Background Neoadjuvant therapy is increasingly used in the first-line setting in people with advanced endometrial cancer despite a paucity of evidence for this approach. Objective To systematically evaluate the literature in this area. Search Strategy Electronic searches of Ovid MEDLINE, Ovid Embase, Clinical trials.gov and the International clinical trials registry platform were performed for studies published between 1990 and 2021 comparing neoadjuvant therapy with upfront debulking surgery in Stage 3 or 4 endometrial cancers. Selection Criteria Studies reporting overall survival, progression free survival, adverse events and/or quality of life in those undergoing neoadjuvant therapy or upfront debulking. Data Collection and Analysis Odds ratios (OR) and log hazard ratios (HR) along with 95% confidence intervals (CI) were calculated and pooled for analysis. Risk of bias was assessed using the ROBINS-I tool. Main Results Eight non-randomised studies with a total of 50,510 patients were identified. These showed that patients undergoing primary chemotherapy had similar survival outcomes to those undergoing primary surgery (HR 1.26 (95% CI 0.95-1.69)). Fewer patients in the neoadjuvant group had surgery but those that did were less likely to be suboptimally cytoreduced (OR 0.24; 95% CI 0.21-0.28). Surgical morbidity was no different between the two approaches (OR 0.51, 95% confidence interval 0.08-3.25). However, the potential for bias in these studies is very high. Conclusion There is significant uncertainty as to whether the outcomes for those undergoing primary cytoreductive surgery or neoadjuvant chemotherapy in the presence of unresectable disease are better. Prospective reporting of outcomes is needed.
Intrapartum stillbirths and early neonatal deaths remain stubbornly high in low income countries. Fetal monitoring in labour can reduce these poor outcomes, but limited progress is being achieved in these settings. Intermittent auscultation and continuous electronic fetal monitoring (CEFM) can both be employed to monitor a fetus during labour. There are challenges and limitations with both modalities. We used AI augmented fetal monitoring in a hospital in Malawi and demonstrated substantial reductions in both intrapartum stillbirths and early neonatal deaths with a small increase in the cesarean delivery rate. AI-CEFM should be studied further to achieve better perinatal outcomes.
Objective To externally validate the “2021 AAGL Endometriosis Classification” staging system. Design Retrospective, diagnostic accuracy study Setting Multicentre Population or Sample Two hundred and seventy-two endometriosis patients (January 2016 - October 2021) Methods Three independent observers analysed coded surgical data to assign an AAGL surgical stage (1 to 4) as the index test, and surgical complexity level (A to D) as the reference standard. Main Outcome Measures The diagnostic accuracy of each AAGL stage to predict corresponding AAGL surgical complexity level was determined. Receiver operating characteristic curves used to determine the accuracy of cut off points used in the AAGL staging system to discriminate between surgical complexity levels. Results 272 cases were analysed. Diagnostic accuracy (sensitivity, specificity, PPV and NPV) for three observers were: stage 1 to predict level A 97.9-98.7%, 60.2-64.2%, 75.0-76.9%, and 96.3-97.5%; stage 2 to predict level B 26.1-30.4%, 93.2-95.6%, 26.3-35.3%, and 92.9-93.6%; stage 3 to predict level C 7.5-10.0%, 93.8-94.8%, 33.3-42.1%, and 70.9-71.5%; stage 4 to predict level D 90.-95.0%, 90.1-91.7% &, 41.9-47.5%, and 99.1-99.6%. For three observers AUROC for A vs B/C/D (cut-point 9) 0.75-0.88, A/B vs C/D (cut-point 16) 0.81 and A/B/C vs D (cut-point 22) 0.95-0.96. Conclusions This external validation study demonstrates that the AAGL Endometriosis Classification performs poorly overall for the prediction of surgical complexity. The results from this external validation study suggest that the system in its current form is not generalizable to all endometriosis patients and should be reviewed before its universal implementation. Funding Nil Keywords Endometriosis, staging, laparoscopy
