Impact of the Israeli Ministry of Health Cytomegalovirus Guidelines on the Local Pregnancy Outcome.

OBJECTIVE: In 2011, the Israeli Ministry of Health (MOH) published standard guidelines for the follow-up of pregnant women infected by CMV, recommending that amniocentesis be performed in cases of maternal serum viral seroconversion or abnormal sonographic findings suggestive of CMV, in order to prove fetal infection before electing for pregnancy termination. METHODS: A retrospective cohort study was performed, describing 448 pregnant women from 2006 to 2017. We collected data from all women that elected to continue their pregnancies after seroconversion and also of those who chose to undergo pregnancy termination. Subsequently, a telephone survey was then conducted to record outcomes of the newborns of women with CMV seroconversion during pregnancy. RESULTS: 325 (73%) women chose to continue their pregnancy, while 123 (27%) opted for termination of pregnancy. We found that pregnancy termination due to CMV infection was reduced by 7%, from 72 cases (32%) to 51 cases (25%) after the implementation of the MOH guidelines in 2011. In addition, 182/305 (60%) of women responded to our telephone questionnaire regarding newborn outcomes. Of these women, 45/305 (14%) reported complications, and no correlation was found between the prenatal findings and postnatal outcome among those who have responded to our survey. CONCLUSION: Implementation of the new MOH guidelines has reduced the rate of pregnancy termination, without increasing the rate of neonatal complications in Israel with a similar outcome of complication rate as reported in the literature.

Risk-reducing salpingo-oophorectomy and breast cancer incidence among Jewish BRCA1/BRCA2-mutation carriers-an Israeli matched-pair study.

OBJECTIVE: To study the association of risk-reducing bilateral salpingo-oophorectomy (RRBSO) and breast cancer risk among BRCA pathogenic sequence variants (PSV). METHODS: Jewish Israeli BRCA carriers who underwent RRBSO were matched with those who did not-by the mutated gene and year of birth (±1 year). Breast cancer rates were compared. RESULTS: Overall, 127 pairs met the inclusion criteria, 79 (60.6%) pairs harbored BRCA1 PSV and 50 (39.4%) pairs harbored BRCA2 PSV. Median follow up was 8.7 years (interquartile range 4.6-16.1 years). Breast cancer rate for all BRCA carriers combined was not affected by RRBSO (RRBSO 21 [16.5%] versus no RRBSO 31 [24.4%], hazard ratio [HR] for breast cancer 0.61, 95% confidence interval [CI] 0.33-1.14, P = 0.127). No association between RRBSO and breast cancer incidence was noted among BRCA1 PSV carriers. In BRCA2 PSV carriers, RRBSO was associated with a decreased overall breast cancer incidence (HR 0.20, 95% CI 0.44-0.91, P = 0.038), as well as after 5, 10, 15, and 20 years. Hormone replacement therapy was used by 62 PSV carriers, 52 in the RRBSO group and 10 in the no-RRBSO group and did not affect breast cancer risk (P = 0.463). CONCLUSION: RRBSO is associated with breast cancer risk reduction in Jewish Israeli BRCA2 PSV carriers. Risk-reducing bilateral salpingo-oophorectomy was associated with breast cancer risk reduction in Jewish Israeli BRCA2 pathogenic sequence variant carriers.

Comparison between a prenatal sonographic scoring system and a clinical grading at delivery for Placenta Accreta Spectrum disorders.

OBJECTIVE: Placenta Accreta Spectrum (PAS) disorders have become a major iatrogenic obstetric complication worldwide. Data on the accuracy of ultrasound examination diagnosis are limited by incomplete confirmation and variability in the description of the different grades of PAS at delivery. The aim of this study was to compare our prenatal routine sonographic screening and diagnostic scoring system with a standardized clinical grading system at birth in patient at risk of PAS. STUDY DESIGN: This is a retrospective cohort study of 607 pregnant patients with at least one prior cesarean delivery between December 2013 and December 2018. All patients were assessed for PAS using our institutional prenatal sonographic scoring system and the corresponding ultrasound findings were compared with those of a standardized clinical intra-operative macroscopic grading system of the degree of accreta placentation at vaginal birth or laparotomy. RESULTS: PAS was diagnosed clinically at birth in 50 (8.2%) cases, 17 of which were confirmed by histopathology. A low (score ≤ 5), medium (score 6-7), high (score ≥ 8) probability for PAS was reported in 502, 61 and 44 cases, respectively. The probability score increased significantly (p < .001) in women ≥2 prior cesarean deliveries, with an anterior low-lying/placenta previa, with absent clear space, increased in retroplacental vascularity and with the size and numbers of lacunae. The number of cases classified clinically as grade 1 (non-PAS) and 3 (adherent PAS) was significantly (p < .001) lower in women with a high probability score whereas the rates of the other grades was significantly (p < .001) higher. The widest discrepancy between ultrasound probability score and clinical grade was found for grade 2 which, describes a partial placental adherence and grades 4 and 5 which, refer to placental percreta which describes tissue having invade trough the uterine serosa and beyond. CONCLUSIONS: Both ends of the spectrum of accreta placentation remain difficult to diagnose antenatal and clinically at birth, in particular when no histopathologic confirmation is available. There is a need to develop ultrasound accuracy score systems that can differentiate between the different grades of PAS and which are validated by standardized clinical and pathology protocols.

Fertility treatments and breast cancer risk in Jewish Israeli BRCA mutation carriers.

OBJECTIVE: To determine whether fertility treatments impact the risk of breast cancer in Jewish Israeli BRCA1/2 mutation carriers. DESIGN: Historical cohort study. SETTING: University-affiliated tertiary medical center. PATIENT(S): A total of 1,824 Jewish Israeli BRCA1/2 mutation carriers from a single center were stratified into 1,492 (81.8%) carriers who were not treated for infertility and 332 (18.2%) carriers who underwent fertility treatment with clomiphene citrate (n = 134), gonadotropin (n = 119), in vitro fertilization (n = 183), or a combination of treatments (n = 89). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Hazard ratios (HR) and 95% confidence intervals (CI) for the association of breast cancer with fertility treatment and other hormonal and reproductive variables. RESULT(S): Breast cancer was diagnosed in 687 BRCA1/2 mutation carriers. Multivariate analysis, either of the whole group or stratified by each gene, showed no association between fertility treatment and breast cancer risk, regardless of the type of treatment (clomiphene citrate: HR 0.77, 95% CI 0.49-1.19; gonadotropin: HR 0.54, 95% CI 0.28-1.01; in vitro fertilization: HR 0.65, 95% CI 0.39-1.08; and combined treatments: HR 1.23, 95% CI 0.49-3.06). An increased breast cancer risk was associated with paternal origin of the mutation (HR 1.43, 95% CI 1.17-1.75) and use of oral contraceptives for >5 years (HR 1.62, 95% CI 1.27-2.06) in both BRCA1 and BRCA2 mutation carriers. Ovarian cancer risk was decreased with the use of any oral contraceptive (HR 0.61; 95% CI 0.46-0.82). CONCLUSION(S): Fertility treatment for BRCA1/2 mutation carriers is not associated with a discernible increase in breast cancer risk.