Antoine Hannoun

Fertility drugs and the risk of breast cancer: a meta-analysis and review

The risk of breast cancer has been associated with reproductive history. The purpose of this study was to determine the relationship between fertility drugs used in assisted reproductive procedures and the risk of breast cancer. We performed a literature search using the MEDLINE, the COCHRANE Library, and Scopus to identify studies linking breast cancer to fertility drugs. We excluded case series, case reports, and review articles from our analysis. The study populations included women who were treated for infertility with clomiphene, gonadotropins, gonadotropin-releasing hormones, or other unspecified fertility agents. We extracted information on study design, sample size, type of fertility drugs and number of treatment cycles, breast cancer incidence, and follow-up time from these studies. Eight case–control studies and fifteen cohort studies were included in the quantitative analyses. The Newcastle–Ottawa Quality Assessment Scales were used. Two investigators independently extracted study methods, sources of bias, and outcomes. We found that the risk of breast cancer was not significantly associated with fertility drug treatment. The follow-up periods were short in some of the studies analyzed in our study; however, we proceeded to test the trend in risk estimates across different durations of follow-up and found a trend for association using the nonparametric test; this was interpreted with caution in view of the lack of adjustment with other confounding factors. The current published data do not suggest higher risk of breast cancer in women who receive fertility treatment, but the lack of long-term follow up and the inherent weaknesses in some of the published studies have to be cautiously taken into account.

Correlation between Group B streptococcal genotypes, their antimicrobial resistance profiles, and virulence genes among pregnant women in Lebanon.

The antimicrobial susceptibility profiles of 76 Streptococcus agalactiae (Group B Streptococci [GBS]) isolates from vaginal specimens of pregnant women near term were correlated to their genotypes generated by Random Amplified Polymorphic DNA analysis and their virulence factors encoding genes cylE, lmb, scpB, rib, and bca by PCR. Based on the distribution of the susceptibility patterns, six profiles were generated. RAPD analysis detected 7 clusters of genotypes. The cylE gene was present in 99% of the isolates, the lmb in 96%, scpB in 94.7%, rib in 33%, and bca in 56.5% of isolates. The isolates demonstrated a significant correlation between antimicrobial resistance and genotype clusters denoting the distribution of particular clones with different antimicrobial resistance profiles, entailing the practice of caution in therapeutic options. All virulence factors encoding genes were detected in all seven genotypic clusters with rib and bca not coexisting in the same genome.

Addition of sphingosine-1-phosphate to human oocyte culture medium decreases embryo fragmentation.

Apoptosis is implicated in the fragmentation of preimplantation mammalian embryos, yet the extent of this association remains controversial. The aim of this study was to assess the ability of sphingosine-1-phosphate (S1P), a known anti-apoptotic substance, to reduce the fragmentation rate of human preimplantation embryos when added to their culture microenvironment. Mature human oocytes were inseminated using intracytoplasmic sperm injection, incubated for 3 days and evaluated for embryo quality and fragmentation by the same embryologist. Oocytes in the study group were manipulated and cultured in culture medium supplemented with S1P to a 20 micromol/l concentration. A total of 46 patients donated 177 mature oocytes for the study group and 546 oocytes for the control group. The fertilization rate was significantly lower in the S1P-supplemented group (52.4% versus 67.3%; P=0.002) and the proportion of grade I embryos with less than 15% fragmentation was significantly higher in the same group (79.5% versus 53.9%; P<0.0001). Sphingosine-1-phosphate added to the culture medium of human preimplantation embryos is associated with a significantly lower fragmentation rate and hence better quality embryos. The clinical significance of these findings on reproductive outcome remains highly speculative awaiting further studies to translate this improvement in embryo quality into better pregnancy rates.

