Prognostic factors for spontaneous resolution of an ectopic pregnancy.

OBJECTIVE: To identify factors that can accurately predict the spontaneous resolution of an ectopic pregnancy. STUDY DESIGN: This retrospective cohort analysis was conducted in the Department of Gynecology of a tertiary, university-affiliated medical center. Patients admitted to the center from January 2015 to July 2022 with a tubal ectopic pregnancy who met the criteria for expectant management were included. Beta-human chorionic gonadotropin (ß-hCG) levels were assessed at admission and at subsequent 24-hour intervals. Patients with declining levels were discharged for routine ambulatory ß-hCG follow-up until levels became undetectable. Patients who achieved a successful outcome were designated as the "spontaneous resolution group," while patients who underwent further hospitalization for methotrexate or surgery constituted the" failure group". Demographic, clinical, laboratory, and ultrasound parameters collected at first admission were compared between groups. RESULTS: Among the initial group of 210 eligible patients, 7 were lost to follow-up, 161 achieved spontaneous resolution, and 42 were readmitted for active intervention. Multivariate logistic regression analysis revealed that the last ß-hCG level before discharge (last ß-hCG) and the ratio between ß-hCG at discharge to ß-hCG at admission were the only independent parameters to predict outcomes. Patients with ß-hCG < 650 IU/L at discharge and a decline of 50% or more in ß-hCG level during hospitalization, had a 97% success rate with expectant management. Patients with ß-hCG discharge levels ≥ 1,000 IU/L had a 50% chance of success, regardless of whether their ß-hCG levels had declined. For all other patients, a 76% success rate was found. CONCLUSION: Short-term, serial ß-hCG follow-up at the initial presentation can help predict the spontaneous resolution of an ectopic pregnancy.

The impact of fragile X premutation carrier status on embryo morphokinetic development.

RESEARCH QUESTION: Does inheritance of the fragile X mental retardation 1 (FMR1) premutation allele affect embryo morphokinetic development? DESIGN: A retrospective cohort analysis of 529 embryos from 126 IVF cycles of 39 FMR1 premutation female carriers undergoing preimplantation genetic testing for monogenic/single gene defects (PGT-M). Morphological and morphokinetic parameters obtained using a time-lapse monitoring system were compared between embryos that inherited the FMR1 premutation allele (FMR1 group, n = 271) and those who received the normal allele (normal group, n = 258). The following embryo outcome measures were compared: morphokinetic parameters up to day 3, start of blastulation time (tSB) for day 5 embryos and the rate of top-quality embryos on days 3 and 5. RESULTS: No differences were found in morphokinetic parameters between the groups from the time of intracytoplasmic sperm injection (ICSI) until a biopsy on day 3. The blastulation rate in the two groups was comparable. However, the start of blastulation was delayed in FMR1 embryos compared to that in the genetically normal embryos (median tSB: 104.2 h [99.3-110.3] versus 101.6 h [94.5-106.7], P = 0.01). In addition, the rate of top-quality FMR1 embryos was lower than that of genetically normal embryos (25.6% versus 38.8%, P = 0.04). CONCLUSION: Embryos that inherit the FMR1 premutation allele are of lower quality at the blastocyst stage compared with those that do not inherit the mutated allele.

Effects of letrozole or tamoxifen coadministered with a standard stimulation protocol on fertility preservation among breast cancer patients.

PURPOSE: To assess the effects of letrozole or tamoxifen coadministration on fertility preservation treatment outcomes. METHODS: Retrospective cohort study of 118 breast cancer patients undergoing fertility preservation treatment between 2008 and 2018. Patients who received letrozole (n = 36) or tamoxifen (n = 30) were compared to controls (n = 52) who underwent standard ovarian stimulation protocols. The primary outcome measures included the number of retrieved oocytes, mature oocytes (MII), fertilization, and top-quality embryo rates. The secondary outcome measures included duration of stimulation, gonadotropin dose and peak estradiol level. RESULTS: The number of oocytes retrieved, MII oocytes, fertilization rate, duration of stimulation, or gonadotropin dose were similar in the letrozole and tamoxifen groups, compared to controls. Top-quality embryo rate was lower in the tamoxifen group compared to controls (25% vs 39.4%, respectively, P = 0.034). The abnormal fertilization rate was higher in the letrozole group compared to controls (7.8% vs 3.60%, respectively, P = 0.015). A stepwise logistic regression analysis revealed that letrozole and peak estradiol were significantly associated with abnormal fertilization (OR 11.94; 95% CI 2.35-60.4, P = 0.003 for letrozole and OR 1.075; 95% CI 1.024-1.12, P = 0.004 per 100 unit change in estradiol). CONCLUSIONS: There may be a negative effect of letrozole or tamoxifen on fertilization and embryo quality, in fertility preservation cycles. Further studies are needed to confirm these findings.

