Interstitial heterotopic pregnancy after bilateral total salpingectomy in IVF patients: a case report and literature review.

OBJECTIVES: Heterotopic pregnancy of an intrauterine pregnancy and an interstitial or stump pregnancy after bilateral salpingectomy is a rare complication of in vitro fertilization (IVF) that can lead to severe hemorrhage; prompt identification and management are important. The aim of this paper was to present a case report and an updated literature review of women who had had combined interstitial/stump and intrauterine pregnancies during an in an IVF cycle after total bilateral salpingectomy. MATERIAL AND METHODS: We conducted a search in PubMed for reported heterotopic pregnancy, of a combined intrauterine pregnancy with an interstitial or stump pregnancy, in women who underwent IVF after bilateral salpingectomy. RESULTS: Our search yielded 13 heterotopic pregnancies in women who underwent IVF after bilateral salpingectomy. Forty-six percent of the women had more than two embryos transferred, and all the women had a history of ectopic pregnancies or tubal infertility. Most of the women presented at 6-7 weeks of pregnancy with vaginal bleeding and/or abdominal pain. A ruptured ectopic pregnancy was presented in 42%. Ultrasound was the main diagnostic tool in most cases. Only two women had been medically treated with local KCL or methotrexate, while 83% underwent surgical treatment. Five women had uncomplicated cesarean sections near or at term. CONCLUSIONS: Women with bilateral total salpingectomy remain at risk of heterotopic pregnancy, which poses a diagnostic and treatment challenge. This risk may be reduced by the reduction in the number of transferred embryos in IVF. For those who wish to preserve intrauterine pregnancy, cornual resection can be performed with good prognosis.

Diagnostic accuracy and characteristics of symptomatic versus asymptomatic retained products of conception: A retrospective cohort study.

OBJECTIVE: To assess the accuracy of diagnosing retained products of conception (RPOC) in symptomatic versus asymptomatic women, and to identify potential divergent ultrasound features between these groups. METHODS: This retrospective study included women aged 17-50 years who underwent hysteroscopy for suspected RPOC during 2018-2021. Clinical and sonographic data were analyzed, and multivariable linear regression models employed, to examine correlations between RPOC and sonographic findings, and to compare diagnostic accuracy between symptomatic and asymptomatic women. RESULTS: Of the 225 women included, 123 (54.7 %) were symptomatic and 102 (45.3 %) were asymptomatic. Hysteroscopy complications were more frequent in asymptomatic women. Regarding sonography, statistically significant differences were not found between the groups in endometrial thickness or uterine fluid presence, but positive Doppler flow was more common in asymptomatic than symptomatic women. Endometrial thickness >1.49 cm demonstrated diagnostic utility, with similar sensitivity and specificity in the two groups. Multivariable models revealed significant associations of RPOC presence with endometrial thickness and Doppler flow in symptomatic women. In both groups, hysteroscopy enhanced diagnostic accuracy, with higher positive predictive values and lower false-positive rates compared to ultrasound alone. CONCLUSION: An endometrial thickness cutoff of 1.49 cm aids diagnosing RPOC. Doppler flow enhances diagnostic value in symptomatic women. Integration of hysteroscopy improves diagnostic accuracy compared to ultrasound alone. Regular sonographic assessment for women with identifiable risk factors assists in RPOC detection irrespective of symptoms.

Ethnic disparities in complete and partial molar pregnancy incidence: a retrospective analysis of arab and jewish women in single medical center.

