Medical treatment for early pregnancy loss following in vitro fertilization compared to spontaneous pregnancies.

BACKGROUND: Misoprostol is a well-studied medical treatment for early pregnancy loss (EPL), with success rates ranging between 70 and 90%. However, treatment failure is associated with major patient discomfort, including the need for surgical intervention to evacuate the uterus. It was previously reported that medical treatment was especially successful among women who conceived after in vitro fertilization (IVF). We aimed to study if there is a difference in rates of medical treatment failures for EPL between pregnancies conceived by IVF and spontaneous pregnancies. METHODS: In this retrospective cohort study, we included all women who underwent medical treatment for EPL at our institute between 07/2015 and 12/2020. Treatment outcome was compared between IVF and spontaneous pregnancies. Treatment failure was defined as a need for surgical intervention, namely, dilation & curettage (D&C) and/or hysteroscopy, due to retained products of conception, which was defined as a gestational sac or endometrial thickness greater than 15 mm in a TVS scan. RESULTS: Overall, 775 patients were included, of which 195 (169/775 = 25.1%) ultimately required surgical intervention. There was no difference between the study groups in the rate of treatment failure. However, among IVF pregnancies, the rate of emergency D&C was lower (3.6% vs. 9.8%, p = 0.001), compared to spontaneous group. CONCLUSION: In cases of medical treatment for EPL, IVF pregnancies had no differences in rates of treatment failure compared to spontaneous pregnancies. That being said, IVF pregnancies have lower chances to undergo emergency D&C, compared to spontaneous pregnancies.

The Poor Prognosis of Acquired Secondary Platinum Resistance in Ovarian Cancer Patients.

OBJECTIVE: The goal of this study was to evaluate response to treatment and survival in epithelial ovarian cancer patients with acquired secondary platinum resistance (SPR) compared to patients with primary platinum resistance (PPR). METHODS: Patients were categorized as PPR (patients with disease recurrence occurring during or <6 months after completing first-line platinum-based chemotherapy) and SPR (patients with previously platinum-sensitive disease that developed platinum resistance on subsequent treatments). Clinico-pathological variables and treatment outcomes were compared. RESULTS: Of the 118 patients included in this study, 60 had PPR and 58 developed SPR. The SPR women had a significantly higher rate of optimal debulking during their upfront and interval operations, significantly lower CA-125 levels during their primary treatment, and a significantly higher complete and partial response rate to primary chemotherapy. Once platinum resistance appeared, no significant difference in survival was observed between the two groups. The median PFS was 2 months in the PPR group and 0.83 months in the SPR group (p = 0.085). Also, no significant difference was found in post-platinum-resistant relapse survival, with a median of 17.63 months in the PPR and 20.26 months in the SPR group (p = 0.515). CONCLUSIONS: Platinum resistance is an important prognostic factor in women with EOC. Patients with SPR acquire the same poor treatment outcome as with PPR. There is a great need for future research efforts to discover novel strategies and biological treatments to reverse resistance and improve survival.

D&C has the best concordance between preoperative and postoperative grades among morbidly obese endometrial cancer patients.

AIM: Endometrial cancer is diagnosed by obtaining uterine biopsies by pipelle, dilatation and curettage (D&C), or hysteroscopy. In 15%-25% of the cases, the preoperative and postoperative grades do not match. This discrepancy may carry significant clinical and prognostic consequences. We aimed to assess how body mass index (BMI) affects preoperative and postoperative grade mismatches and whether biopsy methods mitigate this effect. METHODS: We conducted a retrospective review of patients with endometrial cancer who underwent surgery at our center between 2014 and 2022. We stratified patients into six classes of BMI based on the WHO classification. Preoperative and postoperative grades were compared for concordance with regards to patient BMI and sampling method. RESULTS: A total of 158 patients were included, diagnosed by pipelle (n = 99), hysteroscopy (n = 15), or D&C (n = 44). For all methods, every unit increase in BMI increased the odds of having a gap between histology grades by 5.2%. In the pipelle group, the odds of a larger gap between the histology grades was 62% higher than that of women in the other groups. Among the D&C group, the odds of having a bigger difference between histology grades were 91.8% lower compared to the other groups. Patients with BMI over 30 had nearly 50% discrepancy when diagnosed with pipelle or hysteroscopy, but less than 10% with D&C. CONCLUSIONS: Increasing BMI is associated with decreasing concordance between preoperative and postoperative grades in endometrial cancer, especially when it exceeds 30. This effect is much less pronounced, however, when the diagnostic method is D&C.

