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PubMed2005

Occupational exposures and male infertility.

The purpose of this study was to determine the association between male occupational exposures and infertility. A retrospective case-control study was performed using data collected between 1991 and 1997 at nine US clinical sites as part of a previously conducted large multicenter trial. Cases were defined as infertile males whose partner had an infertility evaluation with normal results, and controls were defined as fertile males whose partner became pregnant within 2 years. Exposures were assessed by means of self-report questionnaires. Bivariate, stratified, and multivariable analyses were performed. A total of 650 infertile cases and 698 fertile controls were compared. In the final model, a protective association with infertility was observed for occupational exposures to radiation (odds ratio=0.21, 95% confidence interval: 0.06, 0.77) and video display terminals (odds ratio=0.30, 95% confidence interval: 0.13, 0.68). No significant associations were noted between infertility and exposure to shift work, metal fumes, electromagnetic fields, solvents, lead, paint, pesticides, work-related stress, or vibration. Overall, no clear, clinically important associations between occupational exposures and male infertility could be identified in this study.

Adult↗
PubMed1997

The cost of infertility diagnosis and treatment in Canada in 1995.

The objectives of this study were to estimate the direct cost of infertility management, including diagnosis and treatment, in Canada during 1995, and the relative cost per live birth by treatment category. The analysis was based on the following estimates: the prevalence of infertility in Canada in 1995; the volume and distribution of infertility services; and the effectiveness and cost of specific infertility treatments. In 1995 there were approximately 330,000 couples experiencing infertility in Canada. It is estimated that <50% (150,000) sought medical advice or treatment during that year. A total of 13 diagnostic and treatment categories account for nearly all of the treatments received, and these categories form the treatment model. The cost of treatment per live birth ranges from Cdn$650 for clomiphene treatment of unexplained infertility to Cdn$41,000 for in-vitro fertilization. For a hypothetical group of 100 couples, the annual cost of diagnosis and treatment would be Cdn$77,000 and Cdn$200,000 respectively for a total of Cdn$277,000, or an average of Cdn$2770 per couple. After 1 year of treatment, it is expected that 26 of these 100 couples would achieve a live birth. The total annual cost of infertility management in Canada, estimated to be approximately Cdn$415 million, is 0.6% of the annual cost of health care.

Adult↗
PubMed1998

Abnormalities for chromosomes 13 and 21 detected in spermatozoa from infertile men.

Sperm samples from infertile men with oligozoospermia or teratozoospermia were studied by multicolour fluorescence in-situ hybridization (FISH) using DNA probes for chromosomes 13 and 21. A total of 90 809 sperm nuclei from nine infertile men and 182 799 sperm nuclei from 18 control donors were analysed. There was a highly significant increase in the frequency of spermatozoa disomic for chromosome 13 in infertile patients (0.28%) compared to control donors (0.13%) (two-tailed Z statistic P < 0.0001) and for chromosome 21 (0.48% in infertile men versus 0.37% in controls, P < 0.0001). Also there was a significantly increased frequency of diploid spermatozoa in infertile men (0.85%) compared to control donors (0.66%) (P < 0.0001). Our previous studies on these same infertile patients demonstrated increased frequencies of sperm disomy for chromosomes 1 and XY. This suggests that infertile men, who are prime candidates for intracytoplasmic sperm injection, may be at a very small increased risk of aneuploid offspring.

Adult↗
PubMed1998

Hysteroscopic septum resection in patients with recurrent abortions or infertility.

