Association of Intrauterine Device Malposition With Previous Cesarean Delivery and Related Uterine Anatomical Changes.

OBJECTIVES: We sought to determine the association between intrauterine device (IUD) malposition and previous cesarean delivery (CD) and related uterine anatomical changes. METHODS: A retrospective cohort of all persons with an IUD presenting for two- and three-dimensional pelvic ultrasonography over 2 years, for any gynecologic indication, was compiled. IUD malposition was defined as IUD partially or completely positioned outside the endometrial cavity. Uterine position, uterine flexion, and cesarean scar defect (CSD) size were assessed. Patient characteristics and sonographic findings were compared between those with normally positioned and malpositioned IUD. Primary outcome was the rate of IUD malposition in persons with and without a history of CD. Logistic regression analysis was used to control for potential confounders. RESULTS: Two hundred ninety-six persons with an IUD had a pelvic ultrasound, 240 (81.1%) had a normally positioned IUD, and 56 (18.9%) had a malpositioned IUD. The most common location of IUD malposition was low uterine segment and cervix (67.9%). Malpositioned IUD was associated with referral for evaluation of pelvic pain (P = .001). Prior CD was significantly associated with a malpositioned IUD, after adjusting for confounders (aOR 3.50, 95% CI 1.31-9.35, P = .01). Among persons with prior CD, uterine retroflexion and a large CSD were independent risk factors for IUD malposition (aOR 4.1, 95% CI 1.1-15.9, P = .04 and aOR 5.4, 95% CI 1.4-20.9, P = .01, respectively). CONCLUSIONS: Prior CD is associated with significantly increased risk of IUD malposition. Among persons with previous CD, those with a retroflexed uterus and a large CSD are more likely to have a malpositioned IUD.

Differences between proximal and distal endometrial monolayer thickness in women aged over 50 years undergoing saline infusion sonohysterography.

BACKGROUND: Saline infusion sonohysterography (SIS) is a procedure performed to evaluate the endometrium in women with postmenopausal bleeding. PURPOSE: To investigate differences in endometrial monolayer measurements in women aged >50 years undergoing SIS. MATERIAL AND METHODS: Retrospective study of women aged >50 undergoing SIS. Endometrial echo (EE) was measured according to the International Endometrial Tumor Analysis (IETA) guidelines. Monolayer thickness was compared between anterior and posterior uterine walls and between the monolayer that was proximal or distal to the ultrasound probe. Presence and location of focal thickening and polyps on each of the monolayers were assessed. RESULTS: SIS was performed in 608 patients. Of them, 485 (79.8%) had anteverted, 85 (14%) retroverted, and 38 (6.2%) a midposition uterus. The mean posterior monolayer was thicker than the anterior monolayer (2.14 mm vs. 1.88 mm; P = 0.002). The distal monolayer was thicker than the proximal layer in both anteverted and retroverted uteri (2.18 mm vs. 1.84 mm; P < 0.0001). In 16% of women, the difference between distal and proximal monolayers was ≥1 mm. Focal thickening was seen 3.3 times more frequently in the distal endometrium. Among women with a double layer EE >4 mm, 18.8% had a proximal layer of <2 mm while only 4.6% had a distal EE <2 mm. CONCLUSION: Distal endometrium measures thicker than the proximal endometrium in most SIS cases and in one out of six women, the difference is >1 mm. The distal layer is three times more likely to contain focal thickening. Sonologists should be conscious of possible enhancement artifact when measuring the EE during SIS.

Cell-free DNA screening for prenatal detection of 22q11.2 deletion syndrome.

