Hysteroscopic resection vs ultrasound-guided dilation and evacuation for treatment of cesarean scar ectopic pregnancy: a randomized clinical trial.

BACKGROUND: Cesarean scar ectopic pregnancy is a type of ectopic pregnancy in which the fertilized egg is implanted in the muscle or fibrous tissue of the scar after a previous cesarean delivery. The condition can be catastrophic if not managed on time and can lead to significant morbidity and mortality. Several approaches have been studied for the management of cesarean scar ectopic pregnancy in women who opted for termination of pregnancy with no consensus on the best treatment modality reached so far. OBJECTIVE: This study aimed to compare the success rate of hysteroscopic resection vs ultrasound-guided dilation and evacuation for the treatment of cesarean scar ectopic pregnancy. STUDY DESIGN: This was a parallel group, nonblinded, randomized clinical trial conducted at a single center in Italy. Women with singleton gestations at <8 weeks and 6 days of gestation were included in the study. Inclusion criteria were women with a cesarean scar ectopic pregnancy with positive embryonic heart activity who opted for termination of pregnancy. Patients were randomized 1:1 to receive either hysteroscopic resection (ie, intervention group) or ultrasound-guided dilation and evacuation (ie, control group). Both groups received 50 mg/m2 of methotrexate intramuscularly at the time of randomization (day 1) and another dose at day 3. A third dose of methotrexate was planned in case of persistence of positive fetal heart activity at day 5. Participants received either ultrasound-guided dilation and evacuation or hysteroscopic resection from 1 to 5 days after the last dose of methotrexate. Hysteroscopic resection was performed under spinal anesthesia using a 15 Fr bipolar mini-resectoscope. Dilation and evacuation were performed by vacuum aspiration with a Karman cannula, followed by sharp curettage, if necessary, under ultrasound guidance. The primary outcome was the success rate of the treatment protocol, defined as no further treatment required until the complete resolution of the cesarean scar ectopic pregnancy. Resolution of the cesarean scar ectopic pregnancy was evaluated based on decline of beta-hCG and the absence of residual gestational material in the endometrial cavity. Treatment failure was defined as the necessity for further treatment required until the complete resolution of the cesarean scar ectopic pregnancy. A sample size calculation indicated that 54 participants were required to test the hypothesis RESULTS: A total of 54 women were enrolled and randomized. Number of previous cesarean deliveries ranged from 1 to 3. Overall, 10 women received a third dose of methotrexate with 7 of 27 (25.9%) participants in the hysteroscopic resection group and 3 of 27 (11.1%) in the dilation and evacuation group. The success rate was 100% (27/27) in the hysteroscopic resection group and 81.5% (22/27) in the dilation and evacuation group (relative risk, 1.22; 95% confidence interval, 1.01-1.48). Additional procedures were required in 5 cases of the control group, namely 3 hysterectomies, 1 laparotomic uterine segmental resection, and 1 hysteroscopic resection. The length of stay in the hospital was 9.0±2.9 days in the intervention group and 10.0±3.5 days in the control group (mean difference, -1.00 days; 95% confidence interval, -2.71 to 0.71). No cases of admission to intensive care unit or maternal death were reported. CONCLUSION: Hysteroscopic resection was associated with an increased success rate in the treatment of cesarean scar ectopic pregnancy when compared with ultrasound-guided dilation and evacuation.

Chromosomal Microarray Analysis versus Karyotyping in Fetuses with Increased Nuchal Translucency.

We have carried out a retrospective study of chromosome anomalies associated with increased nuchal translucency (NT) in order to compare yield rates of karyotype, chromosome microarray analysis (CMA), and non-invasive prenatal testing (NIPT) in this condition. Presenting with increased NT or cystic hygroma ≥3.5 mm as an isolated sign, 249 fetuses underwent karyotype and/or CMA from 11 to 18 gestational weeks. Karyotype and fluorescence in situ hybridization (FISH) analyses detected 103 chromosomal anomalies including 95 aneuploidies and eight chromosomal rearrangements or derivatives. Further, seven pathogenic copy number variants (CNV), five likely pathogenic CNVs, and 15 variants of unknown significance (VOUS) were detected by CMA in fetuses with normal karyotype. Genetic testing is now facing new challenges due to results with uncertain clinical impacts. Additional investigations will be necessary to interpret these findings. More than 15% of the anomalies that we have diagnosed with invasive techniques could not be detected by NIPT. It is therefore definitely not recommended in the case of ultrasound anomalies. These results, while corroborating the use of CMA in fetuses with increased NT as a second tier after rapid aneuploidy testing, do not suggest a dismissal of karyotype analysis.

Incidence of uterine rupture in second-trimester abortion with gemeprost alone compared to mifepristone and gemeprost.

