Decidual-tissue-resident memory T cells protect against nonprimary human cytomegalovirus infection at the maternal-fetal interface.

Congenital cytomegalovirus (cCMV) is the most common intrauterine infection, leading to infant neurodevelopmental disabilities. An improved knowledge of correlates of protection against cCMV is needed to guide prevention strategies. Here, we employ an ex vivo model of human CMV (HCMV) infection in decidual tissues of women with and without preconception immunity against CMV, recapitulating nonprimary vs. primary infection at the authentic maternofetal transmission site. We show that decidual tissues of women with preconception immunity against CMV exhibit intrinsic resistance to HCMV, mounting a rapid activation of tissue-resident memory CD8+ and CD4+ T cells upon HCMV reinfection. We further reveal the role of HCMV-specific decidual-tissue-resident CD8+ T cells in local protection against nonprimary HCMV infection. The findings could inform the development of a vaccine against cCMV and provide insights for further studies of the integrity of immune defense against HCMV and other pathogens at the human maternal-fetal interface.

Primary Resectoscopic Treatment of First-Trimester Miscarriage.

OBJECTIVES: To determine the feasibility and safety of resectoscopic treatment for uterine evacuation of first-trimester miscarriage. METHODS: A single-centre prospective study performed between April 2021 and October 2021 at a university-affiliated tertiary medical centre. Patients diagnosed with early miscarriage of up to 12 weeks from the last menstrual period were eligible for participation. Recruited patients underwent hysteroscopic uterine evacuation under general anaesthesia by a Versapoint 2 bipolar resectoscope 24Fr (Johnson and Johnson, Germany). RESULTS: A total of 15 patients were recruited for the study. The procedural characteristics as well as intra- and postoperative adverse events were recorded. The mean duration of the procedure was 14.3 ± 3.7 minutes. The achievement of complete evacuation was recorded in all cases, and no adverse events occurred during any procedure. Post-procedure follow-up 6 weeks after treatment was conducted by office hysteroscopy in 10 women and by ultrasonography in 4 women. One woman had conceived prior to her scheduled follow-up visit. In total, 2 (13.3%) cases of retained products of conception were diagnosed during office hysteroscopy and they were removed by the "see-and-treat" technique without anaesthesia. The diagnosis was confirmed pathologically. No intrauterine adhesions were detected and none of the women required a second hysteroscopy under anaesthesia due to retained products of conception. CONCLUSIONS: Hysteroscopic evacuation of first-trimester miscarriage by a standard resectoscope is a safe and feasible technique.

Expectant vs medical management for retained products of conception after medical termination of pregnancy: a randomized controlled study.

BACKGROUND: Despite the rise of medical treatments for the termination of pregnancy, to date, no prospective trial has evaluated the efficacy of misoprostol in treating retained products of conception after induced termination of pregnancy. OBJECTIVE: This study aimed to compare medical management with misoprostol with expectant management for retained products of conception after first-trimester medical termination of pregnancy. STUDY DESIGN: This was an open-label randomized controlled trial conducted at a university-affiliated tertiary medical center. Consenting consecutive women who underwent a routine 3-week follow-up evaluation after medical termination of pregnancy and had a sonographic suspicion of retained products of conception, defined as sonographic evidence of intrauterine remnant (>12 mm) with a positive Doppler flow, were recruited. The participants were randomized into a medical treatment group (800 µg of sublingually administered misoprostol) or expectant management. They all underwent repeat ultrasound scans every 2 weeks until a maximum of 6 weeks, and those suspected of persistent retained products of conception were referred to operative hysteroscopy. The primary endpoint was successful treatment defined as no need for surgical intervention because of persistent retained products of conception within 8 weeks from pregnancy termination. RESULTS: There was no marked difference in demographic characteristics between the study groups. The median sonographically demonstrated retained product length was 20 mm (interquartile range, 17-25) in the medically managed group compared with 20 mm (interquartile range, 17-26) in the expectantly managed group (P=.733). Treatment succeeded in 42 of 68 women (61.8%) in the medically managed group compared with 36 of 63 women (57.1%) in the expectantly managed group (relative risk, 1.12; 95% confidence interval, 0.74-1.70; P=.590). There was no difference in adverse outcomes between the 2 groups. CONCLUSION: There was no clinically meaningful advantage for medical treatment with misoprostol compared with expectant management after first-trimester medical termination of pregnancy in women with suspected retained products of conception. Surgical intervention can be avoided in up to 60% of women who are managed expectantly for 8 weeks of follow-up.

