Maternal morbidity after preterm premature rupture of membranes at <24 weeks' gestation.

BACKGROUND: After preterm premature rupture of membranes at <24 weeks' gestation, pregnant women may choose continuation (expectant management) or termination of pregnancy, via either dilation and evacuation or labor induction. Neonatal outcomes after expectant management are well described. In contrast, limited research addresses maternal outcomes associated with expectant management compared to termination of pregnancy. OBJECTIVE: This study aimed to compare maternal morbidity after preterm premature rupture of membranes at <24 weeks' gestation in women who choose either expectant management or termination of pregnancy. STUDY DESIGN: This retrospective cohort study included women with preterm premature rupture of membranes between 14 0/7 and 23 6/7 weeks' gestation with singleton or twin pregnancies at 3 institutions from 2011 to 2018. We excluded pregnancies complicated by fetal anomalies, rupture of membranes immediately after obstetrical procedures (chorionic villus sampling, amniocentesis, cerclage placement, fetal reduction), spontaneous delivery <24 hours after membrane rupture, and contraindications to expectant management. Our primary outcome was the difference in composite maternal morbidity between women choosing expectant management and women choosing termination of pregnancy. We defined composite maternal morbidity as at least 1 of the following: chorioamnionitis, endometritis, sepsis, unplanned operative procedure after delivery (dilation and curettage, laparoscopy, or laparotomy), injury requiring repair, unplanned hysterectomy, unplanned hysterotomy (excluding cesarean delivery), uterine rupture, hemorrhage of >1000 mL, transfusion, admission to the maternal intensive care unit, acute renal insufficiency, venous thromboembolism, pulmonary embolism, and readmission to the hospital within 6 weeks. We compared the demographic and antenatal characteristics of women choosing expectant management with that of women choosing termination of pregnancy and used logistic regression to quantify the association between initial management decision and composite maternal morbidity. RESULTS: We identified 350 women with pregnancies complicated by preterm premature rupture of membranes at <24 weeks' gestation, and 208 women were eligible for the study. Of the 208 women, 108 (51.9%) chose expectant management as initial management, and 100 (48.1%) chose termination of pregnancy as initial management. Among women selecting termination of pregnancy, 67.0% underwent labor induction, and 33.0% underwent dilation and evacuation. Compared to women who chose termination of pregnancy, women who chose expectant management had 4.1 times the odds of developing chorioamnionitis (38.0% vs 13.0%; 95% confidence interval, 2.03-8.26) and 2.44 times the odds of postpartum hemorrhage (23.1% vs 11.0%; 95% confidence interval, 1.13-5.26). Admissions to the intensive care unit and unplanned hysterectomy only occurred after expectant management (2.8% vs 0.0% and 0.9% vs 0.0%). Of women who chose expectant management, 36.2% delivered via cesarean delivery with 56.4% non-low transverse uterine incisions. Composite maternal morbidity rates were 60.2% in the expectant management group and 33.0% in the termination of pregnancy group. After adjusting for gestational age at rupture, site, race and ethnicity, gestational age at entry to prenatal care, preterm premature rupture of membranes in a previous pregnancy, twin pregnancy, smoking, cerclage, and cervical examination at the time of presentation, expectant management was associated with 3.47 times the odds of composite maternal morbidity (95% confidence interval, 1.52-7.93), corresponding to an adjusted relative risk of 1.91 (95% confidence interval, 1.35-2.73). Among women who chose expectant management, 15.7% avoided morbidity and had a neonate who survived to discharge. CONCLUSION: Expectant management for preterm premature rupture of membranes at <24 weeks' gestation was associated with a significantly increased risk of maternal morbidity when compared to termination of pregnancy.

Increasing NIH funding for academic departments of obstetrics and gynecology: a call to action.

The National Institutes of Health funding for reproductive sciences research, specifically in academic departments of obstetrics and gynecology, is disproportionately low. Research is one of the most important pillars in advancing healthcare. Despite US Congress' vision in providing increased funding to the National Institutes of Health as a whole, underfunding for research in the departments of obstetrics and gynecology remains one of the several critical drivers in the decline in reproductive health and healthcare for women in the United States.

Over-the-Counter Oral Contraception as an Opportunity to Reduce Contraceptive Access Inequity.

This Viewpoint argues that making a progestin-only contraceptive pill available for sale as an over-the-counter product will help reduce logistic barriers to safe and effective birth control.

Bleeding patterns for the Liletta® levonorgestrel 52 mg intrauterine system.

