Testicular volume at puberty in boys with congenital cryptorchidism randomised to treatment at different ages.

AIM: To assess testicular volume at puberty for boys who underwent orchidopexy at 9 or at 36 months compared to boys with spontaneous postnatal descent. METHODS: At age 6 months, boys with congenital unilateral cryptorchidism were randomised to surgery at 9 or 39 months of age and followed to 16 years in parallel with boys with spontaneous postnatal descent. Ultrasound was done at 11 and 16 years to determine testicular volume. The ratio of the initially undescended testis to its scrotal counterpart was used to assess testicular growth. RESULTS: At age 16, the ratio was lower (p < 0.00) in the late group compared to the early group. At 16 years, the spontaneously descended testes were significantly smaller than their scrotal counterparts but larger than the operated groups (early p < 0.01 and late p < 0.00). CONCLUSION: Our data at 16 years show that orchidopexy at 9 months results in better testicular growth compared to 3 years but did not reach the corresponding volumes of their scrotal counterparts. This indicates that earlier surgery is beneficial to testicular growth. At age 16, the postnatally descended testes were not only larger than the surgically treated testes but also exhibited impaired testicular growth.

Increased Prevalence of Accidents and Injuries in Congenital Adrenal Hyperplasia: A Population-based Cohort Study.

CONTEXT: It has been suggested that injuries and accidents are increased in females with congenital adrenal hyperplasia (CAH), but the prevalence is unclear. OBJECTIVE: To study the prevalence of injuries and accidents in females and males with CAH. DESIGN, SETTING, AND PARTICIPANTS: Patients with CAH (n = 714, all 21-hydroxylase deficiency) were compared with matched controls (n = 71 400). Data were derived by linking National Population-Based Registers. MAIN OUTCOME MEASURES: Prevalence of injuries and accidents. RESULTS: Mean age was 29.8 ± 18.4 years. Injuries were more prevalent in patients with CAH than in controls (relative risk, 1.34; 95% CI, 1.24-1.44), and this was found in both sexes (females: 1.43; 1.29-1.58; males: 1.25; 1.12-1.38). In the classical phenotype, the prevalence of injuries was higher, especially in females but not in the nonclassic phenotype. In the genotype groups, injuries were mainly increased in females. Head injuries were increased in all patients with CAH and in the different phenotypes and were mainly driven by females. More patients with CAH born before the introduction of neonatal screening had had an injury compared with controls (1.48; 1.35-1.62); this was seen in both sexes. In patients with CAH born after the introduction of screening, the prevalence of injuries was overall increased (1.20; 1.07-1.35), and in females with CAH but not in males. Accidents showed a similar pattern to injuries in all comparisons. CONCLUSION: Patients with CAH had an increased prevalence of both injuries and accidents, especially in females and in those born before the neonatal screening program. Patients with nonclassic phenotype were hardly affected.

Risk of Urological Cancer Among Boys and Men Born with Hypospadias: A Swedish Population-based Study.

Background: Hypospadias is a common genital malformation among boys. Studies indicate that hypospadias is associated with a higher risk of testicular cancer. Other forms of urological cancer may be linked to hypospadias via a mutual aetiology, hormonal dysfunction, or hypospadias complications, but this has not yet been studied. Objective: To investigate the association between hypospadias and testicular cancer and the risk of other urological cancers among individuals born with hypospadias. Design setting and participants: The study used a population-based male cohort born in Sweden in 1964-2018. Exposure was hypospadias diagnosis in national registers. Outcomes were defined using the Swedish Cancer Register. An extended cohort born from 1940 was used to study cancers among older men. Biological brothers and fathers were linked to investigate familial coaggregation. Outcome measurements and statistical analysis: Associations were assessed using Cox proportional-hazards regression analysis, with results presented as hazard ratios. Results and limitations: We found that hypospadias was associated with a higher risk of testicular cancer (hazard ratio 2.04, 95% confidence interval 1.42-2.92), especially for proximal hypospadias, but did not observe any clear familial coaggregation of hypospadias and testicular cancer. Hypospadias was associated with Wilms' tumour in childhood. We also found an association between hypospadias and bladder and urethral cancers, but not prostate cancer. The number of cases with hypospadias was small and the results for cancers among older men may be impacted by limitations in register coverage. Conclusions: Our study supports the hypothesis of a higher risk of testicular cancer for men with hypospadias, especially with proximal phenotypes. Hypospadias may also be associated with a higher risk of lower urinary tract cancers, although this requires further investigation in older cohorts. Patient summary: Boys and men in whom the opening of the urethra is not at the end of the penis (called hypospadias) at birth are at higher risk of developing testicular cancer, although their overall risk is still low. They may also have a higher risk of developing other forms of cancer in the urinary tract.