Failure Rate of Medical Treatment for Miscarriage Correlated with the Difference between Gestational Age According to Last Menstrual Period and Gestational Size Calculated via Ultrasound.

Objective: To study whether the interval between gestational age calculated using the last menstrual period (GA-LMP) and gestational age calculated via ultrasound (GA-US) is correlated with the success rate of medical treatment in cases of miscarriages. Methods: This was a retrospective cohort study conducted in a gynecology unit in a tertiary medical center. Women who underwent medical treatment with Misoprostol for miscarriage at the Edith Wolfson Medical Center between 07/2015 and 12/2020 were included. Incomplete or septic miscarriages, multiple pregnancies, patients with irregular periods, and cases of missing data were excluded. Failure of medical treatment was defined as the need for surgical intervention due to a retained gestational sac, severe bleeding or retained products of conception. The cohort study was divided into two groups: patients with successful treatment and patients for whom surgical intervention was eventually needed. We performed both a univariate and multivariate analysis in order to identify whether a correlation between GA-LMP and GA-US interval is indeed a factor in the success rate of a medical abortion. Results: Overall, 778 patients were included in the study. From this cohort 582 (74.9%) had undergone a successful medical treatment, while 196 (25.1%) required surgical intervention due to the failure of medical treatment, as defined above. The GA-LMP to GA-US interval (in weeks) was 2.6 ± 1.4 in the success group, while the GA in the failure group was 3.1 ± 1.6 (p < 0.001). After performing a multivariant regression analysis, we were able to show that the GA-LMP to GA-US interval was found to be independently correlated with an increase in the treatment failure rate (aOR = 1.24, CI 95% (1.01-1.51), p = 0.03). Conclusions: In cases of miscarriage, longer GA-LMP to GA-US interval has been shown to be an independently correlated factor to lower success rate of the medical treatment option.

Low grade serous ovarian cancer - A rare disease with increasing therapeutic options.

High-grade serous ovarian cancers (HGSOCs) most commonly arise from the fimbrial end of the fallopian tube and harbor TP53 gene mutations. In contrast, low-grade serous ovarian cancers (LGSOCs) appear to have different pathological, epidemiological, and clinical features and should be seen as a distinct serous epithelial ovarian cancer subtype. Our current understanding of LGSOC is limited, and treatment has generally been derived from the more common HGSOCs due to a lack of separate trial data. LGSOCs are characterized by slow tumor growth and are assumed to develop from serous borderline ovarian tumors as precursors. These cancers are often estrogen-receptor positive and show an activated mitogen-activated protein kinase pathway together with KRAS and BRAF mutations and, rarely, TP53 mutations. These characteristics are now commonly used to guide therapeutical decision making and, consequently, a substantial part of treatment consists of maintenance with endocrine treatment, thus balancing disease stabilization and mild toxicity. Additionally, new trials are ongoing that examine the role of targeted therapies such as MEK inhibitors in combination with endocrine treatments. The purpose of this work is to summarize current knowledge and present ongoing trial efforts for LGSOCs.

Surgical intervention after medical treatment for early pregnancy loss according to gestational size.

