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Background: Precision oncology is gradually advancing into mainstream clinical practice, demonstrating significant survival benefits. However, eligibility and response rates remain limited in many cases, calling for better predictive biomarkers. Methods: We present ENLIGHT, a transcriptomics-based computational approach that identifies clinically relevant genetic interactions and uses them to predict a patient’s response to a variety of therapies in multiple cancer types, importantly, without training on previous treatment response data. Consequently, in addition to its ability to predict patients' response to approved and well-studied therapies, ENLIGHT can predict the response to new treatments in early development, even before clinical data has accumulated. Accordingly, we study ENLIGHT in two translationally relevant scenarios: Personalized Oncology (PO), aimed at prioritizing approved treatments to a given patient, and Clinical Trial Design (CTD), selecting the subset of most likely responders in a patient cohort. Results: Evaluating ENLIGHT’s performance on 21 blinded clinical trial datasets spanning 11 indications and 15 different drugs in the PO setting, we show that it can effectively predict a patient’s treatment response across multiple therapies and cancer types, with an overall odds ratio of 2.59 (p=3.41e-8), and a 36% increase in response rate over the baseline (p=3.30e-13). Its prediction accuracy is better than other state-of-the-art transcriptomics-based signatures. Unlike most signatures that are prognostic or provide insights for only very few, specific treatments, ENLIGHT provides matching scores to a broad range of treatments. Quite strikingly, its performance is comparable to that of supervised predictors developed for specific indications and drugs. In combination with the IFN-γ signature, ENLIGHT achieves an odds ratio larger than 4 in predicting response to immune checkpoint therapy. In the CTD scenario, our results show that by excluding non-responders ENLIGHT can enhance clinical trial success for immunotherapies and other monoclonal antibodies, achieving > 90% of the response rate attainable under an optimal exclusion strategy. Conclusion: ENLIGHT is a powerful transcriptomics-based precision oncology pipeline developed by Pangea Biomed that broadly predicts response to both extant and novel targeted and immune therapies, going beyond context-specific biomarkers. Citation Format: Gal Dinstag, Eldad D. Shulman, Efrat Elis, Doreen S. Ben-Zvi, Omer Tirosh, Eden Maimon, Isaac Meilijson, Emmanuel Elalouf, Boris Temkin, Philipp Vitkovsky, Eyal Schiff, Danh-Tai Hoang, Sanju Sinha, Nishanth Ulhas Nair, Joo Sang-Lee, Alejandro A. Schäffer, Ze'ev Ronai, Dejan Juric, Andrea B. Apolo, William L. Dahut, Stanley Lipkowitz, Raanan Berger, Razelle Kurzrock, Antonios Papanicolau-Sengos, Fatima Karzai, Mark R. Gilbert, Kenneth Aldape, Padma S. Rajagopal, Tuvik Beker, Eytan Ruppin, Ranit Aharonov. Prediction of patient response to targeted and immunotherapies from the tumor transcriptome in a wide set of indications and clinical trials [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 957.

BackgroundPrecision oncology is gradually advancing into mainstream clinical practice, demonstrating significant survival benefits. However, eligibility and response rates remain limited in many cases, calling for better predictive biomarkers.MethodsWe present ENLIGHT, a transcriptomics-based computational approach that identifies clinically relevant genetic interactions and uses them to predict a patient’s response to a variety of therapies in multiple cancer types, without training on previous treatment response data. We study ENLIGHT in two translationally oriented scenarios:Personalized Oncology (PO), aimed at prioritizing treatments for a single patient, andClinical Trial Design (CTD), selecting the most likely responders in a patient cohort.FindingsEvaluating ENLIGHT’s performance on 21 blinded clinical trial datasets in the PO setting, we show that it can effectively predict a patient’s treatment response across multiple therapies and cancer types. Its prediction accuracy is better than previously published transcriptomics-based signatures and is comparable to that of supervised predictors developed for specific indications and drugs. In combination with the IFN-γsignature, ENLIGHT achieves an odds ratio larger than 4 in predicting response to immune checkpoint therapy. In the CTD scenario, ENLIGHT can potentially enhance clinical trial success for immunotherapies and other monoclonal antibodies by excluding non-responders, while overall achieving more than 90% of the response rate attainable under an optimal exclusion strategy.ConclusionENLIGHT demonstrably enhances the ability to predict therapeutic response across multiple cancer types from the bulk tumor transcriptome.FundingThis research was supported in part by the Intramural Research Program, NIH and by the Israeli Innovation Authority.

BACKGROUND AND OBJECTIVES Vaginal pixelated low power and long pulses (LPLP) CO2 laser has been suggested as an optional treatment for stress urinary incontinence (SUI) with many studies reporting short-term improvements. The objective of this study was to assess the 1-year subjective and objective efficacy of vaginal CO2 laser in women with urodynamic SUI. STUDY DESIGN/MATERIALS AND METHODS This was a prospective multicenter study. Patients with confirmed urodynamic SUI graded as mild or moderate were included. We used three sessions of fractional pixelated CO2 laser for vaginal application and followed up the patients at 6 and 12 months. We used the following measures at follow-up: 1-hour pad test (ICS protocol), questionnaires including Pelvic Floor Distress Inventory 20 (PFDI-20), Pelvic Floor Impact Questionnaire (PFIQ), Patient Global Impression of Improvement (PGI-I), and a 3-day urinary diary. The urodynamic assessment was repeated at 6 months. RESULTS Fifty-two patients with SUI had three laser treatments, of whom 48 completed a 6-month follow-up and 42 patients completed 12-month follow-up. No serious adverse events were recorded during the study period. A significant reduction on the 1-hour pad test was found from baseline (6.3 ± 1.6 g) to the 12-month follow-up (3.7 ± 1.4 g, P

Fibrolamellar carcinoma (FLC) is a rare cancer of the liver that most commonly affects children and young adults. There is no clear standard of care for the disease, whose response to treatment seems to be very different from that of hepatocellular carcinoma. We present a case of FLC in a patient in her mid 30s that recurred and persisted despite resection and multiple lines of treatment. Following transcriptomic analysis, a combination of ipilimumab (anti-CTLA4) and nivolumab (anti-PD-1) led to complete remission, although common biomarkers for immune checkpoint blockade were all negative in this case. The patient is still in remission. Here, combined checkpoint blockade guided by novel transcriptomic analysis led to complete remission after failure of several lines of treatment.

Background:Until coronavirus disease 2019 (COVID-19) drugs specifically developed to treat COVID-19 become more widely accessible, it is crucial to identify whether existing medications have a protective effect against severe disease. Toward this objective, we conducted a large population study in Clalit Health Services (CHS), the largest healthcare provider in Israel, insuring over 4.7 million members.Methods:Two case-control matched cohorts were assembled to assess which medications, acquired in the last month, decreased the risk of COVID-19 hospitalization. Case patients were adults aged 18 to 95 hospitalized for COVID-19. In the first cohort, five control patients, from the general population, were matched to each case (n=6202); in the second cohort, two non-hospitalized SARS-CoV-2 positive control patients were matched to each case (n=6919). The outcome measures for a medication were: odds ratio (OR) for hospitalization, 95% confidence interval (CI), and the p-value, using Fisher’s exact test. False discovery rate was used to adjust for multiple testing.Results:Medications associated with most significantly reduced odds for COVID-19 hospitalization include: ubiquinone (OR=0.185, 95% CI [0.058 to 0.458], pConclusions:Ubiquinone, ezetimibe, and rosuvastatin, all related to the cholesterol synthesis pathway were associated with reduced hospitalization risk. These findings point to a promising protective effect which should be further investigated in controlled, prospective studies.Funding:This research was supported in part by the Intramural Research Program of the National Institutes of Health, NCI.

