Gad Potashnik

Fertility drugs and the risk of breast and ovarian cancers: results of a long-term follow-up study

OBJECTIVE To investigate a possible linkage between the use of fertility drugs for infertility and the risk of breast and ovarian cancers. DESIGN Long-term, historic-prospective study. SETTING Fertility clinic in a university hospital. PATIENT(S) Files of 1,197 infertile women with a mean (+/- SD) follow-up of 17.9+/-5 years (21,407 person-years) were reviewed. Diagnoses, number of courses, and dosage of fertility drugs were extracted from the files. INTERVENTION(S) Cancers were identified by record linkage to the National Cancer Registry. Histopathologic reports and data on estrogen and progesterone receptors in breast cancer tissue were also reviewed. MAIN OUTCOME MEASURE(S) Standardized incidence ratio with 95% confidence interval (CI) were used for risk assessment. RESULT(S) Of 20 breast cancers (standardized incidence ratio, 1.40 [95% CI, 0.83-2.10]), 16 were detected among 780 women who had been exposed to 3,978 cycles of clomiphene citrate (CC) and/or hMG (standardized incidence ratio, 1.65 [95% CI, 0.94-2.68]). The standardized incidence ratio for this cancer was significantly increased only in patients with one or two CC treatments and a dose of < or =1,000 mg (2.6 [1.19-5.0] and 2.52 [1.21-4.64], respectively). Two cases of ovarian cancer (1 patient unexposed) were observed with no evidence of excessive risk. Six of the eight patients with data on estrogen and progesterone receptors were exposed to CC, and all tested positive for these receptors. CONCLUSION(S) An association between the use of fertility drugs and an increased risk of breast and ovarian cancers has not been confirmed.

Obstetric outcome of singleton pregnancies conceived by in vitro fertilization and ovulation induction compared with those conceived spontaneously

OBJECTIVE To compare the obstetric characteristics of singleton pregnancies conceived by IVF and ovulation induction with those conceived spontaneously. DESIGN Case-control study. SETTING Tertiary care medical center. PATIENT(S) All singleton pregnancies that were achieved by IVF (n = 169) and ovulation induction (n = 646) and were delivered from January 1989 through December 1994 were evaluated. Each group was compared with a separate control group that conceived spontaneously (n = 469 and n = 1,902 for the IVF and ovulation induction groups, respectively) and delivered during the same period and was matched in terms of maternal age, gestational age, and parity. INTERVENTION(S) Ovulation induction, IVF-ET. MAIN OUTCOME MEASURE(S) Obstetric complications. RESULT(S) Multivariate analysis showed that patients who conceived by IVF and ovulation induction had a significantly higher risk for gestational diabetes mellitus (odds ratio [OR] = 2.0; 95% confidence interval [CI] = 1.23-3.30 and OR = 1.9, 95% CI = 1.09-1.79, respectively), pregnancy-induced hypertension (OR = 2.1, 95% CI = 1.04-4.10 and OR = 1.5, 95% CI = 1.04-2.02, respectively), and cesarean section (OR = 3.6, 95% CI = 2.44-5.29 and OR = 1.4, 95% CI = 1.09-1.79, respectively) compared with their matched controls. CONCLUSION(S) After controlling for maternal age, gestational age, and parity, we demonstrated that singleton pregnancies conceived by IVF and ovulation induction are at increased risk for maternal gestational diabetes mellitus and pregnancy-induced hypertension, and at greater risk for delivery by cesarean section.

Suppressive Effect of 1,2-Dibromo-3-Chloropropane on Human Spermatogenesis

Azoospermia was diagnosed in six factory workers who had been chronically exposed to 1,2-dibromo-3-chloropropane. Infertility was the presenting symptom in two patients and a decrease in libido or impotence characterized the others. Hormone studies revealed elevated plasma follicle-stimulating hormone levels and normal plasma luteinizing hormone and testosterone concentrations. Testicular biopsy showed selective atrophy of the germinal epithelium, intact Sertoli cells, and a normal appearance of a relatively increased number of Leydig cells.

Dibromochloropropane (DBCP): An 8-year reevaluation of testicular function and reproductive performance

The current study summarizes an 8-year reassessment of testicular function and reproductive performance in 15 workers with dibromochloropropane (DBCP)-induced azoospermia and oligozoospermia. Recovery of spermatogenesis was observed in four oligozoospermic and three azoospermic men whose plasma follicle-stimulating hormone (FSH) concentration was normal during the whole period. A marked increase in FSH and luteinizing hormone concentrations above the upper limit of normal was found in the azoospermic workers who did not recover. No significant changes in FSH concentrations were detected in both recovered and nonrecovered oligozoospermic men. Testosterone levels of all patients were normal at all times. Paternal exposure to DBCP was not associated with increased risk of fetal malformations or spontaneous abortion.