Effect of war on fertility : a review of the literature

The aim of this study was to review the existing literature on the effect of war on female and male fertility. A MEDLINE search for studies that included participants defined as infertile because they were unsuccessful in achieving a pregnancy after a year and studies that assessed the effect of war on semen parameters and menstrual dysfunction were performed. Twenty articles were included in this review. For female fertility, studies showed that women who were prisoners of war or who were living in areas exposed to bombardment had increased risk of menstrual abnormalities. For male fertility, the results were conflicting. The Vietnam War was not associated with difficulty in conception although one study revealed a decrease in sperm characteristics. Studies of male US and Danish 1990/91 Gulf war veterans showed no evidence of reduced fertility; however, studies of UK and Australian veterans reported increased risk of infertility. The Lebanese and Slovenian civil wars were associated with a decrease in sperm parameters. Exposure to mustard gas was also associated with abnormal semen parameters; however, exposure to depleted uranium had no effect on semen characteristics. Most of the studies examined had major limitations including recall bias and small number of cases included.

FERTILITY DRUGS AND RISK OF OVARIAN CANCER: DISPELLING THE MYTH

Purpose of review Worldwide 50–80 million people suffer from infertility. Assisted reproductive technology has provided a way of overcoming infertility and childlessness. The current article will focus on data linking infertility and its treatment to ovarian cancer. Recent findings Ovarian cancer risks associated with fertility drug treatment are encouraging, but not decisive. In view of the limited ability to evaluate drug effects on borderline tumors, given their rare occurrence, studies involving patient reports of prior drug exposures have noted an elevated risk of borderline tumors associated with fertility drugs. Nevertheless, the risk of invasive ovarian cancer appears to be restricted to those women who remain childless despite the infertility treatment. Summary As long as doubt persists, it might be advisable to reflect on a few clinical recommendations: identify high-risk infertile patients for ovarian cancer, investigate preexisting cancer before fertility treatment, inform patients regarding potential risks, obtain an informed consent, avoid exposure to long periods of ovulation induction cycles that are given before patients are referred for in-vitro fertilization and embryo transfer for women at greater risk and monitor women who have been treated with these drugs, especially those who failed to conceive, regularly and thoroughly.

Effect of war on the menstrual cycle.

OBJECTIVE: To study the effect of a short period of war on the menstrual cycles of exposed women. METHODS: Six months after a 16-day war, women in exposed villages aged 15–45 years were asked to complete a questionnaire relating to their menstrual history at the beginning, 3 months after, and 6 months after the war. A control group, not exposed to war, was also interviewed. The data collected were analyzed to estimate the effect of war on three groups of women: those who stayed in the war zone for 3–16 days (Group A), those who were displaced within 2 days to safer areas (Group B), and women not exposed to war or displacement (Group C-control). RESULTS: More than 35% of women in Group A and 10.5% in Group B had menstrual aberrations 3 months after the cessation of the war. These percentages were significantly different from each other and from that in Group C (2.6%). Six months after the war most women regained their regular menstrual cycles with the exception of 18.6% in Group A. CONCLUSION: We found a short period of war, acting like an acute stressful condition, resulted in menstrual abnormalities in 10–35% of women and is probably related to the duration of exposure to war. This might last beyond the war time and for more than one or two cycles. In most women the irregular cycles reversed without any medical intervention. LEVEL OF EVIDENCE: II

