Development of a multivariable prediction model for congenital unilateral absence of the vas deferens in male partners of infertile couples.

BACKGROUND: Congenital unilateral absence of vas deferens has been diagnosed in fertile and normozoospermic males and is associated with the risk of unilateral renal absence or cystic fibrosis transmembrane conductance regulator mutations; but no prediction model currently exists to diagnose this condition. OBJECTIVES: The study aims to identify clinical and biological variables that may have a predictive value for the diagnosis of congenital unilateral absence of vas deferens in male partners of infertile couples MATERIALS AND METHODS: We designed a retrospective, cross-sectional, case-control study on electronic health records of a single tertiary-care andrological centre collected between 1998 and 2018. We included all subjects diagnosed with congenital unilateral absence of vas deferens using combined scrotal and transrectal ultrasounds. Controls were confirmed free of congenital unilateral absence of vas deferens by the same way. Both groups received standardised exploration procedures. Multivariable logistic regression model was built in a backward stepwise manner. Model performance and calibration were assessed. The study is reported according to TRIPOD statement. RESULTS: We included 69 congenital unilateral absence of vas deferens cases and 78 controls. Cases had a lower semen volume than controls. The congenital unilateral absence of vas deferens risk was associated with history of cryptorchidism and both levels of semen fructose and α-glucosidase. These predictors were confirmed by a random forest algorithm. The area under the curve was 0.886 (95% interval: 0.81-0.92). Calibration was performed with the Hosmer-Lemeshow test (p = 0.88). DISCUSSION AND CONCLUSION: History of cryptorchidism, semen fructose and α-glucosidase were identified as relevant and independent predictors for the diagnosis of congenital unilateral absence of vas deferens. The model enables to identify male patients with a high risk of congenital unilateral absence of vas deferens to whom a transrectal ultrasounds would be proposed to confirm the diagnosis, whatever their semen parameters. It will also help to address the risks of unilateral renal absence and of cystic fibrosis transmembrane conductance regulator mutations carrying during the management of infertile couples.

Management of pemphigus disease in pregnancy.

Pemphigus can cause complications during pregnancy and may cause serious harm to a fetus. For this study, a comprehensive review of common treatments of pemphigus and their adverse effects associated with pregnancy and male fertility was conducted. We concluded that a period of remission with minimal or no therapy before conception could significantly reduce the risk of the disease flaring up, at least in the first trimester. The period of remission causes a delay in the flare-up of the disease, which means lower cumulative doses and the prevention of possible congenital abnormalities caused by corticosteroid or immunosuppressant treatments. All common treatments of pemphigus-azathioprine, mycophenolate mofetil, and methotrexate-should be avoided during pregnancy. However, it appears that systemic corticosteroids in a safe dose with a topical form of corticosteroids may be used without serious risk. Due to the lack of data associated with rituximab therapy, it is recommended that this drug be avoided 12 months before conception. It appears that the safest treatment of pemphigus is intravenous immunoglobulin (IVIg), which may be more effective when used with topical corticosteroids. Due to the delayed effect of IVIg, it should be used some months prior to conception.

Programa de preservación de la fertilidad en pacientes oncológicos / Fertility preservation program in cancer patientes

La infertilidad, es un problema que a día de hoy afecta a una gran cantidad de parejas. Una de las posibles causas es la disminución a nivel mundial de la calidad seminal debido a factores como pueden ser la alimentación, el consumo de alcohol y tabaco, altos niveles de estrés o factores ambientales. Además, el aumento de la incidencia de enfermedades tumorales en pacientes menores de 35 años, pone de manifiesto la necesidad de preservar la fertilidad de estos pacientes mediante técnicas de criopreservación. Es importante, que ésta se realice antes de que reciban ningún tipo de tratamiento (quimioterapia y radioterapia). En este trabajo, se llevará a cabo un estudio comparativo entre las muestras de varones que acuden al Hospital Materno Infantil por problemas de fertilidad y aquellos pacientes oncológicos que antes de iniciar el tratamiento realizan una criopreservación de la muestra seminal analizando las posibles variaciones de estas últimas muestras, mediante un test de post-congelación para comprobar la viabilidad de las muestras criopreservadas. Los parámetros que se van a analizar son: edad del paciente, volumen de la muestra, concentración espermática, porcentaje de espermatozoides móviles e inmóviles, móviles progresivos y espermatozoides tipo 'a'