Ruptured ectopic pregnancies following methotrexate treatment: clinical course and predictors for improving patient counseling.

To determine the predictors for tubal rupture among women treated with methotrexate (MTX) for ectopic pregnancy. We performed a retrospective cohort analysis in a tertiary university-affiliated medical center. Medical records of 401 women who were diagnosed with ectopic pregnancy and were treated with MTX between January 2001 and June 2017 were reviewed. Forty-one women were diagnosed with ruptured ectopic pregnancy (study group) and 360 women with non-ruptured ectopic pregnancy (control group). Descriptive data and predictive variables for rupture ectopic pregnancy following MTX treatment were reviewed. Out of 122 women who failed MTX treatment, forty-one women had tubal rupture (33.6%). The median time interval from MTX treatment to tubal rupture was 6 days (1-25). ß-hCG percentage change in the 48 h preceding MTX treatment and ß-hCG level at day 0 were independent predictors for tubal rupture (odds ratio [OR] = 1.08, 95% confidence interval [CI] = 1.04-1.12, p < 0.001 for every percent change in ß-hCG; OR = 1.001, 95% CI = 1.0003-1.002 for every unit change in ß-hCG, respectively). In a decision tree analysis model, in women with ß-hCG percentage increment >69% in the 48 h preceding methotrexate the probability for tubal rupture was 85%. Risk assessment for tubal rupture should be made before methotrexate treatment according to ß-hCG dynamics and level. The absolute risk for tubal rupture in women with ß-hCG increment<20% is low.

Conception rates after medical versus surgical evacuation of early miscarriage.

OBJECTIVE: To compare short-term fertility rates after medical and surgical management of early miscarriage. DESIGN: Observational cohort study. SETTING: Academic tertiary-care medical center. PATIENT(S): A total of 203 patients were enrolled between June 2017 and May 2018, comprising 106 surgical evacuations and 97 medical evacuations. INTERVENTION(S): Either surgical or medical evacuation of the uterine cavity. MAIN OUTCOME MEASURE(S): Conception rates 6 months after miscarriage. RESULT(S): Conception rates 6 months after miscarriage among women who had attempted to become pregnant were similar between the medically and surgically evacuated groups (68.0% vs. 65.1%). There were no significant differences in background characteristics between the groups, apart from younger age and earlier gestational age among the medically treated group. There was no difference in the proportion of women using assisted reproductive technologies between the medically and surgically managed groups (15.5% vs. 12.6%, respectively). The median time-to-conception was 4 ± 2 months in both groups. Cumulative pregnancy rate 12 months after pregnancy loss, live birth rate, and repeat miscarriage rate also were similar between groups. CONCLUSION(S): Modality of uterine evacuation after early miscarriage does not affect short-term fertility outcomes.

Healthcare Utilization and Prevalence of Symptoms in Women with Menopause: A Real-World Analysis.

OBJECTIVE: Self-reported studies estimated that as many as 50-75% of women experience symptoms during menopause; however, limited real-world clinical data are available to support this observation. The electronic databases of Maccabi Healthcare Services were used to describe the prevalence of menopause symptoms in Israel and to characterize patients with regard to socioeconomic status, comorbidities and use of healthcare services. METHODS: Females aged 45-54 years diagnosed with menopausal symptoms (N=17,046, cumulative incidence of 8% during the study period) were identified from the Maccabi Healthcare Services electronic database and matched to female members without menopause symptoms, one-to-one on birth year and enumeration area. RESULTS: Symptomatic peri- and post-menopausal women, and particularly those under 52 years, were more likely to have a higher prevalence of comorbid conditions such as depression, anxiety, osteoporosis and insomnia in the year following index. Correspondingly, selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors and hypnotic drug use were significantly higher in symptomatic women as was healthcare utilization including hospitalization (OR=1.10; 95% CI=1.00-1.20), primary care visits (1.90; 1.73-2.08), gynecologist visits (24.84; 22.36-27.59) and hysterectomy procedures (2.26; 1.63-3.14). CONCLUSION: Medically documented menopausal symptoms are associated with increased burden of disease (particularly among women diagnosed with menopausal symptoms prior to age 52 years), healthcare utilization and greater likelihood of undergoing hysterectomy within one year of diagnosis. This burden is expected to rise further as awareness and social acceptance of peri- and post-menopausal symptoms increase.