BACKGROUND: Molar pregnancies, encompassing complete and partial moles, represent a rare and enigmatic gestational disorder with potential ethnic variations in incidence. This study aimed to investigate relations of ethnicity with risks of complete and partial molar pregnancies within an Israeli population while accounting for age differences. METHODS: A retrospective study was conducted of data recorded during 2007-2021 in an academic medical center in Israel. The study population comprised 167 women diagnosed with complete or partial moles, for whom data were obtained through histological examination and P57 immunostaining. Maternal age and ethnicity were extracted from electronic medical records. Incidence rates were calculated per 10,000 live births, and a nested case-control study compared demographic characteristics and molar pregnancy incidences between Arab and Jewish women. Statistical analyses included age-adjusted comparisons, relative risk calculations and multivariate logistic regression. RESULTS: The overall risk of molar pregnancy was 22 per 10,000 live births (95% confidence interval [CI] 18-25). Among Arab women, the overall risk was 21 (95% CI 17-25), and for PM and CM: 14 (95% CI 11-17) and 7 (95% CI 5-10), respectively. Among Jewish women, the overall risk was 23 (95% CI 18-29), and for PM and CM: 12 (95% CI 8-17) and 11 (95% CI 7-16), respectively. Among Arab women compared to Jewish women, the proportion of all the partial moles was higher: (65.3% vs. 51.6%, p = 0.05). The incidence of partial mole was higher among Arab than Jewish women, aged 35-39 years (26 vs. 8 per 10,000, p = 0.041), and did not differ in other age groups. After adjusting for age, the relative risk of partial moles was lower among Jews than Arabs (0.7, 95% CI 0.4-1.0, p = 0.053). For Arab compared to Jewish women, the mean age at molar pregnancies was younger: 31.0 vs. 35.1 years. However, other factors did not differ significantly between Arab and Jewish women with molar pregnancies. In multivariate analysis, Jewish ethnicity was significantly associated with a higher risk of complete molar pregnancies (OR = 2.19, 95% CI 1.09-4.41, p = 0.028). CONCLUSION: This study highlights ethnic differences in molar pregnancy risk within the Israeli population. Jewish ethnicity was associated with a higher risk of complete molar pregnancies, while Arab women had a significantly higher risk of partial moles. These findings underscore the need to consider ethnicity when studying gestational disorders. Further research should seek to elucidate the underlying factors contributing to these differences.

Detection and dissection of sentinel nodes in endometrial endometrioid cancer with indocyanine green using PinPoint laparoscopy: Analysis of the learning curve.

OBJECTIVE: Early-stage endometrial endometrioid adenocarcinoma is managed through laparoscopic total hysterectomy with bilateral salpingo-oophorectomy and pelvic lymphadenectomy. Detection of positive nodes is rare, and lymphadenectomy may involve complications. Pelvic sentinel lymph node dissection can prevent complete dissection. Herein, we evaluated the learning curve of sentinel lymph node dissection using indocyanine green. STUDY DESIGN: All surgeries for endometrial endometrioid adenocarcinoma were performed laparoscopically with indocyanine green to detect sentinel nodes. The primary outcome was the ability to identify and resect sentinel lymph nodes on each side. The secondary outcome was correspondence between the frozen section histology of the nodes with the final histology. RESULTS: Among 31 patients with endometrial endometrioid adenocarcinoma treated between October 2018 and August 2020, 29 who underwent laparoscopy using indocyanine green were enrolled. Complete lymphadenectomy was performed in 16 patients. Failure to recognize sentinel nodes on right and left sides occurred in 10.34% and 0% of cases, respectively. The median number of recognized and dissected sentinel nodes was 1 on both sides (range 0-5). One patient had a lymph node positive for malignancy on histology (3.45%) on both sides. There were 13 and 14 cases of negative frozen sections on the right and left sides, respectively, and 1 case of a positive frozen section with positive whole pelvic lymph nodes. CONCLUSION: Sentinel node dissection using indocyanine green in endometrial endometrioid adenocarcinoma has a distinct learning curve; however, it is practical and achievable for skilled surgeons.

Nonelectric shaving of endometrial polyp by hysteroscopy - A new technique to eliminate thermal damage.