Tissue specific trisomy 15 mosaicism associated with urogenital malformations.

We describe a boy born with hypospadias and later diagnosed with vesicoureteral reflux and mild cognitive disability. Routine diagnostic investigation by karyotyping, chromosomal microarray (CMA) and trio analysis with whole exome sequencing was normal. However, later CMA performed on DNA from genital tissue showed trisomy 15, which prompted further analysis. Fluorescent in situ hybridization was performed to verify the CMA result and delineate the mosaic rate. Methylation specific MLPA was performed to investigate the parent of origin of the extra chromosome 15. Further medical examination of the boy identified fine Blaschko's lines, indicative of mosaicism, but earlier unnoticed. CMA on genital tissue showed 80% mosaicism for trisomy 15. Bladder mucosa and muscle showed a high degree of trisomy 15 (56% and 45% respectively), while buccal mucosa and abdominal skin showed low-grade or no trisomy 15. The extra chromosome 15 was of maternal origin. This case report describes a boy with two different malformations in the same organ region that carries a high degree of trisomy 15 mosaicism. Hence, the clinical implication is that there is no recurrence risk for sibs, but the boy in his turn risks producing gametes with an extra chromosome 15. Tissue restricted mutations are not commonly described but may cause congenital malformations that affects the information to the family.

A qualitative content analysis of the experience of hypospadias care: The importance of owning your own narrative.

Objectives: There is a lack of studies on men's individual experiences of living with hypospadias. We aimed to explore the personal experiences of having hypospadias in relation to healthcare and surgery. Subjects and methods: Purposive sampling was used to include men (aged 18 and over) with hypospadias representing different phenotypes (from distal to proximal) and ages in order to maximise the variation and richness of our data. Seventeen informants, aged 20-49, were included in the study. In-depth semi-structured interviews were conducted between 2019 and 2021. Inductive qualitative content analysis was used to analyse the data. Results: We identified three categories: (1) Having surgery, which comprised the decision to operate, the experience of having surgery, and the outcomes of surgery; (2) Going to the doctor, which focused on follow-up care, re-entering care in adolescence or adulthood, and the experience of healthcare interactions; (3) Being informed, both about hypospadias in general, as well as about your specific body and medical history. There was overall a large variation in experiences. The latent theme across the data was the importance of owning your own narrative. Conclusion: The experience of men with hypospadias in healthcare is complex and varied, highlighting the difficulty of fully standardised care. Based on our results, we suggest that follow-up should be offered in adolescence, and that ways of accessing care for late onset complications be made clear. We further suggest clearer consideration for the psychological and sexual aspects of hypospadias. Consent and integrity in all aspects and all ages of hypospadias care should be adapted to the maturity of the individual. Access to trustworthy information is key, both directly from educated healthcare staff and if possible, from websites or patient-led forums. Healthcare can play a key role in providing the growing individual with tools to understand and address concerns that may develop relating to their hypospadias through life, giving them ownership over their own narrative.

Copy number variants suggest different molecular pathways for the pathogenesis of bladder exstrophy.