Objective To investigate the clinical outcomes and toxicity in patients with locally advanced cervical cancer treated with supplementary applicator guided-intensity modulated radiation therapy (IMRT) based on conventional intracavitary brachytherapy (IC/IMRT). Population Large high risk clinical target volume (HR-CTV) volume (>40cc) at the time of brachytherapy cervical cancer patients were recruited. Methods This study is a retrospective analysis of 76 patients with locally advanced cervical cancer (FIGO IIB-IVA) treated with concurrent chemo-radiotherapy followed by IC/IMRT between June 2010 and October 2016. External radiotherapy (45 Gy in 25 fractions) with cisplatin chemotherapy treated before IC/IMRT. The prescription dose for HR-CTV and IR-CTV were 6 Gy and 5 Gy per fraction for 5 fractions respectively. Results: Mean HR-CTV was 65.8±23.6 cc at the time of brachytherapy. D90 for HR-CTV and IR-CTV were 88.7±3.6 Gy and 78.1±2.5 Gy. D2cc for bladder, rectum, sigmoid and small intestine were 71.8±3.8 Gy, 64.6±4.9 Gy, 63.9±5.3 Gy and 56.7±8.7 Gy respectively. Median follow-up was 85 months (47.9-124.2 months). Five-year local recurrence free survival rate, metastasis recurrence free survival rate, disease free survival rate and cancer special survival rate were 87.6%, 82.4%, 70.9% and 76.3%, respectively. The grade 1+2 gastrointestinal and urinary late toxicities were 15.8% and 21.1%, while grade 3 late toxicities were 3.9% and 5.2%, respectively. Neither acute nor late grade 4 gastrointestinal or urinary toxicities were seen. Conclusions: The combination of ICBT with an applicator-guided supplementary IMRT boost achieved an excellent local control and overall survival with low toxicity for bulky residual cervical tumor
Objective: Internal contraction monitoring during the course of labor may identify elevated intrauterine resting tone. Our objective was to assess the association between elevated resting tone during labor and neonatal morbidity. Design: Secondary analysis of a prospective cohort study. Setting and Population: Term singleton patients with ruptured membranes and an intrauterine pressure catheter in place: Tertiary care hospital, United States of America Methods. Intrauterine resting tone was calculated as the average baseline pressure between contractions. The study group had elevated intrauterine resting tone, defined as intrauterine resting tone ≥75th percentile. Main Outcome Measures: Composite neonatal morbidity: hypoxic ischemic encephalopathy, hypothermia treatment, intubation, seizures, umbilical arterial pH ≥ 7.1, oxygen requirement, or death. Results: Of the 8580 patient in the cohort, 2210 (25.8%) were included. The median intrauterine resting tone was 9.7 mmHg (IQR 7.3-12.3 mmHg). Elevated resting tone was associated with shorter median duration of the first stage of labor (10.0 hrs vs 11.0 hrs, p <0.01) and lower rates of labor induction (p < 0.01). Neonatal composite morbidity was higher among patients with elevated intrauterine resting tone (5.1% vs 2.9%, p=0.01). After adjusting for chorioamnionitis and amnioinfusion, elevated intrauterine resting tone was associated with increased risk of neonatal morbidity (aOR 1.70, 95% CI 1.06-2.74). Compared to normal tone, elevated intrauterine resting tone was associated with mild acidemia and elevated lactate (aOR 1.81, 95% CI 1.38-2.37 and aOR 1.45, 95% CI 1.17-1.80, respectively). Conclusion: Elevated intrauterine resting tone is associated with increased risk of neonatal composite morbidity. Funding: None
Objective: To test the feasibility of a randomized trial of home blood pressure monitoring paired with a remote lifestyle intervention vs. home blood pressure monitoring alone vs. control in individuals with a hypertensive disorder of pregnancy in the first year postpartum. Design: Single-blinded randomized clinical trial Setting: Two tertiary hospitals and a community organization Population: Overweight and obese individuals with a hypertensive disorder of pregnancy and without pre-pregnancy hypertension or diabetes. Methods: We assessed the feasibility of recruitment and retention of 150 participants to study completion at one-year postpartum with randomization 1:1:1 into each arm. Secondary aims were to test effects of the interventions on weight, blood pressure and self-efficacy. Results: Over 23 months, we enrolled 148 of 400 eligible, screened individuals (37%); 28% Black or Other race, and mean pre-pregnancy BMI of 33.4±6.7 kg/m2. In total, 129 (87%) participants completed the one-year postpartum study visit. Overall, 22% of participants developed stage 2 hypertension [≥140/90 mmHg or on anti-hypertensive medications] by one-year postpartum. Individuals in the lifestyle intervention arm had a greater, non-significant decrease in mean arterial pressure (MAP) compared to individuals in the HBPM alone and control arm [mean change in MAP (95%CI) -3.7(-6.5, -0.9), -0.5(-1.5, 2.6), -1.0(-4.1, 2.2) mmHg], respectively. There were no differences in weight or self-efficacy by study arms. Conclusion: In this pilot, randomized trial, we demonstrate feasibility of HBPM paired with a lifestyle intervention in the first year postpartum. We detected high rates of ongoing hypertension emphasizing the need for effective interventions in this population.