Vaginal pixelated low power and long pulses (LPLP) COThis was a prospective multicenter study. Patients with confirmed urodynamic SUI graded as mild or moderate were included. We used three sessions of fractional pixelated COFifty-two patients with SUI had three laser treatments, of whom 48 completed a 6-month follow-up and 42 patients completed 12-month follow-up. No serious adverse events were recorded during the study period. A significant reduction on the 1-hour pad test was found from baseline (6.3 ± 1.6 g) to the 12-month follow-up (3.7 ± 1.4 g, P 0.05) was found. PGI-I showed 75.0%, 61.9%, and 64.3% improvements at 3, 6, and 12 months, respectively. PFDI improved significantly and consistently from baseline until 12 months (37.2 ± 3.89 to 16.1 ± 3.7, P 0.05). Similarly, PFIQ showed significant improvements from the first treatment up to 12 months. Urodynamic assessment at 6 months showed that 41.4% of patients had no stress incontinence.The vaginal CO

Objective: Resuming all ART treatments in Israel, following the COVID-19 lockdown put into effect on March 22, 2020, was fraught with concern, as the pandemic is still raging. One of the safety measures implemented was universal screening for SARS-CoV-2 of all ART patients. Our aim was to assess the usefulness of this measure. Design: Cohort study. Materials and Methods: All women initiating ART treatment from May 1st, through July 17, 2020, at one of the two IVF Units of the Assuta Medical Centers, were required to undergo screening with nasopharyngeal swabs and a quantitative polymerase-chain-reaction test to detect SARS-CoV-2 infection. All women with symptoms of Covid-19 or those with recent exposure to an infected person were not allowed to commence ART treatment. Since almost all of the IVF cycles performed at our centers are fully covered by the Israeli national health insurance, treatment is very accessible, and thus we believe that our sample is representative of the country’s COVID-19 prevalence. Results: A total of 4,259 asymptomatic women underwent ART treatments at the Assuta Medical Centers, 2,787 ovum pick-ups and and 1,472 frozen embryo transfers. Overall, 23 women (0.54%) tested positive for SARS-CoV-2. The rate of women who tested positive was similar in our IVF center in Tel-Aviv, 11 of 2,299 women (0.48%), and in our more southern Rishon Lezion center, 12 of 1,970 (0.61%). An additional 11 women had to cancel their IVF treatment as their male partner was tested positive for SARS-CoV-2. Only a fifth of the positive patients came from cities declared by the Ministry of Health as Covid-19 hotspots. Conclusions: Our use of universal SARS-CoV-2 testing in all ART patients initiating ART treatment revealed that at this point in the pandemic in central Israel, one in 200 asymptomatic women starting an ART treatment cycle was positive for SARS-CoV-2. This ratio is approximately 10 times lower than the current rate among women screened in Israel due to Covid-19 related symptoms or exposure to a positive person. The potential benefit of universal testing for Covid-19 includes the ability to protect patients and health care staff during these challenging times by lowering the risk of novel coronavirus exposure in the ART clinic. However, universal screening may burden the limited testing resources and may lead to less vigilant use of personal protective measures.

The COVID‐19 pandemic caused by SARS‐CoV‐2 has is a global health challenge. Angiotensin‐converting enzyme 2 (ACE2) is the host receptor for SARS‐CoV‐2 entry. Recent studies have suggested that patients with hypertension and diabetes treated with ACE inhibitors (ACEIs) or angiotensin receptor blockers have a higher risk of COVID‐19 infection as these drugs could upregulate ACE2, motivating the study of ACE2 modulation by drugs in current clinical use. Here, we mined published datasets to determine the effects of hundreds of clinically approved drugs on ACE2 expression. We find that ACEIs are enriched for ACE2‐upregulating drugs, while antineoplastic agents are enriched for ACE2‐downregulating drugs. Vorinostat and isotretinoin are the top ACE2 up/downregulators, respectively, in cell lines. Dexamethasone, a corticosteroid used in treating severe acute respiratory syndrome and COVID‐19, significantly upregulates ACE2 both in vitro and in vivo. Further top ACE2 regulators in vivo or in primary cells include erlotinib and bleomycin in the lung and vancomycin, cisplatin, and probenecid in the kidney. Our study provides leads for future work studying ACE2 expression modulators., Analyzing large‐scale in vitro and in vivo publicly available transcriptomic data of drug treatments, we identify the effects of hundreds of clinically approved drugs on expression of ACE2, the host receptor of SARS‐CoV‐2.

The COVID-19 pandemic caused by SARS-COV-2 has infected over 500,000 people causing over 25,000 deaths in the last 10 weeks. A key host cellular protein required for the virus entry is angiotensin-converting enzyme 2 (ACE2). Recent studies have reported that patients with hypertension and diabetes treated with ACE inhibitors or angiotensin receptor blockers might be at a higher risk of COVID-19 infection as these drugs have been reported to increase ACE2 expression. This has raised the need to systematically investigate the effect of different drugs including antihypertensives on modulating ACE2 expression. Here, we analyzed a publicly available CMAP dataset of pre/post transcriptomic profiles for drug treatment in cell lines for over 20,000 small molecules. We show that only one subclass of antihypertensives drugs - ACE inhibitors, are significantly enriched for drugs up-regulating ACE2 expression. Studying the effects of the 672 clinically approved drugs in CMAP, we chart the drug categories that affect ACE2 expression. Specifically, we find that panobinostat (an HDAC inhibitor) confers the highest up-regulation of ACE2 expression while isotretinoin (a vitamin A derivative) is its strongest down-regulator. Our results provide initial candidates guiding further in vitro and in vivo studies aimed at assessing drug effects on ACE2 expression.