Diagnostic accuracy of random urinary protein-to-creatinine ratio for proteinuria in patients with suspected pre-eclampsia.

PURPOSE: To evaluate the correlation between urine protein/creatinine ratio (UPCR) and proteinuria in a 24-h urine collection and to calculate the predicative accuracy of different cutoffs of UPCR for the diagnosis of proteinuria. METHODS: A retrospective cohort study including women who admitted for the evaluation for suspected preeclampsia (PET) beyond 20 weeks of gestation in a single tertiary center. Both UPCR test and quantification of proteinuria using 24-h urine collection were obtained during their index hospitalization no more than 48 h apart. Women with pre-existing diabetes mellitus, known renal disease or proteinuria prior to pregnancy or chronic hypertension were excluded. Predictive accuracy of UPCR for several cutoffs of proteinuria was evaluated. Multivariate logistic regression analysis was used to assess diagnostic accuracy of UPCR in sub-populations according to obstetrical characteristics. RESULTS: Overall 463 patients were included. Of them 316 (68.3%) have 24-h urine protein collection of ≥ 300 mg/day. Mean gestational age at evaluation was 34.0 ± 3.4 weeks. Median (and interquartile range) time interval between UPCR and 24-h urine collection was 1.8 (1.6-1.9) days. Sensitivity and specificity of UPCR of 0.3 for predicting proteinuria ≥ 300 mg/day were 90.1% and 63.3%, respectively. The corresponding values for difference proteinuria cutoffs: ≥ 1000 mg/day and 5000 mg/day were 98.4, 100% and 29.1, 36.0%, respectively. The optimal UPCR thresholds for 24-h urine protein collection of ≥ 300 mg/day, ≥ 1000 mg/day and 5000 mg/day were 0.31, 0.70 and 2.49, respectively. The predictive accuracy of UPCR > 0.30 in predicting proteinuria was unaffected by demographic and obstetrical characteristics as maternal age, pre-pregnancy BMI, gestational age at examination, creatinine levels or by multiple gestation [adjusted OR 18.27 (95% CI 9.97-33.47)]. CONCLUSION: UPCR was strongly correlated with various cutoffs of proteinuria obtained by 24-h urine collection. UPCR cutoff varied depending on the specific measured outcome. This correlation was not affected by gestational age at examination.

The Contribution of an Infectious Workup in Understanding Stillbirth.

OBJECTIVE: This study was aimed to assess the utility of diagnostic tests of maternal and fetal infection in the evaluation of stillbirth. STUDY DESIGN: A single-center retrospective study from January 2011 to December 2016 of all women presenting to the hospital with intrauterine fetal death at or after 20 weeks of gestation. Standard evaluation included review of medical records, clinical and laboratory inflammatory workup, maternal serologies, fetal autopsy, placental pathology, and fetal and placental cultures. A suspected infectious etiology was defined as meeting at least two diagnostic criteria, and only after exclusion of any other identifiable stillbirth cause. RESULTS: During the 7-year study period, 228 cases of stillbirth were diagnosed at our center. An infectious etiology was the suspected cause of stillbirth in 35 cases (15.3%). The mean gestational age of infection-related stillbirth was 28 1/7 (range: 22-37) weeks, while for a noninfectious etiology, it was 34 0/7 (range: 25-38) weeks (p = 0.005). Placental histological findings diagnostic of overt chorioamnionitis and funisitis were observed in 31 (88.5%) cases. In 16 (45.7%) cases the placental and fetal cultures were positive for the same pathogen. Serology of acute infection was positive in three (8.5%) of the cases. CONCLUSION: Maternal and fetal infectious workup is valuable in the investigation of stillbirth, particularly before 30 weeks of gestation and should be considered a part of standard evaluation.

Maternal cardiovascular hemodynamics in normotensive versus preeclamptic pregnancies: a prospective longitudinal study using a noninvasive cardiac system (NICaS™).