Objective: To evaluate the performance of INTERGROWTH-21st and World Health Organization (WHO) fetal growth charts to identify small-for-gestational-age (SGA) and fetal growth restriction (FGR) neonates as well as their specific risks for adverse neonatal outcomes. Design: Multicenter cross-sectional study. Setting: Ten maternity units across four Latin American countries, 2016-2018. Population: 67,968 singleton live births. Methods: According to each standard, the neonates were classified as SGA and FGR (birthweight <10th and <3rd centiles, respectively). Main Outcomes Measures: The relative risk (RR) and diagnostic performance for the occurrence of a low Apgar score and low ponderal index were calculated for each standard. Results: The WHO charts identified more neonates as SGA than IG-21st (13.9% vs. 7%, respectively). 6.9% babies were considered SGA only by the WHO chart. Compared to normally grown babies, neonates classified as FGRs by both standards had the highest RR for a low Apgar (RR: 5.57; 95% CI: 3.99–7.78), followed by those SGA by both curves (RR: 3.27; 95% CI: 2.52–4.24), while SGAs identified by WHO alone did not have an additional risk (RR: 0.87; 95% CI: 0.55–1.39). Furthermore, the diagnostic odds ratio for a low Apgar was higher when INTERGROWTH-21st was used than when SGA and FGR were defined by WHO charts. Conclusions: In a large population of singleton deliveries from Latin America, the WHO fetal growth charts seem to identify significantly more SGA neonates than the INTERGROWTH-21st charts, but the diagnostic performance of the latter for low Apgar score and low ponderal index is better.
Contraception use is something that most women utilize during childbearing years. In this regard, unintentional teen pregnancies are divided in half between contraception misuse and contraception nonuse. Barriers to adolescents’ use of more effective contraception methods such as intrauterine devices (IUDs) have been found in both the patients’ and providers’ experience and knowledge of the contraceptives. Two previous surveys showed that a minority of physicians believe implants and IUDs are appropriate in adolescents as most believe abstinence is the most effective. Providers play a critical role in preventing unintended teen pregnancies.
Objective To compare the effect of levonorgestrel-intrauterine system (LNG-IUS) with or without oral megestrol acetate (MA) versus MA alone on fertility preserving treatment in patients with atypical endometrial hyperplasia (AEH). Design Single-center phase II study with open-label, randomized and controlled trial conducted between July 2017 and June 2020. Setting Obstetrics & Gynecology Hospital of Fudan University, Shanghai, China Population A total of 180 patients (18-45 years) with primary AEH were randomly assigned (1:1:1) to MA group (N=60), LNG-IUS group (N=60), or MA+LNG-IUS group (N=60). Methods Patients received MA (160 mg orally daily), LNG-IUS, or MA+LNG-IUS (MA 160 mg orally daily plus LNG-IUS), respectively. Main outcomes and measures The primary endpoint was the complete response (CR) rate at 16 weeks of treatment. The secondary endpoints were the CR rate at 32 weeks of treatment, adverse events, recurrent rate, and pregnancy rate. Results LNG-IUS group yielded a higher 16-week CR rate than MA group (P=0.049; Odds ratio [OR], 2.44; 95% confidence interval [95%CI], 1.00-6.00). However, MA+LNG-IUS group did not yield better 16-week or 32-week CR rates than MA group (P=0.245; P=0.915) or LNG-IUS group (P=0.419; P=0.653). Meanwhile, less side-effects were found in LNG-IUS group compared with the other two groups. No significant difference was seen in recurrence rates and pregnancy rates among all three groups. Conclusions LNG-IUS might be considered as the first-line choice of fertility-sparing treatment in AEH patients with proper size of uterine cavity. LNG-IUS combined with MA might not provide better treatment effect than MA or LNG-IUS alone.