Objective To describe a successful autologous ovarian tissue re-transplantation in a sterile leukemia survivor after evaluation for minimal residual disease and provide a review of the current literature. Design Presentation of a carefully designed workup taken to evaluate tissue for minimal residual disease, its limitations, and applicability to other patients. To date, there have not been any publications of auto-transplantations in leukemia survivors, owing to an estimated high risk for malignancy induction. Setting Large tertiary hospital. Patient(s) A 19-year-old acute myeloid leukemia patient underwent ovarian tissue cryopreservation during complete remission before bone marrow transplantation. After prolonged amenorrhea, the patient desired pregnancy. Laboratory tests showed antimullerian hormone Intervention(s) Ovarian tissue cryopreservation and auto-transplantation. Histology, immunohistochemistry, FISH, next-generation sequencing, and xenotransplantation were done to evaluate thawed tissue samples for the presence of leukemia cells. Main Outcome Measure(s) Evidence for leukemia cells in thawed ovarian tissue, reproductive outcomes and live birth after transplantation, and leukemia-free survival. Result(s) Histology was negative for leukemia cells. Three severe combined immunodeficiency mice, grafted with tissue fragments, were followed for 6 months and showed no macroscopic/microscopic signs for leukemia. Fluorescence in situ hybridization for disease-specific gene rearrangement resulted in a read below the probe's cut-off. A next-generation sequencing panel of genes implicated in myeloproliferative disorders did not reveal any significant molecular event. Transplantation was performed, followed by ovarian stimulation and IVF, resulting in the delivery of healthy newborn. More than 2 years have elapsed since transplantation, and the patient is leukemia free. Conclusion(s) Harvesting during complete remission, combined with intense tissue evaluation before transplantation, allowed a safe, successful transplantation in an acute myeloid leukemia survivor.

Objective Cesarean-induced niche can cause symptoms such as abnormal postmenstrual bleeding, pain and associated infertility. Hysteroscopic niche resection is usually a successful treatment, but can result in a failure to improve symptoms or symptoms can recur. In the present study we aim to evaluate the feasibility, effectiveness, and safety of a second hysteroscopic niche resection for patients in whom an initial hysteroscopic resection failed to improve symptoms. Study design This retrospective cohort study (Canadian Task Force classification II-2) hospital tell hashomer (tertiary center) included all patients who underwent a second hysteroscopic niche resection between 2011 and 2015. Measurements:Fertility,obstetric outcomes, clinical outcome and complications were compared between the first surgery and the second Results Eight patients underwent a second hysteroscopy after failure of the first hysteroscopy to resolve symptoms or after recurrence of symptoms. Abnormal uterine bleeding (AUB) was the most common symptom, occurring in all patients. The average number of days of bleeding per cycle were significantly reduced following the second surgery [14.50 (range 8-21 days) vs 11.75 (range 8-20 days), respectivelyp = 0.009]. The second surgery improved symptoms in 6 out of the 8 patients with AUB and 1 of 2 patients with pain. There were no significant differences in fertility and obstetric outcomes between the first and the second surgery and no complications were reported during any of the surgeries. Conclusion Reintervention with a second hysteroscopic niche resection is both feasible and effective treatment option following a failed first attempt or recurrence of symptoms. The second surgery improved symptoms, especially AUB, with no consequent detrimental effect on obstetric outcomes on our series.

Objective To determine, using four-dimensional (4D) transperineal ultrasound, whether the appearance, position or dimensions of sacrocolpopexy mesh implants or the degree of tissue support change in the long term. Methods Women who had undergone minimally invasive abdominal sacrocolpopexy for pelvic organ prolapse were invited for follow-up assessment at two consecutive visits at least 1 year apart. All participants completed a Pelvic Floor Distress Inventory questionnaire (PFDI-20) and underwent a pelvic examination by one examiner and had 4D ultrasound volumes obtained by a different examiner. Volumes were analyzed offline for mesh position with the woman at rest and on maximal Valsalva maneuver, and for mesh dimensions and characteristics on three-dimensional orthogonal planes and rendered views, with the operator blinded to the clinical data. Findings were compared between the two examinations. Results Thirty women attended follow-up assessment at two time points, a median of 22 (range, 12–37) months apart. The median age at the latter visit was 60 (range, 46–72) years, median body mass index was 25.9 (range, 20.8–31.9) kg/m2, median parity was 3 (range, 1–7) and median time from surgery to first and second visit, respectively, was 11.2 (range, 6–26) months and 33.5 (range, 14–56) months. There were no significant differences between the two time points in symptom scores, reported satisfaction from surgery, pelvic examination findings or pelvic organ descent in any compartment according to ultrasound. While mesh dimensions of anterior and posterior arms did not change significantly over time, both arms descended less on Valsalva at the second follow-up compared with at the first (13.2 ± 6.7 mm vs 21.9 ± 10.0 mm and 9.1 ± 5.3 mm vs 16.1 ± 8.1 mm, respectively, both P < 0.001). There were no mesh erosions, but folding remained a consistent finding, occurring in 80% of women in each assessment. Conclusions Characteristics of tissue support and dimensions of sacrocolpopexy mesh implants remained constant over long-term follow-up, with no mesh shrinkage or erosion. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Purpose: To determine the success rate of induction of labor (IOL) using Foley transcervical balloon (FTB) versus prostaglandin E2 (PGE2) vaginal insert, following failure of cervical ripening with PGE2 vaginal insert.Materials and methods: A retrospective cohort study of all pregnant women admitted for IOL with either FTB or PGE2 vaginal insert. Either second dose of PGE2 vaginal insert or FTB was used as a second line treatment after failure (not giving birth in 24 h from insertion) of first PGE2 vaginal insert.Results: During the study period, 1162 women were admitted for IOL. Failure was reported in 322/852 (37.8%) in the FTB versus 162/310 (52.2%) in the PGE2 group (p

To determine the preferred mode of delivery (vacuum, forceps or cesarean delivery) for second-stage dystocia.Retrospective cohort study of women delivered by forceps, vacuum or cesarean delivery due to abnormalities of the second stage of labor. Primary outcome included neonatal and maternal composite adverse effects.A total of 547 women were included: 150 (27.4%) had forceps delivery, 200 (36.5%) had vacuum extraction, and 197 (36.1%) had cesarean section. The rate of neonatal composite outcome was significantly increased in vacuum extraction (27%) compared to forceps delivery (14.7%) or cesarean section (9.7%) (p 0.001). There was no difference in the rate of maternal composite outcome among the groups. Both operative vaginal delivery modes were associated with significantly lower rate of postpartum infection compared to cesarean delivery (0% versus 3%, p = 0.004).Operative vaginal delivery was associated with reduced postpartum infection compared to cesarean section. Forceps delivery was associated with reduced risk for adverse neonatal outcome compared to vacuum extraction, with no increase in the risk of composite maternal complications.

Objective Investigate a novel office hysteroscopic tubal catheterization therapeutic method for proximal tubal occlusion. Study design Prospective cohort study in a tertiary referral center. We evaluated the procedure on a group of 27 patients that were referred to our unit for proximal tubal occlusion demonstrated by hysterosalpingography, 9 (33.3%) of them with primary infertility and 18 of them (66.6%) with secondary infertility. The intervention included the usage of the modified Novy cornual cannulation set which was inserted through a 5F working cannel during an office operative hysteroscopy, followed by fallopian tube irrigation with saline-air mixture under ultrasonographic imaging. Results Our series revealed no complication during or after the procedure; anesthesia was not required. One patient lost from follow-up. Of the remaining 26, 10 patients (38.4%) conceived either spontaneously or with treatment by clomiphene or gonadotropine associated with intrauterine insemination. The median time to conception was 5 months (range 4–17). Conclusion We therefore concluded that office hysteroscopic tubal catheterization is a simple (without anesthesia required) option for the treatment of patients suffering from proximal tubal occlusion. Fertility outcomes in our series are comparable to other treatments options for tubal catheterization. Therefore, tubal catheterization should not delay the assisted reproducted techniques if indicated but we propose to include it in a global integrated approach.

