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Biomedical subjects

L Bujan

Publications and source records attributed to L Bujan.

At least 19 recordsLinked to original sources
PubMed2006

Geographic variations in probability of pregnancy in four cities of France.

BACKGROUND: Several studies have described geographic variations in human fecundability, but this phenomenon has almost exclusively been studied at an international level rather than within a given country. Our aim was to describe geographic variations in fecundability, the monthly probability of pregnancy, between four cities of France. METHODS: We conducted a cross-sectional study in four French maternity units from Toulouse, Rennes, Lyons and Paris, among partners of pregnant women. Women were asked about the time to pregnancy (TTP) of their current pregnancy. TTP was analysed with a discrete Cox model allowing to estimate fecundability ratios (FR). RESULTS: Time to pregnancy was defined for 894 couples. There was no strong evidence of heterogeneity in fecundability between the four compared cities (p=0.05 without adjustment and p=0.25 after adjustment for behavioural and medical factors). The highest fecundability was observed in Rennes and the lowest in Toulouse (fecundability ratio (FR)=1.28, 95% CI: 1.01-1.63). Differences in fecundability were smaller between the other cities. CONCLUSION: We highlighted a possibly slightly higher fecundability in Rennes compared to Toulouse. Possible explanations for this finding are discussed. We note that the finding is consistent with previous observations indicating a higher sperm concentration among semen donors in Rennes than in Toulouse.

Cross-Sectional Studies↗
PubMed2005

Sperm DNA fragmentation: threshold value in male fertility.

BACKGROUND: The extent of sperm DNA fragmentation, which can be measured by the TUNEL assay, is one of the determinants of male fertility. However, the clinical application of this test to in-vivo situations is difficult owing to the absence of a statistically validated threshold value. METHODS: The aim of this study was to compare the results of TUNEL assay applied to semen samples from men of proven fertility (n = 47) and patients from an infertile population (n = 66), in order to establish a discriminating threshold value. RESULTS: Infertile patients had a higher mean level of DNA fragmentation than men of proven fertility (40.9 +/- 14.3% versus 13.1 +/- 7.3%, respectively; P < 0.001). The area under the receiver operating characteristics curve was 0.93 for 20% sperm DNA fragmentation. The calculated threshold value for TUNEL assay to distinguish between fertile controls and infertile men was 20%. At this threshold, specificity was 89.4 [95% confidence interval (CI) 83.7-95.1] and sensitivity was 96.9% (95% CI 93.8-100). The positive and negative predictive values of the 20% sperm DNA fragmentation threshold were high: 92.8% (95% CI 87.9-97.5) and 95.5% (95% CI 91.6-99.3), respectively. CONCLUSION: This study demonstrates that sperm DNA fragmentation, as measured by TUNEL assay, is a highly valuable indicator of male fertility.

DNA↗
PubMed2005

[Sperm DNA integrity as diagnosis and prognosis element of male fertility].

Recent progress in reproductive biology has improved comprehension physiology of the spermatozoa and on the fertilization mechanisms. This new knowledge has carried out the elaboration of tests on male fertility based on sperm genomic integrity. This review presents some of these techniques and brings a reflexion element on the application and use of sperm DNA integrity in the investigation of male fertility. The single cell gel electrophoresis (COMET assay), Sperm Chromatin Structure Assay (SCSA), In Situ Nick Translation (NT: Nick Translation) and Terminal Uridine Nick-End Labelling (TUNEL assay) are actually the most currently used techniques for the measure of sperm DNA integrity in research clinic. From a certain point of view, TUNEL assay, SCSA, COMET assay and NT assay are complementary. The TUNEL and COMET can measure single and double strand breaks of DNA, the SCSA can detect the abnormalities in the chromatin compaction and the NT assay can detect the single strand breaks of DNA. The exact origin of sperm DNA fragmentation is not established yet. However, several mechanisms have been proposed: defect in the chromatin compaction during spermiogenesis; reactive oxygen species production by immature spermatozoa; apoptosis during spermatogenesis. It becomes important to consider the possible consequences of the oocyte fertilization by a spermatozoon having a high degree of DNA fragmentation. The use in routine of some of these tests must however pass by a standardization of the inter laboratory protocols and obviously, by the establishment of both in vivo and in vitro discriminating threshold values in order for these tests to present a good predictive value for pregnancy outcome.

