Prevention of multiple pregnancies in gonadotropin-insemination cycles.

PURPOSE OF REVIEW: Although elective single embryo transfer has significantly reduced, the rate of multiple pregnancy in IVF cycles, this rate is still relatively high in gonadotropin-insemination cycles. Patients who fail to ovulate or to conceive with oral agents and have constraints for IVF are usually candidates for gonadotropin injections. The current review article provides an up-to-date summation of the different strategies that can be adopted to reduce the risk of multiple pregnancies in gonadotropin-stimulated intrauterine insemination cycles. RECENT FINDINGS: Gonadotropin-insemination treatments should be used judiciously by experienced providers. One should always start with the lowest effective gonadotropin dose (∼37.5 IU), monitor closely the ovarian response, and consider cycle cancellation or conversion to IVF whenever a high response is encountered. Therefore, every infertility practice should define its own cancellation and 'rescue IVF' criteria depending on the number of mature ovarian follicles and the age of the female partner. SUMMARY: These preventive measures amongst others should mitigate the risk of multiple pregnancies that can arise from gonadotropin-insemination cycles.

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.

Parental consanguinity and family history of coronary artery disease strongly predict early stenosis.

BACKGROUND: Coronary artery disease (CAD) is a multifactorial disease with acquired and inherited components. AIM: We investigated the roles of family history and consanguinity on CAD risk and age at diagnosis in 4284 patients. The compounded impact of diabetes, hyperlipidemia, hypertension, smoking, and BMI, which are known CAD risk factors, on CAD risk and age at diagnosis was also explored. METHODS: CAD was determined by cardiac catheterization. Logistic regression and stratification were performed to determine the impact of family history and consanguinity on risk and onset of CAD, controlling for diabetes, hyperlipidemia, hypertension, smoking, and BMI. RESULTS: Family history of CAD and gender significantly increased the risk for young age at diagnosis of CAD (p<0.001). Consanguinity did not promote risk of CAD (p=0.38), but did affect age of disease diagnosis (p<0.001). The mean age at disease diagnosis was lowest, 54.8 years, when both family history of CAD and consanguinity were considered as unique risk factors for CAD, compared to 62.8 years for the no-risk-factor patient category (p<0.001). CONCLUSIONS: Family history of CAD and smoking are strongly associated with young age at diagnosis. Furthermore, parental consanguinity in the presence of family history lowers the age of disease diagnosis significantly for CAD, emphasizing the role of strong genetic and cultural CAD modifiers. These findings highlight the increased role of genetic determinants of CAD in some population subgroups, and suggest that populations and family structure influence genetic heterogeneity between patients with CAD.

Benefit of consolidative radiation therapy in patients with diffuse large B-cell lymphoma treated with R-CHOP chemotherapy.

PURPOSE: The current standard therapy for patients with diffuse large B-cell lymphoma (DLBCL) is rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). The role of consolidative radiation therapy (RT) in the setting of R-CHOP chemotherapy is not well reported. This retrospective analysis is an attempt to clarify this role. PATIENTS AND METHODS: Subjects were 469 patients with histologically confirmed DLBCL treated between January 2001 and December 2007. Variables including age, sex, Ann Arbor disease stage, bulky disease status, standardized uptake values (SUVs) on positron emission tomography (PET), International Prognostic Index (IPI), and Ki67 staining (proliferation). RESULTS: Of 469 patients, 190 (40.5%) had stage I or II disease and 279 (59.5%) had stage III or IV disease, 327 (70%) had at least six cycles of R-CHOP, and 142 (30.2%) had involved-field RT (dose, 30 to 39.6 Gy) after complete response to chemotherapy. Median follow-up was 36 months (range, 8 to 85 months). Multivariate analysis showed that RT (P < .0001), IPI score (P = .001), response to therapy (P = .001), use of six to eight cycles of R-CHOP (P < .001), and combined presence (P = .006) or absence (P = .025) of high Ki67, high PET SUV, and bulky disease influenced overall survival (OS) and progression-free survival (PFS). Matched-pair analyses of patients who received six to eight cycles of R-CHOP with stage I or II disease (44 pairs) and all stages (74 pairs) indicated that RT improved OS (hazard ratio [HR], 0.52 and 0.29, respectively) and PFS (HR, 0.45 and 0.24, respectively) compared with no RT. CONCLUSION: This study showed significant improvements in OS and PFS among patients who received consolidation RT after R-CHOP chemotherapy for DLBCL.