Study Objective To investigate whether hysteroscopic proximal tubal occlusion with Essure microinserts (Conceptus Inc.; Bayer, AG, North Rhine-Westphalia, Germany) can improve pregnancy rates in patients with hydrosalpinges who had failed in vitro fertilization (IVF) treatment. Design A prospective cohort study. Setting University-affiliated tertiary centers. Patients Twenty-four consecutive women with hydrosalpinges who had failed IVF treatment were included. Interventions Hysteroscopic placement of Essure microinserts for hydrosalpinx blockage followed by IVF treatment. Measurements and Main Results Ongoing pregnancy and live birth rates were recorded. Of the 24 patients undergoing a total of 42 IVF cycles after Essure insertion, 18 (75% of patients and 42.8% of IVF cycle attempts) conceived and 16 delivered live births (66.6% of patients and 38.1% of IVF cycle attempts). Conclusion Hysteroscopic proximal occlusion of hydrosalpinges with Essure microinserts is a valuable alternative to laparoscopic salpingectomy, resulting in reasonable pregnancy rates.

Objectives To compare the outcomes of radiofrequency ablation (RFA) and bipolar cord coagulation (BPC) methods for selective feticide in complicated monochorionic (MC) twin gestations and to determine risk factors for adverse pregnancy outcome. Methods This was a retrospective cohort study of all patients with complicated MC twin pregnancy who underwent selective reduction in a single tertiary care center between 2000 and 2014. We compared the two methods with respect to various demographic, obstetric and perinatal outcome variables. Results Fifty-three selective terminations in complicated MC twin gestations were performed, 36 by RFA and 17 by BPC. Each technique resulted in a similar overall survival rate of the remaining twin (88.9% vs 76.5%, P = 0.25). Likewise, the mean procedure-to-delivery interval, the rate of spontaneous preterm delivery

The current study aimed to evaluate the profile of women who are most likely to undergo caesarean delivery on maternal request (CDMR) and clarify their reasons for this decision.For this multicentre case-control study, data were collected from 429 women who underwent CDMR and 429 matched controls who delivered vaginally from June, 2008 through February, 2009. Participants were interviewed by telephone regarding sociodemographic variables, health and lifestyle.CDMR predictors were as follows: increasing age (OR = 1.09/year; 95%CI: 1.05-1.14), family status (unmarried without a steady partner versus married - OR = 3.60; 95%CI: 1.08-11.97), decreasing level of religiosity (secular versus ultra-orthodox - OR = 11.82; 95%CI: 3.75-37.21), and never having engaged, or ceasing sports activity during pregnancy (OR = 1.79; 95%CI: 1.09-2.91 and 2.38; 95%CI: 1.28-4.43, respectively). Above average income reduced the probability of CDMR (OR = 0.56; 95%CI: 0.33-0.94). The most frequent reasons for choosing CDMR were concern for pain (21.9%), concern for their own or baby's health (20.4% and 16.5%, respectively) and emotional aspects (10.0%).Older, unmarried and/or secular women had increased probability of CDMR. Addressing specific concerns regarding vaginal delivery may provide the basis for a patient-oriented intervention for preventing unnecessary surgery.

Objective The aim of this study was to evaluate obstetric outcomes in relation to the extent of donor sperm exposure with and without egg donation. Materials and Methods This is a retrospective cohort study in a single tertiary care center. All women with a singleton pregnancy who conceived following sperm donation (SD) were included. Obstetrics and neonatal outcomes for pregnancies following single SD were compared with pregnancies following repeat SD from the same donor. In a secondary analysis, we compared pregnancy outcomes among three modes of assisted reproductive technology (intrauterine insemination [IUI-SD], in vitro fertilization [IVF-SD], and IVF sperm + egg donation [IVF-SD + ED]). Results A total of 706 pregnant women met the inclusion criteria, 243 (34.4%) following the first SD and 463 (65.6%) following repeat donations. Compared with repeat SDs, single donation was not associated with higher rates of preterm delivery (12.8 vs. 12.7%, respectively, p = 0.99), preeclampsia (7.0 vs. 6.9%, p = 0.999), and intrauterine growth restriction (4.1 vs. 3.9%, p = 0.88). Pregnancies following IVF-SD + ED had increased risk for preeclampsia (adjusted odds ratio [AOR], 3.1; 95% confidence interval [CI], 1.5–6.6), preterm labor (AOR, 2.4; 95% CI, 1.1–5.4), and cesarean section (AOR, 2.1; 95% CI, 1.0–4.3) compared with IUI-SD and IVF-SD. Conclusion The extent of donor sperm exposure did not correlate with obstetrics complications, but double gamete donation was associated with increased risk for preeclampsia, preterm labor, and cesarean section.

Research question What pregnancy rates are achieved after transfer of cryopreserved double slow-frozen embryos in IVF cycles? Patients in whom surplus thawed cleaved embryos (day 2 or 3) were grown to the blastocyst stage, re-frozen and then re-thawed for transfer (double freezing) were included. Design Data were collected on all patients who had undergone the above procedure at the IVF unit of Assuta Ramat Hachayal Hospital, Tel Aviv, during a 7-year period. For each patient in the study group, the two-consecutive, matched-by-age patients treated with frozen–thawed single blastocyst transfer were selected to form a 2:1 ratio control group. All embryos were frozen using the slow freeze protocol. Results A total of 54 patients had 70 embryos that were re-frozen at the blastocyst stage. Twenty-eight of these blastocysts were thawed and 27 underwent transfer to 25 patients. A single embryo was transferred to 23 patients and two embryos were transferred to two patients. The survival rate of the second thawing was 96.4% (27/28). Clinical pregnancy rate was 16% (4/25) and implantation rate was 14.8% (4/27). In the study group, pregnancies were achieved in 22 out of the 25 patients using IVF treatment, indicating good receptivity of the uterus. In the control group, the implantation/pregnancy rates were significantly higher (44.2% [23/52]; P Conclusion The transfer of twice slow-frozen and thawed embryos does not seem to be a beneficial approach in the planned management of cryopreserved surplus embryos owing to the low pregnancy rate achieved after transfer of the re-frozen blastocyst embryos.

ObjectiveTo evaluate ovarian reserve in women after preservative cesarean delivery using uterine artery embolization due to morbidly adherent placenta.Study designA historical cohort study including all women admitted to a single tertiary care center, with morbidly adherent placenta that had preservative cesarean delivery with bilateral uterine artery embolization. Inclusion criteria included gestational age >24 weeks, singleton pregnancy and placenta increta / percreta. Exclusion criteria included maternal age > 43 years old and cesarean hysterectomy. Control group included women attending the infertility clinic due to male factor or single women conceiving via sperm donation, matched by age. Blood samples were collected on day 2-5 of menstruations for hormonal profile and Anti Mullarian Hormone (AMH) levels. Primary outcome was ovarian reserve evaluated by the levels of AMH.Results59 women underwent preservative cesarean delivery using uterine artery embolization during the study period. 21 women met inclusion criteria (33.9%) and were matched controls (n = 40). Circulating levels of E2 and FSH did not differ significantly between the two groups (p = 0.665, p = 0.396, respectively). AMH was lower in the study group (median 0.8 IQR 0.44-1.80) compared to the controls (median 2.08 IQR 1.68-3.71) (p = 0.001). This finding was consistent in linear multivariate regression analysis where the group of cesarean delivery using bilateral artery embolization due to placenta accrete was significantly predictive for the levels of AMH (B = -1.308, p = 0.012).ConclusionWomen post preservative cesarean delivery using uterine artery embolization due to placenta accrete have lower ovarian reserve compare to controls matched by age.

