Genetic male infertility and mutation of CATSPER ion channels.

A clinically significant proportion of couples experience difficulty in conceiving a child. In about half of these cases male infertility is the cause and often genetic factors are involved. Despite advances in clinical diagnostics ∼50% of male infertility cases remain idiopathic. Based on this, further analysis of infertile males is required to identify new genetic factors involved in male infertility. This review focuses on cation channel of sperm (CATSPER)-related male infertility. It is based on PubMed literature searches using the keywords 'CATSPER', 'male infertility', 'male contraception', 'immunocontraception' and 'pharmacologic contraception' (publication dates from January 1979 to December 2009). Previously, contiguous gene deletions including the CATSPER2 gene implicated the sperm-specific CATSPER channel in syndromic male infertility (SMI). Recently, we identified insertion mutations of the CATSPER1 gene in families with recessively inherited nonsyndromic male infertility (NSMI). The CATSPER channel therefore represents a novel human male fertility factor. In this review we summarize the genetic and clinical data showing the role of CATSPER mutation in human forms of NSMI and SMI. In addition, we discuss clinical management and therapeutic options for these patients. Finally, we describe how the CATSPER channel could be used as a target for development of a male contraceptive.

Neonatal inhalatory anesthetic exposure: Reproductive changes in male rats

We investigated the effects of an inhalatory anesthetic (ethyl ether) during the neonatal period of brain sexual differentiation on the later fertility and sexual behavior of male rats. Animals were exposed to ethyl ether immediately after birth. At adulthood, body weight, testes wet weight, and plasma testosterone levels were not affected; however, neonatal exposure to ether showed alterations on male fertility: a decrease in the number of spermatids and spermatozoa, an increase in the transit time of cauda epididymal spermatozoa and a decrease in daily sperm production. An alteration of sexual behavior was also observed: decreased male sexual behavior and appearance of homosexual behavior when the male rats were castrated and pretreated with exogenous estrogen. Probably, the ether delayed or reduced the testosterone peak of the sexual differentiation period, altering the processes of masculinization and defeminization of the hypothalamus. Our results indicate that perinatal exposure to ethyl ether during the critical period of male brain sexual differentiation, acting as endocrine disruptors, has a long-term effect on the fertility and sexual behavior of male rats, suggesting endocrine disruption through incomplete masculinization and defeminization of the central nervous system. © 2002 Elsevier B.V. All rights reserved.

The effects of male age on sperm DNA damage in an infertile population

The objective was to investigate the influence of age on sperm DNA damage. Semen samples were collected from 508 men in an unselected group of couples attending infertility investigation and treatment. DNA fragmentation in spermatozoa was measured by TdT (terminal deoxynucleotidyl transferase)-mediated dUTP nick-end labelling (TUNEL) assay; at least 200 spermatozoa in randomly selected areas of microscope slides were evaluated using a fluorescent microscope and the percentage of TUNEL positive spermatozoa was determined. The number of cells with red fluorescence (TUNEL positive) was expressed as a percentage of the total sample [DNA fragmentation index (DFI)]. Age was treated as a continuous variable for regression and correlation analysis. The following male age groups were used: Group I: ≤35 years, Group II: 36-39 years, and Group III: ≥40 years. DFI was significantly lower in Group I than in Group II (P = 0.034) or III (P = 0.022). There was no difference in DFI between Groups II and III. In addition, regression analysis demonstrated a significant increase in sperm DFI with age (P = 0.02). TUNEL assay clearly demonstrates an increase in sperm DNA damage with age. © 2007 Published by Reproductive Healthcare Ltd.

Avanços em reprodução assistida

Buscou-se, por meio de uma revisão bibliográfica de publicações científicas, atualizar conhecimentos produzidos sobre reprodução assistida. Inicialmente, investigou-se o histórico e, em seguida, foram apresentados conceitos relativos à infertilidade e sobre as técnicas de reprodução assistida, especificando-se ainda alguns temas relacionados a aspectos obstétricos, epidemiológicos e perinatais. Vários artigos que abordam o tema foram apresentados. Foi discutida a situação no Brasil bem como os vários aspectos assinalados

Impact of clinical varicocele and testis size on seminal reactive oxygen species levels in a fertile population: a prospective controlled study

Objective: To investigate: 1) the impact of clinical varicocele on reactive oxygen species (ROS) levels in neat and washed semen in a proven fertile population; and 2) the correlation between ROS levels, testicular volume, and varicocele grade in the same population of fertile men. Design: Prospective controlled clinical study. Setting: Andrology laboratory at tertiary-care hospital. Patient(s): One hundred fourteen healthy fertile men (81 normal fertile and 33 fertile with clinical varicocele) and 30 infertile patients (control subjects). Intervention(s): Standard semen analysis and measurement of sperm ROS production. Main Outcome Measure(s): Seminal parameters, seminal ROS levels, seminal leukocyte levels, clinical varicocele, and testis size. Result(s): Thirty-three of the 11.4 (29%) fertile men had clinical varicocele (grade 1, n = 14; grade 2, n = 11; and grade 3, n = 8), and the remaining 81 (71%) had a normal physical examination. Levels of ROS and semen quality did not differ significantly between the fertile men with or without varicocele. No significant differences in ROS levels in neat and washed semen were observed compared with fertile men with grades 2 and 3 varicocele and with fertile men with varicocele grade 1. The ROS levels in neat and washed semen were not significantly correlated with varicocele grade in fertile men. No significant correlations between ROS levels and testis volume were observed between the fertile groups. Conclusion(s): The presence of clinical varicocele in fertile men is not associated with higher seminal ROS levels or abnormal semen parameters. Levels of ROS are not correlated with varicocele grade or testis volume in the same population of fertile men.

