Preliminary study of elastic-tension digital neoprene orthoses for proximal interphalangeal joint flexion contracture.

Flexion contracture of the proximal interphalangeal joint (PIPJ) is one of the most frequent complications in finger trauma. Orthoses are the most widely used method to optimize total end-range time (TERT). No previous studies showed that an elastic tension orthosis could be applied for longer than 12 h. We aimed to demonstrate that the elastic-tension digital neoprene orthosis (ETDNO) can achieve higher TERT and therefore better range of motion than other elastic-tension orthoses (ETO) described in the literature. A prospective study of treatment of PIPJ flexion contracture included 10 PIP joints in 8 patients who met the selection criteria. They were instructed to use the ETDNO for around 23 h per day as far as possible, during a period of 3 weeks. Patients reported a mean TERT of 20.6 h a day. PIPJ contracture improved by a mean Torque Range of Motion (TROM) of 23.5° at 500 g and 22.9° at 800 g of passive extension force during the 3-week treatment. Based on the results of this study, the ETDNO appears to offer a highly effective approach for improving PIPJ flexion contracture, increasing range of motion in extension. ETDNO's efficacy probably lies in the significantly improved comfort and low-profile design, enabling excellent compliance and thus optimizing TERT. LEVEL OF EVIDENCE: Level III.

Whole-exome sequencing in patients with maturation arrest: a potential additional diagnostic tool for prevention of recurrent negative testicular sperm extraction outcomes.

STUDY QUESTION: Could whole-exome sequencing (WES) be useful in clinical practice for men with maturation arrest (MA) after a first testicular sperm extraction (TESE)? SUMMARY ANSWER: WES in combination with TESE yields substantial additional information and may potentially be added as a test to predict a negative outcome of a recurrent TESE in patients with MA. WHAT IS KNOWN ALREADY: At present, the only definitive contraindications for TESE in men with non-obstructive azoospermia (NOA) are a 46,XX karyotype and microdeletions in the azoospermia factor a (AZFa) and/or AZFb regions. After a first negative TESE with MA, no test currently exists to predict a negative outcome of a recurrent TESE. STUDY DESIGN, SIZE, DURATION: In a cohort study, we retrospectively included 26 patients with idiopathic NOA caused by complete MA diagnosed after a first TESE. PARTICIPANTS/MATERIALS, SETTING, METHODS: Twenty-six men with MA at the spermatocyte stage in all seminiferous tubules, according to a histopathological analysis performed independently by two expert histologists, and a normal karyotype (i.e. no AZF gene microdeletions on the Y chromosome) were included. Single-nucleotide polymorphism comparative genomic hybridization array and WES were carried out. The results were validated with Sanger sequencing. For all the variants thought to influence spermatogenesis, we used immunohistochemical techniques to analyse the level of the altered protein. MAIN RESULTS AND THE ROLE OF CHANCE: Deleterious homozygous variants were identified in all seven consanguineous patients and in three of the 19 non-consanguineous patients. Compound heterozygous variants were identified in another 5 of the 19 non-consanguineous patients. No recurrent variants were identified. We found new variants in genes known to be involved in azoospermia or MA [including testis expressed 11 (TEX11), meiotic double-stranded break formation protein 1 (MEI1), proteasome 26s subunit, ATPase 3 interacting protein (PSMC3IP), synaptonemal complex central element protein 1 (SYCE1) and Fanconi anaemia complementation group M (FANCM) and variants in genes not previously linked to human MA (including CCCTC-binding factor like (CTCFL), Mov10 like RISC complex RNA helicase 1 (MOV10L1), chromosome 11 open reading frame 80 (C11ORF80) and exonuclease 1 (EXO1)]. LARGE SCALE DATA: Data available on request. LIMITATIONS, REASONS FOR CAUTION: More data are required before WES screening can be used to avoid recurrent TESE, although screening should be recommended for men with a consanguineous family background. WES is still a complex technology and can generate incidental findings. WIDER IMPLICATIONS OF THE FINDINGS: Our results confirmed the genetic aetiology of MA in most patients: the proportion of individuals with at least one pathologic variant was 50% in the overall study population and 100% in the consanguineous patients. With the exception of MEI1 (compound heterozygous variants of which were identified in two cases), each variant corresponded to a specific gene-confirming the high degree of genetic heterogeneity in men with MA. Our results suggest that WES screening could help to avoid recurrent, futile TESE in men with MA in general and in consanguineous individuals in particular, but these results need to be confirmed in future studies before clinical implementation. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by the Fondation Maladies Rares (Paris, France), Merck (Kenilworth, NJ, USA), IRSF (Montigny le Bretonneux, France) and Agence de la Biomédecine (Saint Denis, France). There are no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Qualitative and quantitative contrast-enhanced ultrasonography for the characterisation of non-palpable testicular tumours.