Bladder exstrophy is a rare congenital malformation leaving the urinary bladder open in the midline of the abdomen at birth. There is a clear genetic background with chromosome aberrations, but so far, no consistent findings apart from 22q11-duplications detected in about 2%-3% of all patients. Some genes are implicated like the LZTR1, ISL1, CELSR3, and the WNT3 genes, but most are not explained molecularly. We have performed chromosomal microarray analysis on a cohort of 140 persons born with bladder exstrophy to look for submicroscopic chromosomal deletions and duplications. Pathogenic or possibly pathogenic microdeletions or duplications were found in 16 patients (11.4%) and further 9 with unknown significance. Two findings were in regions linked to known syndromes, two findings involved the same gene (MCC), and all other findings were unique. A closer analysis suggests a few gene networks that are involved in the pathogenesis of bladder exstrophy; the WNT-signaling pathway, the chromosome 22q11 region, the RIT2 and POU families, and involvement of the Golgi apparatus. Bladder exstrophy is a rare malformation and is reported to be associated with several chromosome aberrations. Our data suggest involvement of some specific molecular pathways.

A genome-wide association study with tissue transcriptomics identifies genetic drivers for classic bladder exstrophy.

Classic bladder exstrophy represents the most severe end of all human congenital anomalies of the kidney and urinary tract and is associated with bladder cancer susceptibility. Previous genetic studies identified one locus to be involved in classic bladder exstrophy, but were limited to a restrict number of cohort. Here we show the largest classic bladder exstrophy genome-wide association analysis to date where we identify eight genome-wide significant loci, seven of which are novel. In these regions reside ten coding and four non-coding genes. Among the coding genes is EFNA1, strongly expressed in mouse embryonic genital tubercle, urethra, and primitive bladder. Re-sequence of EFNA1 in the investigated classic bladder exstrophy cohort of our study displays an enrichment of rare protein altering variants. We show that all coding genes are expressed and/or significantly regulated in both mouse and human embryonic developmental bladder stages. Furthermore, nine of the coding genes residing in the regions of genome-wide significance are differentially expressed in bladder cancers. Our data suggest genetic drivers for classic bladder exstrophy, as well as a possible role for these drivers to relevant bladder cancer susceptibility.

Long-Term Results of Surgical Treatment and Patient-Reported Outcomes in Congenital Adrenal Hyperplasia-A Multicenter European Registry Study.

Representatives for congenital adrenal hyperplasia (CAH) continue to desire early feminizing surgery in girls with 46,XX-CAH. The aim of this analysis, which included 174 46,XX- individuals with salt-wasting (SW) or simple-virilizing (SV) CAH, a female gender identity, and an age > 16 years participating in a multicenter cross-sectional clinical evaluation study (dsd-LIFE), was to evaluate the long-term results of surgery and patient-reported outcomes (PRO). The gynecological examination (n = 84) revealed some shortcomings concerning surgical feminization. A clitoris was absent in 9.5% of cases, while a clitoral hood was missing in 36.7% of cases. Though all women had large labia, they didn't look normal in 22.6% of cases. Small labia were absent in 23.8% of cases. There was no introitus vaginae, and the urethra and vagina had no separate opening in 5.1% of cases. A mucosal lining was missing in 15.4% of cases. Furthermore, 86.2% of the women had scars at the region of their external genitalia. A vaginal stenosis was described in 16.5% of cases, and a meatal stenosis was described in 2.6% of cases. Additionally, PRO data showed a very-/high satisfaction rate of 21.3%/40.2% with cosmesis and 23.8%/38.1% with functionality, while 3.3%/10.7% showed a very-/low satisfaction with cosmesis as well as 5.6%/10.3% with functionality. The remaining women­24.6% and 23.8%­were indifferent. Satisfaction concerning sex life was very-/high in 9.6%/27.7%. In 12.0%/16.9% it was very-/low. Furthermore, 33.7% had no opinion. Furthermore, 27.0%/31.6% of the women reported that clitoriplasty, but not clitoridectomy, had a very-/positive influence on their lives, while 1.3%/8.9% felt it to be very-/negative, and 28.4% were indifferent. Vaginoplasty had a very-/positive influence in 25.7%/33.8% and a very-/negative effect in 3.6%/6.8%. 29.7% had no opinion. Additionally, 75.7% of the women preferred feminizing surgery during infancy/childhood, especially concerning clitoreduction. In conclusion, though the majority of the participants (76%) preferred early feminizing surgery and 60% described a positive effect on their lives, about 10% felt it to have been negative. About 15% of the women suffered from insufficient cosmesis and functionality after surgery. Sex life was even described as poor in nearly 30%. Therefore, the decision about early genital surgery in 46,XX-CAH girls should be considered carefully. Parents should get detailed information about possible complications of surgery and should receive support to understand that postponing surgery does not inevitably cause harm for their child. Importantly, genital surgery when performed in children should only be performed in expert centers with a specialized team including surgeons who are trained in feminizing surgery.