OBJECTIVE: To study the rate of surgical intervention for unsuccessful medical treatment in early pregnancy loss (EPL), according to gestational size by ultrasound (GS-US). METHODS: This was a retrospective cohort study. All women who were treated with misoprostol for EPL between July 2015 and December 2020 were included. The cohort was divided according to GS-US: group 1: gestational sac without an embryonic pole; group 2: an embryonic pole with crown-rump length (CRL) compatible with <7 weeks; group 3: CRL compatible with 7+0 -7+6 weeks; group 4: CRL compatible with 8+0 -8+6 weeks; group 5: CRL compatible with ≥9 weeks. We compared the rate of any surgical intervention due to treatment failure. RESULTS: Overall, 783 patients were included: group 1, 236 (30.1%); group 2, 319 (40.7%); group 3, 115 (14.7%); group 4, 78 (10.0%); and group 5, 35 (5.0%) patients. The rate of any surgical intervention was significantly lower in groups 1-4 (54, 22.9%; 85, 26.6%; 28, 24.3%; and 22, 28.2%, respectively) compared with group 5 (17, 48.6%; P = 0.030). On multivariant analysis, GS-US greater than 9 weeks was independently associated with the need for surgical intervention (adjusted odds ratio 1.23, 95% confidence interval 1.01-1.51; P = 0.040). CONCLUSION: When treating EPL medically, GS-US greater than 9 weeks increases the risk of undergoing additional surgical intervention compared with younger weeks.

Age Disparities in End of Life Symptom Management Among Patients with Epithelial Ovarian Cancer.

OBJECTIVE: To evaluate the symptoms of women with epithelial ovarian cancer (EOC) during their last admission before death and analyze invasive palliative management administered in relation to symptom control and survival. MATERIALS & METHODS: A retrospective review of Israeli patients with EOC, primary peritoneal cancer (PPC) and tubal cancer, admitted to our department prior to death between 2008-2018. Basic palliative treatment was defined as administration of IV fluids, analgesics, oxygen, antiemetics, antibiotics and/or blood transfusions. Procedures regarded as invasive included: peritoneal or pleural fluid drainage; placement of an indwelling catheter, administration of total parenteral nutrition (TPN), chemotherapy and ventilation. RESULTS: 82 patients were included. Most suffered from weakness and fatigue, gastrointestinal complaints, pain and shortness of breath. 34 patients (41.5%) required only basic palliative treatment to alleviate their symptoms; however, in 48 patients (58.5%) invasive interventions were needed. Patients treated with invasive procedures were younger at death by almost 9 years (mean age of 65.73 ± 9.5 vs. 74.78 ± 9.8; p = 0.001). There were significantly more women with platinum sensitive disease in the invasive interventions group compared to the basic palliative care (60.42% vs. 32.35%; p = 0.012). No survival difference was found between the groups from diagnosis to death, relapse to death, last chemotherapy to death and last admission to death. CONCLUSIONS: EOC patients suffer from high disease burden and multiple symptoms before death. We found that physicians tend to use more invasive care in dying younger patients. However, this aggressive treatment does not prolong survival. Futile treatments influencing quality of life should be avoided.

Prognostic significance of pretreatment thrombocytosis in endometrial cancer: an Israeli Gynecologic Oncology Group study.