Comet Assay↗
PubMed2004

Selection bias in semen studies due to self-selection of volunteers.

BACKGROUND: Reports of a secular decrease in semen quality remain controversial, particularly due to the possibility of selection bias. We aimed to describe the potential bias due to self-selection of volunteers in semen studies involving fecund men. METHODS: Using data from the French multicentre study REPRHOM, we compared the characteristics of the partners of pregnant women for three levels of participation: completion of a refusal questionnaire (n = 698), agreement to complete the study questionnaires only (n = 676) and agreement to complete the study questionnaires and give a semen sample (n = 331, 13% of the subjects approached). RESULTS: Poorly educated men refused more often to participate than highly educated men. Semen providers were more likely to have experienced unfavourable pregnancy outcomes (odds ratio 1.68, 95% confidence interval 1.14-2.49) compared with participants completing the questionnaires only. Time to pregnancy was similar for all participants. CONCLUSIONS: This study demonstrates the existence of selection bias in semen studies associated with fertility and socio-demographic characteristics of men. The results of semen analysis for this population sample cannot be extrapolated to the whole population from which the volunteers originate. More information is required on who participates, and participation rates should be reported in semen studies to make it possible to interpret the results correctly.

Adult↗
PubMed2004

[Impact of reverse transcriptase inhibitors on sperm mitochondrial and genomic DNA in assisted reproduction techniques].

For the last ten years, antiretroviral therapy (ARV) has improved the prognosis in HIV-1 infection and showed a better control of the viral excretion by reducing viral shedding in semen. However, nucleoside analogues reverse transcriptase inhibitors (NRTI) therapy reported important adverse effects. Most of these side effects observed seem to be linked with a common mechanism: mitochondrial activity alteration. Since the introduction of protocols for HIV-1 serodiscordant couples, with male infected partners under NRTI therapy, many results in the literature such as: semen characteristics and pregnancies, drew the attention of research teams. Many studies have suggested that NRTI has an affect on semen parameters, but proposed mechanisms of these effects have rarely been discussed. NRTI have a great affinity for the reverse transcriptase of HIV-1. Because many NRTI are not only inhibitors of reverse transcriptase but also inhibitors of the DNA polymerase beta and gamma, several toxic effects can be considered. Nevertheless, this specificity is not absolute and "accidental" incorporations of NRTI can occur on genomic sperm DNA. Only one study on genomic sperm DNA with patients under NRTI therapy was published without concluding results. Recently, studies have suggested that NRTI exposure could induce an alteration on mitochondrial energy-generating ability of spermatozoa. NRTI are known to induce an increase in the generation of reactive oxygen species, which results in the degradation of mitochondrial transmembrane potential (Deltapsim). This loss of Deltapsim can tend to release some specific apoptosis factors, such as cytochrome c, that initiates programmed cell death. Sperm DNA fragmentation, associated to apoptosis, was reported as a possible cause of recurrent pregnancy loss. If the incorporation of NRTI was reported in genomic DNA of somatic cells, the absence of data on the genomic sperm DNA justifies further studies concerning the effects of paternal exposure to NRTI on the genomic material of the male gamete, in particular because of its implication in the zygote development after fertilization.

Anti-HIV Agents↗
PubMed2001

Increased aneuploidy in spermatozoa from testicular tumour patients after chemotherapy with cisplatin, etoposide and bleomycin.

Testicular cancer is the most common neoplasia occurring in the young male population. The PEB (cisplatin, etoposide and bleomycin) adjuvant chemotherapy usually proposed after orchidectomy in non seminomatous tumours, and in metastatic seminomas, has improved the long-term survival of these patients. Following an azoospermic period, sperm cell recovery is generally observed after treatment delivery, but little is known about the genetic consequences on these new spermatozoa. To estimate the chromosomal consequences of this chemotherapy on sperm cells during the period of recovery of spermatogenesis, sperm cell aneuploidy was studied in testicular cancer patients, at 6-18 months after PEB adjuvant chemotherapy delivery, using fluorescence in-situ hybridization (FISH) of chromosomes 7, 16, 18, X and Y with specific DNA probes. A significant increase in the frequency of diploidy and disomy for chromosomes 16, 18 and XY was observed in treated patients compared with a healthy control group. Spermatozoa aneuploidy occurring during the spermatogenesis recovery period might be a possible side effect of the PEB regimen. Thus, practitioners should be advised to provide counselling about the need for an appropriate duration of contraception. Moreover, genetic counselling should be offered in cases of pregnancy occurring soon after the end of chemotherapy.