Increased androgen-related comorbidity in adolescents and adults born with hypospadias: A population-based study.

BACKGROUND: Hypospadias is a common congenital malformation often related to the effect of androgens in utero. While hypogonadism is associated with many potential health risks including metabolic and cardiovascular disease, the risk of clinical hypogonadism and comorbidities in men with hypospadias later in life has not been studied. OBJECTIVES: Investigate the risk of hypogonadism and somatic comorbidities in adolescents and men born with hypospadias. MATERIALS AND METHODS: We conducted a population-based cohort study using Swedish registers. Associations between hypospadias and hypogonadism, delayed puberty, metabolic, and cardiovascular disease respectively were estimated using Cox proportional hazards regression. Body measurements from military conscription were analysed in a subpopulation as indicators of growth and cardiometabolic risk. We used sibling comparison analyses to control for familial confounding. RESULTS: Using register data, a total of 2,165,255 men including 9,714 men born with hypospadias were followed from the age of 10 to a maximum of 60 years. We found an association between hypospadias and hypogonadism (Hazard ratio (HR) 3.27, 95% confidence interval (CI) 2.33-4.59) which was more pronounced in proximal hypospadias. Men with hypospadias had shorter average height than their brothers and the general population. We further found an increased risk of delayed puberty (HR 1.49, 95% CI 1.08-2.07), diabetes mellitus type 2 (HR 1.57, 95% CI 1.18-2.09) and cardiovascular disease (HR 1.47, 95% CI 1.27-1.71). DISCUSSION: We found an increased risk of hypogonadism, metabolic and cardiovascular disease in men born with hypospadias, increasing with severity of phenotype, as well as impacted growth. These results indicate discruptions in androgen function past childhood, although some of the associations may be due to other underlying aetiologies. CONCLUSION: Hypospadias is associated with an increased risk of androgen-related comorbidity in adolescence and adulthood. We suggest that this can be considered clinically, while further research is needed, especially in older populations.

First genome-wide association study of esophageal atresia identifies three genetic risk loci at CTNNA3, FOXF1/FOXC2/FOXL1, and HNF1B.

