Rossella Mazzilli

Testicular adrenal rest tumors in patients with congenital adrenal hyperplasia: prevalence and sonographic, hormonal, and seminal characteristics.

Testicular adrenal rest tumors have been described in patients with congenital adrenal hyperplasia (CAH). The aim of this work was to (1) evaluate the prevalence of testicular adrenal rest tumors in patients with CAH; (2) study the hormonal profile; (3) define the sonographic features; (4) assess the seminal profile; and (5) initiate a longitudinal study on the possible role of corticotropin (ACTH) plasma levels in the induction and persistence of testicular adrenal rest tumors.

Sexual dysfunction in diabetic women: prevalence and differences in type 1 and type 2 diabetes mellitus.

Background The aim of this work was to evaluate the impact of diabetes on female sexuality and to highlight any differences between sexuality in the context of type 1 and type 2 diabetes mellitus (DM). Methods The subjects selected were 49 women with type 1 DM, 24 women with type 2 DM, and 45 healthy women as controls. Each participant was given the nine-item Female Sexual Function Index questionnaire to complete. The metabolic profile was evaluated by body mass index and glycosylated hemoglobin assay. Results The prevalence of sexual dysfunction (total score ≤30) was significantly higher in the type 1 DM group (25/49, 51%; 95% confidence interval [CI] 18–31) than in the control group (4/45, 9%; 95% CI 3–5; P=0.00006); there were no significant variations in the type 2 DM group (4/24, 17%; 95% CI 3–4) versus the control group (P=0.630, not statistically significant). The mean total score was significantly lower in the type 1 DM group (30.2±6.9) versus the control group (36.5±4.9; P=0.0003), but there was no significant difference between the type 2 DM group and the control group (P=0.773). With regard to specific questionnaire items, the mean values for arousal, lubrication, dyspareunia, and orgasm were significantly lower only in the type 1 DM group versus the control group. The mean values for desire were reduced in type 1 and type 2 DM groups versus control group. Conclusion Type 1 DM is associated with sexual dysfunction. This may be due to classic neurovascular complications or to the negative impact of the disease on psychosocial factors. Larger and ideally longitudinal studies are necessary to better understand the relationship between DM and sexual dysfunction.

Impact of Cystic Fibrosis Transmembrane Regulator (CFTR) gene mutations on male infertility

Objective. The aim of this study was to evaluate the prevalence of most common mutations and intron 8 5T (IVS8-5T) polymorphism of CFTR gene in Italian: a) azoospermic males; b) non azoospermic subjects, male partners of infertile couples enrolled in assisted reproductive technology (ART) programs. Material and methods. We studied 242 subjects attending our Andrology Unit (44 azoospermic subjects and 198 non azoospermic subjects, male partners of infertile couples enrolled in ART programs). Semen analysis, molecular analysis for CFTR gene mutations and genomic variant of IVS8-5T polymorphic tract, karyotype and chromosome Y microdeletions, hormonal profile (LH, FSH, Testosterone) and seminal biochemical markers (fructose, citric acid and L-carnitine) were carried out. Results. The prevalence of the common CFTR mutations and/or the IVS8-5T polymorphism was 12.9% (4/31 cases) in secretory azoospermia, while in obstructive azoospermia was 84.6% (11/13 cases; in these, the most frequent mutations were the F508del, R117H and W1282X). Regarding the non azoospermic subjects, the prevalence of the CFTR and/or the IVS8-5T polymorphism was 11.1% (11/99 cases) in severe dyspermia, 8.1% (6/74 cases) in moderate dyspermia and finally 4.0% (1/25 cases) in normospermic subjects. Conclusions. This study confirms the highly significant prevalence of CFTR mutations in males with bilateral absence of the vas deferens or ejaculatory ducts obstruction compared with subjects with secretory azoospermia. Moreover, the significant prevalence of mutations in severely dyspermic subjects may suggest the possible involvement of CFTR even in the spermatogenic process. This could explain the unsatisfactory recovery of sperm from testicular fine needle aspiration in patients affected by genital tract blockage.

Testosterone replacement in 49,XXXXY syndrome: andrological, metabolic and neurological aspects

Summary We report the case of a 19-year-old boy, presenting several congenital malformations (facial dysmorphisms, cardiac and musculoskeletal abnormalities), mental retardation, recurrent respiratory infections during growth and delayed puberty. Although previously hospitalised in other medical centres, only psychological support had been recommended for this patient. In our department, genetic, biochemical/hormonal and ultrasound examinations were undertaken. The karyotype was 49,XXXXY, a rare aneuploidy with an incidence of 1/85 000–100 000, characterised by the presence of three extra X chromosomes in phenotypically male subjects. The hormonal/biochemical profile showed hypergonadotropic hypogonadism, insulin resistance and vitamin D deficiency. The patient was then treated with testosterone replacement therapy. After 12 months of treatment, we observed the normalisation of testosterone levels. There was also an increase in pubic hair growth, testicular volume and penis size, weight loss, homeostatic model assessment index reduction and the normalisation of vitamin D values. Moreover, the patient showed greater interaction with the social environment and context. Learning points In cases of plurimalformative syndrome, cognitive impairment, recurrent infections during growth and, primarily, delayed puberty, it is necessary to ascertain as soon as possible whether the patient is suffering from hypogonadism or metabolic disorders due to genetic causes. In our case, the diagnosis of hypogonadism, and then of 49,XXXXY syndrome, was unfortunately made only at the age of 19 years. The testosterone replacement treatment, even though delayed, induced positive effects on: i) development of the reproductive system, ii) regulation of the metabolic profile and iii) interaction with the social environment and context. However, earlier and timely hormonal replacement treatment could probably have improved the quality of life of this subject and his family.