Results of microsurgical anastomosis in men with seminal tract obstruction due to inguinal herniorrhaphy

The incidence of vasal injury during inguinal herniorrhaphy is estimated at 0.5%. We sought to assess the patency rates and long-term fertility outcome after microsurgical repair of vasal obstruction related to prior inguinal herniorrhaphy. METHODS: Twenty procedures were performed on 13 men diagnosed with infertility and vasal injury secondary to previous inguinal herniorrhaphy. Eight of these men had undergone bilateral and 5 unilateral inguinal herniorrhaphy. Twelve procedures were vasovasostomies, 3 were crossover vasovasostomies, 2 were vasoepididymostomies, and 3 were crossover vasoepididymostomies. Eight patients were azoospermic, 2 were severely oligospermic (<1 M/mL), 1 was oligospermic, and 2 were asthenospermic. Patency data was obtained on all 13 patients, and pregnancy data was available for 10 couples (77%), with a mean follow-up of 69.5 months. RESULTS: The overall patency rate was 65%. In the vasovasostomy group, the patency rate was 60% (9/15), and in the vasoepididymostomy group it was 80% (4/5). Among the azoospermic patients, 13 procedures were performed. The patency rate was 42.9% for the vasovasostomy (3/7), and 100% for the vasoepididymostomy procedure (4/4). The overall pregnancy rate was 40%. Of the men who underwent vasoepididymostomy, 80% (4/5) established a pregnancy. CONCLUSIONS: Microsurgical vasovasostomy after inguinal vas injury results in a reasonable patency rate but a lower pregnancy rate than that after vasectomy reversal. When microsurgical vasoepididymostomy was possible, it resulted in high patency and pregnancy rate. Crossover vasoepididymostomy, when appropriate, can be a useful alternative to inguinal vasovasostomy.

Quelle assistance psychologique pour les couples requérant une aide médicale à la procréation [Which psychological support for couples seeking medical assistance for procreation?]

OBJECTIVES: The objective of our qualitative study was to define modalities of psychological support to be offered to couples seeking medically assisted procreation. MATERIAL AND METHODS: Forty couples participated in a semi-structured videotaped interview, which touched on themes such as personal and family histories, the couple's relationship, etc. We focused on the "narrative mobility", that is the way in which the couples transmit their personal and family history during the interview and the interviewer's impression that he may or may not share this with the couples. RESULTS: Observed differences in narrative mobility led us to distinguish three groups of couples and to propose various types of psychological support. DISCUSSION AND CONCLUSION: This exploratory study, with its interest for the narrative mobility, concerns the couples' capacity to stand back from their own story as responsible interlocutors. We made the hypothesis that this capacity is linked to their capacity to handle their emotional stress, to act as partners to the medical team and to prepare themselves for their future parenthood.

Adiponectin isoform distribution in serum and in follicular fluid of women undergoing treatment by ICSI.

Adiponectin is an adipokine, present in the circulation in comparatively high concentrations and different molecular weight isoforms. For the first time, the distribution of these isoforms in serum and follicular fluid (FF) and their usefulness as biological markers for infertility investigations was studied. In vitro study. University based hospital. Fifty-four women undergoing intracytoplasmic sperm injection (ICSI). Oocytes were retrieved, fertilized in vitro using ICSI, and the resulting embryos transferred. Serum was collected immediately prior to oocyte retrieval. Adiponectin isoforms (high molecular weight (HMW), medium and low molecular weight) were determined in serum and FF. Total adiponectin and the different isoform levels were compared with leptin and ovarian steroid concentrations. Adiponectin isoforms in serum and FF. Adiponectin isoform distribution differed between serum and FF; the HMW fraction made up half of all adiponectin in the serum but only 23.3% in the FF. Total and HMW adiponectin in both serum and FF correlated negatively with the body mass index and the concentration of leptin. No correlations were observed for total adiponectin or its isoforms with estradiol, progesterone, anti-Mullerian hormone, inhibin B, or the total follicle stimulating hormone (FSH) dose administered during the ovarian stimulation phase. This study shows for the first time that adiponectin isoform distribution varies between the serum and FF compartments in gonadotropin stimulated patients. A trend towards higher HMW adiponectin serum levels in successful ICSI cycles compared to implantation failures was observed; studies with larger patient groups are required to confirm this observation.