The I allele of the angiotensin converting enzyme I/D polymorphism confers protection against coronary artery disease.

BACKGROUND: Mutations in genes regulating lipid metabolism, vasoactivity, and coagulation are important modulators of coronary artery disease (CAD). OBJECTIVE: This study investigated the association between allelic variants of the angiotensin converting enzyme (ACE), methytetrahydrofolate reductase, plasminogen activator inhibitor-1 and factor V genes and CAD. METHODS: Clinical, biochemical, and angiographic information were collected from 300 patients who underwent cardiac catheterization and their DNA was genotyped by restriction fragment length polymorphism. RESULTS: The frequency of the D allele of the ACE gene was significantly higher than the I allele in patients with more than 70% stenosis in any vessel. Among patients with more than 70% stenosis, carriers of the D allele were 2.8 times more likely to be males. The presence of the ACE I allele was negatively associated with CAD with (P=0.02 ,OR=0.38.) CONCLUSION: This study describes a protective role of the ACE I allele in individuals who may be at risk of developing CAD.

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.

ALOX5AP gene variants show differential association with coronary artery disease in different populations.

Coronary artery disease (CAD) is a complex disease with various components, genetic as well as environmental. Previous reports correlating ALOX5AP gene variants and CAD showed conflicting results depending on the population studied. In this study, we examined the contribution of ALOX5AP genetic predisposition to CAD in a group of CAD patients and controls carefully selected from the Lebanese population. We genotyped SNPs for ALOX5AP variants in 289 catheterized patients aged ≤52 years with >50% stenosis in at least one main coronary artery and 227 catheterized control subjects aged 60 years and above with 0% stenosis. Chi-square (χ (2)) tests and logistic regression showed no significant difference in the allele and genotype frequencies between the CAD or myocardial infarction (MI) cases and the healthy controls. Haplotype analysis using PHASE showed that the distribution of the risk haplotypes among cases and controls were not significantly different and had no attributable risk to CAD (P = 1.00 and P = 0.5, respectively) or MI (P = 0.2 and P = 0.5, respectively). Our data revealed that ALOX5AP gene variants are not predictors of CAD risk or MI risk among Lebanese patients.

Effect of powdered gloves, worn at the time of embryo transfer, on the pregnancy outcome of IVF cycles.

PURPOSE: To assess the effect of wearing powdered gloves during embryo transfer as compared to un-powdered gloves on the pregnancy outcome of IVF cycles. METHODS: Patients, undergoing embryo transfer procedures, were prospectively randomized into two groups: In the first (group A, n=356) group embryo transfer was performed while wearing powdered gloves; in the second (group B, n=356) group embryo transfer was performed while wearing un-powdered gloves. The primary end point of the study was the clinical pregnancy rate. RESULTS: The two groups were comparable with respect to the mean age, mean number of grade one embryos obtained, and the mean number of embryos transferred. The clinical pregnancy rates of the two groups were not different. CONCLUSIONS: Powdered gloves, worn during embryo transfer, have no adverse effect on the pregnancy outcome of IVF cycles.

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.

Lateral distribution of endometriomas as a function of age.

The lateral asymmetry of ovarian endometriomas, with a left-sided predilection, seems to disappear with advancing age. This asymmetry does not seem to persist in women >35 years of age.

Filariasis infection is a probable cause of implantation failure in in vitro fertilization cycles.

OBJECTIVE: To describe a parasitic infection that probably affected the implantation of good-quality embryos in an in vitro fertilization (IVF) cycle. DESIGN: Case report. SETTING: Tertiary care center in a university hospital. PATIENT(S): A 36-year-old Caucasian female with primary unexplained infertility. The patient underwent two cycles of IVF with good-quality embryos transferred; however, no pregnancy ensued despite adequate luteal support. INTERVENTION(S): In vitro fertilization cycles, CBC, blood smear, evaluation for eosinophilia including serological evaluation for parasitic infections. MAIN OUTCOME MEASURE(S): Pregnancy. RESULT(S): Following treatment for filariasis, a repeat IVF cycle using the same stimulation protocol yielded a full-term pregnancy. CONCLUSION(S): This case is of particular importance because, to our knowledge, it is the first to describe a parasitic infection that probably affected the implantation of good-quality embryos in IVF cycles.