Objectives: To determine the impact of the diagnostic test method (clinical, diagnostic imaging, or diagnostic laparoscopy) of endometriosis on the individual’s sense of control over their disease and their perceived access to social supports. Design: Retrospective cohort study. Setting: International. Population: 1,634 people aged 18-55 who had received a diagnosis of endometriosis. Methods: This study reports on data collected by the validated Endometriosis Health Profile-30 (EHP-30) section of a larger survey conducted between May and July 2020. Participants were recruited by social media platforms. Scores on the dimensions of interest were analysed with diagnostic method as the variable of interest. Diagnostic method proportionality was also assessed as a secondary outcome by geographical region. Main Outcome Measures: Scores on the dimensions of control and powerlessness and social support on the EHP-30. Results: There was a difference between control and powerlessness scores for patients that received a diagnosis via imaging (ultrasound/magnetic resonance imaging) versus clinical diagnosis (P=0.049). However, this did not reach significance when co-variates were controlled for (P=0.054). No other comparisons between diagnostic method and EHP-30 scores demonstrated a difference. There was a statistically significant (P<0.0001) difference in the rate of utilization of the various diagnostic imaging techniques between geographical regions with diagnostic imaging being relatively uncommon and surgery being the most common method of diagnosis. Conclusions: The diagnostic method of endometriosis does not appear to have a clinically significant impact on an individual’s sense of control over their disease nor their access to social supports.
Objective. To compare the estimates of preterm birth (PTB; 22-36 weeks gestational age, GA) and stillbirth rates during COVID-19 pandemic in Italy with those recorded in the three previous years. Design. A population-based cohort study of liveborn and stillborn infants was conducted using data from Regional Health Systems and comparing the pandemic period (March 1st, 2020-March 31st, 2021, N= 362,129) to an historical period (January 2017- February 2020, N=1,117,172). The cohort covered 84.3% of the births in Italy. Methods. Logistic regressions were run in each Region and meta-analyses were performed centrally. We used an interrupted time series regression analysis to study the trend of preterm births from 2017 to 2021. Main Outcome Measures. The primary outcomes were PTB and stillbirths. Secondary outcomes were late PTB (32-36 weeks’ GA), very PTB (<32 weeks’ GA), and extreme PTB (<28 weeks’ GA), overall and stratified into singleton and multiples. Results. The pandemic period compared with the historical one was associated with a reduced risk for PTB (Odds Ratio: 0.90; 95% Confidence Interval, CI: 0.87, 0.93), late PTB (0.91; 0.87, 0.94), very PTB (0.87; 0.84, 0.91), and extreme PTB (0.88; 0.82, 0.94). In multiples, point estimates were not very different, but had wider CIs. No association was found for stillbirths (1.01; 0.90, 1.13). A linear decreasing trend in PTB rate was present in the historical period, with a further reduction after the lockdown. Conclusions We demonstrated a decrease in PTB rate after the introduction of COVID-19 restriction measures, without an increase in stillbirths.
Objective To assess triage of HPV-positive women by optical coherence tomography (OCT), with or without HPV16/18 genotyping, compare with cytology. Design A prospective cohort study. Setting The Second Xiangya Hospital in China. Population 813 participants with high-risk HPV(hrHPV)-positive and cervical cytology results received OCT before colposcopy between 1 March 2021 and 1 October 2021. Methods OCT examinations were performed on an outpatient basis. Cytological and histological results during follow-up were obtained from the Department of Pathology at the Second Xiangya Hospital. Main outcome measures OCT and cytology results were compared with the pathological results to calculate sensitivity, specificity, and immediate CIN3+ risk. The advantages and disadvantages of OCT and cytology triage of hr-HPV-positive women were compared. Results HPV16/18 genotyping with OCT triage has a specificity of CIN3+ lesions [61.1%; 95% CI, 57.6%-64.6%], CIN2+ [66.0%; 95% CI, 62.4%-69.6%]. HPV16/18 genotyping with cytology triage has a specificity of CIN3+[44.0%; 95% CI, 40.4%-47.6%], CIN2+ [47.0%; 95% CI, 43.2%-50.8%]. The OCT triage has a higher specificity and positive predictive value(PPV) compared to the cytology with a significant difference. The OCT triage has a similar immediate CIN3+ risk compared to the cytology. Conclusion The combination of OCT and HPV triage (both genotyping and non-genotyping) is feasible in terms of immediate CIN2+/CIN3+ risk, and the OCT triage strategy reduces the number of colposcopies and improves the specificity and positive predictive value of the test compared to the cytological triage strategy.