BACKGROUND: Historically, prenatal screening has focused primarily on the detection of fetal aneuploidies. Cell-free DNA now enables noninvasive screening for subchromosomal copy number variants, including 22q11.2 deletion syndrome (or DiGeorge syndrome), which is the most common microdeletion and a leading cause of congenital heart defects and neurodevelopmental delay. Although smaller studies have demonstrated the feasibility of screening for 22q11.2 deletion syndrome, large cohort studies with confirmatory postnatal testing to assess test performance have not been reported. OBJECTIVE: This study aimed to assess the performance of single-nucleotide polymorphism-based, prenatal cell-free DNA screening for detection of 22q11.2 deletion syndrome. STUDY DESIGN: Patients who underwent single-nucleotide polymorphism-based prenatal cell-free DNA screening for 22q11.2 deletion syndrome were prospectively enrolled at 21 centers in 6 countries. Prenatal or newborn DNA samples were requested in all cases for genetic confirmation using chromosomal microarrays. The primary outcome was sensitivity, specificity, positive predictive value, and negative predictive value of cell-free DNA screening for the detection of all deletions, including the classical deletion and nested deletions that are ≥500 kb, in the 22q11.2 low-copy repeat A-D region. Secondary outcomes included the prevalence of 22q11.2 deletion syndrome and performance of an updated cell-free DNA algorithm that was evaluated with blinding to the pregnancy outcome. RESULTS: Of the 20,887 women enrolled, a genetic outcome was available for 18,289 (87.6%). A total of 12 22q11.2 deletion syndrome cases were confirmed in the cohort, including 5 (41.7%) nested deletions, yielding a prevalence of 1 in 1524. In the total cohort, cell-free DNA screening identified 17,976 (98.3%) cases as low risk for 22q11.2 deletion syndrome and 38 (0.2%) cases as high risk; 275 (1.5%) cases were nonreportable. Overall, 9 of 12 cases of 22q11.2 were detected, yielding a sensitivity of 75.0% (95% confidence interval, 42.8-94.5); specificity of 99.84% (95% confidence interval, 99.77-99.89); positive predictive value of 23.7% (95% confidence interval, 11.44-40.24), and negative predictive value of 99.98% (95% confidence interval, 99.95-100). None of the cases with a nonreportable result was diagnosed with 22q11.2 deletion syndrome. The updated algorithm detected 10 of 12 cases (83.3%; 95% confidence interval, 51.6-97.9) with a lower false positive rate (0.05% vs 0.16%; P<.001) and a positive predictive value of 52.6% (10/19; 95% confidence interval, 28.9-75.6). CONCLUSION: Noninvasive cell-free DNA prenatal screening for 22q11.2 deletion syndrome can detect most affected cases, including smaller nested deletions, with a low false positive rate.

Cell-free DNA screening for trisomies 21, 18, and 13 in pregnancies at low and high risk for aneuploidy with genetic confirmation.

BACKGROUND: Cell-free DNA noninvasive prenatal screening for trisomies 21, 18, and 13 has been rapidly adopted into clinical practice. However, previous studies are limited by a lack of follow-up genetic testing to confirm the outcomes and accurately assess test performance, particularly in women at a low risk for aneuploidy. OBJECTIVE: To measure and compare the performance of cell-free DNA screening for trisomies 21, 18, and 13 between women at a low and high risk for aneuploidy in a large, prospective cohort with genetic confirmation of results STUDY DESIGN: This was a multicenter prospective observational study at 21 centers in 6 countries. Women who had single-nucleotide-polymorphism-based cell-free DNA screening for trisomies 21, 18, and 13 were enrolled. Genetic confirmation was obtained from prenatal or newborn DNA samples. The test performance and test failure (no-call) rates were assessed for the cohort, and women with low and high previous risks for aneuploidy were compared. An updated cell-free DNA algorithm blinded to the pregnancy outcome was also assessed. RESULTS: A total of 20,194 women were enrolled at a median gestational age of 12.6 weeks (interquartile range, 11.6-13.9). The genetic outcomes were confirmed in 17,851 cases (88.4%): 13,043 (73.1%) low-risk and 4808 (26.9%) high-risk cases for aneuploidy. Overall, 133 trisomies were diagnosed (100 trisomy 21; 18 trisomy 18; 15 trisomy 13). The cell-free DNA screen positive rate was lower in the low-risk vs the high-risk group (0.27% vs 2.2%; P<.0001). The sensitivity and specificity were similar between the groups. The positive predictive value for the low- and high-risk groups was 85.7% vs 97.5%; P=.058 for trisomy 21; 50.0% vs 81.3%; P=.283 for trisomy 18; and 62.5% vs 83.3; P=.58 for trisomy 13, respectively. Overall, 602 (3.4%) patients had no-call result after the first draw and 287 (1.61%) after including cases with a second draw. The trisomy rate was higher in the 287 cases with no-call results than patients with a result on a first draw (2.8% vs 0.7%; P=.001). The updated algorithm showed similar sensitivity and specificity to the study algorithm with a lower no-call rate. CONCLUSION: In women at a low risk for aneuploidy, single-nucleotide-polymorphism-based cell-free DNA has high sensitivity and specificity, positive predictive value of 85.7% for trisomy 21 and 74.3% for the 3 common trisomies. Patients who receive a no-call result are at an increased risk of aneuploidy and require additional investigation.

Impact of introducing cell-free DNA screening into clinical care on first trimester ultrasound.