Adult↗
PubMed2000

Sperm washing and virus nucleic acid detection to reduce HIV and hepatitis C virus transmission in serodiscordant couples wishing to have children.

BACKGROUND: Use of a motile spermatozoa isolation process was assessed for reducing the transmission of HIV and hepatitis C virus (HCV) during artificial insemination in HIV-serodiscordant couples in which the man is infected. PATIENTS: Thirty-two HIV-1-infected clinically asymptomatic men, having a median CD4 cell count of 396 x 10(6)/l and a median blood plasma HIV-1 RNA content of 414 copies/ml. Of these, 16 were infected with both HIV and HCV. METHODS: Motile spermatozoa were isolated from 51 semen samples by density gradient and 'swim-up'. HIV-1 and HCV genomes were detected and quantified in the blood plasma and seminal plasma, and detected in seminal cell fractions obtained during spermatozoa isolation. RESULTS: HIV-1 RNA was detected in 30% of seminal plasma samples. HIV-1 genomes were found in 18% of seminal cell samples, but in none of the motile spermatozoa fractions after 'swim-up'. There was no correlation between the HIV-1 RNA concentrations in the blood and seminal plasma. HIV-1 genome was detected intermittently in patients who gave more than one sample. HCV RNA was detected in 20% of seminal plasma samples from HCV viraemic patients, but in no seminal cells or motile spermatozoa fractions. CONCLUSIONS: Purification of motile spermatozoa by density gradient plus 'swim-up' reduced the HIV-1 and HCV genomes in the semen of infected individuals to undetectable levels. This method, associated with a standardized virus assay, could be useful for serodiscordant couples (males infected) who wish to have children.

Adult↗
PubMed2000

Congenital bilateral absence of the vas deferens: clinical characteristics, biological parameters, cystic fibrosis transmembrane conductance regulator gene mutations, and implications for genetic counseling.

OBJECTIVE: To evaluate relationships between the phenotypic and genotypic characteristics of patients with congenital bilateral absence of the vas deferens (CBAVD). DESIGN: Retrospective study. SETTING: A university hospital urology-andrology department. PATIENT(S): Forty-one men with CBAVD. INTERVENTION(S): CBAVD was diagnosed during surgical and/or ultrasound exploration of the vasa deferentia (VD) (n = 39), or on the basis of impalpable scrotal VD (n = 2). MAIN OUTCOME MEASURE(S): History, clinical and seminal characteristics, and cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations including IVS-8 polyT analysis. RESULT(S): A palpable scrotal vas deferens was present as a fibrous cord or nonpermeable duct in 13% of patients undergoing surgical exploration. Seminal vesicles were bilaterally absent in 28% of patients. No CFTR gene mutation or 5T allele was detected in 24.5% of the patients. Two CBAVD patients with renal agenesis carried a CFTR gene mutation (DeltaF508/5T-9T and R117G/7T-9T). CBAVD patients who have both a semen volume of < or =1.0 mL and a semen pH of < 7.0 have a significantly higher risk of severe CFTR gene mutation (OR = 9.12 [95% CI = 1.81-49.50]). CONCLUSION(S): A palpable scrotal vas deferens was found in 13% of CBAVD patients. Semen volume of < or =1.0 mL and semen pH of < 7.0 in CBAVD patients were associated with a higher risk of severe CFTR gene mutations. Patients with CBAVD and renal agenesis should be screened for CFTR gene mutations before assisted reproductive techniques are used.

Abnormalities, Multiple↗
PubMed2000

Sex chromosome mosaicism in males carrying Y chromosome long arm deletions.

