Klinefelter Bone Microarchitecture Evolution with Testosterone Replacement Therapy.

Klinefelter Syndrome (KS) patients, defined by a 47 XXY karyotype, have increased risk of fragility fractures. We have assessed bone microarchitecture by high resolution peripheral quantitative CT (HR-pQCT) at the radius and tibia in young KS patients, naïve from testosterone replacement therapy (TRT). Areal bone mineral density (BMD) and body composition were assessed by dual X-ray absorptiometry (DXA). Total testosterone (tT) was measured at baseline. Bone measurements have been repeated after 30 months of TRT. We enrolled 24 KS patients and 72 age-matched controls. KS patients were (mean ± SD) 23.7 ± 7.8 year-old. KS patients had significantly lower relative appendicular lean mass index (RALM) and lower aBMD at spine and hip than controls. Ten patients (42%) had low tT level (≤ 10.4 nmol/L). At baseline, we observed at radius a marked cortical (Ct) impairment reflected by lower Ct.area, Ct.perimeter, and Ct.vBMD than controls. At tibia, in addition to cortical fragility, we also found significant alterations of trabecular (Tb) compartment with lower trabecular bone volume (BV/TV) and Tb.vBMD as compared to controls. After 30 months of TRT, 18 (75%) KS patients were reassessed. Spine aBMD and RALM significantly increased. At radius, both cortical (Ct.Pm, Ct.Ar, Ct.vBMD, Ct.Th) and trabecular (Tb.vBMD) parameters significantly improved. At tibia, the improvement was found only in the cortical compartment. Young TRT naïve KS patients have inadequate bone microarchitecture at both the radius and tibia, which can improve on TRT.

Deciphering balanced translocations in infertile males by next-generation sequencing to identify candidate genes for spermatogenesis disorders.

Male infertility affects about 7% of the general male population. Balanced structural chromosomal rearrangements are observed in 0.4-1.4% of infertile males and are considered as a well-established cause of infertility. However, underlying pathophysiological mechanisms still need to be clarified. A strategy combining standard and high throughput cytogenetic and molecular technologies was applied in order to identify the candidate genes that might be implicated in the spermatogenesis defect in three male carriers of different balanced translocations. Fluorescence in situ hybridization (FISH) and whole-genome paired-end sequencing were used to characterize translocation breakpoints at the molecular level while exome sequencing was performed in order to exclude the presence of any molecular event independent from the chromosomal rearrangement in the patients. All translocation breakpoints were characterized in the three patients. We identified four variants: a position effect on LACTB2 gene in Patient 1, a heterozygous CTDP1 gene disruption in Patient 2, two single-nucleotide variations (SNVs) in DNAH5 gene and a heterozygous 17q12 deletion in Patient 3. The variants identified in this study need further validation to assess their roles in male infertility. This study shows that beside the mechanical effect of structural rearrangement on meiosis, breakpoints could result in additional alterations such as gene disruption or position effect. Moreover, additional SNVs or copy number variations may be fortuitously present and could explain the variable impact of chromosomal rearrangements on spermatogenesis. In conclusion, this study confirms the relevance of combining different cytogenetic and molecular techniques to investigate patients with spermatogenesis disorders and structural rearrangements on genomic scale.

COVID-19 and andrology: Recommendations of the French-speaking society of andrology (Société d'Andrologie de langue Française SALF).

SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) metamorphosed our medical practice. In early June 2020, more than 6,400,000 COVID-19 (coronavirus-19 disease) cases were diagnosed across the world and more than 380,000 deaths were linked to COVID-19. Many medical symptoms of COVID-19 were reported. We will focus, here, on potential impacts of COVID-19 on men's andrological health. Our society (French-speaking society of andrology, SALF) also emitted some recommendations in the andrological management of men infected by SARS-CoV-2. First, considering the fever and the potential presence of SARS-CoV2 in semen, SALF recommends waiting for 3 months (duration of one spermatogenesis cycle and epididymal transit) before re-starting ART in the case of men diagnosed COVID-19 positive. Whatever the nature of testosterone and COVID-19 relationships, we recommend an andrological examination, sperm parameters, and hormonal evaluation at the time of the COVID-19 is diagnosed, and several months later. Furthermore, we are concerned by the potential morbid-mortality of the COVID-19, which mainly affects men. This "andrological bias", if proven, must be reduced by specific andrological diagnosis, therapeutic and prophylactic measures. Research in this direction must be substantiated and financially supported over the next few months (years).