Artemisone demonstrates synergistic antiviral activity in combination with approved and experimental drugs active against human cytomegalovirus.

We have recently shown that the artemisinin derivative artemisone, which was screened against malaria in human clinical studies, is a potent inhibitor of human cytomegalovirus (HCMV). Here we evaluated the antiviral effect of artemisone when employed in 2-drug combinations with approved and experimental anti-HCMV agents. Using the Chou-Talalay method, we found that in-vitro combination of artemisone with cidofovir, brincidofovir, or with the HCMV UL97 inhibitor maribavir resulted in antiviral synergism and the combination of artemisone with ganciclovir or with the viral terminase inhibitors letermovir and BDCRB resulted in moderate synergism. Importantly, the combination of artemisone with maribavir demonstrated synergistic antiviral activity ex-vivo, in a clinically-relevant multicellular model of human placental tissues maintained in organ culture. Our findings provide the basis for the use of artemisone in synergistically acting drug combinations, to enhance viral control and reduce antiviral drug toxicities.

Is outpatient hysteroscopy accurate for the diagnosis of endometrial pathology among perimenopausal and postmenopausal women?

OBJECTIVE: To assess the histological and visual accuracy of outpatient hysteroscopy. METHODS: This was a retrospective analysis of all women referred to a tertiary center outpatient hysteroscopy clinic between March 2011 and October 2016 for the following indications: postmenopausal bleeding, suspected polyp, and/or thick endometrium. Histological accuracy was evaluated by comparing specimens obtained in hysteroscopy with those obtained by hysterectomy, and visual accuracy was evaluated by comparing visual findings with those obtained by biopsies. Sensitivity, specificity, positive predictive value, negative predictive value, and likelihood ratio were calculated to assess visual accuracy. RESULTS: The mean age of participants was 54.14 (interquartile range 43.0-64.0). A total of 408 pathological specimens were obtained from outpatient hysteroscopies during the 712 visits recorded in the clinic log. Histological accuracy was evaluated in 15 participants who eventually underwent hysterectomy. Total percent of agreement between hysteroscopy biopsies and final pathology obtained by hysterectomy was 73% (kappa = 0.47). Overall visual accuracy was calculated with a 93.1% sensitivity, 52.1% specificity, 90.4% positive predictive value, and 61.0% negative predictive value. Visual accuracy for benign pathology was generally higher compared with that for pre and malignant lesions. Visual accuracy was satisfactory for the diagnosis of endometrial carcinoma with sensitivity and specificity of 71.4% and 98.9%, respectively, but poor for diagnosing hyperplasia with sensitivity and specificity of 25.0% and 96.6%, respectively. CONCLUSIONS: Outpatient hysteroscopy is an adequate and reliable tool for the evaluation of benign pathology in the uterine cavity. Visual findings may not suffice, and directed biopsies may be required to improve diagnostic accuracy.

Mother knows best? Comparing primiparous parturients' expectations and predictions with actual birth outcomes.

OBJECTIVE: The literature provides no clear evidence linking maternal optimism/pessimism to birth outcomes. Our objective was to determine whether maternal expectations and predictions regarding mode of delivery and epidural anesthesia aligned with birth outcomes. METHODS: Primiparous, low-risk pregnant women at term filled in questionnaires in which they rated their chances of a vaginal delivery (VD) or a cesarean section (CS), and their intention to receive epidural anesthesia. Their responses were compared to actual outcomes. RESULTS: Pre-birth perceptions of odds of delivery by a CS were significantly higher (P=0.04) among women who eventually had a vacuum extraction (VE) or CS as a result of an arrest disorder, compared with women who had a VD and those who had a CS or a VE due to non-reassuring fetal heart monitor. Intention to receive epidural anesthesia was significantly lower (P<0.001) among women who gave birth without it. CONCLUSION: The pessimistic pre-birth perceptions of women of high odds for a CS may be related to an increased risk of arrest disorders of labor. However, the prenatal assessments of primiparous women are poor predictors of their demand for epidural anesthesia during labor. Larger-scale studies to determine whether pre-partum psychological interventions may contribute to the process of labor and improve obstetric outcomes are warranted.