OBJECTIVE: First-trimester ultrasound is an important component of prenatal care. We investigated the impact of introducing cell-free DNA (cfDNA) aneuploidy screening into routine care, on performance of first-trimester ultrasound. METHODS: Retrospective study of patients who had prenatal care at a tertiary referral center. We compared the performance of any first-trimester ultrasound between three different aneuploidy screening protocols, used consecutively during the study period: (1) combined first-trimester screening (FTS); (2) FTS and cfDNA offered together; (3) patients requested to choose between FTS and cfDNA. Secondary outcomes included performance of nuchal translucency (NT), aneuploidy screens and diagnostic genetic procedures. RESULTS: The number of patients undergoing first-trimester ultrasound remained similar with the second protocol but decreased in the third (68.7% vs. 40.9%, OR 0.32, 95% CI 0.25-0.4, p < 0.001). Diagnostic procedures decreased between protocol 1 and 2 (7.6% vs. 4.4%, OR 0.59, 95% CI 0.37-0.93, p = 0.02) while NT scans decreased between protocol 2 and 3 (6.8% vs. 1.3%, OR 0.18, 95% CI 0.09-0.4, p < 0.001). The rate of FTS decreased over the study period and less women had cfDNA when they had to choose one method (p < 0.001). CONCLUSIONS: Introducing cfDNA screening as an alternative to FTS, resulted in fewer patients receiving ultrasound in the first-trimester.

Patient attitudes toward prenatal diagnostic testing during antenatal care in an urban population.

OBJECTIVE: Investigate factors that influence the decision to accept or decline diagnostic testing for pregnant women referred for genetic counseling. METHODS: Cross sectional anonymous survey of pregnant women undergoing genetic counseling at a tertiary care referral center. Subjects' perceived risk of procedure related loss and fetal chromosomal problem were obtained via survey where patients rated risk from 0 (no risk) to 10 (highest risk). RESULTS: There were no differences in sociodemographic factors between women undergoing a diagnostic procedure compared to those not undergoing a procedure. As the perceived risk for having a baby with genetic problem increased by one point, the estimated odds of having the diagnostic procedure increased by 43% controlling for the perceived risk of procedure related loss (p < .0001). Similarly, as the perceived risk of miscarriage increased by one point, the odds of having the diagnostic procedure decreased by 40%, controlling for the perceived risk of having a baby with a genetic problem (p < .0001). The main reason women cited for not undergoing a procedure was fear of procedure related loss. CONCLUSIONS: Pregnant women that decline diagnostic testing have a higher perceived risk of procedure related loss and lower perceived risk of fetal chromosomal abnormality than those who accept.

Enhanced recovery after surgery at cesarean delivery to reduce postoperative length of stay: a randomized controlled trial.

OBJECTIVE: Our objective was to determine whether an enhanced recovery after surgery pathway at the time of cesarean birth would permit a reduction in postoperative length of stay and improve postoperative patient satisfaction compared to standard perioperative care. MATERIALS AND METHODS: Patients undergoing nonemergent cesarean delivery at ≥37 weeks of gestation were randomized to enhanced recovery after surgery or standard care. Enhanced recovery after surgery involved multiple evidence-based interventions bundled into 1 protocol. The primary outcome was discharge on postoperative day 2. Secondary outcome variables included pain medication requirements, breastfeeding rates, and various measures of patient satisfaction. RESULTS: From September 27, 2017, to May 2, 2018, a total of 58 women were randomized to enhanced recovery after surgery and 60 women to standard care. The groups were similar in medical comorbidities and in demographic and perioperative characteristics. Enhanced recovery after surgery was not associated with a significantly increased rate of postoperative day 2 discharges when compared with standard care (8.6% vs 3.3%, respectively; odds ratio, 2.74; 95% confidence interval, 0.51-14.70), but it was associated with a significantly reduced postoperative length of stay when compared with standard care, with a median length of stay of 73.5 hours (interquartile range, 71.08-76.62) vs 75.5 hours (interquartile range, 72.86-76.84) from surgery, difference in median length of stay (-1.92; 95% confidence interval, -3.80 to -0.29). Enhanced recovery after surgery was not associated with a reduction in postoperative narcotic use (117.16 ± 54.17 vs 119.38 ± 47.98 morphine milligram equivalents; mean difference, -2.22; 95% confidence interval, -20.86 to 16.42). More subjects randomized to the enhanced recovery after surgery protocol reported breastfeeding at discharge (67.2% vs 48.3%; P = .046). When patients were surveyed 6 weeks postpartum, those in the enhanced recovery after surgery group were more likely to feel that their expectations were met and that they had achieved their postoperative milestones earlier, and to report continued breastfeeding. CONCLUSION: Enhanced recovery after surgery at cesarean delivery was not associated with an increase in the number of women discharged on postoperative day 2, but that may have been related to factors other than patients' medical readiness for discharge. Evidence that enhanced recovery after surgery at cesarean delivery may have the potential to improve outcomes such as day of discharge is suggested by the observed reduction in overall postoperative length of stay, improved patient satisfaction, and an increase in breastfeeding rates. Even better results may accrue with more provider and patient experience with enhanced recovery after surgery.

Long-term outcome of postmenopausal women with proliferative endometrium on endometrial sampling.