Fifty-seven patients who underwent hysteroscopic septum resection between January 1991 and December 1996 were studied; nine patients presented with recurrent abortions, 46 with infertility (26 primary and 20 secondary), one with dysmenorrhoea and one with an asymptomatic complete septum. Their reproductive history included 78 pregnancies: 69 (88.4%) abortions, two (2.6%) ectopics, two (2.6%) preterm deliveries and five (6.4%) term deliveries. In patients with infertility, the incidence of unexplained infertility was 19.6% and the incidence of endometriosis was 26.1%. After hysteroscopic septum resection, 42 patients were interested in pregnancy. All patients with recurrent abortions conceived spontaneously. Twenty-one (63.6%) infertile patients achieved a pregnancy, 13 (61.9%) of them after treatment with various assisted reproduction techniques. The reproductive outcome after septum resection yielded 44 pregnancies, including three sets of twins and one set of triplets reduced to twins: 11 (25%) abortions, one (2.3%) ectopic pregnancy, two (4.5%) preterm deliveries (both twins), 28 (63.7%) term deliveries and two (4.5%) as-yet ongoing pregnancies. It seems that the hysteroscopic treatment of uterine septum has a beneficial effect on pregnancy outcome. A septate uterus does not seem to be an infertility factor. The achievement of pregnancy is normal in patients with recurrent abortions, while the chances of conception in patients with infertility seem to be similar to those for the general infertile population.

Abortion, Habitual↗
PubMed2000

Association of molecular variants of luteinizing hormone with male infertility.

Luteinizing hormone (LH) stimulates the interstitial Leydig cells to produce testosterone, which is essential for spermatogenesis. Abnormalities in the function of LH may affect the process of spermatogenesis and thus result in infertility. The aim of this study was to determine the association of three known variants of LH (Gln54Arg [Trp8Arg; Ile15Thr] and Gly102Ser) with male infertility. A total of 145 infertile men and 200 healthy fertile men were recruited and screened for the presence of these three LH variants. The Gln54Arg variant could not be detected in either of the groups studied. Twelve infertile (8.2%) and 15 fertile (7.5%) men were found to carry the [Trp8Ile; I15Thr] variant, but its occurrence did not show any significant difference between the patient and control groups. The Gly102Ser variant was detected in five patients with infertility (3.4%), but not in the control subjects (P = 0.013). This study showed that the Gln54Arg and [Trp8Ile; I15Thr] variants in the LHbeta gene were not associated with male infertility, whereas the Gly102Ser variant might be implicated in infertility in some Singapore Chinese men.

Adult↗
PubMed2002

Infertility in South Africa: women's reproductive health knowledge and treatment-seeking behaviour for involuntary childlessness.

BACKGROUND: Infertility is a major reproductive health problem in Africa. This paper presents the findings of two studies which focus on the knowledge that infertile women have about fertility and the causes of infertility, their treatment-seeking behaviour and their expectations of an infertility clinic. METHODS: A total of 150 infertile women from a culturally diverse, urban community in South Africa participated in the two studies. Both qualitative and quantitative research methods were applied using in-depth, semi-structured interviews and structured questionnaires. RESULTS: The women who participated had little knowledge about human reproduction and modern treatment options for infertility. They were highly motivated to find treatment and accessed both traditional and modern health care. Treatment barriers within modern health care were identified. CONCLUSIONS: The importance of health education and counselling is recognized, and both need to be integrated into infertility management, particularly in the developing world. The introduction of clinical guidelines is recommended in order to overcome treatment barriers and improve the delivery of health services.

Adult↗
PubMed2003

Low 11-deoxycortisol to cortisol conversion reflects extra-adrenal factors in the majority of women with normo-gonadotrophic normo-estrogenic infertility.

BACKGROUND: Women with normogonadotrophic normo-estrogenic oligomenorrhoea often disclose a variety of clinical symptoms. Many of these individuals are obese with features of pseudo-hypercortisolism. In the current study, 11-deoxycortisol and cortisol concentrations were determined in this group and compared with ovulatory controls. METHODS AND RESULTS: Twenty-six women with clomiphene citrate-resistant infertility, 12 lean and 11 obese ovulatory controls were studied. Women with infertility had the highest 11-deoxycortisol concentrations (mean +/- SD: 4.1 +/- 1.5 ng/ml) compared with obese and lean controls (3.1 +/- 1.4 and 2.4 +/- 0.9 ng/ml) (P < 0.01), but similar morning cortisol concentrations (0.47 +/- 0.15, 0.45 +/- 0.16 and 0.47 +/- 0.18 nmol/l). Baseline 11-deoxycortisol/cortisol ratios (>90th percentile of ovulatory controls) were elevated in 23/26 infertile women (88%), and in 3/26 women (12%) after adrenocorticotrophic hormone (ACTH) stimulation. Three out of six lean infertile women had elevated baseline 11-deoxycortisol/cortisol ratios, but none of these women had elevated ratios after ACTH stimulation. Stepwise regression analysis, after exclusion of testosterone, revealed significant correlations between the groups (lean controls, obese controls, infertility) and ACTH-stimulated 11-deoxycortisol/cortisol ratio (P < 0.05), but not with fasting glucose, insulin, cortisol, 11-deoxycortisol and baseline 11-deoxycortisol/cortisol ratios. CONCLUSIONS: Congenital adrenal hyperplasia was not observed in the majority of infertile women. The data indicate that extra-adrenal factors were involved in most of the infertility syndromes that were studied.