Effect of parity on maternal and neonatal outcomes in twin gestations

Objective. To compare maternal and neonatal outcomes of twin gestations in nulliparous and multiparous women. Design. Retrospective analysis of maternal and neonatal records. Setting. American University of Beirut Medical Center, a referral university‐affiliated hospital. Population. Pregnant women who delivered twin gestations beyond 24 weeks from 1990 to 2004. Methods. The data collected were analyzed using Students paired t‐test or χ2test. Logistic regression analysis was used to study the effect of multiple variables on preterm delivery. Main Outcome Measure. Preterm birth rate. Results. Nulliparas (n=333) were more likely to be younger (28.1±5.4 vs. 30.0±5.2years; p<0.001) and the pregnancy a product of assisted reproductive technology (23.1 vs. 4.5%; p<0.001) compared with multiparas (n=508). They were at significantly increased risk of preterm delivery (54.4 vs. 45.1%; p=0.009) at lower gestational age (35.6±3.2 vs. 36.2±3.0 weeks; p=0.004). They had longer first and second stages of labor and a higher cesarean delivery rate (61.3 vs. 44.9%; p<0.001). Except for a higher intensive care nursery admission rate and longer nursery stay for twins of nulliparas, all neonatal morbidities were comparable. On multiple logistic regression analysis, multiparity (relative risk 0.70, 95% confidence interval 0.51–0.97) and growth restriction (relative risk 0.16, 95% confidence interval 0.12–0.22) were protective, while discordance (relative risk 2.24, 95% confidence interval 1.40–3.60) was a predictor of preterm delivery. Conclusions. Nulliparous women with twin gestations are at significantly higher risk for preterm delivery and cesarean delivery compared with multiparous women. Although this was not translated into higher perinatal mortality, these women should be monitored closely and counseled regarding these risks and their attendant morbidity.

Effect of betadine vaginal preparation during oocyte aspiration in in vitro fertilization cycles on pregnancy outcome.

Objective: The objective of this study is to assess the effect of two methods of vaginal scrubbing before egg retrieval on the outcome of in vitro fertilization-embryo transfer (IVF-ET) cycles. Method: 721 consecutive cycles of IVF-ET, at the American University Hospital of Beirut, were randomized prospectively into one of two groups. In the study group the betadine used to scrub the vagina, prior to egg retrieval, was not washed out, whereas in the control group this betadine was cleansed by saline irrigation. The two groups were compared as to the outcome of their IVF-ET cycles. Result: Both groups were similar in age, mean dose of FSH received, the number of oocytes and embryos obtained, the number of grade 1 embryos obtained, and the fertilization rate. There was no difference in the total pregnancy, clinical pregnancy, missed abortion, and multiple pregnancy rates between the two groups. However, the chemical pregnancy rate was higher in the study group as compared to controls. Conclusion: Vaginal preparation by betadine does not seem to affect the results of IVF. However, because it is associated with an increase in the rate of chemical pregnancy, it is advisable to cleanse before oocyte aspiration.

Effect of female nargile smoking on in vitro fertilization outcome.

OBJECTIVE Smoking is a significant health hazard that has been associated with poor reproductive outcome and reduced fertility in reproductive age women. The aim of this study was to assess the effect of nargile smoking on intra-cytoplasmic sperm injection (ICSI) outcome. STUDY DESIGN A prospective analysis of the outcomes of 297 women who underwent ICSI treatment at the ART Unit at the American University of Beirut Medical Center between January 1, and December 31, 2006 was done. The patients were divided into 3 groups based on their smoking status: cigarette smokers (n=42), nargile smokers (n=51) and non-smokers (n=204). RESULTS The mean age of nargile smokers was significantly lower than the other groups; however, the 3 groups were similar with respect to the cause of infertility, total dose of follicular stimulating hormone (FSH), number of oocytes and embryos obtained, and number and quality of embryos transferred. There was no significant difference in the clinical pregnancy rate between nargile smokers and non-smokers (51.0% vs 43.6%). However, cigarette smokers had a significantly lower clinical pregnancy rate compared to non-smokers (23.8% vs 43.6%, p=0.0238). On multiple logistic regression analysis, factors that decreased the clinical pregnancy rates were cigarette smoking and maternal age. CONCLUSION Although this study did not find a deleterious effect of nargile smoking on ICSI outcome, the results need to be confirmed in prospective studies that would include larger number of women with more objective measures of nargile smoke exposure.

Effect of religion on the attitude of primiparous women toward genetic testing

Factors that influence a pregnant womans decision to accept or decline genetic tests are largely undefined. The objective of this study was to determine the acceptance rate of prenatal diagnostic testing in Lebanon according to religion.