PURPOSE: Evaluate bleeding patterns for the Liletta® levonorgestrel 52 mg intrauterine system (IUS) using the World Health Organization Belsey definitions. MATERIAL AND METHODS: This prospective multicenter trial evaluates the efficacy and safety of Liletta® (Clinicaltrials.gov NCT00995150). We evaluated bleeding patterns for 1700 nulliparous and multiparous women using a daily diary completed by participants for the first 2 years and by questionnaire every 3 months thereafter. We assessed amenorrhea rates over 3 years and the proportion of subjects with infrequent, frequent, prolonged and irregular bleeding per 90-day reference period over 2 years for the entire study population as well as comparing nulliparous and parous women and obese and non-obese women. RESULTS: Amenorrhea rates at 1 and 3 years in levonorgestrel 52 mg IUS users were 19 and 37%, respectively. The infrequent bleeding rate increased from 14% in the first 90 days to 30% at the end of Year 1, and was maintained at the same rate through Year 2. Frequent, prolonged and irregular bleeding declined to low levels by the end of the first year. Discontinuation for bleeding-related complaints occurred in 35 (2.1%, 95% CI 1.3-2.7%) women during the first 36 months; only one subject discontinued for amenorrhea (in Year 2). Outcomes did not vary for nulliparous versus parous or obese versus non-obese women. CONCLUSIONS: Among Liletta users, amenorrhea and infrequent bleeding become more prevalent over time and amenorrhea rates continue to increase after the first year of use. Bleeding patterns do not differ significantly by parity or by obesity-status. Discontinuation for bleeding concerns is uncommon with this product.

Postplacental intrauterine device expulsion by 12 weeks: a prospective cohort study.

BACKGROUND: An intrauterine device placed immediately following a delivery can serve as an effective and safe contraceptive strategy in the postpartum period. There is limited evidence that the levonorgestrel intrauterine system may have a higher rate of expulsion compared to the copper intrauterine device; however, rates of expulsion for these 2 intrauterine device types have not been compared directly. OBJECTIVE: We sought to compare expulsion rates by 12 weeks' postpartum for the levonorgestrel intrauterine system and copper intrauterine device. STUDY DESIGN: We enrolled women who received postplacental intrauterine devices at 2 urban hospitals. Eligible women were ≥18 years old, English- or Spanish-speaking, with singleton vaginal delivery at ≥35 weeks' gestation. Intrauterine devices were inserted within 10 minutes of placental delivery by trained providers using ring forceps or the operator's hand. Intrauterine device location was evaluated via abdominal ultrasound at 24-48 hours' postpartum, and via transvaginal ultrasound 6 and 12 weeks later, categorizing position of the intrauterine device at the fundus, below the fundus but above the internal os, any part of the intrauterine device below the internal os (partial expulsion), or no intrauterine device visualized. Outcomes included intrauterine device expulsion and method continuation. We used multivariable logistic regression to identify factors associated with expulsion. RESULTS: We enrolled 123 women ages 18-40 years. Of these, 68 (55%) initiated levonorgestrel intrauterine system and 55 (45%) initiated copper intrauterine device. Groups were similar except more copper intrauterine device users were Hispanic (66% vs 38%) and fewer were primiparous (16% vs 31%). Among the 96 (78%) with 12-week follow-up, expulsion was higher for levonorgestrel intrauterine system users (21/55 or 38%) than for copper intrauterine device users (8/41 or 20%) (odds ratio, 2.55; 95% confidence interval, 0.99-6.55; P = .05). At 24 hours' postpartum, there was no significant difference in median distance from the intrauterine device to the fundus between intrauterine device types or between those who did or did not experience expulsion. Of expulsions, 86% occurred ≤6 weeks' postpartum. All complete expulsions were clinically identified, but of the partial expulsions, only 4/10 (40%) were clinically suspected prior to ultrasound. The only independent predictor of expulsion was intrauterine device type. Including reinsertions, intrauterine device use at 12 weeks was not significantly different for levonorgestrel intrauterine system and copper intrauterine device users (80% vs 93%; P = .14). CONCLUSION: Women initiating postplacental levonorgestrel intrauterine system are more likely to experience complete expulsion than those initiating copper intrauterine device. Using sonographic criteria results in higher expulsion rates than previously reported. It is unclear if such high expulsion rates would be identified following standard clinical practice.

Validity of self-reported history of Chlamydia trachomatis infection.