Adrenal Hyperplasia, Congenital↗
PubMed2003

Restoration of fertility in infertile mice by transplantation of cryopreserved male germline stem cells.

BACKGROUND: The development of a spermatogonial transplantation technique has provided new possibilities for the treatment of male infertility. Previous studies have shown that spermatogonial stem cells could reinitiate spermatogenesis after cryopreservation and reintroduction into the seminiferous tubules of infertile recipient males, and this raised the possibility of banking frozen stem cells for male infertility treatment. It remains unknown, however, whether germ cells from freeze-thawed stem cells are fertile, leaving the possibility that the procedure compromises the integrity of the stem cells. METHODS AND RESULTS: Dissociated mouse testis cells were cryopreserved and transplanted into infertile recipient testes. The freeze-thawed testis cell populations contained higher concentrations of stem cells than fresh testis cell populations. Offspring were obtained from freeze-thawed stem cells transplanted into infertile males, and fertility restoration was more efficient in immature (5-10 days old) than in mature (6-12 weeks old) recipients. However, offspring were also obtained from infertile adult recipients using in-vitro microinsemination. CONCLUSIONS: This first successful application of frozen stem cell technology in the production of offspring by spermatogonial transplantation suggests the superiority of immature recipients for clinical applications. Thus, the combination of cryopreservation and transplantation of stem cells is a promising approach to overcome male infertility.

Animals↗
PubMed2004

Sperm membrane protein profiles of fertile and infertile men: identification and characterization of fertility-associated sperm antigen.

BACKGROUND: Male infertility is the major cause of conception failure in about 25% of all infertile couples. Understanding the causes of male infertility depends to a certain extent on the proteins present on the spermatozoa. The study aim was to investigate first, whether there is any difference in the expression of sperm membrane proteins between fertile and infertile males; and second, whether there is any functional significance of these proteins in the spermatozoa. METHODS: Six different protocols were employed to extract sperm membrane proteins. A 57 kDa protein was identified and purified using different chromatographic techniques. The homogeneity and isoelectric point of the protein was confirmed by 2D-electrophoresis. The protein was characterized by immunofluorescence, ELISA, flow cytometry, SDS-PAGE and Western blot analysis. The role of 57 kDa protein in sperm-oocyte binding was studied in vitro. RESULTS: All six sperm extracts of normozoospermic and infertile subjects showed 16-18 major and 12-15 minor protein bands. However, in one of the methods, the lysis buffer containing N-octyl-beta-D-glycopyranoside (NOG) resulted in an additional protein band at the 57 kDa region in 95% of normozoospermic samples. The protein was either absent (approximately 80%) or negligible (approximately 20%) in infertile subjects. The protein was localized to the head of non-acrosome-reacted spermatozoa (NAR), and shifted to the equatorial segment in acrosome-reacted (AR) spermatozoa. The antibody directed against purified 57 kDa protein inhibited binding of human sperm to zona-free hamster oocytes in a dose-dependent manner. CONCLUSIONS: The results suggest that lack and/or low expression of 57 kDa protein may be one of the reasons for infertility in men. Therefore, the protein could be used as a marker for sperm quality in men.

Animals↗
PubMed2004

Demonstration of Chlamydia trachomatis IgG antibodies in the male partner of the infertile couple is correlated with a reduced likelihood of achieving pregnancy.