The infertility, is a problem affecting a large number of couples today. One of the possible causes is decreasing around the world of the seminal ability due to factors such as food, alcohol and tobacco consumption, high levels of stress or environmental factors. In addition, the increase in the incidence of tumour diseases in patients younger than 35 years, highlights the need to preserve the fertility of these patients through cryopreservation techniques. It is important that this be done before they receive any kind of treatment (chemotherapy and radiotherapy). In this work, we will take place a comparative study between the samples of male couples who come to the mother and child Hospital for fertility problems and cancer patients before treatment carried out a Cryopreservation of spermatozoa by analysing possible variations of these latest samples, using a test of post-congelacion to check the viability of samples criopreserved. The parameters will be analyzed are: the patient's age, volume of sample, sperm concentration, percentage of progressive mobile and stationary, mobile sperm and sperm type 'a'

La percepción del hombre cuando acude a un centro de reproducción asistida / Male perception of assisted reproduction treatments

Objetivo: El objetivo de este trabajo es describir la percepción de varones infértiles que se someten a tratamientos de reproducción asistida (RA). Se recogió información acerca de su experiencia antes y después del tratamiento, pruebas realizadas, atención médica recibida, etc. Material y métodos: Se trata de un estudio prospectivo, observacional y descriptivo, donde se entrevistaron un total de 46 hombres de los muchos que acudieron a la I Feria de Reproducción Asistida, celebrada en Valencia. Todos los individuos completaron un cuestionario con un total de 33 preguntas relacionadas con su experiencia personal durante el tratamiento realizado. Resultados: Durante la anamnesis, el 22% de los hombres manifiestan que no se les interrogó, y el 52% de que fue breve. No se realizó una exploración genital al 67% de los casos. Hasta el 55% de los pacientes declaran que han sido poco o nada informados acerca de la causa de su esterilidad. En la mitad de los casos con un tratamiento previo, no se explican las posibles razones del resultado fallido. Conclusiones: Aunque el número de casos es limitado, las conclusiones son claras acerca de la poca participación de andrólogos/urólogos en los centros de reproducción asistida. Se percibe una falta de información general tanto en la fase diagnóstica como durante el tratamiento. Es imprescindible mejorar esta situación, ampliando este tipo de estudios y adecuándolos como herramientas rutinarias para conocer el grado de calidad asistencial de nuestros pacientes (AU)

Objective: The aim of this paper is to describe the perceptions of infertile men who undergo assisted reproduction treatments. Information about their experience (before and after the treatment), diagnostic tests and medical care were collected. Material and methods: A prospective, observational and descriptive study with a total of 46 men who visited the I Assisted Reproduction Fair held in Valencia was carried out. All subjects completed a questionnaire with a total of 33 questions related to their personal experience during the treatment performed. Results: In the anamnesis phase, men reported they had not been questioned adequately in 22% of cases, and questioned briefly in 52% of cases. A genital exploration was performed in 33% of cases. Clinical information received about the cause of infertility was poor or non-existent in 55% of cases. In previously treated patients, up to 50% of cases were not informed of potential causes of failures. Conclusions: Although the number of cases is limited, the findings are clear about the low participation of andrologists/urologists in assisted reproduction centers. A general lack of information on both the diagnostic phase and during treatment is perceived. It is essential to improve this situation, to extend these studies and adapt them as a routine to determine the care quality of our patients (AU)

Mutation studies in the CFTR gene in Asian Indian subjects with congenital bilateral absence of vas deferens: report of two novel mutations and four novel variants.