Estrogen-dependent variations in 18F-fluorodeoxyglucose uptake in uterine leiomyomas.

OBJECTIVE: Positron emission tomography/computed tomography (PET/CT) is an important tool in oncology for assessment of disease extent and recurrence. Recognition of benign fluorodeoxyglucose (FDG) uptake promotes correct interpretation of imaging data. This study assesses the appearance of benign uterine leiomyomas (ULs) on PET/CT and evaluates possible hormonal influences. PATIENTS AND METHODS: This was a retrospective study performed in a tertiary referral cancer center in Israel. One hundred fifty-two women with nongynecologic malignancies were referred for PET/CT scans, with incidental UL on imaging. Information on menopausal status and menstrual phase and on the use of oral contraceptives, hormone replacement therapy, and selective estrogen receptor modulators (SERM) was collected. Fluorodeoxyglucose uptake measured as standard uptake value (SUV) was obtained for UL, normal myometrium, and gluteus muscle. Changes associated with menopausal status, menstrual cycle phase, and the use of oral contraceptives, hormone replacement therapy, and SERM were assessed. RESULTS: The mean ± SD SUV in UL for the entire cohort was 1.39 ± 0.65 and was higher than in myometrium (1.24 ± 0.33) and gluteus muscle (0.48 ± 0.36). Fluorodeoxyglucose uptake was similar in UL and in myometrium during the preovulatory (1.42 ± 0.31 vs. 1.23 ± 0.34) and postovulatory (1.23 ± 0.34 vs. 1.38 ± 0. 4) periods. During ovulation, SUV was significantly higher in UL (1.62 ± 0.39) than in normal myometrium (1.12 ± 0.15; P = 0.01). Uterine leiomyoma FDG uptake in premenopausal women (1.47 ± 0.32) was higher than in postmenopausal women (1.29 ± 0.41; P < 0.02). The UL/gluteus SUV ratio in patients on hormone replacement therapy (2.53 ± 0.23) was significantly higher than in untreated patients (1.27 ± 0.92; P = 0.05). Lower uptake was recorded in patients on SERM (SUV, 1.1 ± 0.24) than in untreated patients (SUV, 1.41 ± 0.36; P < 0.01). CONCLUSION: Fluorine 18 FDG uptake in UL may be estrogen dependent. Endogenous estrogen and hormone replacement therapy increase FDG uptake, whereas withdrawal of estrogen by menopause or SERM decreases uptake.

[Upper extremity deep vein thrombosis following ovarian stimulation].

Upper extremity deep venous thrombosis (UEDVT) is uncommon as a spontaneous event in the general population and is associated with well-defined risk factors. Thromboembotic events are serious, but fortunately rare, complications following ovarian stimulation for IVF. A review of the Literature indicates that thromboembolic events after ovarian stimulation are usually associated with ovarian hyperstimulation syndrome (OHSS). The incidence of UEDVT is higher in women undergoing assisted reproductive technology (ART) compared to the general population. The incidence of this condition is estimated to be 0.08%-0.11% of treatment cycles. While lower extremity DVT may be considered a natural consequence of OHSS, given the diminished venous return secondary to enlarged ovaries and ascites, it is unclear why there appears to be a predilection for thrombi in the upper extremities in women undergoing ART. Early diagnosis and treatment is crucial for both maternal and fetal well-being. Since infertility treatment is becoming commonplace in today's society, women undergoing treatment and their clinicians should be better informed of the presentation and clinical course of UEDVT to enable early diagnosis and start treatment. Consideration must be given to screening patients at risk for OHSS for thrombophilias, as well as administrating prophylactic anticoagulation therapy to patients who develop OHSS.

Comparison of adnexal torsion between pregnant and nonpregnant women.