BACKGROUND: The objective of this study was to determine the prevalence of Chlamydia trachomatis among both men and women seeking help at an infertility clinic, and to prospectively follow the effect of previous infection on pregnancy rates and pregnancy outcome after a long follow-up period (mean 37 months). METHODS: A total of 244 infertile couples was tested for C. trachomatis IgG antibodies, and IgG(+) couples were also tested for C. trachomatis DNA by PCR in a first-void urine sample. Study parameters were serology, PCR results, clinical diagnoses, treatments, pregnancy rates and pregnancy outcome. As controls, age-matched and spontaneously pregnant women were also tested with serology. RESULTS: The prevalence of IgG antibodies was 24.2, 20.1 and 15.6% among infertile women, infertile men and control women respectively. The prevalence of C. trachomatis DNA was 6.8 and 7.1% among tested women and men respectively. The presence of C. trachomatis IgG antibodies in women was related to tubal factor infertility (TFI) (P = 0.002). Decreased pregnancy rates were seen in couples where the man was IgG(+) (P = 0.005) with no relationship to TFI. Among women who achieved pregnancy, there was no difference in pregnancy outcome between IgG(+) or negative couples. CONCLUSIONS: C. trachomatis IgG antibodies in the man of the infertile couple was related to decreased pregnancy rates and to the presence of IgG antibodies in the woman. There was a high prevalence of asymptomatic persistent infections among infertile couples.

Adult↗
PubMed2004

Pregnancy outcome after IVF and ICSI in unexplained, endometriosis-associated and tubal factor infertility.

BACKGROUND: This study was undertaken in order to compare pregnancy outcome after IVF and ICSI in unexplained and endometriosis-associated infertility using tubal factor infertility as controls. METHODS: This was a retrospective cohort study of early IVF/ICSI pregnancies verified by serum hCG measurement, comparing the subsequent outcome in unexplained (n = 274) and minimal endometriosis-associated (n = 212) with tubal factor (n = 540) infertility as controls. From January 1990 to December 2002, 1026 conception cycles after treatment with IVF or ICSI complied with the inclusion criteria. RESULTS: Live birth rate, twin birth rate after transfer of two embryos and abortion rate prior to 6 weeks of gestation were superior for the unexplained (78.8, 23.5 and 11.7%) compared to endometriosis-associated (66.0, 15.0 and 19.3%) and tubal factor (66.7, 18.1 and 18.0%) infertility groups (P < 0.05). Compared to the endometriosis-associated, the unexplained infertility group attained a higher pregnancy rate after the first treatment cycle (P < 0.05). CONCLUSIONS: The overall better outcome for the unexplained infertility group with respect to live birth rate, twin birth rate and early abortion rate compared to the minimal peritoneal endometriosis-associated and tubal factor infertility groups might be a guide to select diagnostic groups for single embryo transfer and be useful in patient counselling.

Abortion, Spontaneous↗
PubMed2005

Clinical adaptation of the sperm ubuquitin tag immunoassay (SUTI): relationship of sperm ubiquitylation with sperm quality in gradient-purified semen samples from 93 men from a general infertility clinic population.

BACKGROUND: The proteolytic chaperone peptide ubiquitin accumulates in defective human spermatozoa. Immunodetection of ubiquitin in human sperm samples correlates with semen quality and male fertility. METHODS: Semen samples from 93 men from couples seeking infertility treatment were separated on a PureSperm density gradient and screened by immunofluorescence microscopy with anti-ubiquitin antibodies. The percentage of spermatozoa with head ubiquitylation was recorded and compared with clinical semen evaluation and embryo development data after IVF or ICSI. Subjects were divided into the following four groups based on the initial clinical diagnosis of the couples; group 1, male factor; group 2, idiopathic infertility; group 3, female infertility with neither partner having children previously; and group 4, female infertility with male partners having children from previous relationships. RESULTS: The percentage of sperm with ubiquitylated heads remaining after PureSperm separation in the respective groups was 4.0% (male factor), 2.5% (idiopathic infertility), 0.7% (female infertility and presumed fertile male) and 0.9% (female infertility with established fertile male). Negative correlations between sperm ubiquitin and several parameters reflective of embryo development after assisted fertilization were found within the male factor group. CONCLUSIONS: Use of this simplified ubiquitin-based sperm quality assay is feasible in a clinical environment. Since the gradient separation does not completely deplete the defective spermatozoa, the modified light microscopic sperm ubiquitin tag immunoassay could add a new level of stringency to the selection of human spermatozoa for ICSI.