Exosomes are nano-sized vesicles derived from the endosomal system and involved in multitudinous biological and pathological processes. Emerging evidence has demonstrated that exosomes are closely related to the tumorigenesis and progression of ovarian cancer. Ovarian cancer-related exosomes have cell-specific constituents that could be leveraged for diagnosis. Additionally, exosomes are promising to treat ovarian cancer through functioning as delivery systems or participating in immunotherapy or serving as direct targets. In this review, we discussed the association of exosomes in ovarian cancer progression and look forward to the clinical significance of exosomes relevant to diagnosis and treatment.
Backgroud: The clinical efficacy and safety of cervical pessary versus cervical cerclage in preventing spontaneous preterm birth remain uncertain. Objectives: To systematically review the clinical efficacy of cervical pessary versus transvaginal cervical cerclage in preventing spontaneous preterm birth caused by cervical shortening. Search Strategy: The Cochrane Library, PubMed, EMbase, WanFang Data, CNKI, VIP Data and CBM Data were electronically searched. Selection Criteria: Randomized controlled trials (RCTs) and non-randomized controlled trials (non-RCTs, including cohort studies) comparing cervical pessary and transvaginal cervical cerclage in preventing spontaneous preterm birth from the inception of the database to August 2020. Main Results: A total of 9 studies (2 RCTs and 7 non-RCTs) were included, involving 1174 patients with a short cervix in the second trimester (cervical length <25mm), 693 in the cervical pessary group and 481 in the cervical cerclage group. The results of meta-analysis showed that the incidence of preterm premature rupture of the membranes (PPROM) in the cervical pessary group was significantly lower than that in the cervical cerclage group (RR=0.48, 95% CI: 0.35 to 0.67, P<0.00001), and the premature birth rate before 34 weeks in the cervical pessary group was also significantly lower than that in the cervical cerclage group (RR=0.68, 95%CI: 0.51 to 0.89, P<0.006). Conclusion: Compared with transvaginal cervical cerclage, use of a cervical pessary may decrease the risks of PPROM and premature birth before 34 weeks. Given its advantages of easy-to-use and minimal damage, cervical pessary may become a useful preventive intervention that deserves widespread clinical application.
Background Fatigue is a burden for a substantial proportion of women in the postpartum period. A wide array of patient-reported outcome measures (PROMs) are used for assessment, which makes comparison of data difficult. Objective To identify the best PROM for postpartum fatigue using Consensus Based Standards for the Selection of Health Measurement Instruments (COSMIN) guidelines. Search strategy We searched Web of Science, Embase, PubMed and CINAHL, with no date limiters, in July 2020 for validated PROMs used to assess fatigue in the postpartum period. Selection criteria Studies evaluating at least one author-defined domain of postpartum fatigue and one psychometric measurement property of a PROM. Data collection and analysis An overall rating was assigned based upon COSMIN criteria and the quality of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE). Main results We identified 49 validation studies using 18 PROMs in 21 209 women that evaluated postpartum fatigue. All three fatigue domains (Physical, Mental, Interference) were assessed by four PROMs: Fatigue Assessment Scale (FAS), Brief Fatigue Inventory (BFI), Checklist Individual Strength (CIS) and Fatigue Severity Scale (FSS). The FAS, which is freely available online, was the only PROM to demonstrate adequate content validity and at least a low level evidence of sufficient internal consistency, resulting in a Class A recommendation. Conclusion The FAS is the best available PROM to assess postpartum fatigue. However, it fails to assess important areas of postpartum recovery. Future studies should aim to develop a more specific PROM for postpartum fatigue.