Esophageal atresia with or without tracheoesophageal fistula (EA/TEF) is the most common congenital malformation of the upper digestive tract. This study represents the first genome-wide association study (GWAS) to identify risk loci for EA/TEF. We used a European case-control sample comprising 764 EA/TEF patients and 5,778 controls and observed genome-wide significant associations at three loci. On chromosome 10q21 within the gene CTNNA3 (p = 2.11 × 10-8; odds ratio [OR] = 3.94; 95% confidence interval [CI], 3.10-5.00), on chromosome 16q24 next to the FOX gene cluster (p = 2.25 × 10-10; OR = 1.47; 95% CI, 1.38-1.55) and on chromosome 17q12 next to the gene HNF1B (p = 3.35 × 10-16; OR = 1.75; 95% CI, 1.64-1.87). We next carried out an esophageal/tracheal transcriptome profiling in rat embryos at four selected embryonic time points. Based on these data and on already published data, the implicated genes at all three GWAS loci are promising candidates for EA/TEF development. We also analyzed the genetic EA/TEF architecture beyond the single marker level, which revealed an estimated single-nucleotide polymorphism (SNP)-based heritability of around 37% ± 14% standard deviation. In addition, we examined the polygenicity of EA/TEF and found that EA/TEF is less polygenic than other complex genetic diseases. In conclusion, the results of our study contribute to a better understanding on the underlying genetic architecture of ET/TEF with the identification of three risk loci and candidate genes.

Increased Prevalence of Fractures in Congenital Adrenal Hyperplasia: A Swedish Population-based National Cohort Study.

CONTEXT: Low bone mineral density has been reported in individuals with congenital adrenal hyperplasia (CAH), but the prevalence of fractures is unclear. OBJECTIVE: To study the prevalence of fractures in CAH. DESIGN, SETTING, AND PARTICIPANTS: Patients with CAH (n = 714, all 21-hydroxylase deficiency) were compared with controls matched for sex and year and place of birth (n = 71 400). Data were derived by linking National Population-Based Registers. MAIN OUTCOME MEASURES: Number and type of fractures. RESULTS: Mean age was 29.8 ±â€…18.4 years. Individuals with CAH had more fractures compared to controls [23.5% vs 16.1%, odds ratio (OR) 1.61, 95% CI 1.35-1.91], and this was found in both sexes (females: 19.6% vs 13.3%, OR 1.57, 95% CI 1.23-2.02; males: 28.7% vs 19.6%, OR 1.65, 95% CI 1.29-2.12). Fractures were significantly increased in patients born before the introduction of neonatal screening but not in those born afterwards. Any major fracture associated with osteoporosis (spine, forearm, hip, or shoulder) was increased in all individuals with CAH (9.8% vs 7.5%, OR 1.34, 95% CI 1.05-1.72). The highest prevalence of fractures was seen in SV phenotype and I172N genotype while nonclassic phenotype and I2 splice genotype did not show increased prevalence. A transport accident as a car occupant and fall on the same level were more common in patients with CAH, both sexes, than in controls. CONCLUSIONS: Patients with CAH had an increased prevalence of both any fracture and fractures associated with osteoporosis (both sexes) but not for patients neonatally screened. We conclude that fracture risk assessment and glucocorticoid optimization should be performed regularly.

Masculinizing surgery in disorders/differences of sex development: clinician- and participant-evaluated appearance and function.

OBJECTIVES: To report the long-term follow-up outcomes of masculinizing surgery in disorders/differences of sex development (DSD), including both physicians' and patients' perspectives on appearance and functional outcome, including sexuality. PATIENTS AND METHODS: In total, 1040 adolescents (age ≥16 years) and adults with a DSD took part in this multicentre cross-sectional clinical study in six European countries in 2014/2015. Of those, 150 living in other than the female gender had some kind of masculinizing surgery: hypospadias repair, orchidopexy, breast reduction and/or gonadectomy. The study protocol included medical data collection, an optional genital examination, and patient-reported outcomes including satisfaction with appearance and current sexual functioning. RESULTS: Diagnoses included partial and mixed gonadal dysgenesis (45,XO/46,XY; n = 38), Klinefelter syndrome/46,XX males (n = 57), and various 46,XY DSDs (n = 42; e.g. partial androgen insensitivity syndrome, severe hypospadias) and 13 with other diagnoses. Of the participants, 84 underwent hypospadias surgery, 86 orchidopexy, 52 gonadectomy and 32 breast reduction (combinations possible). Physicians evaluated anatomical appearance at genital examination as poor in approximately 11% of patients. After hypospadias surgery, 38% of participants reported that they were (very) dissatisfied with anatomical appearance and 20% with function. The physician and patient evaluations were moderately correlated (r = 0.43). CONCLUSION: The majority of participants were neutral to satisfied with the appearance and function in the long-term after masculinizing surgery. Given the initial severe phenotype and a risk of unsatisfactory results after masculinizing surgery in DSD, treatment should be handled by experienced multidisciplinary teams in order to optimize the postoperative results.