BACKGROUND: Proliferative endometrium has been reported in 15% of endometrial biopsies of women aged 50 years and older. Contrary to endometrial hyperplasia, proliferative endometrium has not been associated with the risk of endometrial cancer. OBJECTIVE: This study aimed to report on the long-term outcome of postmenopausal women who received a diagnosis of proliferative endometrium. STUDY DESIGN: This is a retrospective cohort study of 1808 women aged 55 years and older who underwent endometrial sampling between January 1997 and December 2008. Outcome data were available through February 2018. Women with a proliferative endometrium were compared with those with an atrophic endometrium for future development of endometrial hyperplasia or cancer. A subanalysis was performed for those who presented with postmenopausal bleeding. Uni- and multivariable logistic regression analyses were used to assess for confounders. RESULTS: In this study, 297 women (16.4%) received a diagnosis of proliferative endometrium. Furthermore, 962 women met the inclusion criteria. Among those women, 278 had a proliferative endometrium, and 684 had an atrophic endometrium. Women with a proliferative endometrium were younger (61.2 vs 64.5 years; P<.0001) and had a higher body mass index (33.9 vs 30.6 kg/m2; P<.0001). More African American women had a proliferative endometrium. Both groups had a similar length of surveillance (11.9 vs 11.5 years; P=.27). Women with a proliferative endometrium had a higher risk of developing endometrial hyperplasia or cancer (11.9% vs 2.9%; P<.0001), any endometrial cancer (5.8% vs 1.8%; P=.002), atypical endometrial hyperplasia (2.2% vs 0.4%; P=.02), and nonatypical endometrial hyperplasia (2.0% vs 0.7%; P=.001). The risk of developing endometrial cancer and endometrial hyperplasia remained similar after excluding cases on hormonal replacement therapy (12.2% vs 3%; P=.001). On logistic regression analysis, proliferative endometrium histology (odds ratio, 3.89; 95% confidence interval, 2.03-7.49; P<.0001), age >60 years (odds ratio, 1.98; 95% confidence interval, 1.03-3.82; P=.04), and body mass index >35 kg/m2 (odds ratio, 2.3; 95% confidence interval, 1.09-4.83; P<.0001) remained significant risk factors for progression to cancer. CONCLUSION: One of the 6 postmenopausal women who underwent endometrial sampling had a proliferative endometrium. Furthermore, 11.9% of women developed endometrial hyperplasia or cancer, a 4-fold greater incidence than women with an atrophic endometrium. The findings of this study suggest that long-term monitoring is warranted for women with postmenopausal bleeding and a proliferative endometrium histology. Further studies are needed to examine if a treatment is required to negate the risk of unopposed estrogen.

Inhibition of autophagy in peripheral blood mononuclear cells by vaginal fluid from women with a malignant adnexal mass.

Inhibition of autophagy is a characteristic of ovarian cancer. We determined whether inhibition of autophagy by vaginal fluid could provide a non-invasive test for cancer risk stratification in women presenting with an adnexal mass. Vaginal fluid supernatants from 90 women undergoing evaluation for a suspicious adnexal mass were incubated with peripheral blood mononuclear cells (PBMCs) obtained from healthy women under conditions that induce autophagy. Rapamycin, an autophagy inducer, was added to some cultures. After 48 hr the cells were collected, lysed and assayed by ELISA for intracellular p62 concentration. p62 is a cytoplasmic protein that is consumed during autophagy induction. Its concentration is inversely proportional to the extent of autophagy induction. Clinical information including pathological diagnoses was obtained after completion of laboratory studies. Mean p62 levels were 9.4 ng/ml in the 21 women with a subsequent malignant diagnosis, 4.5 ng/ml in the eight women with a borderline tumor diagnosis and 3.6 ng/ml in the 61 women with benign disease (p < 0.0001, malignant vs. others). When rapamycin was added to the vaginal fluid-PBMC co-incubation, p62 levels in samples from women with a malignant diagnosis decreased to 3.3 ng/ml, a level comparable to what was observed with the nonmalignant samples. Vaginal fluid inhibition of autophagy can differentiate between women with malignant and benign adnexal masses.

First-trimester screening for placenta accreta spectrum.

In recent years, there has been a significant rise in cases of placenta accreta spectrum, a group of life-threatening placental disorders that can arise during childbirth. Early detection plays a crucial role in facilitating meticulous delivery planning, ultimately leading to a reduction in mortality and morbidity rates and improved overall outcomes. Although third-trimester ultrasound has traditionally been the primary method for prenatal screening for placenta accreta spectrum, it often falls short in identifying cases or diagnosis is too late for optimal delivery planning. Emerging evidence has highlighted the option of early detection of placenta accreta spectrum indicators during the first trimester of pregnancy. This comprehensive review delves into our current knowledge of sonographic assessment of the uterine cervicoisthmic complex in the first trimester, examining the location and appearance of cesarean scars and exploring first-trimester screening strategies, ultimately paving the way for improved maternal and neonatal outcomes.