OBJECTIVE: Endometrial cancer prognosis is related to stage, histology, myometrial invasion, and lymphovascular space invasion. Several studies have examined the association between pretreatment thrombocytosis and patient outcomes with contrasting results regarding prognosis. Our aim was to evaluate the association of pretreatment platelet count with outcomes in endometrial cancer patients. METHODS: This is an Israeli Gynecologic Oncology Group multicenter retrospective cohort study of consecutive patients with endometrial cancer, who underwent surgery between January 2002 and December 2014. Patients were grouped as low risk (endometrioid G1-G2 and villoglandular) and high risk (endometrioid G3, uterine serous papillary carcinoma, clear cell carcinoma, and carcinosarcoma). Those with stage I disease were compared with stages II-IV. Disease stages were reviewed and updated to reflect International Federation of Gynecology and Obstetrics (FIGO) 2009 staging. All patients underwent pelvic washings for cytology and total abdominal or laparoscopic hysterectomy with bilateral salpingo-oophorectomy. Pelvic lymph node assessment was performed in patients with tumors of moderate-high risk histology or deep myometrial invasion. Para-aortic sampling was performed at the surgeon's discretion. Patients were categorized by pretreatment platelet count into two groups: ≤400×109/L and >400×109/L (defined as thrombocytosis). Clinical and pathological features were compared using Student t-test, χ2 or Fisher's exact test. Survival measures were plotted with the Kaplan-Meier method and compared using the log-rank test. A Cox proportional hazards model was used for multivariable comparison of associations. RESULTS: Of the 1482 patients included, most had stage I disease (961; 74.8%) and most had endometrioid histology (927; 64.1%). A total of 1392 patients (94%) had pretreatment platelet counts ≤400×109/L and 90 (6%) had pretreatment thrombocytosis. Patients with thrombocytosis had a significantly higher rate of high-grade malignancy, advanced stage, lymphovascular space invasion, low uterine segment involvement, and lymph node metastases. They also had shorter 5 year disease-free survival (65% vs 80%, p=0.003), disease-specific survival (63% vs 83%, p<0.05) and overall survival (59% vs 77%, p<0.05). On multivariate analysis, an elevated pretreatment thrombocyte count remained a significant independent predictor for disease-specific survival and overall survival. CONCLUSIONS: Pretreatment thrombocytosis is an independent prognostic factor for decreased disease-specific survival and overall survival among patients with endometrial cancer, and can serve as a predictor of poor outcome.

The effect of subcutaneous and intraperitoneal anesthesia on post laparoscopic pain: a randomized controlled trial.

A few modes of perioperative local analgesia have been studied in order to reduce postoperative pain after laparoscopy, including preemptive local anesthetics in the trocar sites and intraperitoneal anesthetics administration at the end of the surgery. However, the evidence regarding their efficacy are conflicting. In addition, the combination of both aforementioned methods has been rarely studied. Our aim was to evaluate whether subcutaneous trocar site and/or intraperitoneal analgesia reduce pain after gynecologic operative laparoscopy. This was a single-centered, randomized, controlled, double-blinded trial. The patients were randomly assigned to one of four equally sized groups: group 1-subcutaneous and intraperitoneal analgesia; group 2-subcutaneous analgesia and intraperitoneal placebo; group 3-subcutaneous placebo and intraperitoneal analgesia; Group 4-subcutaneous and intraperitoneal placebo. The patients, the surgeons, and the pain evaluators were all blinded to the patient's allocation. Included were patients who underwent elective operative laparoscopy. Exclusion criteria were: active infection, pregnancy, known sensitivity to Bupivacaine-Hydrochloride, chronic pelvic pain, surgeries with additional vaginal procedures, conversion to laparotomy, and malignancy. A total of 9 ml of Bupivacaine-Hydrochloride (Marcaine) 0.5%, or Sodium-Chloride 0.9%, as a placebo, were injected subcutaneously to the trocar sites (3 ml to each trocar site), prior to skin incision. In addition, 10 ml of Bupivacaine-Hydrochloride 0.5%, diluted with 40 ml of Sodium-Chloride 0.9% (a total of 50 ml solution), or 50 ml of Sodium-Chloride 0.9%, as a placebo, were injected intraperitoneally at the end of the surgery. By utilizing the 10 cm Visual-analogue-scale (VAS) we assessed post-operative pain at rest at 3, 8, and 24 h, and during ambulation at 8 and 24 h. The study was approved by the local Institutional Review Board and has been registered at clinicaltrials.gov. We conformed to the CONSORT recommendations. Between December 2016 and July 2019, a total of 119 patients were included in the study. Demographic and interventional characteristics were similar among the groups. The level of postoperative pain, either at rest or with change of position, was not significantly different between the groups, at all-time points. Application of subcutaneous and/or intraperitoneal analgesia is not effective in reducing pain after gynecologic operative laparoscopy.Clinical trial identification number: NCT02976571. Date of trial registration 11/29/2016. URL of the registration site: https://clinicaltrials.gov .