OBJECTIVE: The purpose of this study was to compare clinical manifestations, treatment, and pregnancy outcome of adnexal torsion in pregnant and nonpregnant women. STUDY DESIGN: We conducted a retrospective case-control study in the Departments of Gynecology at 2 tertiary centers between 1999-2008. Forty-one pregnant and 77 nonpregnant women with surgically proved adnexal torsion were assessed. RESULTS: Recurrence rate of torsion was 19.5% in pregnant women and 9.1% in control subjects; 73% of pregnant women conceived through assisted reproductive technologies. Doppler blood flow was falsely normal in 61% of pregnant women and in 45% of nonpregnant women; 83.3% of pregnant women delivered at term. Laparoscopic detorsion was the main surgical procedure. CONCLUSION: Presentation of adnexal torsion is similar in pregnant and nonpregnant women. Past assisted reproductive technology is an important risk factor in pregnancy. Doppler blood flow has a high false-negative rate and should not outweigh clinical suspicion. Although pregnancy outcome is favorable, the high rate of recurrence raises the issue of surgical fixation at the first episode.

Detection of measles virus by reverse-transcriptase polymerase chain reaction in a placenta.

INTRODUCTION: Measles virus (MV) during pregnancy is associated with maternal morbidity and mortality and can put the fetus and newborn at risk of a wide range of complications. Reverse-transcriptase polymerase chain reaction (RT-PCR) for detecting MV in the placenta has not been reported. CASE: A case of RT-PCR detection of MV in the placenta of a 38-year-old woman who presented with premature rupture of membranes at 16 weeks' gestation is presented.

Emergency laparoscopy for suspected ovarian torsion: are we too hasty to operate?

OBJECTIVE: To reevaluate the rate of correct diagnosis of ovarian torsion (OT) in our department. DESIGN: Retrospective computerized chart review. SETTING: Tertiary referral center. PATIENT(S): Seventy-eight women who underwent laparoscopy for suspected OT. INTERVENTION(S): Laparoscopy. MAIN OUTCOME MEASURE(S): Rate of true diagnosis of torsion, correlation with Doppler studies. RESULT(S): The preoperative diagnosis of OT was confirmed in only 36 (46.1%) of the patients. Immediate operation (<10 hours) after admission (n = 48) was associated with a statistically significantly higher likelihood of operatively confirming OT (56.2% vs. 28.6%). We found that the lack of ovarian blood flow on Doppler sonography was a good predictor of OT; women with pathologic flow were statistically significantly more likely to have OT (77% vs. 29%). The sensitivity and specificity of abnormal ovarian flow for OT were 43.8% and 91.7%, respectively, with a positive and negative predictive value of 78% and 71%, respectively. CONCLUSION(S): Despite 20 years of research, the accuracy of the preoperative diagnosis of OT remains low. The urge to operate can be attributed to the importance of preserving ovarian function in young women as well as to the availability and the low associated complication rate of laparoscopy.

Association of statin therapy and the risk of atrial fibrillation in patients with a permanent pacemaker.

BACKGROUND: Recent studies have shown conflicting results regarding a protective effect of statin therapy on atrial fibrillation (AF). HYPOTHESIS: We sought to determine whether statins are effective in reducing the risk of developing arrhythmia in a cohort of 264 patients (49% women, mean age [+/-standard deviation] 71 [+/-12] years) with permanent pacemakers who are at high risk for AF. METHODS: All patients who underwent implantation of a permanent pacemaker over a 3-year period were eligible for inclusion in the study. We excluded patients with AF at implantation, incomplete medication information, or less than a yearly follow-up visit. Atrial fibrillation was diagnosed by ECG documentation, pacemaker interrogation, and Holter monitoring. Statin treatment was verified through a central pharmacy-computerized database (for most patients) or by chart review. Of the 264 patients, 36% had coronary artery disease. RESULTS: Atrial fibrillation developed in 70 patients (26%) at a median of 359 days post pacemaker implantation. The incidence rate for the first occurrence of AF post pacemaker implantation among patients treated and not treated with statins was 10.5 versus 9.8 events per 100 patient-years, respectively (p = 0.81). Even after controlling for baseline differences, the hazard ratio (HR) for developing AF among statin users did not achieve statistical significance (HR = 0.59 [0.31-1.12]). CONCLUSIONS: We could not demonstrate that statin therapy had a protective effect against the risk of AF in patients implanted with a permanent pacemaker. The low prevalence of coronary artery disease in our patients may partly explain our results.