is approaching practical relevance such as in pediatrics and forensics. Furthermore, a reanalysis of all SNPs at the 180 GIANT loci in our data identified novel secondary association signals for extreme tall stature at TGFB2 (P = 1.8 × 10(-13)) and PCSK5 (P = 7.8 × 10(-11)) suggesting the existence of allelic heterogeneity and underlining the importance of fine analysis of already discovered loci. Extrapolating from our results suggests that the genomic prediction of at least the extreme forms of common complex traits in humans including common diseases are likely to be informative if large numbers of trait-associated common DNA variants are available.

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At a mean follow-up of 21 yr after high-dose androgen treatment, we conclude that fatherhood and semen quality in tall treated men are not affected. Serum testosterone levels, however, are reduced in androgen-treated men. Future research is required to determine whether declining testosterone levels may become clinically relevant for these men as they age.

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