OBJECTIVES: To compare uterine rupture rates in women having a medical abortion receiving gemeprost alone to those receiving mifepristone plus gemeprost. STUDY DESIGN: We reviewed the records of women undergoing medical abortion at 13 0/7-23 6/7 weeks from January 2007 to December 2014 at a single center in Italy. Prior to January 2011, we used gemeprost 1 mg vaginally every 3 h up to a maximum of five doses. After January 2011, we added mifepristone 200 mg orally 24 h prior to the same gemeprost protocol. The primary outcome of the study was the incidence of uterine rupture. We compared the outcome between women receiving gemeprost alone with the combination of gemeprost and mifepristone. RESULTS: One thousand and sixty-one (58.5%) and 753 (41.5%) women underwent medical abortion in the gemeprost-alone and the gemeprost/mifepristone groups, respectively. Five (0.47%) uterine ruptures occurred in the gemeprost and four uterine ruptures occurred in the gemeprost/mifepristone groups, respectively (0.53%) (p=.89). All uterine ruptures occurred in women with prior cesarean delivery. CONCLUSIONS: We rep orted no difference in the incidence of uterine rupture between the gemeprost-alone and gemeprost and mifepristone groups. IMPLICATIONS: Uterine rupture is a rare complication of second-trimester medical abortion with gemeprost. Use of mifepristone prior to gemeprost does not affect this risk.

Validation of a method for noninvasive prenatal testing for fetal aneuploidies risk and considerations for its introduction in the Public Health System.

OBJECTIVE: The aim of this study was to validate noninvasive prenatal testing (NIPT) for fetal aneuploidies by whole-genome massively parallel sequencing (MPS). METHODS: MPS was performed on cell-free DNA (cfDNA) isolated from maternal plasma in two groups: a first set of 186 euploid samples and a second set of 195 samples enriched of aneuploid cases (n = 69); digital PCR for fetal fraction (FF) assessment was performed on 178/381 samples. Cases with <10 × 106 reads (n = 54) were excluded for downstream data analysis. Follow-up data (invasive testing results or neonatal information) were available for all samples. Performances in terms of specificity/sensitivity and Z-score distributions were evaluated. RESULTS: All positive samples for trisomy 21 (T21) (n = 43), trisomy 18 (T18) (n = 6) and trisomy 13 (T13) (n = 7) were correctly identified (sensitivity: 99.9%); 5 false positive results were reported: 3 for T21 (specificity = 98.9%) and 2 for T13 (specificity = 99.4%). Besides FF, total cfDNA concentration seems another important parameter for MPS, since it influences the number of reads. CONCLUSIONS: The overall test accuracy allowed us introducing NIPT for T21, T18 and T13 as a clinical service for pregnant women after 10 + 4 weeks of gestation. Sex chromosome aneuploidy assessment needs further validation due to the limited number of aneuploid cases in this study.

"In patient" medical abortion versus surgical abortion: patient's satisfaction.

OBJECTIVE: To compare patients' satisfaction with medical and surgical abortion, implementing the Italian guidelines on medical abortion entailing an "in patient" procedure. METHODS: A total of 1832 pregnant chose between surgical (vacuum aspiration) or medical abortion (mifepristone p.o. followed after 3 days by sublingual misoprostol) and expressed their expected satisfaction on a visual analog scale (VAS). A total of 885 women chose surgical and 947 medical abortion. The primary end-point was satisfaction VAS score 20 days after the procedure. Secondary end-points were: difference between pre- and post-abortion VAS score; difference in satisfaction VAS scores according to parity and previous abortion; incidence of side effects. RESULTS: VAS score was high in each group but significantly higher for the 1-day surgical than for the 3-day medical abortion procedure (7.9 ± 1.0 versus 7.2 ± 1.2; p < 0.0001). In the surgical group the VAS score increased after the treatment (6.9 ± 1.6 versus 7.9 ± 1.0, p < 0.0001), while it decreased in the medical group (7.5 ± 1.0 versus 7.2 ± 1.2; p < 0.0001). Multiparous women reported higher satisfaction with medical abortion; women with a previous abortion preferred surgical abortion. CONCLUSIONS: Both procedures are considered satisfactory by the patients. Performing medical abortion as a 3-day "in patient" procedure, decreased women's satisfaction scores from their baseline expectations.

Effects of a prolonged, 72 hours, interval between mifepristone and gemeprost in second trimester termination of pregnancy: a retrospective analysis.

OBJECTIVE: To evaluate if the 72 hours interval between mifepristone and gemeprost has a similar efficacy compared to the 48 hours interval for second trimester termination of pregnancy STUDY DESIGN: Two-hundred and fifteen consecutive pregnant women, admitted to our hospital, for second trimester TOP, were included in this retrospective analysis. Standard protocol was followed for all patients. On the first day of the procedure oral mifepristone 200 mg was administered. After 72 (group A, n = 78) or 48 hours (group B, n = 113) women were admitted for administration of gemeprost 1 mg pessary as per protocol. The induction to abortion time was defined as the interval between the insertion of the first gemeprost pessary and the expulsion of the fetus. RESULTS: There are no significant differences in the number of pessaries in the two groups. The induction to abortion interval was longer in group A than in group B. Twenty-one women required surgical evacuation of the uterus for retained placenta or incomplete abortion without difference between groups. CONCLUSION: A 48-hours interval between mifepristone and gemeprost leads to better results than a 72-hours interval, with a shorter abortion length and represents the elective method for second trimester TOP.