BACKGROUND: Chlamydia trachomatis infection is common and largely asymptomatic in women. If untreated, it can lead to sequelae such as pelvic inflammatory disease and infertility. It is unknown whether a patient's self-reported history of Chlamydia trachomatis infection is a valid marker of past infection. OBJECTIVE: Our objective was to evaluate the validity of women's self-reported history of Chlamydia trachomatis infection compared with Chlamydia trachomatis serology, a marker for previous infection. STUDY DESIGN: We analyzed data from the Fertility After Contraception Termination study. We compared participants' survey responses with the question, "Have you ever been told by a health care provider that you had Chlamydia?" to serological test results indicating the presence or absence of antibodies to Chlamydia trachomatis as assessed by a microimmunofluorescence assay. Prevalence of past infection, sensitivity, specificity, predictive values, and likelihood ratios were calculated. The Cohen's kappa statistic was computed to assess agreement between self-report and serology. RESULTS: Among 409 participants, 108 (26%) reported having a history of Chlamydia trachomatis infection, whereas 146 (36%) had positive serological test results. Relative to positive microimmunofluorescence assay, the sensitivity and specificity of self-reported history of Chlamydia trachomatis infection were 52.1% (95% confidence interval, 43.6-60.4%) and 87.8% (95% confidence interval, 83.3-91.5%), respectively. The positive predictive value of the self-report was 70.4% (95% confidence interval, 60.8-78.8%), and the negative predictive value was 76.7% (95% confidence interval, 71.6-81.4%). The likelihood ratio was found to be 4.28. Agreement between self-report and serology was found to be moderate (kappa = 0.42, P < .001). CONCLUSION: Self-reported history of Chlamydia trachomatis infection commonly yields false-negative and false-positive results. When definitive status of past Chlamydia trachomatis infection is needed, serology should be obtained.

Medication Abortion.

This JAMA Patient Page describes medication abortion and its risks and effectiveness.

A prospective assessment of pelvic infection risk following same-day sexually transmitted infection testing and levonorgestrel intrauterine system placement.

BACKGROUND: Misperceptions persist that intrauterine device placement is related to pelvic infections and Chlamydia and gonorrhea testing results are needed prior to placement. OBJECTIVE: We sought to evaluate the relationship of Chlamydia and gonorrhea screening to pelvic infection for up to 2 years following placement of the levonorgestrel 52-mg intrauterine system. STUDY DESIGN: A total of 1751 nulliparous and multiparous females 16 to 45 years old enrolled in a multicenter trial designed to evaluate the efficacy and safety of a new levonorgestrel intrauterine system for up to 7 years. Participants had Chlamydia screening at study entry and yearly if they were age ≤25 years. Women also had baseline gonorrhea screening if testing had not been performed since starting their current sexual relationship. Those who changed sexual partners during the trial had repeated Chlamydia and gonorrhea testing. Intrauterine system insertion could occur on the same day as screening. Participants did not receive prophylactic antibiotics for intrauterine system placement. Investigators performed pelvic examinations after 12 and 24 months and when clinically indicated during visits at 3, 6, and 18 months after placement and unscheduled visits. Pelvic infection included any clinical diagnosis of pelvic inflammatory disease or endometritis. RESULTS: Most participants (n = 1364, 79.6%) did not have sexually transmitted infection test results available prior to intrauterine system placement. In all, 29 (1.7%) participants had positive baseline testing for a sexually transmitted infection (Chlamydia, n = 25; gonorrhea, n = 3; both, n = 1); 6 of these participants had known results (all with Chlamydia infection) prior to intrauterine system placement and received treatment before enrollment. The 23 participants whose results were not known at the time of intrauterine system placement received treatment without intrauterine system removal and none developed pelvic infection. The incidence of positive Chlamydia testing was similar among those with and without known test results at the time of intrauterine system placement (1.9% vs 1.5%, respectively, P = .6). Nine (0.5%) participants had a diagnosis of pelvic infection over 2 years after placement, all of whom had negative Chlamydia screening on the day of or within 1 month after intrauterine system placement. Infections were diagnosed in 3 participants within 7 days, 1 at 39 days, and 5 at ≥6 months. Seven participants received outpatient antibiotic treatment and 2 (diagnoses between 6-12 months after placement) received inpatient treatment. Two (0.1%) participants had intrauterine system removal related to infection (at 6 days and at 7 months after placement), both of whom only required outpatient treatment. CONCLUSION: Conducting Chlamydia and gonorrhea testing on the same day as intrauterine system placement is associated with a low risk of pelvic infection (0.2%). Over the first 2 years of intrauterine system use, infections are infrequent and not temporally related to intrauterine system placement. Pelvic infection can be successfully treated in most women with outpatient antibiotics and typically does not require intrauterine system removal. Women without clinical evidence of active infection can have intrauterine system placement and sexually transmitted infection screening, if indicated, on the same day.

