Liat Lerner-Geva

The effect of antioxidant treatment on human spermatozoa and fertilization rate in an in vitro fertilization program

OBJECTIVE To study the possible influence of antioxidant treatment on human spermatozoa and the fertilization rate in an IVF program. DESIGN Prospective study. SETTING In Vitro Fertilization Unit, Serlin Maternity Hospital, and the Laboratory of Male Fertility, Bar-Ilan University, Ramat-Gan, Israel. PATIENTS Fifteen fertile normospermic male volunteers who had low fertilization rates in their previous IVF cycles. INTERVENTIONS Vitamin E (alpha-tocopherol) 200 mg daily by mouth for 3 months. MAIN OUTCOME MEASURES Lipid peroxidation potential (amount of malondialdehyde [MDA]), quantitative ultramorphologic analysis of spermatozoa, and fertilization rate per cycle. RESULTS The high MDA levels significantly decreased from 12.6 +/- 9.4 nmol/10(8) spermatozoa to normal levels of 7.8 +/- 4.2 nmol/10(8) spermatozoa after 1 month of treatment. The fertilization rate per cycle increased significantly from 19.3 +/- 23.3 to 29.1 +/- 22.2 after 1 month of treatment. No additional effects on MDA levels and fertilization rate were observed after completion of treatment. With regard to the quantitative ultramorphologic analysis, none of the sperm cell subcellular organelles were affected significantly by vitamin E treatment. CONCLUSION Vitamin E may improve the fertilization rate of fertile normospermic males with low fertilization rates after 1 month of treatment, possibly by reducing the lipid peroxidation potential, and with no change of the quantitative ultramorphologic analysis of subcellular organelles.

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.

Multicenter Cross-Sectional Study of Nontuberculous Mycobacterial Infections among Cystic Fibrosis Patients, Israel

A multicenter cross-sectional study showed prevalence appears to be increasing.

Cancer incidence in a cohort of infertile women who underwent in vitro fertilization

OBJECTIVE To assess whether ovarian hyperstimulation and IVF increase the risk for cancer. DESIGN Historical cohort analysis. SETTING; IVF units of two medical centers in Israel. PATIENT(S) Five thousand twenty-six women who underwent IVF between 1981 and 1992. INTERVENTION(S); Cancer incidence rates were determined through linkage to the National Cancer Registry and were compared with expected rates with respect to age, sex, and place of birth. MAIN OUTCOME MEASURE(S) Development of cancer. RESULT(S) Twenty-seven cases of cancer were observed, and 35.6 were expected (standardized incidence ratio, 0.76 [95% CI, 0.50-1.10]). Eleven cases of breast cancer were observed, whereas 15.86 were expected (standardized incidence ratio, 0.69 [95% CI, 0.46-1.66]). One case of ovarian cancer and 1 case of cervical cancer were observed, compared with 1.74 and 1.73 cases expected, respectively. The type of infertility, number of IVF cycles, and treatment outcome did not significantly affect risk for cancer. CONCLUSION(S) In a cohort of women treated with IVF, no excess risk for cancer was noted.

Patients with stages III and IV endometriosis have a poorer outcome of in vitro fertilization- embryo transfer than patients with tubal infertility

OBJECTIVE To evaluate the outcome of IVF in patients with stages III and IV endometriosis. DESIGN Retrospective study. SETTING The Sara Racine IVF Unit, Lis Maternity Hospital, Tel Aviv Sourasky Medical Center, Israel. PATIENT(S) Fifty-eight patients with stages III and IV endometriosis and 60 patients with tubal infertility. INTERVENTION(S) IVF-ET for all couples. MAIN OUTCOME MEASURE(S) Fertilization, pregnancy, and birth rates. RESULT(S) The comparison between patients with endometriosis and those with tubal infertility indicated that the former had a poor IVF outcome in terms of reduced fertilization rate (40% vs. 70%), reduced pregnancy rate per cycle (10.6% vs. 22.4%), and reduced birth rate per cycle (6.7% vs. 16.6%). The differences were statistically significant. CONCLUSION(S) The results show an unfavorable outcome of IVF-ET in patients with endometriosis when compared with those who have tubal infertility.

Outcome of early-onset sepsis in a national cohort of very low birth weight infants.

BACKGROUND: Early-onset sepsis (EOS) is associated with significant morbidity and mortality among infants with a very low birth weight (VLBW); however, there is a sparse amount of complete data on large cohorts. OBJECTIVE: To evaluate the mortality and major morbidities among VLBW infants with EOS. METHODS: This was a population-based observational study. Data were prospectively collected by the Israel Neonatal Network on all VLBW infants born in Israel from 1995 through 2005. Univariate and multivariable analyses were performed to assess the independent association of EOS on morbidity and mortality of VLBW infants. RESULTS: The study cohort included 15 839 infants, of whom 383 (2.4%) developed EOS. EOS was associated with significantly increased odds for mortality (odds ratio [OR]: 2.57 [95% confidence interval (CI): 1.97–3.35]), severe intraventricular hemorrhage (OR: 2.24 [95% CI: 1.67–3.00]), severe retinopathy of prematurity (OR: 2.04 [95% CI: 1.32–3.16]), and bronchopulmonary dysplasia (OR: 1.74 [95% CI: 1.24–2.43]). EOS was associated with an increased risk of death and/or severe neurologic morbidity (OR: 2.92 [95% CI: 2.27–3.80]). CONCLUSIONS: Although only 2.4% of VLBW infants had an episode of EOS, these infants were at an approximately threefold excess risk of death or major neurologic morbidities.