Anatomic Asymmetry in Sentinel Lymph Node Detection in Endometrial Cancer.

STUDY OBJECTIVE: To determine whether the concomitant use of indocyanine green (ICG) with technetium-99m-filtered sulfur colloid (Tc99m-FSC) improves bilateral sentinel lymph node (SLN) detection rate in endometrial cancer and whether anatomic concordance of pelvic lymph nodes exists and can be used to predict SLN location in cases of unilateral mapping failure. DESIGN: Retrospective cohort study. SETTING: Tertiary academic medical center in Holon, Israel. PATIENTS: Patients diagnosed with endometrial cancer, who underwent SLN mapping with Tc99m-FSC, ICG, or both, at our center between 2014 and 2019. INTERVENTIONS: A total of 111 patients were included in the study. SLN mapping using Tc99m-FSC was performed in 101 (91.9%) patients, and ICG injection was given to 64 (57.6%) patients of whom 55 (49.5%) received both. We compared SLN detection rates (unilateral and bilateral) and anatomic symmetry for each method alone and for a combination of the 2. MEASUREMENTS AND MAIN RESULTS: The overall detection rate for unilateral SLNs was 96.4%; 96.9% with ICG, 93.1% with gamma-probe, and 98.2% by combining both methods. The total bilateral detection rate was 72.1%, with ICG performing better as a single tracer than Tc99m-FSC (75% vs 63.4%, respectively). In 55 women in whom both tracers were used, the bilateral detection rate was significantly higher compared with Tc99m-FSC alone. Symmetric pelvic anatomic concordance of SLN was found in only 35 of 80 patients with bilateral SLN detection (43.8%). CONCLUSION: The combination of preoperative radioisotope injection and intraoperative ICG administration may yield the best bilateral SLN detection rate. In cases of unilateral mapping failure, one cannot rely on the anatomic location of the ipsilateral SLN detected to harvest the complementary node because the symmetric concordance is poor.

Characteristics and prognosis of borderline ovarian tumors in pre and postmenopausal patients.

OBJECTIVE: To compare patient characteristics, imaging results, surgical management and prognosis of borderline ovarian tumors (BOT) between pre and postmenopausal patients. MATERIALS AND METHODS: A retrospective cohort of all cases of histologically verified BOT between 1990-2018, comparing presentation, imaging, surgical procedures and recurrence. Patients were included in the postmenopausal group if they reported 12 months of amenorrhea with or without menopausal symptoms. RESULTS: During this 28 year study period, 66 operations were performed in which BOT was confirmed. Postmenopausal patients were 37-89 years old and premenopausal patients 18-50 years old, with an average age of 63.9 ± 13.4 and 36.2 ± 8.4 years, respectively (p < 0.001). The majority of patients in both groups were diagnosed due to abdominal pain, followed by incidental diagnosis on routine ultrasound. Imaging and CA-125 levels upon presentation were similar. Almost sixty percent of postmenopausal and 26.3% of premenopausal patients underwent laparotomy (p = 0.01), while those who underwent laparoscopy were 35.7% and 60.5%, respectively (p = 0.03). Most postmenopausal patients underwent bilateral salpingo-oophorectomy (BSO), whereas premenopausal surgeries involved cystectomy. Nearly all study patients were diagnosed in stage one. Malignant transformation occurred in 7.1% of postmenopausal patients. No malignant transformation was found in premenopausal patients. CONCLUSION: BOT's present similarly in pre and postmenopausal patients. Postmenopausal patients undergo more extensive surgery, and are diagnosed in early stage disease. Despite a tendency for a more conservative approach in premenopausal patients, prognosis is similar in both groups.