BACKGROUND: Congenital bilateral absence of vas deferens (CBAVD) is a form of male infertility in which mutations occur in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The molecular basis of CBAVD is not completely understood, especially in developing countries. METHODS: We characterized the mutations/variants in the CFTR gene by single strand conformation polymorphism followed by sequencing in 35 CBAVD patients. None of the patients had systemic manifestations of cystic fibrosis. Fifty normal subjects were studied as controls. RESULTS: Mutations/variants in the CFTR gene were found in all CBAVD patients. Five mutations and 10 variants were detected in 35 patients. The most frequent severe mutation was F508del (34.2%) and the most common variant was IVS8-5T (54.2%). Two novel severe mutations (p.E217Gfs*11 and p.A1285V) and four novel variants (pT438A, c.4095+30insCT, c.-737G>A, and c.2909-92A>G) were detected. CONCLUSION: The protocol for identification of mutations in cases of CBAVD in developing countries would have to include a different set of mutations than those reported from western countries.

Fibrosis quística: diagnóstico tardío en el adulto presentación de caso / Delayed diagnosis of the cystic fibrosis in adulthood: a case report

Se presenta el caso de un paciente blanco de 47 años con cuadros respiratorios a repetición que cedían con tratamiento sintomático o con el uso de antibióticos por vía oral desde la infancia. A los 39 años de edad, comenzó con agudizaciones más frecuentes que requirieron tratamientos con antibióticos e ingresos en varios hospitales de Ciudad de La Habana, y se le diagnosticó Bronquiectasias diseminadas bilaterales e infectadas con Pseudomonas Aeruginosas, secundarias a una posible Tuberculosis adquirida en la antigua URSS a los 21 años. La falta de lesiones hacia los vértices pulmonares en la radiografía de tórax y el hecho de no haber nunca tenido hijos despertó la sospecha clínica de Fibrosis Quística, la cual fue confirmada por los estudios realizados posteriormente. Nuestro propósito al presentar este caso es alertar que esta enfermedad ha dejado de ser una patología exclusiva de Pediatría y que debe sospecharse ante un cuadro florido de bronquiectasias(AU)

The case of a 47 years old white patient, that presented repeated respiratory symptoms that only improve using symptomatic treatment or oral antibiotics. In 2000 when, he was 39 years old their symptoms increased and he required antibiotic intensive treatment and incomes at several hospital in Havana. After that, he was diagnosed with multiple bronchiectasis spread bilateral and infected Pseudomona Auriginosa, that could brings about, TB acquired at URSS when he was 21 years old. In 2008 because of the absence of lesions toward pulmonary apex in the Rx and the fact he couldn't have children aroused the clinical suspicion of Cystic Fibrosis and it was later confirmed by the accomplished studies. Our purpose to present this case is to alert and prevent that this disease has stopped being Pediatric's exclusive pathology and it should be taking into account when there is a complete picture of a multiple spread bronchiectasis(AU)

Activated caspases in thawed epididymal and testicular spermatozoa of patients with congenital bilateral absence of the vas deferens and intracytoplasmic sperm injection outcome.

OBJECTIVE: To analyze the expression of activated caspases and membrane permeability in thawed epididymal and testicular spermatozoa of patients with congenital bilateral absence of the vas deferens (CBAVD). DESIGN: Retrospective study. SETTING: Biology and medicine of reproduction in University hospital. PATIENT(S): Eight CBAVD patients. INTERVENTION(S): Staining of activated caspases and viability (propidium iodide, PI); intracytoplasmic sperm injection (ICSI). MAIN OUTCOME MEASURE(S): Proportion of viable (Casp-/PI-) or dead (Casp-/PI+) spermatozoa without activated caspases, viable (Casp+/PI-) or dead (Casp+/PI+) spermatozoa with activated caspases. ICSI results. RESULT(S): Higher percentage of dead (Casp+/PI+; 84.0% vs. 57.5%) and viable (Casp+/PI-; 12.0% vs. 0) spermatozoa with activated caspases were observed in testicular than in epididymal samples. No significant difference was observed between the percentage of total testicular and epididymal spermatozoa permeant for PI. The outcome of ICSI fertilization (67.5% vs. 57.4%), good morphology embryo at day 2 (75.9% vs. 61.3%), clinical pregnancy (26.7% vs. 15.4%), and implantation (15.6% vs 9.5%) rates were better when ICSI were performed with epididymal sperm samples. CONCLUSION(S): These results support the hypothesis of an abortive apoptotic process and demonstrate that combined staining of the activated caspases and membrane permeability provide complementary measurements for the evaluation of viable and functional spermatozoa to better understand ICSI outcomes with epididymal and testicular spermatozoa.

