An intrauterine cavity morcellator: A novel approach to high volume uterus morcellation. Ex-vivo study.

OBJECTIVE: Uterine size is one of the essential factors determining the feasibility of a minimally invasive gynecologic surgery approach. A traditional electromechanical morcellator is a well-known tool but not without flaws. We aim to assess feasibility and safety of a novel intrauterine power morcellation device for uterine size reduction to overcome these limitations during hysterectomy. METHODS: This single-arm, observational study was conducted in a single tertiary care medical center from April 2022 to July 2022. Feasibility and safety of a novel intrauterine morcellation device for uterine size reduction was tested in ten post-hysterectomy uteri (Ex-vivo). MEASUREMENTS AND MAIN RESULTS: Ten uteri were examined in this trial. No major complications occurred during the procedure. All ten (10) uteri were successfully reduced in size (size reduction range was between 9% to 54%). The average resection time using the Heracure Device was 4.3 minutes (range: 1min- 10min). Mean uterus weight reduction was 21%, with a mean circumference reduction of 25%. No leakage was observed from the outer surface of the uterus/serosa after the saline injection post-procedure examination. CONCLUSION: In this novel experiment, we verified the feasibility and safety of the Heracure device for vaginal intra-uterine morcellation for uterine size reduction. This technique could enable rapid and easy removal of the uterus through the vaginal orifice. CLINICAL TRIAL REGISTRATION: Name of the registry: ClinicalTrials.gov; Number Identifier: NCT05332132.

"What you see is what you get"-abnormal endometrial sonographic findings are sufficient for direct surgical hysteroscopy: Retrospective cohort study.

OBJECTIVE: To evaluate the possibility of referring women with uterine polyps larger than 1.5 cm directly to surgical hysteroscopy. METHODS: This retrospective cohort study included all women referred to a university-affiliated tertiary medical center for hysteroscopy, with the diagnosis of endometrial polyp, from 01/2013 to 05/2016. Women were referred for surgical hysteroscopy based on TVUS findings. PPV of TVUS for detecting intrauterine polyps was evaluated relating to pathology as gold standard, with sub-group analysis relating to polyp size and other parameters. RESULTS: We selected 1.5 cm as a cutoff size for subgroup analysis of endometrial polyps. PPV of TVUS for the entire cohort of 295 cases eligible for analysis, was 79.3%. TVUS describing polyps ≥1.5 cm had PPV of 92.1%, higher than the PPV for smaller polyps. Among post-menopausal women in this group, PPV was as high as 96.2%. Use of doppler or saline was found to improve PPV in the entire cohort. Indication for performing TVUS did not affect the PPV. CONCLUSION: TVUS describing polyps ≥1.5 cm may suffice for direct referral of women to surgical hysteroscopy. A personalized approach based on the initial diagnosis may avoid unnecessary invasive procedures for patients.

A novel method for office aspiration curettage in cases of retained products of conception: A randomized controlled trial.

INTRODUCTION: Missed abortion can be treated with medication or aspiration curettage. A Karman aspiration cannula is another option. We evaluated its success in evacuating retained products of conception (RPOC) based on symptoms, endometrial thickness, endometrial irregularity, and blood flow seen on Doppler ultrasound (indicative of placenta). MATERIAL AND METHODS: This prospective, randomized, nonblinded trial was conducted in a university-affiliated medical center. It included 40 women diagnosed with missed abortion and two failed courses of 600 µg buccal misoprostol, one  week apart, randomly assigned to treatment or controls. One week after the second misoprostol course, immediately after evaluating endometrial thickness, endometrial irregularity using Doppler ultrasound, and with blood flow indicative of RPOC, women in the aspiration group underwent endometrial suction with a Karman aspiration cannula. The 5-6 mm cannula attached to a 60 mL syringe was inserted into the uterus under ultrasound guidance. The contents were aspirated until the uterus was empty. Control group patients did not receive additional treatment. All were scheduled for ambulatory, operative hysteroscopy under anesthesia 1 month later (departmental protocol). On that day, all women with RPOC on Doppler ultrasound underwent hysteroscopy. Bleeding days, days with pain, pain according to visual analog scale, length of hospitalization, and infection rate were recorded. NIH clinical trial registration number NCT02917785. RESULTS: In the study group, 90% did not need hysteroscopy, compared with 50% of controls (p = 0.014). No complications were noted. At all visits, we used Doppler ultrasound to exclude or confirm RPOC. Pathology revealed RPOC in all women who underwent aspiration. Average visual analog scale score for office aspiration (n = 20) was 4.9 ± 3.6. vs. 6.3 ± 3.4 for the first (p = 0.157) and 4.7 ± 3.3 for the second (p = 0.836) misoprostol treatment cycle. The treatment group experienced 6.1 days of bleeding and the control group experienced 1.4 days (p = .006). CONCLUSIONS: Based on our criteria of diagnosing RPOC according to symptoms, endometrial thickness, endometrial irregularity, and blood flow indicative of placental tissue seen on Doppler ultrasound and histo-pathological confirmation, aspiration using Karman cannula can be an effective therapeutic approach. It may be a safe alternative for women with RPOC after misoprostol failure.