Antibodies, Monoclonal↗
PubMed1989

Cancer risk after evaluation for infertility.

To evaluate cancer risk by various causes of infertility, the authors conducted a retrospective cohort study among 2,335 women evaluated for infertility at the Mayo Clinic between 1935 and 1964. Most cancers occurred at expected frequencies, with the exception of cancers of the thyroid (standardized incidence ratio (SIR) = 2.6) and other endocrine glands (SIR = 6.7), although analyses were based on small numbers. Patients with progesterone deficiencies (31 per cent of the study subjects) had a 20 per cent higher cancer risk than did those with other causes of infertility, with excesses deriving primarily from cancers of the lung, cervix, ovary, and thyroid and from melanoma. Breast cancer risk, however, was not elevated in either patients with progesterone deficiencies (SIR = 0.9) or patients with other causes of infertility (SIR = 1.0). Examination of other parameters of infertility, including age at evaluation, type of infertility (primary vs. secondary), and years of attempted conception, showed no elevated risks of breast cancer in any subgroup. These results fail to support previous studies that have linked progesterone deficiencies among infertile women to elevated breast cancer risk. However, the data suggest a possible involvement of a progesterone deficiency in the etiology of other cancers, particularly thyroid cancer and melanoma.

Adult↗
PubMed1990

Infertility and breast cancer: a population-based case-control study.

To investigate whether a history of infertility affects a woman's risk of developing breast cancer, the authors analyzed case-control data collected between 1980 and 1982 as part of the Cancer and Steroid Hormone Study. The 4,730 cases were women aged 20-54 years with a first diagnosis of breast cancer ascertained from eight population-based cancer registries; the 4,688 controls were women randomly selected from the general population of these same eight areas. After controlling for age, age at first birth, and parity, the odds ratio (OR) for breast cancer associated with infertility was 1.01 (95% confidence interval (CI) 0.89-1.15) among gravid women. Controlling for age, the odds ratio was 0.82 (95% CI 0.59-1.14) among nulligravid women. Women who reported that the reason for their infertility was a problem with their ovaries had a risk similar to that for women without a history of infertility (OR = 0.75, 95% CI 0.48-1.24). Women whose physicians reported that the reason for their infertility was anovulation or Stein-Leventhal syndrome also had risks similar to those for women without a history of infertility (OR = 1.26 (95% CI 0.67-2.34) and OR = 1.13 (95% CI 0.46-2.78), respectively). Menopausal status, age at menarche, history of spontaneous abortions, drinking or smoking behavior, use of exogenous hormones, or family history of breast cancer did not appreciably alter the observed odds ratios. If infertility has an effect on breast cancer that is independent of age at first birth, then the effect is small.

Adult↗
PubMed1996

Changes in nuclear morphology in the human endometrial glandular epithelium in women with unexplained infertility.

In the light and electron microscopical study reported here, we documented the structure of the nucleus, nucleolus and nuclear channel system (NCS) in the uterine glandular epithelium in both fertile and infertile women during the early luteal phase. Nuclear volume was found to be larger in the infertile group at day 5 after the luteinizing hormone surge (LH+5) compared to day-matched fertile subjects. A two-way analysis of variance performed on nucleolar volume data from fertile and infertile women biopsied on days LH+5, +5, and +6 revealed a significant effect of condition but no effect of day or interaction. Nucleolar volume decreased from day LH+2 to day LH+6 in the fertile group, the sharpest decrease occurring between day LH+3 and day LH+4. The largest mean volume of the NCS was found at day LH+5 in the fertile group and day LH+6 in the infertile group. The results suggest a delay in the development of this organelle in the infertile women. The present study has documented alterations in the nuclei of uterine glandular cells from infertile patients. In these infertile women, there is also a delayed elaboration of the secretory apparatus and this delay correlates well with the delayed/reduced expression of a luteal-specific glyco-protein.