Transmission of male infertility and intracytoplasmic sperm injection (mini-review).

The fact that genetic aetiology is responsible for approximately one third of all kinds of male sterility has led to concerns regarding the application of artificial reproductive technologies in the cases of azoospermia and severe oligozoospermia. Congenital sterility could be caused by gene mutation, quantitative or structural abnormality of sexual chromosomes or autosomes. The possibility of inherited transmission of male sterility within the context of applying artificial reproductive technologies is analysed in the article. Klinefelter's syndrome, mutation of cystic fibrosis transmembrane conductance regulator (CFTR) gene, which causes cystic fibrosis, and mutation of azoospermia factor zone (AZF) of Y-chromosome are among the most frequent genetic causes of severe oligozoospermia and azoospermia. The probability of a mutation of the CFTR gene being transmitted to the next generation is 50%. The probability of inherit transmission of Klinefelter's syndrome of mosaic karyotype could reach 70%. The probability of transmission of AZF mutation to children of male sex, generated with ICSI, is 100%. The percent of men with AZF mutation among users of ICSI centers, ranges from 3.2% to 14%. It means that at least 3.2 % of all boys conceived with ICSI will be sterile because of mutation in the AZF zone of Y-chromosome. It should be noted that genetic analysis and counselling do not always occur before the beginning of artificial fertilization cycles. Parents-to-be do not always have an opportunity to learn about the genetic risks of their unborn child and make any subsequent and responsible decisions. Among the decisions is a choice of not resorting to ART, but to live with the infertility and explore other opportunities for parenthood. Responsibility for high risk of conceiving a child with genetic anomalies rests not only with the parents, but also with all of society, including those responsible for research, technology, and legislation, in the health care profession.

Mutation spectrum of the CFTR gene in Taiwanese patients with congenital bilateral absence of the vas deferens.

BACKGROUND: Clinically affected cystic fibrosis (CF) patients present a spectrum of genital phenotypes ranging from normal fertility to moderately impaired spermatogenesis and congenital bilateral absence of vas deferens (CBAVD). Little is known about the CF incidence in the Taiwanese population. It has been shown that the CBAVD in men without clinical evidence of CF is associated with a high incidence of mutated CFTR (cystic fibrosis transmembrane conductance regulator) alleles. In order to understand the involvement of the CFTR gene in the aetiology of Asian/Taiwanese male infertility, we screened the entirety of the CFTR gene in 36 infertile males with CBAVD. METHODS: Temporal temperature gradient gel electrophoresis (TTGE) followed by direct DNA sequencing was used. RESULTS: Five mutations, p.V201M, p.N287K, c.-8G > C (125G > C), p.M469I and p.S895N, were found in five of the patients. p.N287K occurred in the first transmembrane-spanning domain, p.M469I in the first ATP-binding domain and p.S895N in the second transmembrane-spanning domain, were novel. In addition, seven homozygous and seven heterozygous 5T alleles in the intron 8 poly(T) tract were found. The overall frequency of CFTR mutant alleles in Taiwanese CBAVD males was 26 out of 72 = 36%. This finding was lower than the published frequency of CFTR mutations in other ethnic CBAVD patients (ranging from 50 to 74%). The frequency of p.M470V in Taiwanese CBAVD patients is not significantly different from that in the general population (P = 0.12). CONCLUSIONS: The results of this study add to the short list of Taiwanese/Asian CFTR mutations. Unlike Caucasian patients, the CFTR mutations cannot account for the majority of Taiwanese CBAVD. This is consistent with the low incidence of CF in the Asian/Taiwanese population. Furthermore, the mutation spectrum of CFTR in CBAVD patients does not overlap with the Caucasian CFTR mutation spectrum.

Delayed motherhood increases the probability of sons to be infertile.