Le SRAS-CoV-2 (nouveau coronavirus ou coronavirus numéro 2 responsable du syndrome respiratoire aigu sévère) a métamorphosé notre pratique médicale. Début juin 2020, plus de 6,400,000 cas de COVID-19 (maladie à coronavirus 2019) ont été diagnostiqués dans le monde et plus de 380,000 décès ont été reliés à cette maladie. De nombreux symptômes médicaux de cette infection virale ont été signalés. Nous nous concentrerons, ici, sur les impacts potentiels de COVID-19 sur la santé andrologique des hommes. Notre société (Société d'andrologie de langue Française, SALF) émet ici quelques recommandations dans la prise en charge andrologique des hommes infectés par le SRAS-CoV-2. Tout d'abord, compte tenu de la fièvre et de la présence potentielle du SRAS-CoV2 dans le sperme, la SALF recommande d'attendre 3 mois (durée d'un cycle de spermatogenèse et transit épididymaire) avant de recommencer les techniques d'assistance médicale à la procréation pour les hommes diagnostiqués COVID-19 positifs. Quelle que soit la nature des relations entre la testostérone et l'infection à SARS-CoV-2, nous recommandons un examen andrologique, un examen des paramètres du sperme et une évaluation hormonale au moment du diagnostic de l'infection, ainsi qu'à distance (3­6 mois plus tard). De plus, nous sommes préoccupés par la morbidité et la mortalité potentielles de l'infection COVID-19, qui touche principalement les hommes. Ce "biais andrologique", s'il est. prouvé, doit être réduit par un diagnostic andrologique spécifique et des mesures thérapeutiques et prophylactiques. La recherche dans ce sens doit être étayée et soutenue financièrement au cours des prochains mois (années).

[Social cognition disorders in Klinefelter syndrome: A specific phenotype? (KS)]. / Troubles de la cognition sociale dans le syndrome de Klinefelter : un trait phénotypique ?

INTRODUCTION: The Klinefelter syndrome (KS) is a genetic condition characterized by an X supernumerary sex chromosome in males. The syndrome is frequently associated with cognitive impairment. Indeed, the different areas of the executive sphere can be affected such as inhibition, cognitive flexibility but also attentional and visual-spatial domain. Social cognition disorders, predominantly on emotional recognition processes, have also been documented. In addition, the syndrome may be associated with psychiatric symptoms. MATERIAL AND METHOD: Our study aims to characterize of the various components of social cognition in the SK: facial emotional recognition, theory of mind and attributional style. For this two groups (SK group versus control group) of participants (n=16) matched for age and sociocultural level were recruited. Participants with intellectual disabilities, psychiatric or neurological disorders were excluded. Three social cognition tests were available: the TREF, the MASC, the AIHQ. Neurocognitive functions were assessed by the fNart, the subtest "logical memory" of the MEM-III, the subtests of the two VOSP battery, the d2, the TMT and the Stroop test. RESULTS: The SK group had specific social cognition disorders in comparison to the control group. Two emotions in particular were less well recognized: fear and contempt. In addition, the SK group had significantly lower results in theory of mind. Regarding the hostile attribution bias, no significant difference was found. Finally, the results showed correlations between specific attentional disorders and facial emotional recognition. DISCUSSION-CONCLUSION: Our study emphasizes social cognition disorders in SK. These disorders could be considered as a phenotypic trait in the syndrome. The interest of better characterizing the cognitive phenotype of genetic disorders that can affect the neurodevelopment is to offer specific cognitive remediation strategies.

[Predictive value of vitamin D plasma levels on pregnancy rates in a cohort of IVF patients]. / Valeur prédictive du dosage de vitamine D sur les taux de grossesse dans une cohorte de patientes suivies en FIV.

OBJECTIVE: To determine a possible correlation between plasma levels of vitamin D and pregnancy rates obtained by in vitro fertilization (IVF). PATIENTS AND METHODS: One hundred and ninety-eight womens participated in an IVF cycle from January to May 2012 in a prospective study. During the follicular phase locking, serum fluid was collected for vitamin D, calcium, FSH and estradiol analysis. The serum bhCG was checked 16 days after oocyte collect. Clinical pregnancy was confirmed by transvaginal sonography with at least one gestational sac in the uterine cavity. RESULTS: The mean levels of vitamin D was 31.7 nmol/L. A total of 169 patients (85.3%) had a vitamin D insufficiency (< 50 nmol/L). Only 29 patients (14.7%) had a sufficient vitamin D status (vitamin D 50 nmol/L). Pregnancy rate was 29.8% (59/198). There was no significant correlation between the levels of vitamin D and mean age (P = 0.92), BMI (P = 0.16) and etiology of infertility (P = 0.78). In contrast, the levels of vitamin D mean were significantly lower in patients from North Africa (P < 0.0001) and Black African (P = 0.0003) compared to Caucasian patients. DISCUSSION AND CONCLUSION: No correlation was found between serum vitamin D level and the pregnancy rate in IVF cycle.

[Medical optimisation of sperm retrieval in non obstructive azoospermia]. / Optimisation médicale du recueil de spermatozoïdes dans les azoospermies non obstructives.