Analysis of Variance↗
PubMed1989

Tubal infertility and silent chlamydial salpingitis.

Antibodies to Chlamydia trachomatis (serum IgG antibodies with a titre of at least 32) were detected in 141 (86.0%) of 164 infertile women with tubal infertility (TF group) and in 20 (28.6%) in 70 infertile women with normal tubes (NTF group). The difference was highly significant (P less than 0.001), as was the difference in geometric mean titre of antibody-positive cases, 181 and 87, respectively. Pregnant, age-matched women were used as controls. Significantly fewer of these women (P less than 0.001) had antibodies, when compared with the TF group, 60 (36.6%) of 164, but not when the comparison was made with the NTF group, 31 (44.3%) of 70. There was a history of salpingitis in 64 (39.0%) of the 164 infertile women with damaged tubes. Neither the frequency nor the geometric mean titre of chlamydial antibodies differed between tubal factor infertility patients with and without a history of salpingitis. Previous chlamydial infection, reflected by serological markers, is strongly associated with tubal damage leading to tubal infertility. A large proportion of these cases run a silent course, since a majority of the antibody-positive patients with tubal infertility have never had salpingitis.

Adult↗
PubMed2002

Physical activity, body mass index, and ovulatory disorder infertility.

Few studies have examined whether activity and adiposity levels typical of American women affect their risk of ovulatory disorder infertility, and none has examined moderate and vigorous intensity exercise separately. We investigated these associations in the Nurses' Health Study II, comparing prospectively collected data on adiposity and activity for 830 cases of incident ovulatory infertility and 26,125 pregnancies. We observed a U-shaped association between body mass index (BMI) and relative risk of ovulatory infertility, with increased risk for BMI below 20.0 or above 24.0 kg/m2. On the basis of the BMI distribution of U.S. women, these findings suggest that 12% (95% confidence interval = 7-20%) of ovulatory infertility in the U.S. may be attributable to underweight (BMI <20.0) and 25% (95% CI = 20-31%) to overweight (BMI > or = 25.0). An increase in vigorous activity (but not moderate activity) was associated with reduced relative risk of ovulatory infertility. Each hour per week of vigorous activity was associated with a 7% (95% CI = 4-10%) lower relative risk of ovulatory infertility. After adjustment for BMI, a 5% (95% CI = 2-8%) reduction in relative risk per hour of weekly activity remained. These data suggest that, among American women, more ovulatory infertility is attributable to overweight and a sedentary lifestyle than to underweight and overexertion.

Body Mass Index↗
PubMed1998

Sperm acrosome status and sperm antibodies in infertility.

PURPOSE: We studied whether the spermatozoa from sperm autoimmune infertile men undergo premature acrosomal loss and whether this relates to the presence of sperm antibodies in wives. MATERIALS AND METHODS: We evaluated acrosome status of live washed native and overnight capacitated spermatozoa from 17 sperm nonautoimmune fertile and 23 sperm autoimmune infertile men using an immunofluorescent peanut lectin binding assay. We used cytotoxic and immunobead binding assays to prescreen the serum and seminal plasma of these men, and serum and cervical mucus of the wives for immunological infertility. We performed immunofluorescent sperm antibody assays on all study samples to ascertain sperm antibody isotype levels in each sample. Levels of acrosomal loss in husband native and capacitated spermatozoa were correlated with levels of IgG, IgA and IgM sperm antibodies in the study samples. RESULTS: Sperm autoimmune infertile men had a significantly larger percentage of sperm (p <0.0001) that had lost the acrosome and a lower percentage of sperm with intact acrosome (p <0.0001) in native and capacitated preparations in contrast to those of fertile controls. Levels of cytotoxic and IgA antibodies, especially in seminal plasma and cervical mucus, correlated significantly with percentages of sperm with a total loss of acrosome in native and capacitated sperm preparations (p < or = 0.01). CONCLUSION: Infertile men with sperm antibodies in serum and seminal plasma undergo premature acrosome loss. This loss may expose the reproductive tract immune system, especially that involving IgA, in autoimmune infertile men and the wives to high immunogenic levels of sperm acrosome membrane antigens, thereby rendering them immunologically infertile.

Acrosome↗