Microdeletions of the long arm of the Y chromosome (Yq) are a common cause of male infertility. Since large structural rearrangements of the Y chromosome are commonly associated with a 45,XO/46,XY chromosomal mosaicism, we studied whether submicroscopic Yq deletions could also be associated with the development of 45,XO cell lines. We studied blood samples from 14 infertile men carrying a Yq microdeletion as revealed by polymerase chain reaction (PCR). Patients were divided into two groups: group 1 (n = 6), in which karyotype analysis demonstrated a 45,X/46,XY mosaicism, and group 2 (n = 8) with apparently a normal 46,XY karyotype. 45,XO cells were identified by fluorescence in-situ hybridization (FISH) using X and Y centromeric probes. Lymphocytes from 11 fertile men were studied as controls. In addition, sperm cells were studied in three oligozoospermic patients in group 2. Our results showed that large and submicroscopic Yq deletions were associated with significantly increased percentages of 45,XO cells in lymphocytes and of sperm cells nullisomic for gonosomes, especially for the Y chromosome. Moreover, two isodicentric Y chromosomes, classified as normal by cytogenetic methods, were detected. Therefore, Yq microdeletions may be associated with Y chromosomal instability leading to the formation of 45,XO cell lines.

Adult↗
PubMed2000

Increase in scrotal temperature in car drivers.

Several recent studies have reported a gradual decline in sperm production in men. Endocrine disrupters as well as lifestyle have been suggested as risk factors. One lifestyle factor that may affect human fertility is driving a vehicle for a prolonged period. Several authors have suggested that driving position may increase the scrotal temperature. In order to validate this hypothesis we conducted continuous monitoring of scrotal temperature in real conditions, i.e. in men driving a car for a prolonged period. Nine volunteer men were asked to walk outside for 40 min and then to drive a car for 160 min. Scrotal temperatures were measured from thermocouples and values recorded every 2 min on a portable data recorder. Scrotal temperature increased significantly (P < 0.0001) in driving posture after 2 h of driving, reaching a value 1.7-2.2 degrees C higher than that recorded while walking. This link between driving position and increased scrotal temperature indicates a potential exposure of male reproductive function to lifestyle factors.

Adult↗
PubMed1998

Clinical characteristics and light and transmission electron microscopic sperm defects of infertile men with persistent unexplained asthenozoospermia.

OBJECTIVE: To determine, with the use of transmission electron microscopy (TEM), the proportion of patients with permanent unexplained asthenozoospermia (<30% motility) who have an abnormality of sperm axonemal and periaxonemal structures. DESIGN: Retrospective study. SETTING: A university-affiliated public hospital. PATIENT(S): Sixty-one infertile men whose semen was submitted to TEM analysis because of persistent unexplained asthenozoospermia. MAIN OUTCOME MEASURE(S): The results of quantitative TEM analysis of the tails of the spermatozoa. INTERVENTION(S): None. RESULT(S): Based on a comparison with the axonemal anomalies observed in nine fertile control patients, the infertile population was divided into three groups: group I, with no detectable axonemal defects (26.2%); group II, with axonemal anomalies in either the midpiece or the principal piece (29.5%); and group III, with axonemal anomalies in both the midpiece and the principal piece (44.3%). However, defects in the mitochondrial sheath, fibrous sheath, and sperm head (acrosomic and postacrosomic cap) were observed in at least 50%, 30%, and 50%, respectively, of the patients in each group. The proportion of dense fiber anomalies of the midpiece increased significantly from group I to group III. No differences were observed between the three groups in sperm characteristics, anamnesis information, or clinical data. CONCLUSION(S): In patients with persistent unexplained asthenozoospermia, the frequent association of periaxonemal anomalies with axonemal deficiencies strongly suggests that axonemal deficiencies are not the unique cause of decreased motility.

Adult↗
PubMed1998

Quantification by magnetic resonance spectroscopy of metabolites in seminal plasma able to differentiate different forms of azoospermia.

The aim was to determine whether proton magnetic resonance spectroscopy (1H-MRS) of metabolites such as glycerophosphorylcholine (GPC), choline, citrate and lactate in human seminal plasma can be used to differentiate (i) different azoospermic patients and (ii) different forms of spermatogenic failure including those who had undergone radiation therapy or chemotherapy. Semen samples were provided by men with obstructive azoospermia and spermatogenic failure who had serum follicle stimulating hormone (FSH) values within the normal range and either more or less than normal. Four prominent constituents of seminal plasma were identified by 1H-MRS: GPC, choline, citrate and lactate. The peak area ratios of choline/citrate as well as choline/lactate were significantly different (P < 0.01) between groups with spermatogenic failure and obstructive azoospermia. When the serum FSH values were normal in men with spermatogenic failure and obstructive azoospermia, a significant difference was found in the GPC/choline ratio (P < 0.001). When the FSH values were normal, the GPC/choline ratio appeared to be a very important parameter able to differentiate not only between cases of spermatogenic failure and obstructive azoospermia but also between different forms of spermatogenic failure. These results demonstrate the potential use of 1H-MRS on human seminal plasma in a new approach in the management of male infertility.