AIM: To assess the diagnostic performance of conventional ultrasound (US) and contrast-enhanced ultrasonography (CEUS) in the differential diagnosis of non-palpable intratesticular tumours. MATERIALS AND METHODS: The local ethics review board approved the protocol, and all of the patients provided written informed consent. Between December 2011 and February 2014, men with non-palpable testicular tumours and normal tumour markers who were referred for surgery were included. The tumours were analysed by conventional US, including B-mode and colour Doppler US (CDUS) as well as by CEUS. Morphological aspects and qualitative and quantitative CEUS criteria, based on visual enhancement and time-intensity curves, were assessed for each lesion. RESULTS: Forty patients were ultimately included. Based on histopathological results, the tumours were classified into three groups: benign tumours (n=16), malignant tumours (n=15), and burned-out tumours (n=9). In B-mode, the morphological aspects were significantly different between benign and malignant tumours (p-values from 0.0002 to 0.008). Qualitative and quantitative analyses of the CEUS images revealed that burned-out tumours exhibited significantly less enhancement than malignant and benign tumours: in burned-out tumours, time-intensity curves were flat, whereas in both benign and malignant tumours the curves had a bell-shaped pattern. All intensity parameters were lower for burned-out tumours compared to benign and malignant tumours (p-value from 0.0001 to 0.026). Both benign and malignant tumours enhanced strongly, however, and no significant difference between the two was noted (p-value from 0.0721 to 0.0953). CONCLUSION: Unlike conventional US, which enable benign lesions to be differentiated from malignant or burned-out tumours, CEUS failed to enabled differentiation between benign lesions and malignant vascularised testicular tumours. CEUS appears to have the potential, however, to differentiate burned-out tumours from vascularised testicular tumours.

[Non-obstructive azoospermia: option of the testicular sperm extraction performed on the day of oocyte retrieval]. / Azoospermie non obstructive: intérêt du prélèvement testiculaire synchrone du recueil ovocytaire.

OBJECTIVE: Analyzing the results and validating the procedure of testicular sperm extraction (TESE) performed on the day of oocyte retrieval in non obstructive azoospermia (NOA) patients. PATIENTS AND METHODS: Sixty TESE were performed on the day of oocyte retrieval (dOR), in 52 NOA men. Patients were sorted into three groups according to the results of the surgical procedure: 1: sperm recovery with possible sperm freezing (n=20); 2: sperm recovery without freezing (n=27); 3: "negative" biopsy (n=13). ICSI outcomes in the two groups with sperm recovery were compared to those of ICSI performed with frozen-thawed sperm obtained from TESE performed (n=13). RESULTS: The rate of positive sperm retrieval was 78%. While the overall clinical pregnancy rate was 50%, no difference in the fertilization, implantation and clinical pregnancy rates was found in the two groups with positive sperm retrieval as compared to frozen-thawed sperm group. Twelve pregnancies were obtained in patients without further sperm cryopreservation. CONCLUSION: After TESE in NOA men, cryopreserved sperm produced comparable results with freshly obtained sperm. However, TESE performed on dOR can offer the opportunity, in patients with rare sperm that might not survive freeze-thaw, to have a possible fresh embryo transfer. Couples should be counselled regarding the possibility of oocyte retrieval without sperm for ICSI.

[Optimal evaluation of the infertile male. 2007 French urological association guidelines]. / Evaluation de l'homme infertile: recommandations AFU 2007.

An infertility evaluation should be performed if a couple has not achieved conception after one year of unprotected intercourse. An evaluation should be performed earlier if male or female infertility risk factors exist and if the couple questions its fertility potential. The initial screening of the male should include a reproductive history and a physical examination performed by a urologist or a specialist in male fertility and two semen analyses. Additional procedures and testing may be used to elucidate problems discovered during the full evaluation. The minimal initial endocrine evaluation should include serum total testosterone and serum follicle-stimulating hormone levels. An endocrine evaluation should be performed if sperm concentration is abnormally low, sexual function is impaired, and when other clinical findings suggest a specific endocrinopathy. A postejaculatory urinalysis should be performed if ejaculate volume is less than 1 mL, except in patients with bilateral vasal agenesis or possible hypogonadism. With a diagnosis of retrograde ejaculation, specific management should be considered before advising assisted reproductive technology. Scrotal ultrasonography is indicated when physical examination of the scrotum is difficult or inadequate, or when a testicular mass is suspected. Transrectal ultrasonography (TRUS) is indicated in patients who are azoospermic or have a low ejaculate volume. Specialized testing of semen is not required for routine diagnosis of male infertility. However, some tests may be useful for a few patients to identify a male factor contributing to unexplained infertility, or to select therapy (e.g., assisted reproductive technology). Before performing intracytoplasmic sperm injection, karyotyping and Y-chromosome analysis should be offered to men who have nonobstructive azoospermia and severe oligospermia. Genetic testing for gene mutations of the ABCC7 (ex-CFTR) gene should be offered to male and female partners before proceeding with treatments that use the sperm of men with congenital bilateral absence of the vasa deferentia or congenital unilateral abnormality of the seminal tract. Genetic counseling may be offered when a genetic abnormality is suspected in the male or female partner, and it should be provided when a genetic abnormality is detected. Genetic testing in the female partner, when non symptomatic, should only be advised by a physician from a multidisciplinary team registered by the ministry of health. Evaluation by testis biopsy and deferentography should be performed by a urologist or an andrologist registered for sperm retrieval.