PURPOSE: To ascertain whether advanced maternal age at birth is associated with offspring infertility. METHODS: A written questionnaire was completed by infertile couples attending our clinic in the presence of a researcher. RESULTS: Maternal age at birth (odds ratio 1.236, 95% CI 1.100-1.388) and birth order of all respondents and their respective siblings (odds ratio 0.551, 95% CI 0.351-0.865) were significant predictors of male infertility. The probability of a man being infertile increased as mother's age at birth increased (regression coefficient +/- standard error 0.212 +/- 0.059; P < 0.001), but decreased as birth order increased (regression coefficient +/- standard error -0.596 +/- 0.230; P = 0.010). CONCLUSIONS: Delayed motherhood may enhance the probability of sons to be infertile. The probability of a man being infertile would be greater if he comes from a small family than if he comes from a large family.

Percutaneous epididymal sperm aspiration in a man with congenital bilateral absence of the vas deferens undergoing an assisted reproduction program.

Surgical retrieval of spermatozoa for in-vitro fertilisation (IVF) programs for severely oligospermic men has been in use for several years now. In the recent 2 to 3 years, clinicians have begun to move towards non-surgical methods of retrieving sperm in certain selected groups of men. Percutaneous epididymal sperm aspiration (PESA) has had good results in terms of number of sperm obtained, as well as the fertilisation and pregnancy rates. The first reported use of such a technique in Singapore is described.

Is infertility after surgery for cryptorchidism congenital or acquired?

We evaluated whether deletions of the DAZ (deleted in azoospermia) gene, abnormal karyotypes or hypogonadotropic hypogonadism (HH) were demonstrable in infertile men who had undergone surgery in childhood for cryptorchidism with a simultaneous testicular biopsy that demonstrated no or almost no germ cells. In six men with infertility after surgery for cryptorchidism, the adult karyotype and analyses for the DAZ gene, serum follicle-stimulating hormone, luteinizing hormone, and testosterone were performed from a peripheral blood sample. Testicular volume was also measured. All patients exhibited a 46,XY karyotype. There were no deletions of the DAZ-gene, no HH and no testicular atrophy. The infertility was thus not proved to be congenital, and consequently, surgical treatment is indicated before the germ cells disappear from undescended testes. This appears to be before 15 months of age.

Genetic findings in congenital bilateral aplasia of vas deferens patients and identification of six novel mutatations. Mutations in brief no. 138. Online.

Congential bilateral aplasia of vas deferens (CBAVD), a form of male sterility, has been suggested to represent a "genital" form of cystic fibrosis (CF), as mutations in the CFTR gene have been identified in most patients with this condition. Interestingly, the 5T allele in intron 8 appeared to be the most frequent mutation associated with CBAVD. However, the molecular basis of CBAVD is not completely understood. We have analysed the complete coding and flanking CFTR sequences by PCR-DGGE in 64 men with CBAVD from southern France with the aim to list any sequence alteration. Fourty-two of the 64 patients (65.6%) had mutations on both copies of the CFTR gene, including one patient with two mutations in the same copy (DF508 + A1067T). The 5T allele was present in 21/64 cases (33%). Six of the 28 different mutations identified in this study had never been described previously, and appeared to be specific to CBAVD (P111L, M244K, A1364V, G544V, 2896insAG,-33G->A).

[Causes and studies of male sterility in an urban French Canadian population]. / Causes et investigations de la stérilité mâle dans une population canadienne francophone urbaine

PIP: The causes of sterility were examined in 98 French-speaking males 20-41 years of age at a Montreal hospital. 59 submitted to testicular biopsy and 31 received more complete hormonal workups. The etiologies were: congenital, 11; hormonal, 0; acquired, 14; varicocele, 31; duct obstruction, 1; immunologic, 0; and idiopathic, 41. Hypospermatogenesis (25%) and hyalinization (22%) were the most common biopsy findings. Urinary follicle stimulating hormone was notably elevated in both the azoospermic and oligospermic patients studied. Clinical procedures for investigating male infertility and notes on the interpretation of the spermogram are given in the discussion section.^ieng