Congenital anomalies of upper extremities: prenatal ultrasound diagnosis, significance, and outcome.

OBJECTIVE: We sought to assess the role of ultrasound in the prenatal characterization of fetal malformations of the upper extremities (MUE). STUDY DESIGN: Ultrasound findings, associated anomalies, pregnancy, and fetoneonatal outcome were analyzed in 100 fetuses with MUE, categorized after Swanson classification of hand congenital abnormalities. Follow-up information was available in all. RESULTS: Twelve cases had an isolated defect, while 88 showed associated abnormalities involving other organ systems. Fetuses with multiple malformations showed a 76% syndromic risk (32% chromosomal, 41% nonchromosomal), with unfavorable outcome in almost all cases (only 4 survivors, 2 with neurodevelopmental delay). In 27% of syndromic fetuses, the sonographic evidence of the MUE represented the key finding leading to the final diagnosis. The prognosis was usually favorable in cases of isolated defects. CONCLUSION: A thorough prenatal ultrasound characterization of fetal MUE can assist in the differential diagnosis of many syndromic conditions. When isolated, MUE tend to have a good outcome.

Cardiac troponin T and amino-terminal pro-natriuretic peptide concentrations in fetuses in the second trimester and in healthy neonates.

We measured the concentrations of cardiac troponin T (cTnT) and amino-terminal pro-natriuretic peptide (NT-proBNP) in umbilical cord blood during the second trimester (20-25 weeks of gestation) and at delivery in 109 uncomplicated pregnancies to define reference values. Using the 97.5th percentile, the upper reference limits for cTnT and NT-proBNP were 0.308 ng/mL and 5402 pg/mL in fetuses in the second trimester, and 0.038 ng/mL and 1690 pg/mL in healthy neonates, respectively. We also evaluated whether labor and delivery mode affected the concentrations of the two analytes. We found significantly higher (p<0.001) umbilical blood NT-proBNP and cTnT levels at 20-25 weeks of gestation than at term. In addition, within the term group, NT-proBNP concentrations were significantly higher in women delivering by elective cesarean section than in women delivering spontaneously (p<0.001), and higher than in women delivering by cesarean section during active labor. This indicates that the decrease in NT-proBNP levels is probably due to labor rather than delivery mode. Finally, we confirmed the at-birth reference values previously established for cTnT and NT-proBNP.

Diagnosis and outcome of congenital heart disease in fetuses from multiple pregnancies.

OBJECTIVES: (1) To assess the diagnostic accuracy of fetal echocardiography and (2) to evaluate the type and the outcome of congenital heart disease (CHD) detected in fetuses from multiple pregnancies. SETTING: tertiary referral center for prenatal diagnosis of CHD. DESIGN: observational study. In the period 1994-2003, 711 fetuses from 330 multiple pregnancies (282 twins, 45 triplets and 3 quadruplets) underwent fetal echocardiography at our unit. CHD were present in 45 of them. Diagnostic accuracy (sensitivity, specificity, positive and negative predictive values) was calculated for fetal echocardiography. For the fetuses with CHD, the following variables were analysed: gestational age at diagnosis, type of CHD, associated anomalies, fetoneonatal outcome. Confirmation of the diagnosis was obtained in 45/48 cases with CHD and in 580/610 without CHD. Mean follow-up time for diseased neonates was 52 months (range 6-127). RESULTS: In the study population, there were 40 true positives, 5 false negatives, 1 false positive and 632 true negatives, which yields the following figures: sensitivity 88.8% (40/45), specificity 99.8% (632/633), positive predictive value 97.6% (40/41) and negative predictive value 99.2% (632/637). As for the 45 cases with CHD, type of CHD was evenly distributed among left and right heart, conotruncal and septal defects, with 6/7 right heart lesions occurring in recipient fetuses of pregnancies complicated by TTTS. The aneuploidy rate was 7.0% (3/43). As for the outcome, 26 (57.8%) neonates survived and 17 (37.7%) died prior to or after surgery. Very low birthweight accounted for 7 of the 17 perinatal deaths. CONCLUSIONS: Our data show that the diagnostic performance of fetal echocardiography in multiple gestations is comparable with that obtained in singletons, as far as twin pregnancies are concerned. Data on triplets and quadruplets are too scant to be of statistical relevance. In addition, the importance of prematurity as primary cause of death in this subset of fetuses should be considered when counseling couples with multiple pregnancies and a fetus with CHD.