Insertion characteristics of intrauterine devices in adolescents and young women: success, ancillary measures, and complications.

OBJECTIVE: The objective of the study was to evaluate success and safety of intrauterine device (IUD) placement in a large cohort of adolescents. STUDY DESIGN: We examined the medical records of patients aged 13-24 years at the Children's Hospital Colorado Adolescent Family Planning Clinic with at least 1 attempt at IUD placement. We abstracted demographic, reproductive, and procedural variables. The primary outcome was successful placement at first IUD insertion visit. We compared nulliparous with parous adolescents and patients younger than 18 years with those 18 years of age and older. RESULTS: Between April 2009 and December 2011, 1177 adolescent women aged 13-24 years (mean age 20.8 ± 2.5 years) had an attempted IUD placement, 1012 (86%) of which were with an advanced practice clinician. The first attempt was successful for 1132 women (96.2%). The first-attempt success rate was 95.8% for nulliparous women and 96.7% for parous women (P = .45). The first-attempt success rate was 95.5% (n = 169) for women aged 13-17 years compared with 96.3% (n = 963) for women aged 18-24 years (P = .6). Only 1.8% (n = 21) of all first-attempt successful insertions required ancillary measures. Of the 45 patients with a failed first insertion attempt, 40% (n = 18) had a second attempt with a physician, of which 78% (n = 14) were successful. Within the first 6 months of IUD placement, no perforations were identified and 24 patients (3.0%) expelled the IUD. Insertion failures and IUD expulsions were not related to IUD type, age, or parity. CONCLUSION: Intrauterine devices can be inserted in nulliparous adolescents of any age with similar success to parous adolescents, by both physicians and advanced practice clinicians. Inability to provide ancillary measures such as paracervical block or cervical dilation should not limit access to this first-line contraceptive method.

Preventing repeat pregnancy in adolescents: is immediate postpartum insertion of the contraceptive implant cost effective?

OBJECTIVE: The objective of the study was to determine the cost-effectiveness of a hypothetical state-funded program offering immediate postpartum implant (IPI) insertion for adolescent mothers. STUDY DESIGN: Participants in an adolescent prenatal-postnatal program were enrolled in a prospective observational study of IPI insertion (IPI group, n = 171) vs standard contraceptive initiation (comparison group, n = 225). Implant discontinuation, repeat pregnancies and pregnancy outcomes were determined. We compared the anticipated public expenditures for IPI recipients and comparisons at 6, 12, 24, and 36 months postpartum using the actual outcomes of this cohort and Colorado Medicaid reimbursement estimates. Costs were normalized to 1000 adolescents in each arm and included 1 year of well-baby care for delivered pregnancies. RESULTS: At 6 months, the expenditures of the IPI group exceed the comparison group by $73,000. However, at 12, 24, and 36 months, publicly funded IPIs would result in a savings of more than $550,000, $2.5 million, and $4.5 million, respectively. For every dollar spent on the IPI program, $0.79, $3.54, and $6.50 would be saved at 12, 24, and 36 months. Expenditures between the IPI and comparison groups would be equal if the comparison group pregnancy rate was 13.8%, 18.6%, and 30.5% at 12, 24, and 36 months. Actual rates were 20.1%, 46.5%, and 83.7%. CONCLUSION: Offering IPIs to adolescent mothers is cost effective. Payors that do not currently cover IPI should integrate these data into policy considerations.

Rapid repeat pregnancy in adolescents: do immediate postpartum contraceptive implants make a difference?

OBJECTIVE: The purpose of this study was to determine contraceptive continuation and repeat pregnancy rates in adolescents who are offered immediate postpartum etonogestrel implant (IPI) insertion. STUDY DESIGN: Participants in an adolescent prenatal-postnatal program were enrolled in a prospective observational study of IPI insertion (IPI group, 171) vs other methods (control group, 225). Contraceptive continuation and repeat pregnancies were determined. RESULTS: Implant continuation at 6 months was 96.9% (156/161 participants); at 12 months, the continuation rate was 86.3% (132/153 participants). At 6 months, 9.9% of the control participants were pregnant (21/213); there were no IPI pregnancies. By 12 months, 18.6% of control participants (38/204) experienced pregnancy vs 2.6% of IPI recipients (4/153; relative risk, 5.0; 95% confidence interval [CI], 1.9-12.7). Repeat pregnancy at 12 months was predicted by not receiving IPI insertion (odds ratio, 8.0; 95% CI, 2.8-23.0) and having >1 child (odds ratio, 2.1; 95% CI, 1.1-4.3; P = .03). CONCLUSION: IPI placement in adolescents has excellent continuation 1 year after delivery; rapid repeat pregnancy is significantly decreased compared with control participants.