Cytogenetic, molecular and testicular tissue studies in an infertile 45,X male carrying an unbalanced (Y;22) translocation: case report.

(Y;autosome) translocations have been reported in association with male infertility. Different mechanisms have been suggested to explain the male infertility, such as deletion of the azoospermic factor (AZF) on the long arm of the Y chromosome, or meiosis impairment. We describe a new case with a de novo unbalanced translocation t(Y;22) and discuss the genotype-phenotype correlation. A 36 year old male with azoospermia was found to have a mosaic 45,X/46,X, + mar karyotype. Fluorescence in situ hybridization (FISH) showed the presence of a derivative Y chromosome containing the short arm, the centromere and a small proximal part of the long-arm euchromatin of the Y chromosome and the long arm of chromosome 22. The unstable small marker chromosome included the short arm and the centromere of chromosome 22. This unbalanced translocation t(Y;22)(q11.2;q11.1) generated the loss of the long arm of the Y chromosome involving a large part of AZFb, AZFc and Yq heterochromatin regions. Testicular tissue analyses showed sperm in the wet preparation. Our case shows the importance of documenting (Y;autosome) translocations with molecular and testicular tissue analyses.

[Tension force in dynamic splints made of neoprene]. / Le collage en tension dans les orthèses dynamiques en matériau néoprène.

Dynamic splints are the most difficult ortheses to make. Unrestricted finger joint mobility is usually prevented by the size of their components. Ortheses made out of neoprene material have the advantage of being pliable and at the same time can be constructed as dynamic splints. Neoprene material elasticity allows conforming it into a tube that can be fitted over a finger, spreading uniform pressure. A traction slip can be cemented to the neoprene finger tube. With neoprene splints, lever arms are more efficient. Their tubular design applies and spreads traction and countertraction forces in all directions. Neoprene material's elasticity contributes in reducing edema formation as well as distributes forces applied to the finger over a large area. The risk of excessive pressure is the only drawback of an elastic tubular design, it may cause pain and tissue ischemia. A meticulous tailoring prevents this potential risk.

[Intracytoplasmic sperm injection (ICSI) in the management of azoospermia]. / L'injection intra cytoplasmique de spermatozoïdes (ICSI) dans la prise en charge des azoospermies.

OBJECTIVES: The objective of this study was to analyse all attempts of ICSI performed in our centre between 1995 and 1997 with surgically harvested sperm for the treatment of secretory and excretory azoospermia. MATERIAL AND METHODS: 71 infertile couples, in which the man suffered from secretory (n = 8) or excretory azoospermia (n = 63), were managed with 94 attempts of ICSI. RESULTS: ICSI was able to be performed 85 times with 82 embryo transfers resulting in 29 clinical pregnancies. The clinical pregnancy rate per ICSI attempt was comparable with sperm obtained on the day of ICSI or previously harvested and frozen (30.5% and 31.4% respectively). The clinical pregnancy rate per ICSI attempt was 33.3% for testicular sperm (n = 18), and 30.3% for epididymal sperm (n = 76). Twenty-seven clinical pregnancies (32.1%) were obtained for men with excretory azoospermia (47.2% for vas deferens agenesis and 20.8% for acquired urinary tract obstruction, p = 0.01), and 2 (20%) for men with secretory azoospermia. CONCLUSION: ICSI can achieve pregnancy in infertile couples in whom no other solution can be considered. Cryopreservation allows surgical harvesting to be dissociated from ICSI without decreasing the pregnancy rate, justifying freezing of sperm during any surgical procedure on the seminal tract. The better results obtained in congenital excretory azoospermia compared to acquired obstructions, usually post-infectious, suggest a harmful effect of infection on the quality of sperm.

[Is today's man really less fertile?]. / L'homme d'aujourd'hui est-il vraiment moins fertile?