Distinct expression levels of cytokines and soluble cytokine receptors in seminal plasma of fertile and infertile men

OBJECTIVE To compare the levels of interleukin (IL) 1 beta, IL-6, tumor necrosis factor (TNF) alpha, and soluble TNF (sTNF) receptors types I and II, and IL-1 receptor antagonist in seminal plasma of fertile and infertile men. DESIGN Prospective and comparative study. SETTING Andrology clinic of a university hospital. PATIENTS Four groups of normogonadotropic men: group 1, donors with proven fertility (controls, n = 15); group 2, azoospermic men (n = 12); group 3, infertile men with oligoteratoasthenospermia (n = 20); and 11 men with oligoteratoasthenospermia and genital infection (n = 11). INTERVENTIONS None. MAIN OUTCOME MEASURE Measurement of cytokines and cytokine-soluble receptors in the semen by specific commercial kits. RESULTS The levels of IL-1 beta, TNF-alpha, and IL-6 were similar in seminal plasma of controls and infertile men. The mean level of sTNF-I receptor in the seminal plasma of group 4 was 2.4 +/- 0.2 ng/mL, which was significantly lower than observed in seminal plasma of group 1 (3.88 +/- 0.5 ng/mL), the group 3 (4.1 +/- 0.4 ng/mL), or group 2 (3.03 +/- 0.35 ng/mL). The soluble receptor of TNF-II could not be detected in any group. Interleukin 1ra was 120 +/- 10 pg/mL in seminal plasma of group 1, but increased levels were detected in group 2 (420 +/- 180 pg/mL), group 3 (480 +/- 90 pg/mL), and even higher (760 +/- 120 ng/mL) in group 4 patients. CONCLUSIONS During genital infection cytokines and various soluble receptors of immunoregulatory cytokines are expressed distinctly in seminal plasma. These factors also may be involved in the regulation of sperm cell functions and thus may affect male fertility. Our results may indicate local production of these factors in the secondary sex glands, independently of spermatogenesis.

Dibromochloropropane (dbcp): A 17-year Reassessment of Testicular Function and Reproductive Performance

The current study summarizes a 17-year revaluation of testicular function and reproductive performance of 15 production workers with dibromochloropropane (DBCP)-induced testicular dysfunction. Sperm count recovery was evident within 36 to 45 months in three of the nine azoospermic and in three of the six oligozoospermic men with no improvement thereafter. A significant increase in plasma folliclestimulating hormone (FSH) and luteinizing hormone (LH) and a nonsignificant decrease in testosterone level were detected in the severely affected individuals. There was no increase in the rate of spontaneous abortions and congenital malformations among pregnancies conceived during or after exposure. A low prevalence of male infants conceived during paternal exposure was found as compared with the preexposure period (16.6% versus 52.9%; P<.025). Restoration of fertility was followed by a gradual increase of this value to 41.4%.

Gene expression microarray profiles of cumulus cells in lean and overweight-obese polycystic ovary syndrome patients

The aim of this work was to study gene expression patterns of cultured cumulus cells from lean and overweight-obese polycystic ovary syndrome (PCOS) patients using genome-wide oligonucleotide microarray. The study included 25 patients undergoing in vitro fertilization and intra-cytoplasmic sperm injection: 12 diagnosed with PCOS and 13 matching controls. Each of the groups was subdivided into lean (body mass index (BMI) < 24) and overweight (BMI > 27) subgroups. The following comparisons of gene expression data were made: lean PCOS versus lean controls, lean PCOS versus overweight PCOS, all PCOS versus all controls, overweight PCOS versus overweight controls, overweight controls versus lean controls and all overweight versus all lean. The largest number of differentially expressed genes (DEGs), with fold change (FC) |FC| >or= 1.5 and P-value < 0.01, was found in the lean PCOS versus lean controls comparison (487) with most of these genes being down-regulated in PCOS. The second largest group of DEGs originated from the comparison of lean PCOS versus overweight PCOS (305). The other comparisons resulted in a much smaller number of DEGs (174, 109, 125 and 12, respectively). In the comparison of lean PCOS with lean controls, most DEGs were transcription factors and components of the extracellular matrix and two pathways, Wnt/beta-catenin and mitogen-activated protein kinase. When comparing overweight PCOS with overweight controls, most DEGs were of pathways related to insulin signaling, metabolism and energy production. The finding of unique gene expression patterns in cumulus cells from the two PCOS subtypes is in agreement with other studies that have found the two to be separate entities with potentially different pathophysiologies.