Autoimmunity and reproduction

OBJECTIVE To review the association between autoimmunity and reproductive failure. DESIGN A MEDLINE search done from 1965 to 1996. More than 300 original and review articles were evaluated, from which the most relevant were selected. RESULT(S) Autoimmune processes now are accepted widely as one of the possible mechanisms of many human diseases. The presence of autoimmune disorders has been associated repeatedly with reproductive failure. On the other hand, reproductive failure may be the first manifestation of autoimmune disorders. CONCLUSION(S) When abnormal autoantibody levels are present in women with reproductive failure, the reproductive failure alone should be considered as one of the possible clinical expressions of autoimmune disorders. Two relevant questions of whether these patients should be treated for autoimmunity remain unsolved. A prospective, placebo-controlled trial is necessary to evaluate the importance of any treatment.

Age-related efficacy of Shigella O-specific polysaccharide conjugates in 1–4-year-old Israeli children

BACKGROUND Despite its high worldwide morbidity and mortality, there is yet no licensed vaccine for shigellosis. We reported the safety and immunogenicity of Shigella O-specific polysaccharide-protein conjugates in adults and young children and efficacy of Shigella sonnei conjugate in young adults. METHODS A double-blinded, randomized and vaccine-controlled Phase 3 evaluation of S. sonnei and Shigella flexneri 2a O-SP-rEPA conjugates, 25 microg, injected IM twice, 6 weeks apart, into healthy 1-4 years old, is reported. The children were followed for 2 years by telephone every other week and stool cultures were obtained for each episode of acute diarrhea (> or =3 loose stools/day or a bloody/mucous stool). Sera were taken randomly from 10% of the participants for IgG anti-LPS and anti-carrier levels. RESULTS Of the 2799 enrollees, 1433 received S. sonnei and 1366 S. flexneri 2a conjugates; 2699 (96.4%) completed the 2-year follow-up. Local reactions occurred in approximately 5% and approximately 4% had temperatures > or =38.0 degrees C lasting 1-2 days. There were no serious adverse events attributable to the vaccines. Of the 3295 stool cultures obtained, 125 yielded S. sonnei and 21 S. flexneri 2a. Immunogenicity and efficacy were age-related. The overall efficacy of the S. sonnei conjugate was 27.5%; 71.1% (P=0.043) in the 3-4 years old. The numbers for S. flexneri 2a were too few for meaningful analysis. Cross-protection by S. flexneri 2a for non-vaccine S. flexneri types was found, but the numbers were too few for statistical significance. There was an age-related rise of vaccine-specific IgG anti-LPS in both groups, peaking at about 10 weeks and declining thereafter, but remaining > or =4-fold higher than in the controls 2 years after the second dose. CONCLUSIONS Shigella conjugates are safe and immunogenic in 1-4 years old. The S. sonnei conjugate elicited 71.1% efficacy in the 3-4 years old and can be predicted to be efficacious in individuals older than 3 years of age. These results urge studies with our improved conjugates.

Safety and immunogenicity of Shigella sonnei-CRM9 and Shigella flexneri type 2a-rEPAsucc conjugate vaccines in one- to four-year-old children.

Background and objective. Shigella conjugate vaccines have been shown to be safe, immunogenic and efficacious in adult volunteers. We have now investigated the safety and immunogenicity of investigational Shigella sonnei and Shigella flexneri 2a conjugate vaccines in 1- to 4-year-old children, the age group at greatest risk for shigellosis. Methods. The O-specific polysaccharides of S. sonnei and S. flexneri 2a, the two most common shigellae from patients in Israel, were bound to medically useful carrier proteins to form conjugates. Eighty healthy 1- to 4-year-olds were randomized to receive two 0.5-ml im injections 6 weeks apart of either S. sonnei-CRM9 or S. flexneri 2a-r EPAsucc. Blood was taken before, 6 weeks after the first injection, 4 weeks after the second injections and 2 years after immunization for assay of IgG anti-lipopolysaccharide, diphtheria toxin and Pseudomonas aeruginosa exotoxin A antibodies by enzyme-linked immunosorbent assay. Results. During an 8-day surveillance period after each immunization, low fever (37.8–39.0°C) lasting only 24 to 48 h occurred in 2 of 40 recipients after the first injection and 4 of 40 recipients after the second injection of S. flexneri 2a-r EPAsucc and in 2 of 38 of S. sonnei-CRM9 after the second injection; no fever was detected after the first injection. Liver function tests were normal in all vaccinees. S. sonnei-CRM9 elicited a >4-fold rise in IgG anti-LPS in 92.1% and S. flexneri 2a-r EPAsucc in 85% (P < 0.0001) after the second injection; both conjugates elicited type-specific booster responses. At 2 years the geometric mean concentrations of both IgG anti-lipopolysaccharides were significantly higher than preimmunization levels. A >4-fold rise of IgG anti-diphtheria (65.8%) and IgG anti-ETA (77.5%) was observed. Conclusion. These experimental Shigella conjugate vaccines were safe and immunogenic in 1- to 4-year-old children.

Major motives in non-acceptance of A/H1N1 flu vaccination: The weight of rational assessment

Recent efforts of health authorities to promote vaccination against influenza A/H1N1 were met with low compliance rates in most industrialized countries. Here we analyzed the attitudes of the Israeli public towards A/H1N1 vaccination based on a telephone survey conducted several months after the peak of the outbreak. The findings attest to the low uptake of the A/H1N1 vaccine (17%) in Israel, and identify the socio-demographic characteristics associated with non-compliance. In addition, the survey reveals passiveness, fear and distrust as motives leading to non-compliance. Most importantly, the study identified the substantial weight of reflective assessment in the attitude of lay individuals towards the A/H1N1 vaccine. As many as 30% of the non-vaccinated responders provided reasoned arguments for rejecting the vaccine, based mainly on assessment of threat versus actual risk. These observations highlight the need to consider the opinion of the lay public when implementing new vaccination programs.