Sexual Function in Women With Differences of Sex Development or Premature Loss of Gonadal Function.

BACKGROUND: Previous studies have suggested that sexual function may be compromised in women born with differences of sex development (DSD) or early loss of gonadal function. AIM: To describe sexual function and sexual wellbeing in women with complete androgen insensitivity syndrome (CAIS), complete gonadal dysgenesis (GD) and premature ovarian insufficiency (POI) in relation to gynecological measures and in comparison with unaffected women. METHODS: A cross sectional study including 20 women with CAIS, 8 women with 46,XY GD, 8 women with 46,XX GD, 21 women with POI, and 62 population-derived controls. Study participants underwent gynecological examination for anatomical measurements and evaluation of tactile sensitivity. They responded to the validated Sexual Activity Log (SAL), Profile of Female Sexual Function (PFSF), and the Personal Distress Scale (PDS). RESULTS: The women with CAIS, XY GD, XX GD and POI showed overall satisfying sexual function in comparison to unaffected age-matched population female controls with a median of 1 to 2 satisfying sexual episodes per week among both the patients and the controls depending on available partner. Women with CAIS had shorter vagina and smaller clitoris and women with XY GD had a significantly shallower vagina in comparison to controls. Clitoral width was also significantly smaller among women with XX GD compared to controls. However, results showed overall good genital touch sensitivity with no significant differences between groups. CLINICAL IMPLICATIONS: Women with DSD or POI can be informed on overall satisfactory sexual function and normal genital touch sensitivity. STRENGTHS & LIMITATIONS: The strength is the use of age-matched population-based controls to these rare conditions of DSD and POI. Limitations are the nonresponder rate of recruited controls, as well as the small groups of women with DSD. CONCLUSION: Women with differences of sex development or early loss of gonadal function show overall good sexual well-being, however clinicians have to make efforts to optimize caretaking and treatment to ensure good sexual quality of life for all patients. Engberg H, Strandqvist A, Berg E, et al., Sexual Function in Women With Differences of Sex Development or Premature Loss of Gonadal Function. J Sex Med 2022;19:249-256.

Role of Genetic Counseling for Patients with Hypospadias and Their Families.

Congenital malformations often have a genetic background associated with a recurrence risk and may be part of a syndrome. Therefore, for children with a congenital malformation, the parents should be offered genetic counseling, and the child should also be offered the same when they reach adulthood. Hypospadias is a common malformation in boys that arises during genital development in weeks 8 to 16. This results in an underdevelopment of the ventral aspect of the penis with a misplacement of the urethral opening somewhere along the penis, scrotum, or in the perineum and with different degrees of penile curvature. The cause can be monogenic, but generally it is regarded as a complex disorder caused by both genetic and environmental factors. Severe hypospadias and familial cases should be genetically investigated, as for other forms of disorders of sex development, according to current guidelines with sequencing of relevant genes. Hypospadias associated with another independent malformation may be part of a syndrome and should be investigated. Fortunately, boys born with milder hypospadias generally have a good outcome and thus the clinical value of finding a disease-causing mutation appears to be limited especially in light of the present cost of genetic analysis. However, all men born with hypospadias should be advised on the recurrence risk and risk for reduced fertility.

Neurodevelopmental and psychiatric disorders in females with Turner syndrome: a population-based study.