Investigation of health inequities in maternal and neonatal outcomes of patients with placenta accreta spectrum: a multicenter study.

BACKGROUND: Placenta accreta spectrum is associated with significant maternal and neonatal morbidity and mortality. There is limited established data on healthcare inequities in the outcomes of patients with placenta accreta spectrum. OBJECTIVE: This study aimed to investigate health inequities in maternal and neonatal outcomes of pregnancies with placenta accreta spectrum. STUDY DESIGN: This multicentered retrospective cohort study included patients with a histopathological diagnosis of placenta accreta spectrum at 4 regional perinatal centers between January 1, 2013, and June 30, 2022. Maternal race and ethnicity were categorized as either Hispanic, non-Hispanic Black, non-Hispanic White, or Asian or Pacific Islander. The primary outcome was a composite adverse maternal outcome: transfusion of ≥4 units of packed red blood cells, vasopressor use, mechanical ventilation, bowel or bladder injury, or mortality. The secondary outcomes were a composite adverse neonatal outcome (Apgar score of <7 at 1 minute, morbidity, or mortality), gestational age at placenta accreta spectrum diagnosis, and planned delivery by a multidisciplinary team. Multivariable logistic regression was used to estimate the associations of race and ethnicity with maternal and neonatal outcomes. RESULTS: A total of 408 pregnancies with placenta accreta spectrum were included. In 218 patients (53.0%), the diagnosis of placenta accreta spectrum was made antenatally. Patients predominantly self-identified as non-Hispanic White (31.6%) or non-Hispanic Black (24.5%). After adjusting for institution, age, body mass index, income, and parity, there was no difference in composite adverse maternal outcomes among the racial and ethnic groups. Similarly, adverse neonatal outcomes, gestational age at prenatal diagnosis, rate of planned delivery by a multidisciplinary team, and cesarean hysterectomy were similar among groups. CONCLUSION: In our multicentered placenta accreta spectrum cohort, race and ethnicity were not associated with inequities in composite maternal or neonatal morbidity, timing of diagnosis, or planned multidisciplinary care. This study hypothesized that a comparable incidence of individual risk factors for perinatal morbidity and geographic proximity reduces potential inequities that may exist in a larger population.

A polymorphism in an autophagy-related gene, ATG16L1, influences time to delivery in women with an unfavorable cervix who require labor induction.

Autophagy is an intracellular process that maintains homeostasis by the removal of damaged organelles and proteins. A single nucleotide polymorphism (SNP) in the autophagy-related 16-like 1 (ATG16L1) gene results in decreased autophagy. We evaluated whether the ATG16L1 polymorphism influenced the time to delivery during labor induction in pregnant women with an unfavorable cervix. DNA from 69 women with an unfavorable cervix who required labor induction due to post-term (>294 days) (n=26), oligohydramnios (n=17), hypertension or pre-eclampsia (n=10), abnormal fetal heart rate (n=8), diabetes (n=3) or other reasons (n=5) was tested by gene amplification and endonuclease digestion for a SNP in ATG16L1 (rs2241880). The mean hours (SD) from induction to delivery was 20.8 (9.7) for women who were A,A homozygotes, 19.2 (8.8) for A,G heterozygotes and 14.3 (6.6) for homozygote carriers of the G,G variant (P=0.03 A,A vs. G,G, P=0.04 A,A/A,G vs. G,G). The G,G prevalence was 24.4% and 4.2% for those who delivered in ≤24 and >24 h, respectively (P=0.04). There was no difference in genotype distribution by indication for induction. A decreased genetic capacity for autophagy may be beneficial in women with an unfavorable cervix whose labor has to be induced.

Standard quality criteria in retracted vs nonretracted obstetrical randomized controlled trials.

BACKGROUND: The number of retracted articles in peer-reviewed journals is increasing within the field of obstetrics. The most common reason for article retraction is scientific misconduct. Unfortunately, article retraction often occurs years after publication, allowing inaccurate data to be widely distributed to readers. There exists a great need for validated screening criteria for obstetric journals to use when reviewing randomized controlled trials for scientific misconduct. OBJECTIVE: This study aimed to compare retracted obstetric randomized controlled trials with nonretracted randomized controlled trials with regard to their inclusion of 7 quality metrics: prospective trial registration, trial registration number, ethics approval statement, name of the approving committee, statement of informed consent, adherence to the Consolidated Standards of Reporting Trials guidelines, and a data sharing statement. STUDY DESIGN: Obstetric randomized controlled trials retracted between 1995 and 2021 identified through Retraction Watch were compared with nonretracted randomized controlled trials published between 2018 and 2020 with regard to inclusion of the 7 quality metrics. The main outcome was the difference in prospective trial registration. Secondary outcomes were the percentage of individual criteria met and the screening performance of quality criteria in predicting article retraction. RESULTS: A total of 150 randomized controlled trials were identified, of which 14 (9.3%) were retracted and 136 (90.7%) nonretracted. Retracted randomized controlled trials were less likely than nonretracted randomized controlled trials to be prospectively registered (14.3% vs 80.1%; P<.001). The median number of quality criteria met was lower for retracted randomized controlled trials (3 vs 6; P<.01). Using a cutoff of ≤4 criteria was associated with 85.7% (95% confidence interval, 57.2-98.2) sensitivity and 92.0% (95% confidence interval, 86.2-96.0) specificity in distinguishing the retracted randomized controlled trials from nonretracted studies. CONCLUSION: Retracted obstetric randomized controlled trials were less likely to include the 7 quality metrics required on submission by most top obstetrics and gynecology journals.