The consanguinity effect on QF-PCR diagnosis of autosomal anomalies.

OBJECTIVES: Quantitative Fluorescent PCR (QF-PCR) is a simpler and faster method of detecting common chromosomal abnormalities when compared to cytogenetic analysis. The aim of our study is to investigate the applicability of this methodology in a population where consanguineous marriages are common and to estimate the heterozygous frequency of the PCR markers used. METHODS: Four hundred and twenty-three DNA samples were extracted from uncultured amniocytes and amplified with 18 short tandem repeats (STR) markers specific to chromosomes 13, 18 and 21. Amplification products were analyzed using the GeneScan software. RESULTS: QF-PCR correctly identified all the numerical abnormalities related to chromosomes 13, 18 and 21. A total of 24 autosomal trisomies (5.7%) were detected. The markers D21S1432 and D21S11 were the most consistent in providing unequivocal positive results for chromosome 21 and the heterozygosity percentages of the markers used were lower than the values reported in Western populations. CONCLUSION: QF-PCR is reliable for the prenatal diagnosis of numerical anomalies of the chromosomes 13, 18 and 21 in our study population. The absence of STR heterozygosity data from Lebanon and surrounding countries makes our study very useful for the development of a reliable QF-PCR trisomy detection test.

Contraceptive options during perimenopause.

During the transition years leading to menopause, the possibility of conception persists, although at a lower rate. Contraceptive choices available to perimenopausal women are as varied as those for their younger counterparts, albeit with some limitations related predominantly to coexisting medical conditions rather than the advancing age itself. In this review, different contraceptive choices pertaining to this age group will be discussed, with a focus on evidence-based data.

Patients with early onset of type 1 diabetes have significantly higher GG genotype at position 49 of the CTLA4 gene.

Type 1 diabetes (T1D) is a complex autoimmune disease. Several genetic loci have been implicated in the susceptibility to this illness. Evaluated was the role of the CTLA4 exon 1 A49G polymorphism and its role as a risk factor for T1D in our population. DNA from 190 patients with T1D and their families and 96 control individuals were genotyped for CTLA4 exon 1 polymorphism and human leukocyte antigen (HLA)-DQB1*0201 and *0302 haplotypes by polymerase chain reaction (PCR) amplification-restriction enzyme analysis and PCR amplification that used sequence-specific primers, respectively. Patients were nonobese and <26 years old. The CTLA4 G allele was found to be more frequently present in patients with T1D (32.4%) as compared with its frequency in control individuals (24.5%). The GG genotype was also significantly higher among patients (12.6%) than in controls (4.2%). chi(2) analysis and family-based association studies were performed and suggested the association of CTLA4 exon 1 G polymorphism with T1D (p = 0.0229). Furthermore, in HLA-DQB1*0201-positive patients with T1D, the GG and AA genotypes were higher and lower, respectively, than those found in control individuals. This study suggests that CTLA4 is a candidate susceptibility gene for T1D.

Amniotic fluid embolus: can we affect the outcome?

PURPOSE OF REVIEW: Amniotic fluid embolism is a rare catastrophe unique to pregnancy. Its mortality rate remains high despite efforts at prompt and aggressive management protocols, highlighting the need to maintain a high index of suspicion. RECENT FINDINGS: The intrusion of amniotic fluid into the maternal bloodstream may lead in certain women to a complex series of physiological reactions mimicking those seen in human anaphylaxis or sepsis, negating the purely embolic phenomenon theory as previously understood. The clinical picture is the sudden onset of cardiovascular collapse, cyanosis, haemorrhage or disseminated intravascular coagulopathy, during or soon after delivery. SUMMARY: The mainstay of a successful outcome remains the identification of high-risk patients, as well as early clinical diagnosis and management.