Did COVID-19 quarantine redirect habitual patient visits in the gynecology emergency room?

OBJECTIVE: COVID-19 pandemic caused a dramatic decline in the gynecology emergency department (ED) visits. The Israeli government took a determined step of quarantine to suppress and control the spread. This study evaluates the effect of the COVID -19 quarantine on gynecology emergency department (ED) visits compared to the previous year. MATERIALS AND METHODS: A retrospective case-control study was conducted during the first half-year of the COVID-19 pandemic and focused on the quarantine during April. In order to identify differences in the population's epidemiology and changes in the amount and type of emergency gynecological visits and surgeries, we compared patients during April 2020 (COVID-19 quarantine) to those who visited the gynecology ED during April 2019. RESULTS: During January-June 2020 period, there was an overall 3707 patient visits in the gynecology ED, which represents a 22.8% decrease in patient visits compared to the previous year (2019, 4803 patients). There was a 36% decrease in the gynecology ED visits during the quarantine period. Patient demographics were similar between groups. Visits of nulliparous women were more common in the study group (p = .0001) and self-referral (p = .017). More post-operative complications and fewer patients with abdominal pain were admitted to the study group (p = .034 and p = .054, respectively). During the study, the hospitalization rate did not change 18.2% vs. 17.5% (p = 0.768). Hospitalization duration was significantly longer in the COVID-19 quarantine (2.8 ± 1.3 vs. 3.1 ± 1.5, p < 0.001). There was no significant difference among surgical procedure incidents. CONCLUSION: Visits in the gynecology ED service decreased during the COVID-19 quarantine without compromising the treatment of gynecology emergencies. Many gynecologic complaints can be managed in community care settings without referral to an ED.

Verbal analgesia is as good as oral tramadol prior to intrauterine device (IUD) insertion, among nulliparous women: A randomized controlled trial.

OBJECTIVE: To compare two pain management strategies: oral tramadol or a verbal analgesia technique during insertion of an intrauterine device (IUD) among nulliparous women. STUDY DESIGN: In this randomized, controlled trial, 54 nulliparous women undergoing insertion of a levonorgestrel-releasing intrauterine device (IUD), from December 2015 to December 2018 were randomized to receive oral tramadol for analgesia or verbal analgesia prior to IUD insertion. Demographic data, clinical symptoms, visual analogue scale (VAS) and complications were reviewed from patient records. RESULTS: There was no difference between the two groups regarding gravidity, age, smoking or body mass index. No significant differences were detected between the groups regarding the procedure, including ease of insertion (p = .415), number of insertion attempts (p = .514) and complications during the insertion (p = .150). Mean pain level by VAS was 4.5 ± 1.6 (range 2-8) for the tramadol group and 4.8 ± 2.4 (0-10) for the verbal analgesia group (p = .610). There was no spontaneous ejection of the IUD in either group, and no endometritis or discomfort that resulted in IUD removal. CONCLUSION: There was no benefit in using oral tramadol for analgesia prior to IUD insertion among nulliparous women. Verbal analgesia can be a suitable technique for this process and clinicians should become more familiar with its use.