BACKGROUND: Turner syndrome is the result of the partial or complete absence of an X chromosome in phenotypic girls. This can cause an array of medical and developmental difficulties. The intelligence quotient in females with Turner syndrome has previously been described as uneven, but considered within normal range. Although their social, intellectual, and psychiatric profile is described, it is unclear to what extent these females meet the clinical criteria for neurodevelopmental or psychiatric diagnoses. The aim of this study was to examine the prevalence of neurodevelopmental and psychiatric disorders in females with Turner syndrome. METHODS: A retrospective cohort study was performed with a total of 1392 females with Turner syndrome identified through the Swedish National Patient Register and compared with 1:100 age- and sex-matched controls from the general population. The associations between Turner syndrome and diagnoses of neurodevelopmental and/or psychiatric disorders were calculated using conditional logistic regression and is presented as estimated risk (odds ratio, OR, 95% confidence interval, CI) in females with Turner syndrome compared with matched controls. RESULTS: Females with Turner syndrome had a higher risk of neurodevelopmental or psychiatric disorder (OR 1.37, 95% CI 1.20-1.57), an eightfold increased risk of intellectual disability (OR 8.59, 95% CI 6.58-11.20), and a fourfold increased risk of autism spectrum disorder (OR 4.26, 95% CI 2.94­6.18) compared with the controls. In addition, females with Turner syndrome had twice the risk of a diagnosis of schizophrenia and related disorders (OR 1.98, 95% CI 1.36-2.88), eating disorders (OR 2.03, 95% CI 1.42-2.91), and behavioral and emotional disorders with onset in childhood (OR 2.01, 95% CI 1.35-2.99). CONCLUSIONS: Females with Turner syndrome have an increased risk of receiving a diagnosis of neurodevelopmental or psychiatric disorder. This warrants extensive assessment of intellectual and cognitive functions from early age, and increased psychiatric vigilance should be a part of lifelong healthcare for females with Turner syndrome.

[On micropenis, diagnosis and differential diagnoses]. / Mikropenis och liknande tillstånd ­ kunskap sparar mycket oro.

The term inconspicuous penis in children covers both micropenis with a penile length less than 2.5 SD for age and other conditions with a normal length of corpora, but when the penis looks smaller due to other diagnoses. Micropenis in a newborn is a serious condition that needs immediate attention by a paediatric endocrinologist. The boy should have a continuous support until adulthood. Other conditions that resembles micropenis are for example buried or webbed penis that only affects the skin or the adherence of the skin to the penile body, so that penis looks smaller even though the corpora are of normal length. Such conditions are treated and often operated by pediatric urologists. A proper clinical examination distinguishes between these diagnoses and gives a possibility to direct the child to the proper treatment without unnecessary concern for the parents.

Early Genital Surgery in Disorders/Differences of Sex Development: Patients' Perspectives.

Controversy continues over a proposed moratorium on elective genital surgery in childhood for disorders/differences of sex development (DSD). Empirical evidence on patient preference is needed to inform decision-making. We conducted a multicentre survey by cross-sectional questionnaire in 14 specialized clinics in six European countries. The sample comprised 459 individuals (≥ 16 years) with a DSD diagnosis, including individuals with congenital adrenal hyperplasia (CAH) (n = 192), XY DSD with prenatal androgen effect (A) (n = 150), and without (nA) (n = 117). Main outcome measures were level of agreement with given statements regarding genital surgery, including clitoris reduction, vaginoplasty, and hypospadias repair. A total of 66% of individuals with CAH and 60% of those with XY DSD-A thought that infancy or childhood were the appropriate age for genital surgery. Females with XY DSD were divided on this issue and tended to prefer vaginoplasty at a later age (XY DSD-A 39%, XY DSD-nA 32%). A total of 47% of males preferred early hypospadias surgery. Only 12% (CAH), 11% (XY DSD-A), and 21% (XY DSD-nA) thought they would have been better off without any surgery in childhood or adolescence. Individuals who had early genital surgery were more likely to approve of it. Outcome data failed to support a general moratorium on early elective genital surgery. Participant perspectives varied considerably by diagnostic category, gender, history of surgery, and contact with support groups. Case-by-case decision-making is better suited to grasping the ethical complexity of the issues at stake.Trial registration: German Clinical Trials Register DRKS00006072.