Background Pregnancy-induced hypertension (PIH) is associated with chronic hypertension (HTN) and cardiovascular complications. We investigated the factors that predict the development of chronic HTN in women with PIH. Methods The study population comprised 108 women with PIH and 87 healthy age-matched women control subjects who gave birth during the years 1990-1994 at the Chaim Sheba Medical Center, Israel, and were followed for up to 23 years (average 20.8 ± 1.4). We analyzed the association between PIH and subsequent HTN and cardiovascular complications, aiming to identify predicting factors for the development of chronic HTN in this subject population. Results At the time of index pregnancy, women with PIH were more likely to be overweight, had elevated blood pressure (BP) levels, a shorter gestational period, required more cesarean sections, and were more likely to deliver small infants than the control group. Compared to women with normotensive pregnancy, women with PIH had 11-fold higher age-adjusted risk of developing HTN. They also had a higher body mass index (BMI), and were more likely to develop diabetes mellitus (DM) and coronary artery disease, during follow-up. Among women with PIH, those subjects who developed HTN were older during pregnancy, had higher BMI and more deliveries before the index pregnancy. Conclusion Our findings confirm the association between PIH and chronic HTN. In women with PIH, high BMI and more previous pregnancies are risk factors for developing HTN. Thus, obese women with multiple pregnancies who develop PIH should be more closely followed for the development of HTN.

Objective Bed rest or activity restriction is a common obstetrical practice, despite a paucity of data to support its efficacy. The aim of this study was to determine whether physical activity, as assessed by a smart band activity tracker, is associated with preterm birth in pregnant women at high risk for preterm delivery. Methods This was a pilot prospective cohort study including pregnant women at high risk for preterm delivery between 24 and 32 weeks-of-gestation. Physical activity level was assessed by smart band activity. Patients with sonographic short cervical length (≤ 20 mm) were asked to wear the smart band activity tracker continuously for at least one week, including one weekend. Both physicians and patients were blinded to the data stored in the smart band activity tracker. No specific recommendations were given to participants as to the level or intensity of physical activity. The primary outcome was the rate of preterm birth (< 37 weeks-of-gestation). Secondary outcomes included the rate of delivery before 34 weeks of gestation and neonatal outcome. Parametric and nonparametric statistics were used for analysis. Results Study population included 49 pregnant women: 37 women (75.7%) delivered preterm and 12 (24.5%) delivered at or after 37 weeks-of-gestation. The median steps per day was significantly lower in patients who delivered preterm (3576, IQR: 2478–4775 vs. 4554, IQR: 3632–6337, p = 0.02). Regression analysis revealed that the median number of steps per day was independently inversely associated with preterm birth, after adjustment for maternal age, body mass index, gestational age at recruitment, cervical length, cervical dilatation and plurality. Conclusion This pilot study represents the first quantitative assessment of the association between physical activity and preterm birth. The results of this pilot study do not support the efficacy of decreased physical activity in the prevention of preterm birth in patients with sonographic short cervical length.

Background Methods available for assessing the learning curve, such as a predefined number of procedures or direct mentoring are lacking. Our aim was to describe the use of a statistical method to identify the minimal training length of an experienced sonographer, newly trained in deep infiltrating endometriosis (DIE) mapping by evaluating the learning curve of transvaginal ultrasound (TVUS) in the preoperative assessment of endometriosis. Methods A retrospective study in a tertiary referral center for endometriosis. Reports and stored data from TVUS scans performed by one operator with training in general gynecological ultrasound, but not in endometriosis mapping, were analyzed retrospectively for patients who subsequently underwent laparoscopy, which served as a reference standard. The performance of TVUS was assessed for the following sites: endometriomas, bladder, vagina, pouch of Douglas, bowel and uterosacral ligaments, and correlated with laparoscopic findings. Sensitivity, specificity, PPV, NPV, and accuracy were calculated, and the operator’s diagnostic performance was assessed using the learning curve cumulative summation test (LC-CUSUM). Results Data from 94 women were available for analysis. The learning curve using the LC-CUSUM graph showed that the sonographer reached the predefined level of proficiency in detecting endometriosis lesions after 20, 26, 32, 31, 38, and 44 examinations for endometriomas, bladder nodules, vaginal nodules, pouch of Douglas obliteration, bowel nodules, and uterosacral ligament nodules, respectively. Conclusions LC-CUSUM allows monitoring of individual performance during the learning process of new methodologies. This study shows that a sonographer trained in general gynecologic ultrasonography, who devotes time to learn TVUS for DIE mapping, can achieve proficiency for diagnosing the major types of endometriotic lesions after examining less than 50 patients who subsequently undergo surgery in a training setting.

Intracytoplasmic sperm injection (ICSI) is commonly used during pre-implantation genetic diagnosis (PGD) in vitro fertilization (IVF), aiming to eliminate the risk of contamination from extraneous sperm DNA. Recently, ICSI "overuse" in non-male infertility has been doubted, since it does not offer an advantage over IVF. Prompted by the aforementioned observations, we sought to assess the accuracy of IVF vs ICSI in PGD cases, as might be reflected by a difference in the prevalence of discarded embryos as a consequent of parental contamination.Cohort-historical study of all consecutive patients admitted to the IVF-PGD program in a large tertiary center. The percentages of complete, incomplete diagnosis, PCR failure, abnormal embryos, and the contamination rate with paternal DNA in the IVF-only and the ICSI-only groups. We reviewed the computerized files of all consecutive women admitted to our IVF for a PGD-PCR cycle. Patients were divided accordingly into three groups: an IVF group-where all the oocytes underwent IVF only, an ICSI group-where all oocytes underwent ICSI, and a mixed group-where sibling oocytes underwent both IVF and ICSI. The laboratory data and the genetic diagnostic results were collected and compared between the different insemination groups.Nine-hundred and twenty-seven patients underwent IVF-PGD cycles in our program, 315 in the IVF group, 565 in the ICSI group, and 47 in the mixed group. No differences were observed in fertilization rates, the percentage of embryos available for biopsy, and the percentages of complete, incomplete diagnosis, PCR failure, or abnormal embryos, between the IVF-only and the ICSI-only groups and between the IVF and the ICSI of sibling oocytes in the mixed group. Moreover, contamination with paternal DNA, through contamination with sperm cells, was negligible. Not one single case of misdiagnosis was encountered during the study period.It might be therefore concluded that IVF should be the preferred insemination methods in PGD cycles, and ICSI should be indicated only in cases of male-factor infertility.