Prevalence of XXY karyotypes in human blastocysts: multicentre data from 7549 trophectoderm biopsies obtained during preimplantation genetic testing cycles in IVF

STUDY QUESTION Which is the prevalence of a 47,XXY karyotype in human blastocysts biopsied during preimplantation genetic testing for aneuploidies (PGT-A) cycles? SUMMARY ANSWER The prevalence of a 47,XXY karyotype amongst male blastocysts without autosomal aneuploides is ~1%. WHAT IS KNOWN ALREADY The prevalence of Klinefelter syndrome is estimated as 0.1-0.2% in male newborns. However, the KS phenotype is extremely variable and there are men with a 47,XXY karyotype and less evident signs, who may go undetected. No risk factor for the 47,XXY karyotype in products of conception has been yet clearly defined, and no data are available regarding the prevalence of this karyotype among human preimplantation embryos. STUDY DESIGN, SIZE, DURATION This multicentre cohort study involved 7549 blastocysts obtained during 2826 PGT-A cycles performed between April 2013 and September 2017 at six IVF clinics in Italy. PARTICIPANTS/MATERIALS, SETTING, METHODS During 2826 PGT-A cycles, 7549 blastocysts underwent trophectoderm biopsy and quantitative-PCR-based comprehensive chromosomal testing to predict the karyotype of the corresponding embryos. The results were also presented according to ranges of maternal and paternal age at oocyte retrieval as well as sperm factor and blastocyst quality. Univariate and multivariate logistic regression analyses were conducted to investigate the correlation of possible confounding factors with the prevalence of 47,XXY karyotype. MAIN RESULTS, THE ROLE OF CHANCE Overall, 62 blastocysts were 47,XXY or had an XXY karyotype associated with autosomal aneuploidies. After exclusion of the latter, the prevalence of a 47,XXY karyotype among male blastocysts without autosomal aneuploidies was 0.9% (n = 17/1794). A significant correlation was only found for maternal age and blastocyst quality (OR: 1.20, 95% CI: 1.01-1.42; P = 0.04 and OR: 1.6, 95% CI: 1.13-2.45; P = 0.01). LIMITATIONS, REASONS FOR CAUTION These retrospective data have been produced based on a population of infertile couples undergoing IVF and PGT-A, and the women were mainly of advanced maternal age. Moreover, the qPCR technique is validated only to detect full-chromosome uniform aneuploidies in trophectoderm biopsies. WIDER IMPLICATIONS OF THE FINDINGS The 0.9% prevalence of the 47,XXY karyotype among male blastocysts, when compared with the 0.1-0.2% prevalence reported in the prenatal and postnatal periods, suggests four possible scenarios that require further investigations: (i) the latter prevalence is underestimated; (ii) 47,XXY blastocysts result in a lower implantation rate than euploid embryos (estimated to be ≈50%); (iii) 47,XXY blastocysts result in a higher early miscarriage rate than euploid embryos (estimated to be ≈10%); or (iv) infertile patients of advanced maternal age and referred to IVF/PGT-A produce a higher rate of 47,XXY blastocysts. STUDY FUNDING/COMPETING INTEREST(S) None. TRIAL REGISTRATION NUMBER N/A.

Impact of long-term and short-term therapies on seminal parameters

AIM The aim of this work was: i) to evaluate the prevalence of male partners of subfertile couples being treated with long/short term therapies for non andrological diseases; ii) to study their seminal profile for the possible effects of their treatments on spermatogenesis and/or epididymal maturation. METHODS The study group was made up of 723 subjects, aged between 25 and 47 years. Semen analysis was performed according to World Health Organization (WHO) guidelines (1999). The Superimposed Image Analysis System (SIAS), which is based on the computerized superimposition of spermatozoa images, was used to assess sperm motility parameters. RESULTS The prevalence of subjects taking pharmacological treatments was 22.7% (164/723). The prevalence was 3.7% (27/723) for the Short-Term Group and 18.9% (137/723) for the Long-Term Group. The subjects of each group were also subdivided into subgroups according to the treatments being received. Regarding the seminal profile, we did not observe a significant difference between the Long-Term, Short-Term or the Control Group. However, regarding the subgroups, we found a significant decrease in sperm number and progressive motility percentage in the subjects receiving treatment with antihypertensive drugs compared with the other subgroups and the Control Group. CONCLUSIONS In the management of infertile couples, the potential negative impact on seminal parameters of any drugs being taken as Long-Term Therapy should be considered. The pathogenic mechanism needs to be clarified.