Risk of endometrial polyp and surgical intervention in postmenopausal women with proliferative endometrium.

OBJECTIVE: To study the long-term risks of postmenopausal women with proliferative endometrium developing benign uterine pathologies (endometrial polyps and uterine fibroids) and requiring future gynecological interventions, and to compare them with women with atrophic endometrium. DESIGN: Retrospective cohort study of all women aged 55 or over who underwent endometrial biopsy between 1/1997 and 12/2008. Outcome data were available through to 2/2018. Women with proliferative endometrium were compared with those with atrophic endometrium for the presence of endometrial polyps, uterine fibroids, future endometrial biopsy for recurrent vaginal bleeding, and future hysteroscopy or hysterectomy. Logistic regression models were used to evaluate the association of endometrial histology and other covariates with the risk of morbidities. MAIN FINDINGS: Postmenopausal women with proliferative endometrium are at higher risk of developing endometrial polyps, uterine fibroids and need for surgical intervention. Of 1808 women who underwent endometrial biopsy during the study period, 962 met inclusion criteria: 278 had proliferative and 684 had atrophic endometrium. Length of surveillance was similar in the two groups (11.9 vs. 11.5 years, p = 0.2). Compared with women with atrophic endometrium, women with proliferative endometrium had significantly higher rates of endometrial polyps (17.3 % vs 9.7 % p = 0.001). Multivariable logistic regression confirmed that women with proliferative endometrium had more fibroids on ultrasound (62.1 % vs 50.3 % 3 = 0.02), and had increased risks of developing endometrial polyps (aOR 1.9, 95 % CI 1.28-3.07, p = 0.002), repeat endometrial biopsy (34.9 % vs. 16.8%p < 0.001) and future hysterectomy or hysteroscopy (26.6 % vs 16.2 % p < 0.001). CONCLUSIONS: In addition to the long-term increased risk of cancer, postmenopausal women with proliferative endometrium are more likely to have future bleeding, surgical interventions and diagnosis of endometrial polyps. Medical management to reduce estrogenic activity and associated risks may be considered in these cases.

Number and quality of randomized controlled trials in obstetrics published in the top general medical and obstetrics and gynecology journals.

BACKGROUND: There has been an increasing number of randomized controlled trials published in obstetrics and maternal-fetal medicine to reduce biases of treatment effect and to provide insights on the cause-effect of the relationship between treatment and outcomes. OBJECTIVE: This study aimed to identify obstetrical randomized controlled trials published in top weekly general medical journals and monthly obstetrics and gynecology journals, to assess their quality in reporting and identify factors associated with publication in different journals. STUDY DESIGN: The 4 weekly medical journals with the highest 2019 impact factor (New England Journal of Medicine, The Lancet, The Journal of the American Medical Association, and The BMJ), the top 4 monthly obstetrics and gynecology journals with obstetrics-related research (American Journal of Obstetrics & Gynecology, Ultrasound in Obstetrics & Gynecology, Obstetrics & Gynecology, and the BJOG: An International Journal of Obstetrics and Gynaecology), and the American Journal of Obstetrics & Gynecology Maternal-Fetal Medicine were searched for obstetrical randomized controlled trials in the years 2018 to 2020. The primary outcome was the number of obstetrical randomized controlled trials published in the obstetrics and gynecology journals vs the weekly medical journals and the percentage of trials published, overall and per journal. The secondary outcomes included the proportion of positive vs negative trials overall and per journal and the assessment of the study characteristics of published trials, including quality assessment criteria. RESULTS: Of the 4024 original research articles published in the 9 journals during the 3-year study period, 1221 (30.3%) were randomized controlled trials, with 137 (11.2%) randomized controlled trials being in obstetrics (46 in 2018, 47 in 2019, and 44 studies in 2020). Furthermore, 33 (24.1%) were published in weekly medical journals, and 104 (75.9%) were published in obstetrics and gynecology journals. The percentage of obstetrical randomized controlled trials published ranged from 1.5% to 9.6% per journal. Overall, 34.3% of obstetrical trials were statistically significant or "positive" for the primary outcome. Notably, 24.8% of the trials were retrospectively registered after the enrollment of the first study patient. Trials published in the 4 weekly medical journals enrolled significantly more patients (1801 vs 180; P<.001), received more often funding from the federal government (78.8% vs 35.6%; P<.001), and were more likely to be multicenter (90.9% vs 42.3%; P<.001), non-United States based (69.7% vs 49.0%; P=.03), and double blinded (45.5% vs 18.3%; P=.003) than trials published in the obstetrics and gynecology journals. There was no difference in study type (noninferiority vs superiority) and trial quality characteristics, including pretrial registration, ethics approval statement, informed consent statement, and adherence to the Consolidated Standards of Reporting Trials guidelines statement between studies published in weekly medical journals and studies published in obstetrics and gynecology journals. CONCLUSION: Approximately 45 trials in obstetrics are being published every year in the highest impact journals, with one-fourth being in the weekly medical journals and the remainder in the obstetrics and gynecology journals. Only about a third of published obstetrical trials are positive. Trials published in weekly medical journals are larger, more likely to be funded by the government, multicenter, international, and double blinded. Quality metrics are similar between weekly medical journals and obstetrics and gynecology journals.