Relationship between age and semen parameters in men with normal sperm concentration: analysis of 6022 semen samples

This study evaluates retrospectively the relationship between age and semen parameters among men with normal sperm concentration. It was based on computerized data and performed in an Academic Fertility and IVF Unit. Six thousand and twenty‐two semen samples with sperm concentrations of ≥20 × 106 ml−1 were examined according to WHO criteria and analysed in relation to patients’ age. For each age group, mean values ± SD of semen volume, sperm concentration, percentage of motile spermatozoa, normal morphology, acrosome index, total sperm count/ejaculate, total motile sperm count/ejaculate and sexual abstinence duration were examined. A peak semen volume of 3.51 ± 1.76 ml−1 was observed at age ≥30 to <35 years and a lowest volume of 2.21 ± 1.23 ml−1 was observed at age ≥55 years (P < 0.05). Sperm motility was found to be inversely related to age with peak motility of 44.39 ± 20.69% at age <25 years and lowest motility of 24.76 ± 18.27% at age ≥55 years (P < 0.05). A reduction of 54% was observed for total motile sperm, between values of 103.34 ± 107 × 106 at age ≥30 to <35 years and 46.68 ± 53.73 × 106 (P < 0.05) at age >55 years. A statistically significant and inverse relationship was observed between semen volume, sperm quality and patient age, in spite of prolonged sexual abstinence duration. Top sperm parameters were observed at age ≥30 to <35 years, while the most significant reduction in sperm parameters occurred after the age of 55 years.

Potential association between male infertility and occupational psychological stress.

Learning ObjectivesRecall past findings associating sperm parameters with occupational exposure to chemicals or work-related psychological distressUnderstand in what occupational, health, and demographic respects workers with male factor infertility differ from those seen for female infertility.Note which if any aspects of occupational stress were associated with male infertility in this study.Identify any clinical implications of these findings. The purpose of this work was to investigate the influence of working conditions, occupational exposures to potential reproductive toxic agents, and psychological stress on male fertility. The study population consisted of 202 consecutive male patients attending a fertility clinic. Of those, 106 patients had attended the clinic because of a male infertility problem (case group), 66 patients had attended the clinic because of a female infertility problem (control group), and 30 patients had a combined infertility problem (male and female). Male infertility was associated with working in industry and construction as compared with other occupations (78.6% vs 58.3%, P = 0.044). Industry and construction workers were of lower educational level than the other workers (mean: 12.1 vs 13.4 years, P = 0.021). These patients also tended to smoke more than the other workers (OR = 2.53, 95% CI = 1.08 to 5.98), more often worked in shifts (OR = 3.12, 95% CI = 1.19 to 8.13), reported physical exertion in work (OR = 3.35, 95% CI = 1.44 to 7.80), and were more exposed to noise and welding (OR = 3.84, 95% CI = 1.63 to 9.14, OR = 4.40, 95% CI = 1.11 to 1.76, respectively). Male infertility (case group) was found to be statistically related to higher marks in all four measures of burnout as compared with the controls. The largest difference was obtained in the measure of cognitive weariness (mean:2.9vs 2.1, P < 0.001). In a multiple logistic regression analysis, industry and construction jobs (adjusted OR = 2.2, 95% CI 1.2 to 2.7) and cognitive weariness (adjusted OR = 1.8, 95% CI = 1.03 to 4.6) were found to be independent risk factors for male infertility problems. Male infertility was independently associated with industry and construction jobs as well as job burnout.

Dibromochloropropane‐induced Reduction of the Sex‐ratio in Man

The present study evaluated the effect of paternal exposure to Dibromochloropropane (DBCP) during its production, on the sex ratio of offsprings conceived during the exposure period. The study population consisted of 30 families of which 13 fathers became azoospermic, 8 oligozoospermic and 9 normozoospermic. Of the 89 pregnancies recorded, 68 culminated in the birth of live infants. The prevalence of male infants conceived during the pre‐exposure period was 52.9%, in contrast to 35.2% for boys conceived during exposure. For the combined azoospermic and oligozoospermic groups, a significantly low prevalence of male infants of 16.6% (p < 0.025) was found. It is concluded that paternal exposure to DBCP during its production process is associated with a significant decrease in the sex ratio of offsprings conceived during the exposure period. This drop in the sex ratio might be a reflection of the early effect of DBCP on male reproductive performance before a state of severe testicular dysfunction and infertility is reached.