Placental supernatants' enhancement of the metastatic potential of breast cancer cells: is estrogen receptor (ERα) essential for this phenomenon?

PURPOSE: Pregnancy-associated breast cancer (PABC) is usually diagnosed at an advanced stage in comparison to non-pregnant women. The placenta secretes hormones and cytokines, which affect breast cancer progression. Previously, we demonstrated that human placental secretome facilitates the survival and migration of ERα+ breast cancer cells (BCCL), but pregnant women have a relatively high frequency of ERα-negative tumors. In the current study, we analyzed the effect of placental secretome on ERα-negative BCCL. METHODS: BCCL [MCF-7(estrogen/progesterone receptor positive (ERα+/PR+), ERα reduced MCF-7 (siRNA, MCF-7 ERα-), HS-578 and BT-549 cells (both ER-/PR-)] were exposed to supernatants (collected from first trimester human placental explants and from control BCCL) or to E2 + P4 (estrogen + progesterone) in placental supernatant concentrations and then tested for cell proliferation (number, cell cycle, PCNA), cell-death, cell migration, STAT3 pathway activation and functionality. RESULTS: Silencing ERα in the MCF-7 cells negated the placental supernatant and E2 + P4 enhancement of cell migration (> 130%, p < 0.05), number (> 120%) and survival (~ 130%). However, it had no such effect on MCF-7-ER- migration, which was still elevated in the presence of placental secretome. ER-/PR- BCCL were unaffected by the hormones, but placental secretome significantly elevated their migration (115%), number (140-170%), STAT3 phosphorylation (~ 180%) and BT-549 STAT3 level. These effects were negated by the STAT3 inhibitor. CONCLUSIONS: Placental supernatant facilitates BCCL malignant characteristics by activating ERα in estrogen responsive cells and STAT3 in ERα- BCCL. This indicates a possible mechanism that may underlie PABC's advanced state and suggests STAT3 pathway as a therapeutic target for PABC.

Adnexal Torsion during Pregnancy: Outcomes after Surgical Intervention-A Retrospective Case-Control Study.

STUDY OBJECTIVE: To investigate the pregnancy and neonatal outcomes of surgical treatment for adnexal torsion (AT) during pregnancy. DESIGN: A retrospective case-control study (Canadian Task Force classification II-2). SETTING: A tertiary care academic medical center. MEASUREMENTS AND MAIN RESULTS: The study group included all parturients who underwent surgery for suspected AT during pregnancy from January 2005 to January 2017. The control group included parturients with an uneventful pregnancy matched by maternal age, parity, multiple gestation, and pregnancy complications. The primary outcome was gestational age at delivery. Secondary outcomes were perinatal outcomes and intraoperative and immediate postoperative complications. Among 85 study group patients with suspected AT, 78 (91.7%) underwent laparoscopy and 7 (8.3%) laparotomy. Torsion was diagnosed in 84 patients (98.8%). The gestational age at delivery was similar between the study and control groups (38.7 ± 1.5 vs 38.6 ± 1.6 weeks, respectively; p = .908) as was preterm labor (5.8% in both groups, p = 1.00). There was no significant difference between the study and control groups in pregnancy and neonatal outcomes, including Apgar scores, mean cord blood pH (7.25 ± 0.1 and 7.26 ± 0.08, respectively), and birth weight (3040 ± 473 g and 3115 ± 584 g, respectively). In the study group, the mean gestational age at surgery was 11.2 ± 6 weeks (range, 4-34 weeks). The average operative time was 40.2 ± 22 minutes. In the postoperative follow-up, 3 (3.5%) patients had a first trimester miscarriage. A previous cesarean delivery was a risk factor for ovarian torsion during pregnancy (p = .012). CONCLUSION: Adnexal detorsion with or without additional surgical procedures during pregnancy did not affect the gestational age at delivery and did not appear to increase fetal or maternal complication rates.