Resident and program director confidence in resident preparedness for operative vaginal deliveries in Obstetrics and Gynecology Training Programs in the United States.

BACKGROUND: Operative vaginal delivery is used to expedite a safe vaginal delivery in the second stage of labor and is considered an essential part of residency training in obstetrics and gynecology. OBJECTIVE: To assess the self-reported readiness of obstetrics and gynecology residents in the United States to perform vacuum-assisted vaginal delivery and forceps-assisted vaginal delivery compared with the perceptions of program directors. STUDY DESIGN: The Council on Resident Education in Obstetrics and Gynecology surveyed the residents in all US training programs about their readiness to perform forceps-assisted and vacuum-assisted deliveries. The program directors were simultaneously surveyed about the readiness of their cohort to perform operative deliveries with and without attending oversight. The primary outcome of the survey was the residents' self-reported confidence in their ability to autonomously and independently perform operative deliveries. RESULTS: Α total of 5084 out of 5514 (92.9%) resident physicians and 241 out of the 292 (83%) residency program directors completed the survey. Eighty-seven percent (95% confidence interval, 84.9-88.9) of the graduating residents reported feeling that they could autonomously perform a vacuum-assisted vaginal delivery, compared with 49.5% (95% confidence interval, 46.6-52.4) for forceps-assisted vaginal delivery (P<.01). Similarly, whereas 95.9% (95% confidence interval, 94.6-97.0) of the residents felt that they could confidently perform an emergency vacuum-assisted vaginal delivery, only 42.3% (95% confidence interval, 39.4-45.2) felt confident performing an emergency forceps-assisted vaginal delivery (P<.01). The residency program directors significantly overestimated their residents' confidence in independently performing an emergency forceps-assisted vaginal delivery or vacuum-assisted vaginal delivery than the residents themselves (54% [95% confidence interval, 47.1-60.5] vs 24% [95% confidence interval, 22.5-24.9] and 98.6% [95% confidence interval, 97.0-100] vs 71.9 [95% confidence interval, 70.6-73.2] respectively P<.01). Trainees in military-based residency programs and those interested in pursuing a career as generalists or maternal-fetal medicine specialists reported significantly higher preparedness to perform a forceps-assisted vaginal delivery. CONCLUSION: Graduating obstetrics and gynecology residents report feeling less prepared to independently perform a forceps-assisted vaginal delivery than a vacuum-assisted vaginal delivery. The program directors had more confidence in the ability of their residents to perform an operative vaginal delivery than the residents themselves.

A comparison of pregnancy-specific risk scoring systems for venous thromboembolic pharmacoprophylaxis in hospitalized maternity patients.

OBJECTIVE: Venous thromboembolism (VTE) remains a leading cause of maternal mortality. The American College of Obstetricians and Gynecologists (ACOG) and the Royal College of Obstetricians & Gynecologists (RCOG) have proposed pregnancy-specific risk scoring guidelines for antepartum (AP) and postpartum (PP) thromboprophylaxis. We compared the impact of scoring thresholds and their potential preventative effect. STUDY DESIGN: We conducted a retrospective cohort study of hospitalized maternity patients over a 4-month period. Patients were assigned an AP and PP risk score using each guideline. Hospitalization-associated VTE was accessed over a 6-year period. Comparison was by Fischer's exact and Chi Square tests. RESULTS: 638 women were included. Of AP patients, 20% met pharmacoprophylaxis criteria for baseline characteristics and 100% for length of stay using RCOG, and 12% met phrarmacoprophylaxis criteria using ACOG (p < .001). For PP patients, 53% met criteria for RCOG compared to 24% using ACOG (p < .001). If pharmacoprophylaxis were performed at a threshold 1 point above recommendation, 7% of AP patients and 11% of PP women would meet ACOG criteria. This increased ACOG threshold captured all cases of VTE following hospitalization. CONCLUSION: In our population, using ACOG prophylaxis guidelines at an increased threshold would have potentially prevented all hospitalization related VTE without excessive anti-coagulation.