BACKGROUND: Preeclampsia is among the most common medical complications of pregnancy. The clinical utility of invasive hemodynamic monitoring in preeclampsia (e.g., Swan-Ganz catheter) is controversial. Thoracic impedance cardiography (TIC) and Doppler echocardiography are noninvasive techniques but they both have important limitations. NICaS™ (NI Medical, PetachTikva, Israel) is a noninvasive cardiac system for determining cardiac output (CO) that utilizes regional impedance cardiography (RIC) by noninvasively measuring the impedance signal in the periphery. It outperformed any other impedance cardiographic technology and was twice as accurate as TIC. METHODS: We used the NICaS™ system to compare the hemodynamic parameters of women with severe preeclampsia (PET group, n = 17) to a cohort of healthy normotensive pregnant women with a singleton pregnancy at term (control group, n = 62) (1/2015-6/2015). Heart rate (HR), stroke volume (SV), CO, total peripheral resistance (TPR) and mean arterial pressure (MAP) were measured 15-30 min before CS initiation, immediately after administering spinal anesthesia, immediately after delivery of the fetus and placenta, at the abdominal fascia closure and within 24-36 and 48-72 h postpartum. RESULTS: The COs before and during the CS were significantly higher in the control group compared to the PET group (P < .05), but reached equivalent values within 24-36 h postpartum. CO peaked at delivery of the newborn and the placenta and started to decline afterwards in both groups. The MAP and TPR values were significantly higher in the PET group at all points of assessment except at 48-72 h postpartum when it was still significantly higher for MAP while the TPR only exhibited a higher trend but not statistically significant. The NICaS™ device noninvasively demonstrated low CO and high TPR profiles in the PET group compared to controls. CONCLUSIONS: The immediate postpartum period is accompanied by the most dramatic hemodynamic changes and fluid shifts, during which the parturient should be closely monitored. The NICaS™ device may help the clinician to customize the most optimal management for individual parturients. Our findings require validation by further studies on larger samples.

Maternal hemodynamics in late gestation and immediate postpartum in singletons vs. twin pregnancies.

PURPOSE: Differences in hemodynamic changes during a cesarean section (CS) between twin and singleton pregnancies are poorly defined. The Non-Invasive Cardiac System (NICaS) is an impedance device that measures cardiac output (CO) and its derivatives. We compared maternal cardiac parameters using NICaS™ in singleton and twins before and during delivery, as well at the early puerperium in healthy women undergoing CS at term. METHODS: This prospective longitudinal study included women with twin (n = 27) or singleton pregnancies (n = 62) whose hemodynamic parameters were assessed by NICaS before an elective CS, after spinal anesthesia, immediately after delivery, after fascia closure, and within 24-36 and 48-72 h postpartum. RESULTS: By 24-36 h postpartum, the mean arterial pressure and the total peripheral resistance equaled preoperative values in both groups. The CO increased throughout the CS and peaked immediately after delivery in the singleton group (P < 0.0001), after which it abruptly began to decline until reaching a nadir 24-36 h after delivery (P < 0.0001), while it remained steady throughout the CS and then dropped until 24-36 h after delivery in the twin group (P < 0.05). None of the studied parameters differed significantly between the groups for the 24-36 and 48-72 h postpartum measurements. CONCLUSIONS: Hemodynamic parameters immediately before, during and shortly after CS in singleton and twin pregnancies are equivalent. Further evaluations of the value of NICaS™ in assessing cardiovascular-related pregnancy complications are warranted.

Casting doubt on the value of assessing the cardiac index in pregnancy.

OBJECTIVES: The objective of this study is to assess the reliability of the cardiac index (CI) in healthy pregnant women at term by investigating the correlation between the cardiac output (CO) and the body surface area (BSA) using a novel non-invasive cardiography technique (NICaS™). METHODS: Sixty-one healthy, normotensive women with a singleton pregnancy at term (≥37 gestational weeks) participated in this prospective observational study between 1/2015 and 6/2015 L. Each woman was assessed for CO by the NICaS™, an impedance device that non-invasively measures the CO and its derivatives. The NICaS™ demonstrated a very good correlation with the gold standard Swan-Ganz catheter. BSA was determined by the Dubois nomogram. RESULTS: The mean ± standard deviation maternal age was 34.2 ± 5.3 years, mean height 166 ± 6 cm, and mean body mass index 23.9 ± 4.9 kg/m2. The mean gestational age was 38.8 ± 0.7 weeks. The correlation between the CO and the BSA was poor (Pearson r = 0.254, p < .005). CONCLUSIONS: The current study demonstrated poor correlation between the CO and the BSA in pregnant women, therefore, making the CI a non-reliable variable for assessing CO in pregnant women. We, therefore, suggest that the CO rather than the CI is the preferred parameter for hemodynamic measurements in this population.