Placenta-conditioned extracellular matrix (ECM) activates breast cancer cell survival mechanisms: A key for future distant metastases.

The extracellular matrix (ECM) affects cancer cell characteristics. Inability of normal epithelial cells to attach to the ECM induces apoptosis (anoikis). Cancer cells are often anoikis resistant, a prerequisite for their metastatic spread. Previously we demonstrated that the placenta manipulates its surrounding ECM in a way that prevents breast cancer cells (BCCL) attachment and induces their motility and aggregation. This fits with the fact that although breast cancer during pregnancy is often advanced, metastasis to the placenta is rarely observed. Placental intervillous space provides suitable conditions for cancer cell arrival. Yet, the outcome of the short communication between the placental ECM to the BCCL and its effect on BCCL malignant potential are unknown, and are the focus of our study. In the current study we analyzed the effect of placental ECM on BCCL survival pathways and drug resistance. Microarray analysis suggested activation of the NF-κB and stress response pathways. Indeed, the placenta-conditioned ECM induced autophagy in ERα + BCCL, inactivated the NF-κB inhibitor (IκB) and increased integrin α5 in the BCCL. The autophagy mediated MCF-7 and T47D migration and the placental ECM-BCCL interactions reduced the BCCL sensitivity to Taxol. We also demonstrated by using siRNA that integrin α5 was responsible for the MCF-7 autophagy and suggest this molecule as a suitable target for therapy.

"In God we trust" and other factors influencing trial of labor versus Repeat cesarean section.

PURPOSE: To investigate factors influencing women's decisions to undergo trial of labor after cesarean (TOLAC) or elective repeat cesarean delivery (ERCD) based on the Multidimensional Health Locus of Control (MHLC), religious observance and family planning. MATERIALS AND METHODS: Cross-sectional study of candidates for TOLAC or ERCD at two hospitals in Israel. Eligible women completed a demographic questionnaire and Form C of the MHLC scale. RESULTS: The study included 197 women. Those who chose TOLAC (N = 101) were more religiously observant, wanted more children and had higher Internal and Chance health locus of control. Women who chose ERCD (N = 96) were more likely to be secular and had a higher health locus of control influenced by Powerful Others, notably physicians. Women not influenced by others were more likely to choose TOLAC. CONCLUSIONS: A woman's choice of TOLAC or ERCD is influenced by her sense of control over her health, degree of religious observance and number of children desired. Healthcare providers can use this information to better understand, counsel and educate women regarding appropriate delivery decisions. Women who feel in control of their health, educated about delivery options and are less influenced by provider preference, might choose TOLAC; thus, reducing the rate of unnecessary ERCD.

First trimester human placenta prevents breast cancer cell attachment to the matrix: The role of extracellular matrix.

The extracellular matrix (ECM) affects cancer cell characteristics. Its detachment from the ECM induces cell apoptosis, termed anoikis. Cancer cells can develop anoikis resistance, a necessary step for metastasis, by switching integrins, over-expressing growth factor receptors, and inducing epithelial mesenchymal transition (EMT). The placenta is a non-supportive microenvironment for cancer cells. We showed that breast cancer cells (BCCL) were eliminated from placental implantation sites. During implantation, the placenta manipulates its surrounding matrix, which may induce BCCL elimination. Here, we explored the effect of placenta-induced ECM manipulations on BCCL. During experiments, BCCL (MCF-7/T47D) were cultured on placenta/BCCL-conditioned ECM (Matrigel used for first trimester placenta/BCCL culture and cleared by NH4 OH). After culturing the cells, we analyzed cancer cell phenotype (death, count, aggregation, MMP) and signaling (microarray analysis and pathway validation). We found that the BCCL did not attach to previous placental implantation sites and instead, similarly to anoikis-resistant cells, migrated away, displayed increased MMP levels/activity, and formed aggregates in distant areas. T47D were less affected than the MCF-7 cells, since MCF-7 also showed modest increases in cell death, EMT, and increased proliferation. Microarray analysis of the MCF-7 highlighted changes in the integrin, estrogen, EGFR, and TGFß pathways. Indeed, placental ECM reduced ERα, induced Smad3/JNK phosphorylation and increased integrin-α5 expression (RGD-dependent integrin) in the BCCL. Addition of RGD or TGFßR/JNK inhibitors reversed the phenotypic changes. This study helps explain the absence of metastases to the placenta and why advanced cancer is found in pregnancy, and provides possible therapeutic targets for anoikis-resistant cells. © 2016 Wiley Periodicals, Inc.