Association Between Obesity and Fetal Acidosis at Scheduled Cesarean Delivery.

OBJECTIVE: To evaluate whether patients with obesity who undergo scheduled cesarean delivery under neuraxial anesthesia are at increased risk for umbilical artery pH less than 7.1 and base deficit 12 mmol or greater. METHODS: We conducted a multicenter, retrospective cohort study of individuals who delivered a term, singleton, nonanomalous neonate at one of four academic medical centers in New York City from 2013 to 2019 by scheduled cesarean under neuraxial anesthesia for whom fetal cord blood gas results were available. The primary study outcome was rate of fetal acidosis , defined as umbilical artery pH less than 7.1. This was compared between patients with obesity (body mass index [BMI] 30 or higher) and those without obesity (BMI lower than 30). Base deficit 12 mmol or greater and a composite of fetal acidosis and base deficit 12 mmol or greater were also compared. Secondary outcomes included neonatal intensive care unit admission rate, 5-minute Apgar score less than 7, and neonatal morbidity. Associations between maternal BMI and study outcomes were assessed using multivariable logistic or linear regression and adjusted for age, race and ethnicity, insurance type, cesarean delivery order number, and neuraxial anesthesia type. RESULTS: Of the 6,264 individuals who met inclusion criteria during the study interval, 3,098 had obesity and 3,166 did not. The overall rate of umbilical artery cord pH less than 7.1 was 2.5%, and the overall rate of umbilical artery base deficit 12 mmol or greater was 1.5%. Patients with obesity were more likely to have umbilical artery cord pH less than 7.1 (adjusted odds ratio [aOR] 2.7, 95% CI 1.8-4.2) and umbilical artery base deficit 12 mmol or greater (aOR 3.2, 95% CI 1.9-5.3). This association was not significantly attenuated after additional adjustments for potential mediators, including maternal medical comorbidities. We found no differences in secondary outcomes between groups. CONCLUSION: Maternal obesity is associated with increased odds of arterial pH less than 7.1 and base deficit 12 mmol or greater at the time of scheduled cesarean delivery under neuraxial anesthesia.

Targeting Both Autophagy and Immunotherapy in Breast Cancer Treatment.

As clinical efforts towards breast-conserving therapy and prolonging survival of those with metastatic breast cancer increase, innovative approaches with the use of biologics are on the rise. Two areas of current focus are cancer immunotherapy and autophagy, both of which have been well-studied independently but have recently been shown to have intertwining roles in cancer. An increased understanding of their interactions could provide new insights that result in novel diagnostic, prognostic, and therapeutic strategies. In this breast cancer-focused review, we explore the interactions between autophagy and two clinically relevant immune checkpoint pathways; the programmed cell death-1 receptor with its ligand (PD-L1)/PD-1 and the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)/CD80 and CD86 (B7-1 and B7-2). Furthermore, we discuss emerging preclinical and clinical data supporting targeting both immunotherapy and autophagy pathway manipulation as a promising approach in the treatment of breast cancer.

Alterations of the 70 kDa heat shock protein (HSP70) and sequestosome-1 (p62) in women with breast cancer.

Peripheral blood mononuclear cells (PBMCs) respond to altered physiological conditions to alleviate the threat. Production of the 70 kDa heat shock protein (HSP70) is up-regulated to protect proteins from degradation. Sequestosome-1 (p62) binds to altered proteins and the p62-protein complex is degraded by autophagy. P62 is also a regulator of intracellular kinase activity and cell differentiation. We hypothesized that the PBMC response to a malignant breast mass involves elevated production of HSP70 and a decrease in intracellular p62. In this study 46 women had their breast mass excised. PBMCs were isolated and intracellular levels of HSP70 and p62 were quantitated by ELISA. Differences between women with a benign or malignant breast mass were determined. A breast malignancy was diagnosed in 38 women (82.6%) while 8 had a benign lesion. Mean intracellular HSP70 levels were 79.3 ng/ml in PBMCs from women with a malignant lesion as opposed to 44.2 ng/ml in controls (p = 0.04). The mean PBMC p62 level was 2.3 ng/ml in women with a benign breast lesion as opposed to 0.6 ng/ml in those with breast cancer (p < 0.001). Mean p62 levels were lowest in women with invasive carcinoma and a positive lymph node biopsy when compared to those with in-situ carcinoma or absence of lymphadenopathy, respectively. Intracellular HSP70 and p62 levels in PBMCs differ between women with a malignant or benign breast lesion. These measurements may be of value in the preoperative triage of women with a breast mass.