Prenatally diagnosed neuroblastomas are predominantly adrenal in origin and frequently cystic. The liver is the most common site of dissemination and bone involvement is notably absent. The vast majority of these infants have a favorable stage of disease (I, II, and IV-S) and favorable biologic features, and consequently have an excellent prognosis. Although surgery alone is curative for most patients, a period of observation may avoid surgery in some individuals who may achieve spontaneous regression.

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Surgically corrected hypospadias should not be considered a risk factor for poor psychosocial adaptation in childhood, but emotional problems increase with the number of hospital-related experiences.

BACKGROUND Klinefelter syndrome (KS) has been defined by sex chromosome aneuploidies (classically 47, XXY) in the male patient. The peripubertal timeframe in KS patients has been associated with the initiation of progressive testicular fibrosis, loss of spermatogonial stem cells (SSC), hypogonadism and impaired fertility. Less than half of KS patients are positive for spermatozoa in the ejaculate or testis via semen analysis or testicular sperm extraction, respectively. However, the chance of finding spermatogonia including a sub-population of SSCs in KS testes has not been well defined. Given the recent demonstration of successful cell culture for mouse and human SSCs, it could be feasible to isolate and propagate SSCs and transplant the cells back to the patient or to differentiate them in vitro to haploid cells. OBJECTIVE AND RATIONALE The main objective of this study was to meta-analyse the currently available data from KS patients to identify the prevalence of KS patients with spermatogonia on testicular biopsy across four age groups (year): fetal/infantile (age ≤ 1), prepubertal (age 1 ≤ x ≤ 10), peripubertal/adolescent (age 10 < x < 18) and adult (age ≥ 18) ages. Additionally, the association of endocrine parameters with presence or absence of spermatogonia was tested to obtain a more powered analysis of whether FSH, LH, testosterone and inhibin B can serve as predictive markers for successful spermatogonia retrieval. SEARCH METHODS A thorough Medline/PubMed search was conducted using the following search terms: ‘Klinefelter, germ cells, spermatogenesis and spermatogonia’, yielding results from 1 October 1965 to 3 February 2019. Relevant articles were added from the bibliographies of selected articles. Exclusion criteria included non-English language, abstracts only, non-human data and review papers. OUTCOMES A total of 751 papers were identified with independent review returning 36 papers with relevant information for meta-analysis on 386 patients. For the most part, articles were case reports, case-controlled series and cohort studies (level IV-VI evidence). Spermatogonial cells were present in all of the fetal/infantile and 83% of the prepubertal patients’ testes, and in 42.7% and 48.5% of the peripubertal and adult groups, respectively were positive for spermatogonia. Additionally, 26 of the 56 (46.4%) peripubertal/adolescent and 37 of the 152 (24.3%) adult patients negative for spermatozoa were positive for spermatogonia (P < 0.05). In peripubertal/adolescent patients, the mean ± SEM level for FSH was 12.88 ± 3.13 IU/L for spermatogonia positive patients and 30.42 ± 4.05 IU/L for spermatogonia negative patients (P = 0.001); the mean ± SEM level LH levels were 4.36 ± 1.31 and 11.43 ± 1.68 IU/L for spermatogonia positive and negative, respectively (P < 0.01); the mean ± SEM level for testosterone levels were 5.04 ± 1.37 and 9.05 ± 0.94 nmol/L (equal to 145 ± 40 and 261 ± 27 and ng/dl) for the spermatogonia positive and negative groups, respectively (P < 0.05), while the difference in means for inhibin B was not statistically significant (P > 0.05). A similar analysis in the adult group showed the FSH levels in spermatogonia positive and negative patients to be 25.77 ± 2.78 and 36.12 ± 2.90 IU/L, respectively (mean ± SEM level, P < 0.05). All other hormone measurements were not statistically significantly different between groups. WIDER IMPLICATIONS While azoospermia is a common finding in the KS patient population, many patients are positive for spermatogonia. Recent advances in SSC in vitro propagation, transplantation and differentiation open new avenues for these patients for fertility preservation. This would offer a new subset of KS patients a chance of biological paternity. Data surrounding the hormonal profiles of KS patients and their relation to fertility should be interpreted with caution as a paucity of adequately powered data exists. Future work is needed to clarify the utility of FSH, LH, testosterone and inhibin B as biomarkers for successful retrieval of spermatogonia.