In 1992, a statistical analysis of data from 61 studies of semen quality among normal men led to the conclusion that human sperm count fell of 40% from 1940 to 1990. This meta-analysis has since been invalidated for methodological reasons as well as for statistical reasons, but it caused enormous concern to both the scientific community and to the international media. A decline of human fertility was speculated. To date, the most popular hypothesis offered to explain this alleged decline has been increasing exposure to environmental estrogen mimicking chemicals. However, there is no evidence that male or mammal fertility is declining. Moreover, the sperm count of breeding mammals did not declined in the meanwhile. Since 1992, numerous papers reported on men investigated during the last 20 years have shown conflicting results, from sperm count improvement to sperm count decline. However, several publications included methodological and analytical biases. In fact, the techniques used for semen analysis have to be questioned. It is a subjective exam, lacking laboratory standards and quality control procedures. This induces very important variations between laboratories and between biologists. For the sperm count itself, numerous errors can occur, provoked by the technique, the equipment and the reader: for the same sperm, the coefficient of variation can exceed 40% between two technicians. Therefore, the current techniques of semen analysis cannot warrant epidemiological studies. It is indispensable to admit the limits of the semen analysis in order to improve as much as possible its quality and its reliability.

A double blind, placebo controlled study of a platelet activating factor antagonist in patients with rheumatoid arthritis.

OBJECTIVE: To evaluate the efficacy and tolerance of a platelet activating factor-acether (PAF) antagonist, BN 50730, in patients with rheumatoid arthritis (RA). METHODS: A total of 56 patients with active RA were enrolled in a multicenter, double blind, placebo controlled study of BN 50730. Patients received either BN 50730 (40 mg orally bid) or placebo for 84 days. RESULTS: Treatment with BN 50730 resulted in no improvement and was no more effective than placebo in improving clinical and biological indices of RA activity. Adverse events were observed in the 2 treatment groups, and BN 50730 was generally well tolerated. CONCLUSION: PAF antagonist BN 50730 at a daily dose of 80 mg was ineffective in the treatment of RA.

[Intra-cytoplasmic sperm injection with testicular sperm: what strategy?]. / ICSI avec sperme testiculaire: quelle stratégie?

The pregnancy rate after ICSI with surgically retrieved spermatozoa varies according to the etiology and to the level of sperm retrieval in the genital tract. The use of testicular sperm in all cases is discussed.

Molecular diagnosis of congenital bilateral absence of the vas deferens: analyses of the CFTR gene in 64 French patients.

Congenital bilateral absence of the vas deferens is a congenital reproductive disorder that affects about one in 1000 male individuals. Screening of the entire coding and flanking sequences of the cystic fibrosis transmembrane conductance regulator (CFTR) gene in 64 males with CBAVD revealed that in only 23% CBAVD was caused by two CFTR mutations. The 5T allele in one copy, that causes reduced levels of the normal CFTR protein, in combination with a CFTR mutation in the other copy, was one of the most common causes of CBAVD. Twenty six per cent of men with CBAVD had the 5T allele. The presence of only one CFTR mutation or the 5T allele in 34% of patients suggests that undetected changes in CFTR may be involved in CBAVD. These molecular defects are probably mutations with partial penetrance. Moreover, the high proportion (20%) of patients with CBAVD who did not have CFTR mutations or the 5T allele allows to propose that another gene or genes could be responsible for CBAVD. In these cases, in vitro fertilization may be required and the genetic counselling appears to be very complex and additional studies, including CFTR mRNA and linkage analyses, are required to resolve these questions.

Treatment of rheumatoid arthritis with platelet activating factor antagonist BN 50730.

OBJECTIVE: To determine the efficacy and safety of a platelet activating factor (PAF) antagonist, BN 50730, in patients with rheumatoid arthritis. METHODS: Ten patients with an active disease were treated for 4 weeks with a PAF receptor antagonist, BN 50730, given orally (40 mg twice daily). The treatment period was followed by a 4 weeks followup period. RESULTS: Clinical indicators of disease activity significantly improved during the treatment period, with a progressive return to baseline values during the followup period. No significant change in laboratory variables was observed. The tolerance of the treatment was excellent, and no clinical or laboratory evidence of side effects was recorded. CONCLUSION: These results need to be confirmed in a controlled study, but suggest an antiinflammatory effect. PAF antagonists could represent a new class of therapeutic agents in inflammatory arthropathies.

[Surgery for male infertility]. / Chirurgie de la stérilité masculine.

Biological improvement reduces number of infertile couples, but surgical treatment of male infertility still remains disappointing. Surgeons play an important role within multi-disciplinary teams dealing with infecund couples. Even through biological and microsurgical approach in the operating room, postoperative results with carefully selected patients remain poor. Surgery will be reserved for the only clear and simple cases, and surgeons will not yield under pressure of patients or practitioners and carry out a "last chance" procedure.