Heat shock protein-27 (HSP27) regulates STAT3 and eIF4G levels in first trimester human placenta.

During placental implantation, cytotrophoblast cells differentiate to extravillous trophoblast (EVT) cells that invade from the placenta into the maternal uterine blood vessels. The heat shock protein-27 (HSP27), the signal transducer and activator of transcription-3 (STAT3) and the eukaryotic translation initiation factor 4E (EIF4E) are involved in regulating EVT cell differentiation/migration. EIF4E and EIF4G compose the translation initiation complex, which is a major control point in protein translation. The molecular chaperone distinctiveness of HSP27 implies that it directly interferes with many target proteins. STAT3, EIF4E, and EIF4G were found to be HSP27 client proteins in tumor cells. We aimed to analyze if HSP27 regulate STAT3 and EIF4G levels in first trimester human placenta. We found that like STAT3, EIF4G is highly expressed in the EVT cells (immunohistochemistry). Silencing HSP27 in HTR-8/SVneo cells (siRNA, EVT cell line) and in placental explants reduced STAT3 level (47 and 33 %, respectively, p < 0.05). HSP27 silencing reduced the levels of STAT3 phosphorylation (33 % reduction, p < 0.05) and targets (IRF1, MUC1, MMP2/9 and EIF4E, 30-49 % reduction, p < 0.05) in the HTR-8/SVneo cells. Moreover, HSP27 silencing significantly reduced EIF4G level and elevated the level of its fragments in HTR-8/SVneo cells and in the placental explants (p < 0.05). In conclusion, Placental implantation and development are accompanied by trophoblast cell proliferation and differentiation, which necessitates intense protein translation and STAT3 activation. HSP27 was found to be regulator of translation initiation and STAT3 level. Therefore, it suggests that HSP27 is a key protein during placental development and trophoblast cell differentiation.

Placenta-breast cancer cell interactions promote cancer cell epithelial mesenchymal transition via TGFß/JNK pathway.

Women diagnosed with pregnancy associated breast cancer often have advanced cancer with metastases and reduced expression of ERα compared to non-pregnant women. Nevertheless, metastases to the placenta are uncommon. Previously, we demonstrated that breast cancer cells (MCF-7/T47D) migrated from ex vivo human placental explant implantation sites. We aimed to analyze the effect of factors produced during placental implantation or as a result of the interaction between the implanted placentae to cancer cells on cancer cells migration and aggressiveness. We collected supernatants from implanted placentae and placental-breast cancer cells cocultures and analyzed their effects on cancer cells phenotype and pathways. Supernatants collected from breast cancer cells served as controls. We found that supernatants collected from implanted placentae induced modest cancer cells migration that was not accompanied by epithelial to mesenchymal transition (EMT), supported breast cancer cells survival and elevated MCF-7 cell number. The coculture supernatant induced excessive motility and EMT of the MCF-7 cells. This EMT was mediated by Smad3 and JNK/ERK activation. Both placenta and coculture supernatants reduced ERα expression in the cancer cells. Finally, we showed that MCF-7 cocultured with the human placental explants underwent continuous activation of JNK and Smad3 pathways and the EMT process, which led to their migration away from the placental implantation sites. These findings may explain the reduced ERα and elevated metastases found in breast cancer during pregnancy and highlights pathways involved in it.

[Use of fertility drugs and risk of breast cancer].