OBJECTIVE: To present a new technique for complete endometrial polypectomy, using the bipolar loop hysteroscope, but without the activation of electrical energy, and follow its efficiency and safety for the patient. STUDY DESIGN: This is a prospective descriptive study conducted at a university hospital. Forty four patients were recruited to the study according to an intra uterine polyp diagnosed by transvaginal ultrasound (TVS). Out of them 25 really had an endometrial polyp which was inspected by hysteroscopy. Eighteen were at menopause age and seven in their reproductive age. The hysteroscopic removal of the endometrial polyp was performed using the operative loop resectoscope without using electricity, meaning by cold loop. We called this unique technique SHEPH: Shaving of Endometrial Polyp by Hysteroscopy. RESULTS: The range age was 21-77 years old. All patients with apparently endometrial polyp, underwent a complete removal of the polyp which could be directly seen through hysteroscopy. No bleeding was seen in all cases. The other nineteen patients had normal uterine cavity, so a biopsy was taken according to the indication. The specimen from all cases were sent to histological evaluation. An endometrial polyp was histologically confirmed in all cases who underwent the SHEPH technique, while fragments of an endometrial polyp was revealed by histology in six cases from the group that had normal uterine cavity. No complications were noted for the short and long periods. CONCLUSIONS: Nonelectric Shaving of Endometrial Polyp by Hysteroscopy (SHEPH technique) is a safe and effective procedure which allows the surgeon to achieve a complete endometrial polypectomy but without using electrical energy within the body of the patient. The technique which is easy to learn, is new and unique by eliminate thermal damage in a very common gynecologic indication.

Alternative beta-hCG follow-up protocols after single-dose methotrexate therapy for ectopic pregnancy: A retrospective cohort study.

OBJECTIVE: This study assessed the relevance of reductions in beta-hCG levels between days 0 and 4 and between days 0 and 7 after single-dose methotrexate therapy, and the success of the therapy. STUDY DESIGN: A retrospective cohort study of 276 women diagnosed with ectopic pregnancy who received methotrexate as first-line treatment. Demographics, sonographic findings and beta-hCG levels and indexes were compared between women with successful and failed treatment outcomes. RESULTS: The median beta-hCG levels were lower in the success than the failure group on days 0, 4 and 7: 385 (26-9134) vs. 1381 (28-6475), 329 (5-6909) vs. 1680 (32-6496) and 232 (1-4876) vs. 1563 (33-6368), respectively, P < 0.001 for all. The best cut-off for the change in beta-hCG level from day 0 to 4 was a 19% decrease; the sensitivity was 77.0% and specificity 60.0%, positive predictive value (PPV) was 85% CI 95 [78.7.1%-89.9%]. The best cut-off for the change in beta-hCG level from day 0 to 7 was a 10% decrease; the sensitivity was 80.1% and specificity 70.8%, PPV was 90.5% CI 95 [85.1%-94.5%]. CONCLUSIONS: A decrease of 10% in beta-hCG between days 0 and 7 and 19% between days 0 and 4 can be used as a predictor of treatment success in specific cases.

The impact of the COVID-19 pandemic on ectopic pregnancy presentation and treatment: A retrospective cohort study.

OBJECTIVE: We examined ectopic pregnancy (EP) incidence, presentation and management, before and during the COVID-19 pandemic, and following initiation of vaccination against COVID-19. STUDY DESIGN: In a single-center retrospective cohort study, we compared incidence, presentation and management of EP, between 98 women who presented during the pandemic (March 1 2020 to August 31, 2021), and 94 women diagnosed earlier (March 1 2018 to August 31, 2019). Sub-periods before and after introduction of the vaccination were compared. RESULTS: Age and parity were similar between the periods. For the pandemic compared to the earlier period, the median gestational age at EP presentation was higher (6.24 ± 1.25 vs. 5.59 ± 1.24, P<0.001), and the proportions were higher of symptomatic women (42.9% vs. 27.7%, p = 0.035) and urgent laparoscopies (42.9% vs. 24.5%, p = 0.038). In a multivariable linear model, women who presented during the pandemic were more likely to undergo an urgent laparoscopy [OR 2.30, 95%CI (1.20-4.41)], P = 0.012. In urgent surgeries performed during the pandemic compared to the earlier period, the proportion of women with a hemoglobin drop >2 gr/dL was greater (60% vs. 30%, p = 0.024). Statistically significant differences were not found in sonographic or laboratory findings, in rupture or massive hemoperitoneum rates, or in the need for blood transfusion in urgent laparoscopy. Outcomes were similar before and after introduction of vaccinations. CONCLUSION: During the pandemic, and even after the introduction of vaccination, women with EP were more likely to undergo urgent surgery, and blood loss was greater. This is likely due to delayed diagnosis.