Objective: To study the outcomes of new pregnancies after previous complete uterine rupture. Design: Descriptive study based on population data from the Medical Birth Registry of Norway, the Patient Administration System, and medical records. Sample: Maternities with previous complete uterine rupture in Norway during the period 1967–2011 (N=72), extracted from 2 455 797 maternities. Method: We measured the rate of new complete ruptures and partial ruptures, as well as the maternal and perinatal outcomes of these pregnancies. The characteristics of both previous ruptures and new ruptures were described. Results: Among 72 maternities, there were thirty-seven with previous ruptures in the lower segment (LS) and 35 outside the LS. We found three new complete ruptures and six uneventful partial ruptures, resulting in a rate of 4.2% and 8.3%, respectively. All three complete ruptures occurred preterm in scars outside the LS. The rate of new complete rupture was 0% in those with previous rupture in the LS, and 8.6% in previous ruptures outside the LS. The corrected perinatal mortality was 1.3%, and prematurity (<37 weeks) was high (36.1%); this was noticed even in the absence of new ruptures and was mostly iatrogenic. Two hysterectomies were performed in the absence of rupture and two cases had abnormal invasive placenta. Conclusion: The prognosis for pregnancies after previous complete uterine rupture is favorable. Prematurity is a problem caused by both obstetrician and mother anxiety, so the timing of delivery is most challenging. Careful counseling, vigilance for symptoms, and immediate delivery are most important.
Objective Describe changes over time regarding mode of birth and perinatal outcomes in women with one previous caesarean section in the Netherlands over the past 20 years. Design Population-based study. Setting Nationwide. Population All women with one previous caesarean section and no previous vaginal birth, who gave birth to a term singleton in cephalic presentation between 2000 and 2019 (n=143,308). Methods Analysis of Dutch perinatal registry data. Main outcome measures Primary: mode of birth per year, intended vaginal birth versus planned caesarean section. Secondary: failed versus successful vaginal birth in case of intended vaginal birth after caesarean (VBAC), and adverse perinatal outcome (perinatal mortality up to 28 days, low Apgar score at 5 minutes, asphyxia, and NICU admission >24 hours). Results A decrease of 21.5% was seen in women with one previous caesarean section intending VBAC in a subsequent pregnancy, from 77.2% in 2000 to 55.7% in 2019, with a marked acceleration from 2009 onwards. The VBAC success rate dropped gradually, from 71.0% to 65.3%. Overall caesarean section rate (planned and unplanned) increased from 45.1% to 63.6%. Adverse perinatal outcomes were higher in women intending VBAC compared to planned caesarean section. However, after an initial decrease, perinatal mortality remained stable from 2009 onwards with only a minimal difference between both modes of birth. Conclusions In the Netherlands, the proportion of women intending VBAC after a previous caesarean section has decreased markedly, particularly from 2009 onwards. This decrease was not accompanied by a synchronous decrease in perinatal mortality after that year.
Background: Cancers have become highly prevalent in developing countries and Africa is not far from it. The treatment of these cancers increases the risk of infertility in women. Objectives: This review aims to understand the effects of different types of cancer treatments on the fertility of women. Search strategy: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were wielded for this systematic review. We systematically searched PubMed, Google Scholar and Medline databases to identify eligible articles on the effects of cancer treatments on the fertility of women. Selection criteria: The articles published between the years 2000 and 2021 were included in the current review. The search was limited to studies in humans and published in English. Data collection and analysis: The selected studies were scrutinized, and relevant data were extracted from the selected articles using excel sheet. Main results: A total of 19 articles were encompassed in this cutting-edge systematic review that met the selection criteria. Overall fertility deficits were observed in female survivors of cancers. Treatment with alkylating agents, second-line therapy and age> 35 years also influence chances of pregnancy. Pre-term delivery was also found to be linked to cancer-related therapy. Conclusions: The present study indicates that future measures should be taken to include assessment of women’s desire for future fertility and also provide fertility preservation options. Counseling tools and guidelines for referral to oncofertility specialists should be developed for newly diagnosed young patients. Funding: None.