Long term evaluation of morphometric and ultrastructural changes of testes of alloxan-induced diabetic rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Organotins: A review of their reproductive toxicity, biochemistry, and environmental fate

The review purposes are to (1) evaluate the experimental evidence for adverse effects on reproduction and metabolism and (2) identify the current knowledge of analytical procedures, biochemistry and environmental aspects relating to organotins. Organotins are pollutants that are used as biocides in antifouling paints. They produce endocrine-disrupting effects in mollusks, such as imposex. In rodents, organotin exposure induces developmental and reproductive toxicity as well as alteration of metabolic homeostasis through its action as an obesogen. The adverse effects that appear in rodents have raised concerns about organotins' potential health risk to humans in relation to organotin exposure. At present, triorganotin, such as tributyltin, have been demonstrated to produce imposex, and mammalian reproductive and metabolic toxicity. For most mammals, triorganotin exposure predominantly occurs through the ingestion, and this compound can cross the placenta. With these risks in mind, it is important to improve our knowledge of organotins' effects on environmental health. © 2012 Elsevier Inc.

Grade 3 Varicocele in Fertile Men: A Different Entity

Purpose: Although varicocele size has an inverse relationship with baseline semen parameters and a direct relationship with seminal reactive oxygen species in infertile patients, to our knowledge the effect of varicocele grade in fertile men is unknown. We evaluated the impact of varicocele grade on seminal parameters, testicular size and seminal reactive oxygen species in fertile men. Materials and Methods: We prospectively evaluated 194 men from July 2004 to April 2010. Of the men 156 were fertile and classified by presence of varicocele. A total of 38 infertile patients with varicocele as the only identifiable cause of infertility comprised the control group. Physical examination, semen parameters and seminal reactive oxygen species were compared between the groups. Results: Of 156 fertile men 43 (24.3%) had clinical varicocele, which was grade 1 to 3 in 22, 11 and 10, respectively. The remaining 113 men (72.7%) had no varicocele. Infertile men had smaller testes, decreased semen parameters and higher seminal reactive oxygen species than the fertile groups. Testicular size, reactive oxygen species and semen parameters did not differ between fertile men with vs without varicocele. Fertile men with varicocele grade 3 had higher seminal reactive oxygen species than those with lower grade varicocele. As varicocele grade increased, seminal reactive oxygen species increased and sperm concentration decreased. Conclusions: Although fertile men have more efficient defense mechanisms to protect against the consequences of varicocele on testicular function, these mechanisms may not be sufficient in those with varicocele grade 3. Further research is needed to clarify whether they are at increased risk for future infertility.

Splenogonadal fusion and testicular cancer: case report and review of the literature

A 36 year-old man after tests for assessing male infertility was diagnosed with primary infertility, bilateral cryptorchidism, non-obstructive azoospermia and discontinuous splenogonadal fusion. Carcinoma in situ was found in his left testicle, which was intra-abdominal and associated with splenogonadal fusion. To our knowledge, this is the fourth case of splenogonadal fusion associated with testicular cancer reported. One should always bear in mind the possibility of this association for the left cryptorchid testicle.

Measuring male infertility: epidemiological aspects

Evidence suggests that human semen quality may have been deteriorating in recent years. Most of the evidence is retrospective, based on analysis of data sets collected for other purposes. Measures of male infertility are needed if we want to monitor the biological capacity for males to reproduce over time or between different populations. We also need these measures in analytical epidemiology if we want to identify risk indicators, risk factors, or even causes of an impaired male fecundity-that is, the male component in the biological ability to reproduce. The most direct evaluation of fecundity is to measure the time it takes to conceive. Since the time of conception may be missed in the case of an early abortion, time to get pregnant is often measured as the time it takes to obtain a conception that survives until a clinically recognized pregnancy or even a pregnancy that ends with a live born child occurs. A prolonged time required to produce pregnancy may therefore be due to a failure to conceive or a failure to maintain a pregnancy until clinical recognition. Studies that focus on quantitative changes in fecundity (that does not cause sterility) should in principle be possible in a pregnancy sample. The most important limitation in fertility studies is that the design requires equal persistency in trying to become pregnant and rather similar fertility desires and family planning methods in the groups to be compared. This design is probably achievable in exposure studies that make comparisons with reasonable comparable groups concerning social conditions and use of contraceptive methods.

Finasteride-associated male infertility

Finasteride is a potent and specific inhibitor of the 5alpha-reductase enzyme in men. Clinical studies have shown that finasteride 1mg/day is effective for promoting hair growth in men with male pattern hair loss. However, there is a concern about the use of finasteride, especially in young fertile patients, because of its action on testosterone metabolism. This paper describes 3 cases of young patients who had very poor seminal quality during finasteride treatment (1 mg/day), and their seminal quality greatly improved after cessation of finasteride treatment. Two of them presented with a left varicocele and the other was obese. We hypothesize that finasteride may not dramatically change the spermatogenesis process in healthy men, but in patients with conditions related to infertility, an amplification of the negative influence of finasteride could occur. Future studies should be done to clarify the extent of the effect of finasteride in patients fertility problems.