To determine whether antenatal corticosteroids administration prior to an elective cesarean section (ECS) at 34-37 weeks gestation is associated with improved neonatal outcome.A case control study of women with singleton pregnancies who underwent ECS between 34 and 37 weeks of gestation including two groups: (1) study group in which patients were treated with betamethasone prior to ECS (n = 58) and (2) control group matched for gestational age at delivery in which patients did not receive betamethasone (n = 107). Neonatal measures including respiratory distress syndrome (RDS), transient tachypnea of the newborn (TTN), oxygen requirement, admission to the special care unit, hypoglycemia, hyperbilirubinemia and length of hospitalization were determined in both groups. Composite respiratory morbidity was defined as the presence of either RDS, TTN, mechanical ventilation or oxygen requirement.There was no significant difference in the rate of composite respiratory morbidity nor its components between patients with and without betamethasone treatment (25.9 vs. 25.2%, respectively, p = 0.9).Antenatal treatment with corticosteroids prior to ECS at 34-37 weeks of gestation did not result in significant reduction in neonatal respiratory morbidity in our cohort of patients.

Study Objective To determine an effective method of intrauterine device (IUD) retrieval from pregnant women who had previous unsuccessful ultrasound-guided IUD extraction failure. Design A retrospective cohort study (Canadian task force classification II-1). Setting A gynecology department of an outpatient clinic. Patients Pregnant patients in their first trimester with IUD in situ who underwent prior unsuccessful ultrasound-guided IUD extraction. Interventions Hysteroscopic IUD extraction guided by transabdominal ultrasound. Measurements and Main Results Between 2011 and 2014, 7 of 8 pregnant patients who had undergone previous failed attempts at IUD retrieval via ultrasound guidance underwent successful removal via ultrasound-guided hysteroscopy performed without anesthesia. The sole patient with extraction failure was in her 12th week of pregnancy, and the procedure was concluded to avoid risk to the fetus. Minimal vaginal bleeding was experienced by 2 patients after the procedure. Seven of 8 patients delivered at term without any obstetric complications. One patient had a miscarriage in her 8th week of pregnancy, 2 weeks after successful IUD removal. Conclusion A novel, easy outpatient hysteroscopic technique without anesthesia is presented in case of failure of previous ultrasound-guided IUD removal in early pregnancy. Results are encouraging in this difficult context.

Objectives. To determine the prevalence of ultrasound features suggestive of adenomyosis in women undergoing surgery for endometriosis compared with a control group of healthy women without endometriosis. Methods. Retrospective case-control study comparing women with intractable pain or infertility, who underwent transvaginal ultrasound and subsequent laparoscopic surgery, with a control group of healthy women without a previous history of endometriosis. A diagnosis of adenomyosis on TVUS was made based on asymmetrical myometrial thickening, linear striations, myometrial cysts, hyperechoic islands, irregular endometrial-myometrial junction, parallel shadowing, and localized adenomyomas and analyzed for one sign and for three or more signs. Results. The study and control groups included 94 and 60 women, respectively. In the study group, women were younger and had more dysmenorrhea and infertility symptoms. The presence of any sonographic feature of adenomyosis, as well as three or more signs, was found to be more prevalent in the study group, which persisted after controlling for age, for all features but linear striations. Women in the study group who had five or more sonographic features of adenomyosis had more than a threefold risk of suffering from infertility (OR = 3.19, p=0.015, 95% CI; 1.25–8.17). There was no association with disease severity at surgery. Conclusions. Sonographic features of adenomyosis are more prevalent in women undergoing surgery for endometriosis compared to healthy controls. Women with more than five features had an increased risk of infertility.

Objective Monochorionic twins treated by fetoscopic laser coagulation (FLC) for twin–twin transfusion syndrome (TTTS) are at increased risk of neurodevelopmental impairment. Our aim was to evaluate the additional value of diffusion-weighted imaging (DWI) over fetal sonography and T2 magnetic resonance imaging (MRI) in the detection of acute ischemic cerebral lesions shortly following FLC. Methods This was a prospective cohort study of fetuses with TTTS treated by FLC. All fetuses underwent brain DWI and T2-MRI within 24–96 h after the procedure and a follow-up MRI at 30–32 weeks' gestation. All fetuses also had frequent ultrasound evaluation until delivery. Results Thirty pregnancies with TTTS were included in the study. Eight resulted in survival of only one twin after the procedure (Group A), while the other 22 pregnancies resulted in the survival of both twins (Group B), as assessed at the time of initial MRI. Two fetuses in Group A and four in Group B had evidence of transient bleeding in the germinal matrix. Three fetuses in Group B and none in Group A had diffuse ischemic changes in the white matter. One fetus died in utero 24 h after MRI. The other two fetuses in Group B demonstrated an acute infarct 24–48 h after the procedure. Subsequent scans at 28–29 and 32 weeks showed brain atrophy compatible with an old infarct. Conclusions DWI can demonstrate cerebral damage immediately after FLC. Larger cohorts are needed to determine the role of fetal MRI in the prenatal assessment and follow-up of patients with TTTS. Copyright © 2013 ISUOG. Published by John Wiley & Sons Ltd.

Objective To characterize, using three-dimensional (3D) transperineal ultrasound, the appearance, position and dimensions of mesh implants following minimally invasive abdominal sacrocolpopexy. Methods In women who underwent sacrocolpopexy, mesh was evaluated at rest and on maximal Valsalva, on all 3D orthogonal planes and rendered views. Mesh dimensions were obtained by 3D processing in the midsagittal and coronal planes (anterior, posterior and sacral arm) and were analyzed offline, the operator blinded to clinical data. Results Overall, 62 women, mean age 58.4 (range, 42–79) years were evaluated at a median of 9 (range, 1–26) months following surgery. The anterior arm of the mesh was caudal to the lowermost point of descent of the anterior compartment in 56 (90.3%) women, was equally positioned in five (8.1%) and was cranial in one. The posterior arm was caudal in 44 (71%) women, was equally positioned in 16 (25.8%) and was cranial in two (3.2%). The Y connection and the sacral arm of the mesh could not be adequately seen because of physical limitations of ultrasound (lower resolution at greater depth), large recurrent rectoceles, echogenic stools or folding of mesh remnants. Folding of the mesh was seen in 46 (74.2%) women, folding of the anterior arm in five (8.1%) and folding of the posterior arm in 23 (37.1%). Folding occurred caudally in 26 (41.9%) women, proximally in 11 (17.7%) and in both areas in nine (14.5%). There were no erosions. Conclusion Mesh visualization following minimally invasive abdominal sacrocolpopexy procedures using transperineal 3D/four-dimensional (4D) ultrasound is feasible. Studies are needed to evaluate the correlation between ultrasound measures and prolapse recurrence or mesh erosion. Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.