The strong desire to bring children into the world is the foundation of human existence. Fertility problems arise in approximately 10% of the population. The literature presents controversies regarding whether fertility treatment and ovarian hyperstimulation can be harmful to the patient. Can high estrogen levels that accompany the treatment cause or promote breast cancer? Dr. Riskin-Mashiach in her article: "Infertility, fertility treatment and breast cancer risk", reviews recent articles on the subject and concludes that most studies do not indicate a direct link but larger studies are needed to verify the safety of these treatments for patients.

Hair-thread tourniquet syndrome of labia minor.

BACKGROUND: Several organs may be damaged by strangulation by hair or strings that cause ischemia and necrosis. There have been sporadic case reports of such events. Injuries to the hands, feet, and fingers, as well as penile(1-5) and clitoral injuries(6-8) have been reported. CASES: Three cases of labia minor strangulation by hair are described. A review of the relevant literature is included. CONCLUSIONS: Pediatricians, gynecologists, and family physicians must be aware of labial tourniquet syndrome. If the diagnosis is missed or remains without immediate attention, the hair or string may cause necrosis and the resulting amputation of the vital body part.

Fluorescent in situ hybridization: an effective and less costly technique for genetic evaluation of products of conception in pregnancy losses.

OBJECTIVE: In this study, we applied the fluorescent in situ hybridization (FISH) technique and compared the common numerical abnormalities with chromosomes 13, 16, 18, 21, X, and Y in spontaneous to artificial abortion. This would cover about 75% of the common aneuploidy in spontaneous abortion. METHODS: Placentas were taken from 59 patients with a first trimester spontaneous abortion and 61 patients who underwent an elective first trimester pregnancy termination. The range of growth was from 5 to 12 gestational weeks. Placentas were processed according to direct chorionic villi preparation. Direct dual color FISH was performed according to Vysis protocol with the probes for the following chromosomes: 13, 16, 18, 21, X, and Y. RESULTS: The aneuploidy rate in spontaneous abortion was 55.9% and in artificial abortion 8.2%. There was a significant difference between the two groups in the aneuploidy rate (P = 6 x 10(-9)). CONCLUSION: FISH is a rapid, efficient, and relatively inexpensive tool in detecting aneuploidy in placentas from cases of spontaneous abortions. Our rate of detected aneuploidy is compatible with other reports in which conventional cytogenetics was utilized.

Fetal urinoma as a sign of a dysplastic kidney.

We describe a female neonate in whom a urinoma was first diagnosed at 20 weeks of gestation without any evidence of underlying urinary tract obstruction. The urinoma became apparent following the performance of a "bloody tap" amniocentesis. Sequential ultrasonography, both fetal and up to 3 months after birth, showed eventual resorption of the urinoma in parallel with the development of a shrunken, non-functioning kidney. Except for the onset of high-renin hypertension, which spontaneously remitted at 1 year of age, the baby's postnatal course was uneventful. Renal function was normal. The presence of a fetal urinoma as a sign of a dysplastic kidney is discussed.

Ambulatory blood pressure monitoring in children with isolated haematuria.

Ambulatory blood pressure monitoring (ABPM) was performed in 29 children, ages 8.5-10.5 years (mean 11.6+/-3.0) with isolated haematuria (IH) and in 27 age, sex, weight and height matched healthy controls (C). Isolated haematuria was defined as >or=5 RBC/HPF on three separate urinalyses over a 3-month period with normal renal function, a normal appearing ultrasound examination of the kidneys and the absence of hypercalciuria. Haematuria had been documented for at least 3 years prior to ABPM. Daytime and nighttime periods were 0800-2200 and 2200-0800 hours, respectively. The total number of successful blood pressure readings was 21.8 and 20.7 per subject (90.0 and 86.1% of all attempted measurements) in IH and C, respectively. Mean 24-h, daytime and nighttime heart rate, mean arterial pressure, and systolic and diastolic blood pressure in IH did not differ from that of controls. Nocturnal dipping was present in all IH patients and was of equal magnitude to C (9.5 vs 8.4 and 13.7 vs 10.3% for average systolic blood pressure (SBP) and diastolic blood pressure (DBP) dips, respectively). We conclude that normal blood pressure values, as well as the circadian rhythm of blood pressure, are maintained in children with IH of at least 3 years' duration.