Fertility in men with hypospadias: A nationwide register-based study using dizygotic twinning rates as an indicator of semen quality.

BACKGROUND: It is not known if impaired fertility in men with hypospadias is caused by decreased semen quality or other factors. Semen quality in men born with hypospadias may be impaired due to effects of androgens or testicular dysgenesis but has been very little studied. OBJECTIVES: To study semen quality in men with hypospadias using dizygotic twinning rates as an epidemiological indicator. We further aimed to study men treated for cryptorchidism, given a hypothesized mutual etiology for decreased semen quality. MATERIALS AND METHODS: We conducted a population-based study using national Swedish registers. A total of 4,363,165 births between 1964 and 2013 were included. The association between hypospadias and cryptorchidism, and fathering dizygotic multiple births was estimated using logistic regression and presented as odds ratios. The main analyses excluded births conceived using assisted reproductive technology (ART). RESULTS: We identified a total of 5317 births with fathers with hypospadias, including 26 dizygotic births conceived unassisted. No significant association was found between hypospadias and dizygotic twinning (OR 1.10, 0.75-1.61). We estimated a significantly increased odds for dizygotic multiple births in men treated for cryptorchidism (OR 1.35, 1.01-1.81) which was decreased after exclusion of ART, but the estimate was not significant (OR 0.75, 0.48-1.18). DISCUSSION: Using dizygotic twinning rates as an indicator of semen quality, we did not find any difference between fathers with hypospadias and controls. Due to sample size, we could not analyze phenotypes separately and can therefore not exclude impaired semen quality in severe hypospadias. We could not demonstrate any association between dizygotic twinning and cryptorchidism. Men treated for cryptorchidism were more likely than controls to use ART to conceive. CONCLUSION: Men with hypospadias who conceived without ART were not shown to have impaired semen quality using dizygotic twinning as an epidemiological indicator.

Reproductive and Perinatal Outcomes in Women with Congenital Adrenal Hyperplasia: A Population-based Cohort Study.

CONTEXT: Reduced fertility has been reported for women with congenital adrenal hyperplasia (CAH), especially for those with the salt-losing form. However, data are sparse on reproductive and perinatal outcomes in these women. OBJECTIVE: To investigate reproductive and perinatal outcomes in women with CAH. DESIGN AND SETTING: Population-based and nationwide study using the National CAH Register, the Total Population Register, and the Medical Birth Register of Sweden. PARTICIPANTS: A total of 272 women with CAH due to 21-hydroxylase deficiency and 27 200 controls matched by sex, age, and place of birth. The median age was 31 years. MAIN OUTCOME MEASURES: The proportion of CAH women that have given birth, and reproductive and perinatal outcomes. RESULTS: Of the 272 women with CAH, 69 gave birth to at least 1 child (25.4%), which was a lower frequency than for the controls (45.8%) (P < .001). Furthermore, women with CAH had fewer children than controls and were slightly older at birth of their first child. More women with CAH were diagnosed with gestational diabetes than controls, 4.9% versus 1.4% (P < .05), and more women with CAH were delivered through cesarean section, 51.4% versus 12.3% (P < .05). There was no difference in Apgar score or frequency of small-for-gestational age between children born to mothers with CAH and controls. CONCLUSIONS: This is, to our knowledge, the largest cohort designed to investigate reproductive and perinatal outcomes in women with CAH. We found the birth rate to be lower in women with CAH; gestational diabetes and cesarean section were more common, but perinatal outcomes were comparable with controls.