Objective To assess the role of transperineal ultrasound in the postoperative evaluation of patients undergoing colpocleisis. Methods Patients who underwent colpocleisis between July 2009 and January 2011 completed the Pelvic Floor Distress Inventory questionnaire (PFDI-20) and underwent pelvic organ prolapse quantification (POP-Q) examination and four-dimensional (4D) transperineal ultrasound. Volumes were analyzed offline for assessment of pelvic organ descent, levator hiatal dimensions, levator avulsion trauma and the location of the colpocleisis scar. Results The study included 16 women, of mean ± SD age 75.7 ± 2.9 years, median body mass index 28 (range, 21–32) kg/m2 and median parity 2 (range, 0–5); one woman was nulliparous. Nine (56.2%) women were posthysterectomy. The median interval from surgery to ultrasound examination was 6.5 (range, 2–19) months. Most patients did not have symptoms of prolapse. The median Pelvic Organ Prolapse Distress Inventory (POPDI-6) score was 37.5 (range, 0–75) and the median postoperative clinical POP-Q stage was 1 (range, 0–2). Ultrasound demonstrated clear visualization in all patients. Ten had avulsion defects (six were bilateral). Ultrasound estimated greater prolapse descent for all compartments when compared with the clinical examination. However, this difference was significant for anterior and posterior descent, but not for apical descent. In two women urethral diverticulum was detected on ultrasound; it was neither symptomatic nor clinically apparent. Conclusions 4D transperineal ultrasound seems to be a potentially effective tool for the evaluation of vaginal anatomic and functional changes following colpocleisis surgery. Future investigation of the association between ultrasound findings and patients' subjective symptoms in a larger cohort is warranted. Copyright © 2012 ISUOG. Published by John Wiley & Sons, Ltd.

Study Objective To evaluate the clinical and surgical features of thoracic endometriosis syndrome (TES) represented by catamenial pneumothorax and pelvic endometriosis and to describe their association with infertility. Design Retrospective clinical study (Canadian Task Force classification: II-2). Setting Academic tertiary referral endometriosis center. Patients Seven patients who had undergone surgery because of thoracic and pelvic endometriosis between 2004 and 2010. Interventions Thoracic and pelvic exploration and treatment and fertility treatment. Measurements and Main Results Concurrently, thoracic and pelvic endometriosis, and subsequent fertility were determined during long-term follow-up after combined surgical and pharmacologic interventions. The most frequent thoracic finding was diaphragmatic implants. Except for 1 patient with recurrent pleurodesis at 1 month after video-assisted thoracoscopy, no patients experienced recurrence of thoracic symptoms during a median (range) follow-up of 31.4 (1–61) months. Severe pelvic endometriosis was diagnosed in 6 patients with notable urologic and gastrointestinal tract involvement. Only 1 patient with catamenial pneumothorax had no macroscopic pelvic lesions. There was a considerable delay between the onset of pelvic symptoms and diagnosis. Median postoperative follow-up was 31.5 (7–84) months. Most patients who tried to conceive had primary infertility. Conclusion Thoracic endometriosis syndrome, represented by catamenial pneumothorax, was strongly associated with severe pelvic endometriosis and a high rate of infertility. Inasmuch as many patients with thoracic endometriosis syndrome are treated by thoracic surgeons using video-assisted thoracoscopy, it is desirable to involve an experienced gynecologist who can diagnose and treat concurrent pelvic endometriosis.

To determine the success rate of induction of labor (IOL) using Foley transcervical balloon (FTB) versus prostaglandin EA retrospective cohort study of all pregnant women admitted for IOL with either FTB or PGEDuring the study period, 1162 women were admitted for IOL. Failure was reported in 322/852 (37.8%) in the FTB versus 162/310 (52.2%) in the PGEIOL with FTB was not superior to PGE

Aims: To determine the clinical yield of abdominal ultrasound in the evaluation of elevated liver enzymes (ELEs) in the second and the third trimester of pregnancy. Methods: A retrospective cohort study including all pregnant women admitted to a single tertiary care center was conducted between April 2011 and January 2015 with ELE. Inclusion criteria included gestational age above 24 weeks and ELEs, abdominal ultrasound report, and live fetus. Exclusion criteria included known maternal liver disease, structural or chromosomal fetal anomalies, and positive serology for viral hepatitis. All patients underwent abdominal ultrasound. A significant finding of this study led to a change in treatment. Results: One hundred and twenty patients (41.8%) met inclusion criteria: 93 (77.5%) had a normal scan and 27 (22.5%) had abnormal findings. Significant ultrasound findings were found only in 2 (1.6%) patients: gallstones in the common bile duct and suspected autoimmune hepatitis. There were no significant differences between patients with and without ultrasound findings in the rate of cholestasis of pregnancy, preeclampsia, chronic hypertension, and gestation diabetes. Conclusion: Abdominal ultrasound examination in this population has a low clinical yield. The decision to perform an abdominal ultrasound must be individualized based on the obstetric history, clinical findings, and the level of liver enzymes.

Objective To report the single-center results of orthotopic retransplantations of cryopreserved ovarian tissue in cancer survivors and evaluate the validity of commonly accepted procedure limitations. Design Prospective cohort study. Setting Tertiary university-affiliated assisted reproduction technology (ART) and oncology centers. Patient(s) Twenty cancer survivors who underwent ovarian transplantation of frozen-thawed ovarian tissue with the aim to conceive. Intervention(s) Ovarian tissue cryopreservation (OTCP) and transplantation, endocrine monitoring, in vitro fertilization (IVF). Main Outcome Measure(s) Endocrine profile, IVF, pregnancies, live births. Result(s) The patient ages at tissue harvesting ranged from 14 to 39 years. Fifteen women had hematologic malignancies, and two had leukemia (chronic myelogenous leukemia and acute myelogenous leukemia). Ten patients were exposed to nonsterilizing chemotherapy before OTCP. After transplantation, the endocrine recovery rate was 93%. Fourteen patients underwent IVF treatments with a fertilization rate of 58%. Sixteen pregnancies were achieved (10 after IVF, 6 spontaneous), resulting in 10 live births, two (twins) after harvesting from the mother at the age of 37. Two pregnancies are currently ongoing. After transplantation, 53% of patients conceived, and 32% delivered at least once. One patient conceived four times. Preharversting chemotherapy exposure was not associated with inferior outcomes. All patients, including two leukemia survivors, remained cancer free. Conclusion(s) Orthotopic transplantation of thawed ovarian tissue is a highly effective measure to restore fertility in sterilized cancer patients. Chemotherapy exposure before harvesting and age >35 is a realistic option in selected patients. Retransplantation in leukemic patients is possible after application of maximal safety measures. These results have led the national ethical and professional authorities to decide for the first time not to consider OTCP as an experimental modality for fertility preservation. Clinical Trial Registration Number NCT02659592.