Changes in diagnostic sensitivity, incidence and presentation of complete and partial hydatidiform mole over the years.

OBJECTIVE: Molar pregnancy is the most common type of gestational trophoblastic disease. Several recent reports have described changes in the clinical representation, the incidence and the diagnostic sensitivity of molar pregnancy. These changes could be due to widespread use of transvaginal ultrasound and beta-hCG testing in the management of routine first-trimester investigations. STUDY DESIGN: This is a retrospective study of 144 women diagnosed with partial or complete mole at a regional medical center during 2007-2020. Incidence, demographics, clinical features and diagnostic sensitivity were compared between 2007 and 2014 and 2015-2020, and attempts were made to understand the bases of the changes between the time periods. RESULTS: Sixty-two moles were diagnosed during 2007-2014 and 82 during 2015-2020. The proportions of complete moles in the respective periods were 65% (40) and 18% (15). From the earlier to the later period, the incidence and proportion of complete moles decreased, and of partial moles, increased. The median gestational age at diagnosis of molar pregnancy was 9.3 weeks. In the later period, women presented less frequently with vaginal bleeding, though this remained the most common presenting symptom. The proportion of women who underwent surgical evacuation of the uterus due to suspected molar pregnancy decreased, as did the proportion of moles that was suspected in ultrasound evaluation (P < 0.001). CONCLUSION: The proportion of complete moles decreased between the periods examined. Gestational age at diagnosis was similar to data from 1994 to 2013. Some typical presenting symptoms of molar pregnancy decreased. However, earlier diagnosis of missed abortion can miss diagnoses of molar pregnancy.

The Modulatory Effect of Adipose-Derived Stem Cells on Endometrial Polyp Fibroblasts.

Endometrial polyps (EPs) are benign overgrowths of the endometrium, with the potential to cause severe complications, ranging from discomfort to inflammation and infertility. Dysfunction of endometrial fibroblasts may be a critical component leading to the development of polyps. Although surgical intervention is the common remedy for severe cases, it comes with drawbacks, including infection, bleeding, and risk of damage to the cervix and adjacent tissues. Adipose-derived mesenchymal stromal cells (ASCs) are at the focus of modern medicine, as key modulators of tissue homeostasis, inflammation, and tissue repair, rendering them prime candidate agents for tissue regeneration and cell-based therapies. In this study, EPs were isolated from patients admitted to the OB/GYN department at the Galilee Medical Center and extracted fibroblasts (endometrial polyp fibroblasts, EPFs) were isolated and characterized. ASCs were isolated from healthy patients. The effect of EPF- and ASC-conditioned media (CM) on polyp-derived fibroblasts was evaluated, in both 2D and 3D assays, as well as on the expression of matrix-related gene expression. Herein, EPFs exposed to ASC-CM exhibited reduced migration, invasion, contraction of hydrogels, and extracellular matrix deposition, compared with those exposed to EPF-CM. Altogether, this study suggests that ASCs may have a modulating effect on fibroblasts involved in forming EPs and may serve as the basis for conservative treatment strategies aimed at treating severe cases of EPs.

Coexisting Epithelioid Trophoblastic Tumor and Placental Site Trophoblastic Tumor During Asymptomatic Relapse: A Case Report and Literature Review.