The association between the number of vaginal examinations during labor and perineal trauma: a retrospective cohort study.

PURPOSE: To study the association between the number of vaginal examinations (VEs) performed during labor and subsequent severe perineal trauma. METHODS: This is a retrospective cohort study. We included all women admitted to the delivery ward between 2008 and 2017, in active labor. Exclusion criteria included preterm deliveries (< 37 weeks), Cesarean deliveries and episiotomy during delivery. The primary outcome, severe perineal trauma, was defined as perineal tears grades 3-4. The cohort was divided into 4 groups, based on the number of VEs performed during labor: Group 1-up to two VEs (n = 4588), Group 2-three to four VEs (n = 5815), Group 3-five to six VEs (n = 4687), and Group 4-seven or more VEs (n = 7297). RESULTS: Overall, 22,387 women were included in the study. The rate of severe perineal trauma in groups 1, 2, 3 and 4 was 0.4%, 0.1%, 0.8%, and 0.4%, respectively (p < 0.001). Performing five or more VEs during labor was associated with a higher risk of severe perineal trauma (0.26% vs. 0.53%, p < 0.01), as compared to four VEs or less. Using a logistic regression model, we found that performing five or more VEs during labor (aOR = 1.72 CI 95% (1.21-2.47), p < 0.001) or performing an instrumental delivery (aOR = 2.65 CI 95% (1.72-4.07), p < 0.001) were directly associated with the risk for severe perineal trauma. Applying epidural anesthesia showed an inverse association with severe perineal trauma (aOR = 0.54 CI 95% (0.38-0.77), p < 0.001). CONCLUSION: Performing five or more VEs during active labor is associated with an increased risk for severe perineal trauma.

Amniotic fluid transitioning from clear to meconium stained during labor-prevalence and association with adverse maternal and neonatal outcomes.

OBJECTIVE: The objective of this study is to compare pregnancy outcomes in deliveries complicated by primary meconium-stained amniotic fluid (MSAF, present at membrane rupture) and secondary MSAF (transitioned from clear to MSAF during labor). METHODS: The medical records and neonatal charts of all deliveries ≥ 370/7 weeks between October 2008 and July 2018 were reviewed. The primary outcome was composite adverse neonatal outcome that included early neonatal complications. RESULTS: Of 30,215 deliveries during the study period, 4302 (14.2 %) were included: 3845 (89.4%) in the primary MSAF group and 457 (10.6%) in the secondary MSAF group. The rate of the primary outcome was higher in the secondary MSAF group (p = 0.006). This association remained significant after controlling for background confounders. The secondary MSAF group had higher rate of cesarean deliveries (CDs) and assisted vaginal deliveries. There was a higher rate of composite adverse neonatal outcome when secondary MSAF was diagnosed < 3 vs. >3 h before delivery (p = 0.004). CONCLUSION: Secondary MSAF was associated with higher rates of adverse neonatal outcome, CDs, and assisted vaginal deliveries, compared with primary MSAF.

The association between abnormal coagulation testing in preeclampsia, adverse pregnancy outcomes, and placental histopathology.

Objective: We aimed to determine whether abnormal coagulation laboratory testing results in preeclampsia, are associated with adverse pregnancy outcomes and placental histopathology lesions. Methods: Demographic, labor, laboratory-testing, and placental histopathology reports of pregnancies complicated by preeclampsia were compared between those with and without abnormal coagulation profile (ACP). Results: Of 348 cases of preeclampsia 16.1% had ACP. There were no differences between the groups in GA at delivery, severe features, placental-abruption, SGA, composite adverse neonatal outcome and placental histopathology lesions. Conclusion: ACP in pregnancies complicated by preeclampsia was not associated with any of the studied outcomes. Our data question the usefulness of routine coagulation tests in the initial assessment of women presenting with preeclampsia.