BACKGROUND AND PURPOSE: Monochorionic twin pregnancies complicated by the IUFD of 1 twin are associated with substantial morbidity to the survivor twin. The aim of this study was to determine whether fetal sonography, T2 MR imaging, and DWI can diagnose acute cerebral lesions in the survivor of an MC twin pregnancy shortly after fetal death of the co-twin. MATERIALS AND METHODS: During the study period (2007–2010) 34 cases of single IUFD were evaluated. Group A included 6 cases complicated by spontaneous IUFD. Group B had 10 cases of fetal death shortly after treatment of severe TTTS. These were compared with group C, with 18 pregnancies treated by selective termination due to severe complications in MC pregnancies. RESULTS: Altogether 9/34 patients had abnormal prenatal cerebral findings. In group A, in 2/6 of pregnancies with spontaneous death, MR imaging showed findings of severe cerebral infarct, while cerebral damage was not evident by sonography. In another case, the surviving fetus was found to be hydropic on sonography, while MR imaging findings were normal. In group B, in 1/10 cases, cerebral infarct was demonstrated only by DWI. In 2 other cases, sonographic findings were normal, but MR imaging showed germinal matrix bleeding. In group C, in 1/18 cases, only DWI showed bilateral cerebral ischemia. In 2 other cases, MR imaging findings suggested germinal matrix bleeding and focal changes in the basal ganglia. In both cases, fetal sonographic findings were normal. CONCLUSIONS: In our study, early manifestations of cerebral ischemia in monochorionic twin pregnancies were better diagnosed with MR imaging, especially with DWI.

Objectives In light of the potential physical and emotional costs to both woman and child, this study was conducted to assess pregnancy complications and birth outcomes in primiparae at very advanced maternal age (VAMA, aged ≥45) compared to younger primiparae. Methods Retrospective cohort study comparing 222 VAMA primiparae and a reference group of 222 primiparae aged 30–35, delivering at Sheba Medical Center from 2008 through 2013.Results VAMA primiparae were more likely than younger primiparae to be single, to have chronic health conditions, and higher rates of gestational diabetes mellitus (GDM), gestational-hypertension (GHTN) and preeclampsia-eclampsia. VAMA primiparae conceived mostly by oocyte donation. They were more likely to be hospitalized during pregnancy, to deliver preterm and by cesarean birth. Infants of VAMA primiparae were at greater risk for low birthweight and Neonatal Intensive Care Unit admission. There were no differences in outcomes between VAMA primiparae with or without preexisting chronic conditions, or between those aged 45–49 and ≥50. In multivariable analysis VAMA was an independent risk factor for GDM, GHTN and preeclamsia-eclampsia, with adjusted odds ratio of 2.38 (95 % CI 1.32, 4.29), 5.80 (95 % CI 2.66, 12.64) and 2.45 (95 % CI 1.03, 5.85); respectively. The effect of age disappeared in multiple pregnancies. Conclusions Primiparity at VAMA holds a significant risk for adverse pregnancy and birth outcomes. The absence of chronic medical conditions or the use of a young oocyte donor does not improve these outcomes. Multiple pregnancies hold additional risk and may diminish the effect of age. Primiparity at an earlier age should be encouraged.

Objective: To evaluate the perinatal outcome of MC twins with selective IUGR (sIUGR).Study design: A prospective study, which included three groups of MC twins: Group A, uncomplicated MC twin pregnancies (n = 91); group B, sIUGR with normal umbilical artery Doppler (n = 19); and group C, sIUGR with abnormal (absence or reversed EDV) umbilical artery Doppler (n = 18). The latter were routinely hospitalized in the high-risk ward under strict surveillance.Results: Neonatal outcome of fetuses complicated with sIUGR and normal Doppler was similar to controls. Neonates born to pregnancies complicated by sIUGR and abnormal Doppler had significantly increased incidence of CNS findings, RDS, NEC, sepsis, and neonatal death compared to controls. Adverse outcome in this group was independently associated only with gestational age at birth.Conclusion: The perinatal outcomes of MC twins complicated with sIUGR and normal Doppler are similar to uncomplicated MC pregnancies. MC twins with sIUGR and abnormal Doppler have reasonable outcomes, yet significantly more neonatal complications compared to non-complicated MC twins.

Objective. To investigate whether in patients with antiphospholipid syndrome (APS), high positive antibody titers are associated with adverse pregnancy outcome. Design. A retrospective cohort study of prospectively collected data. Setting. Sheba Medical Center, Israel, a tertiary referral center. Population sample. Pregnant women with APS. Methods. Anticardiolipin, a-β2-glycoprotein I antibodies, and lupus anticoagulant were measured before pregnancy. Women were divided into those with antibody titers >four times the upper limit of normal (high positive titer, HPT group), and the rest, into the positive titer (PT) group. All women were treated with daily enoxaparin and aspirin. Main outcome measures. Composite adverse fetal/neonatal outcome, defined as one or more of the following: fetal/neonatal loss, preterm birth ≤32 weeks, and birthweight below than 10th percentile. Composite adverse fetal/neonatal outcome was compared between the HPT and PT groups. Maternal adverse outcomes were also compared. Results. 51 women with APS were followed during 55 pregnancies, 20 in the HPT and 35 in the PT groups. The two groups were similar with regard to previous obstetric and clinical characteristics. Among HPT women, only 7/20 (35%) pregnancies culminated in appropriately grown, live-born infants >32 weeks’ gestation, compared with 27/35 (77%) PT pregnancies. The risk of adverse fetal/neonatal outcome was 5.7 times higher (95%CI 1.9–17.7) for HPT than for PT women. Conclusions. Pregnant women with APS and high positive antiphospholipid antibody titers are a unique and extremely high risk group for adverse fetal/neonatal outcome. Stricter surveillance and possibly additional therapy options should be explored for this patient population.

To define the characteristics of placental stillbirth and the possible contribution of thrombophilic risk factors.A prospective cohort study was performed. Women diagnosed with antenatal stillbirth (20 weeks) of singleton pregnancies between 2006 and 2008 were referred postpartum for evaluation. Maternal risk factors, fetal, placental and cord abnormalities, and a detailed thrombophilia screening, including inherited and acquired thrombophilia, were evaluated. Fetal autopsy and placental pathology were encouraged. Placental stillbirth was defined as death of a normally-formed fetus with evidence of intrauterine fetal growth restriction, oligohydramnios, placental abruption and/or histological evidence of placental contribution to fetal death. Pregnancy characteristics and thrombophilia profiles were compared between placental and non-placental stillbirth cases.Sixty-seven women with stillbirth comprised the study group. Placental stillbirth was evident in 33/67 (49.3%). Significantly more women with placental stillbirth were nulliparous, when compared with non-placental stillbirth women (21/33 vs. 9/34, p=0.002). Mean gestational age was lower for placental, compared with non-placental stillbirth (31.1 ± 6.1 weeks vs. 33.9 ± 4.8 weeks, p=0.04), as was birth weight. Thirty-six of the 67 women (53.7%) tested positive for at least one thrombophilia. The prevalence of maternal thrombophilia was higher for placental stillbirth women (63.6%), and even higher (69.6%) for women after preterm (37 weeks) placental stillbirth. Factor V Leiden and/or prothrombin G20210A mutation were much more prevalent in placental versus non-placental stillbirth women (OR 3.06, 95% CI 1.07-8.7).Placental stillbirth comprises a unique subgroup with specific maternal characteristics. Maternal thrombophilia is highly prevalent, especially in preterm placental stillbirth. This may have implications for the management strategy in future pregnancies in this subgroup.