Antineoplastic Agents↗
PubMed1998

Occupational heat exposure and male fertility: a review.

In humans, as in most mammals, spermatogenesis is temperature dependent. This temperature dependence has been clearly demonstrated by several experimental studies showing that artificial increases in scrotum or testicle temperature in fertile men reduce both sperm output and quality. Our knowledge of the effects of occupational heat exposure on male fertility comes mostly from a small number of epidemiological studies. We conducted an extensive review of these published reports, focusing on methodology and design (retrospective or prospective; reference group; number of subjects) and principal results (using several indicators such as the time taken to obtain a pregnancy or sperm characteristics). We concluded that occupational heat exposure is a significant risk factor for male infertility, affecting sperm morphology and resulting in delayed conception. The limits and biases involved in this type of research are also discussed.

Animals↗
PubMed1998

[Environment and spermatogenesis].

An alteration of the male reproductive system as well as regional differences in this alterations were recently reported in several studies. That suggest a relationship between environmental conditions and spermatogenesis. Histories of dibromochloropropane distilbene and gossypol are indicative of the influence of occupational and drug exposure, or of the life style on the male reproductive tract. The present review deals with chemical (pesticides, metals ...), physical (ionising and non-ionising radiation's, endogenous heat) and life style factors (exogenous heat, posture, clothing, alcohol, tobacco, stress, sport, nutrition) susceptible to have a deleterious effect on spermatogenesis. Besides, the hypothesis of endocrine disrupters is discussed with inclusion of the information of regional differences from recent studies. While further studies are required to precisely determine the function of the quoted factors in the secular decrease and regional variations of spermatogenesis, it is suggested that sperm is an indicator of public health and that the principle of precaution is to be considered with the usual implication: 1) effective preventive action in occupational world, 2) avoiding of a risk factor discovered during infecondity consulting, 3) non use of substances which innocuity is not proved by toxicologic studies in animals.

Environmental Exposure↗
PubMed1997

Effect of male occupational heat exposure on time to pregnancy.

The relationship between male occupational heat exposure and the time required to achieve a pregnancy [TTP] was studied in a retrospective survey of 402 fertile couples. The TTP for t he subgroups 'exposure t o heat' (median = 4 .0 months; mean 11.8; SD = 13.3) and 'professional driver >3 h/day' (median = 4.5; mean = 14.4; SD = 28.5) was significantly longer (both p < 0.05) than for the controls (median = 2.8; mean = 7.8; SD = 13.3). Bakers and welders showed comparable results: only 14% of the bakers' partners became pregnant within 3 months (cf. 55% of controls, p < 0.05) and only 29% became pregnant within 6 months (cf. 74% of controls, p < 0.02). This study suggests that occupational exposure to heat is a 'weak' risk factor for male subfertility.

Adult↗
PubMed1997

Seminal cytokine concentrations (IL-1beta, IL-2, IL-6, sR IL-2, sR IL-6), semen parameters and blood hormonal status in male infertility.

Several lines of evidence indicate that cyokines are involved in male fertility. They are secreted by different parts of the male genital tract and may exert effects on steroidogenesis, spermatogenesis and sperm functions. We measured the concentrations of interleukins (IL-beta, IL-2, IL-6) and those of interleukin soluble receptors (sR IL-2, SR IL-6) in semen of fertile subjects (n = 21) and of patients with a range of andrological diseases (n = 119). The seminal concentrations of cytokines were analysed according to semen parameters as well as to the blood hormonal profiles of follicle stimulating hormone, luteinizing hormone and testosterone. An increase of IL-1beta was observed in the group of patients with infertility. No difference was found between the different subgroups defined on the basis of progressive motility, percentage of abnormal forms and diagnosis of infection. The seminal cytokine concentrations were independent of the blood hormonal status. Our data suggest that the determination of interleukins (-1beta, -2 and -6) or interleukin soluble receptors (sR IL-2, sR IL-6) in human spermatozoa does not provide convenient information in male routine infertility work-up.

Antigens, CD↗