Medical optimisation of sperm retrieval in non-obstructive azoospermia is reviewed. Gonadotropin treatment of hypogonadotropic hypogonadism allows obtaining sperms in the ejaculate in about 90% of cases provided the duration of treatment was long enough. TESE is indicated in case of persistent azoospermia at 2 years of continuous treatment. Some publications reported a possible effect of hormonal treatments (FSH, hCG, anti-estrogens, aromatase inhibitors) in primary spermatogenic failure, but mainly in cases selected for their favourable histology and normal hormonal levels. The effect on unselected cases remains doubtful. Conversely, the effect of the treatment of varicoceles is significant. Other medical treatments or advises need further investigations.

Decrease of anti-Mullerian hormone in genetic spermatogenic failure.

The aim of this study was to compare anti-Mullerian hormone (AMH) plasma levels in patients with azoospermia according to the physiopathology. In a prospective clinical study from April 2008 to March 2009 in University Hospital, we measured AMH levels in 49 consecutive patients with azoospermia. AMH plasma levels were correlated with FSH, inhibin B, bioavailable testosterone plasma levels and testicular volume and compared between nonobstructive azoospermia (NOA) and obstructive azoospermia (OA) and within four physiopathological subgroups of NOA: genetic, cryptorchidism, cytotoxic and unexplained. AMH, FSH, inhibin B, bioavailable testosterone plasma levels and testicular volumes were all related to each other. AMH plasma levels were lower in NOA relatively to OA. Lowest values were observed in cases of genetic NOA and on the other hand, the values observed in case of cytotoxic NOA were as high as the values observed in OA. FSH, inhibin B, bioavailable testosterone and testicular volume were not different between genetic and cytotoxic NOA. These results suggest that the decrease in AMH plasma levels is related to the origin of NOA, with low values in genetic NOA and values similar to OA in cytotoxic NOA. Further studies will be useful to understand the fine regulation of AMH production.

[Infertility treatment in Klinefelter syndrome]. / Prise en charge de l'infertilité dans le syndrome de Klinefelter.

Until few years ago, Klinefelter syndrome with a homogenous 47.XXY caryotype was considered a model of absolute male sterility. In this review, we will discuss the fertility issue following TEsticular Sperm Extraction-IntraCytoplasmic Sperm Injection (TESE-ICSI) and the potential advantage of searching for and cryopreserving spermatozoa in adolescent instead of adult patients.

[Is it useful to modify the care of Klinefelter's syndrome to improve the chances of paternity?]. / Faut-il modifier la prise en charge du syndrome de Klinefelter pour améliorer les chances de paternité ?

Until a few years ago, Klinefelter syndrome with a homogeneous 47.XXY karyotype was considered a model of absolute male sterility. In this review, we will discuss: (1) potential fertility following TEsticular Sperm Extraction-IntraCytoplasmic Sperm Injection (TESE-ICSI), (2) the physiopathology of spermatogenic failure and the origin of focal spermatogenesis and risk of aneuploidy in potential offspring, (3) the advantage of searching for and cryopreserving spermatozoa in adolescent instead of adult patients. In previous published series, TESE was successful in almost 50% of patients and pregnancy rate following ICSI was not obviously different from other causes of spermatogenic failure. The rate of positive sperm extraction seemed to be better for younger patients. During childhood, the survival rate of 47.XXY spermatogonia is low. However, a few spermatogonia are able to eliminate their extra X chromosome, giving rise to rare clones of 46.XY gonia which are the origin of rare foci of complete spermatogenesis after puberty. Several arguments suggest that this focal spermatogenesis decreases with age. This suggests there would be a benefit to patients if TESE were performed in adolescences and spermatozoa were cryopreserved. In addition, androgenotherapy is a common treatment of Klinfelter syndrome but carries a risk of decreasing focal spermatogenesis by lowering gonadotropins. Preservation of spermatozoa from adolescence by TESE would allow androgenotherapy to be prescribed with less concern for future reproductive capacity. Controlled studies should be done to determine the best age for TESE-ICSI in 47.XXY homogeneous Klinefelter syndrome patients.

Are conventional targets for metabolic control sufficient to prevent fetal macrosomia during diabetic pregnancy?

We report the case of a 26 year-old woman, with an uncomplicated type 1 IDDM of 17 yr duration followed for her first pregnancy. At conception, HbA1c (measured by HPLC) was 6.5% and fructosamine was 280 u.mol.l (normal range below 285). During the follow-up, 15-days-interval frutosamine never exceeded the normal range and HbA1c values were under 6.5% excepted in the third trimester (7.0 +/- 0.8%) coinciding with a bad control of the 2 hours post-prandial blood glucose. A fetal macrosomy was discovered at 34 weeks of gestation and a heavy-for-date 4680 g baby was delivered by caesarean section at 38 weeks of gestation. Our case report outlines again the need to achieve the recommended target of metabolic control for the diabetic pregnant woman (blood preprandial glucose: 3.9-5.6 mM; post-prandial 2 h < 6.7 mM) specially during the third trimester of pregnancy. The use of computer databases might be helpful for precise monitoring during this narrow window period.