Gestational trophoblastic neoplasms are a group of trophoblastic tumors that include choriocarcinoma (CC), epithelioid trophoblastic tumors (ETTs), and placental site trophoblastic tumors (PSTTs). Mixed gestational trophoblastic neoplasms include combinations of CCs with ETTs and/or PSTTs; combinations of ETTs and PSTTs have also been described. This report describes the case of a 49-yr-old female with mixed ETT and PSTT discovered due to menstrual delay and a positive beta-human chorionic gonadotropin in serum 11 yr after normal pregnancy; it is an asymptomatic recurrence of the neoplasm after 2 yr. Moreover, only the ETT recurred without evidence of PSTT by biopsy and without any increase in human chorionic gonadotropin levels, even though human chorionic gonadotropin was positive in the first onset of the disease. We also reviewed published English literature, which revealed that there are only 36 cases of mixed trophoblastic tumors to date, of which pure mixed ETT and PSTT were reported only in four cases including our case. The most common combination is CC admixed with an ETT (52%), followed by CC with PSTT in 30.5%. CC admixed with an ETT and/or PSTT account for 83% of the cases, of which pure mixed ETT and PSTT were reported only in 4 cases (11%). The rarity of this condition entails reporting of all cases to facilitate future research and clinical management.

A possible association between hydatidiform mole and the COVID-19 pandemic: A retrospective cohort study.

OBJECTIVE: To confirm an increase in the number of women with molar pregnancy during the COVID-19 pandemic. METHODS: In this retrospective cohort study, all patients with complete or partial mole diagnosed at our institution between January 1, 2010 and October 31, 2020, were included. To verify whether there was an increase in the incidence of hydatidiform mole (HM) and deliveries in 2020, the incidences for each year from January 2010 to October 2020 were recorded. In addition, we identified all women who were diagnosed with HM from January to October 2020, and compared them with a control group who underwent uterine evacuation for missed abortion of a singleton pregnancy during the same period. We also documented the time taken to diagnose missed abortion or molar pregnancy to check if a delay in diagnosis can explain the increase in HM incidence. RESULTS: Between 2016 and 2019, there was a statistically significant increase in the incidence of molar pregnancy. A further increase occurred in 2020 (odds ratio = 2.071). The mean gestational age of the embryo at the time of diagnosis was smaller in the HM group than in the missed abortion group (6.3 ± 1.67-7.4 ± 2.4, one-sided P = 0.034), meaning that it took more time (days) to diagnose molar pregnancy than missed abortion (22.38 ± 10.32 vs. 15.83 ± 7.83 days, P = 0.012). CONCLUSION: There was a significant increase in the incidence of molar pregnancy during the COVID-19 pandemic, possibly because of the delay in receiving medical care. We recommend providing gynecological primary care services during a crisis, such as a pandemic.

Early prediction of methotrexate treatment outcome in tubal ectopic pregnancy based on days 0 and 4 human chorionic gonadotropin levels.

AIM: Methotrexate (MTX) is an efficient treatment for ectopic pregnancy, used according to 'single-dose' protocol. Treatment success is evaluated on days 4 and 7 after dose administration, and defined as a decline of ≥15% in beta-human chorionic gonadotropin (ß-hCG) levels, with a positive predictive value of 93%. A decrease on day 4 ß-hCG levels was determined to be a good predictor for treatment success. We retrospectively examined changes in ß-hCG levels between days 0 and 4 after MTX treatment as an early predictor for treatment outcome. METHODS: The 'success group' consisted of patients with resolved ectopic pregnancy after a single MTX dose and 'failure group' included patients who required additional MTX doses or underwent surgery after the first dose. For each group, demographic and pregnancy data were analyzed as well as initial (admission day), days 0, 4 and 7 ß-hCG levels. RESULTS: Of 159 women included in the study, MTX treatment was successful in 117 patients (73.6%) while 42 patients (26.4%) were defined as treatment failure. In the success group, most patients (58.9%) demonstrated a decrease in ß-hCG values between days 0 and 4 as opposed to the failure group in which an increase in ß-hCG values was observed (76.2%). Decrease of >18% in ß-hCG levels was predictive of treatment success (positive predictive value 92%). Increase in ß-hCG values is less predictive of treatment failure with positive predictive value of 54%. CONCLUSION: Differences in ß-hCG levels between days 0 and 4 may serve as an early predictor for treatment outcome.