Continuation rates of two different-sized copper intrauterine devices among nulliparous women: Interim 12-month results of a single-blind, randomised, multicentre trial.

Background: The most widely used copper intrauterine device (IUD) in the world (the TCu380A), and the only product available in many countries, causes side effects and early removals for many users. These problems are exacerbated in nulliparous women, who have smaller uterine cavities compared to parous women. We compared first-year continuation rates and reasons/probabilities for early removal of the TCu380A versus a smaller Belgian copper IUD among nulliparous users. Methods: This 12-month interim report is derived from a pre-planned interim analysis of a sub population and focused on key secondary comparative endpoints. In this participant-blinded trial at 16 centres in the USA, we randomised participants aged 17-40 in a 4:1 ratio to the NT380-Mini or the TCu380A. In the first year, participants had follow-up visits at 6-weeks and 3, 6, and 12-months, and a phone contact at 9 months; we documented continued use, expulsions, and reasons for removal. Among participants with successful IUD placement, we compared probabilities of IUD continuation and specific reasons for discontinuation using log-rank tests. This trial is registered with ClinicalTrials.gov number NCT03124160 and is closed to recruitment. Findings: Between June 1, 2017, and February 25, 2019, we assigned 927 nulliparous women to either the NT380-Mini (n = 744) or the TCu380A (n = 183); the analysis population was 732 (NT380-Mini) and 176 (TCu380A). Participants using the NT380-Mini, compared to the TCu380A, had higher 12-month continuation rates (78·7% [95% CI: 72·9-84·5%] vs. 70·2% [95% CI: 59·7-80·7], p = 0·014), lower rates of removal for bleeding and/or pain (8·1% vs. 16·2%, p = 0·003) and lower IUD expulsion rates (4·8% vs. 8·9%, p = 0·023), respectively. Interpretation: The NT380-Mini offers important benefits for a nulliparous population compared to the TCu380A in the first twelve months, when pivotal experiences typically occur. Higher continuation rates with the NT380-Mini may avert disruptions in contraceptive use and help users avoid unintended pregnancy. Funding: Bill & Melinda Gates Foundation, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and Mona Lisa, N.V. (Belgium).

Six-year contraceptive efficacy and continued safety of a levonorgestrel 52 mg intrauterine system.

OBJECTIVE: To assess 6-year contraceptive efficacy and safety of a levonorgestrel 52 mg intrauterine system (IUS). STUDY DESIGN: We assessed pregnancy rates through 72 months in women aged 16-35 years at enrollment and safety in all participants (aged 16-45 years, n = 1751) in an ongoing 10-year phase-3 trial. RESULTS: Over six years, nine pregnancies occurred (none in year 6) for a life-table pregnancy rate of 0.87 (95% CI 0.44-1.70). Adverse event rates remain low through 6 or more years of use. Two expulsions occurred in year 6. CONCLUSION: This levonorgestrel 52 mg IUS is a highly effective and safe contraceptive over 6 years of use. IMPLICATIONS: The levonorgestrel 52 mg IUS shows high 6-year contraceptive efficacy and a low rate of adverse events through 6 or more years of use.

Decreased placental folate transporter expression and activity in first and second trimester in obese mothers.

Obese women have an approximately twofold higher risk to deliver an infant with neural tube defects (NTDs) despite folate supplementation. Placental transfer of folate is mediated by folate receptor alpha (FR-α), proton coupled folate transporter (PCFT), and reduced folate carrier (RFC). Decreased placental transport may contribute to NTDs in obese women. Serum folate levels were measured and placental tissue was collected from 13 women with normal BMI (21.9±1.9) and 11 obese women (BMI 33.1±2.8) undergoing elective termination at 8-22 weeks of gestation. The syncytiotrophoblast microvillous plasma membranes (MVM) were isolated using homogenization, magnesium precipitation, and differential centrifugation. MVM expression of FR-α, PCFT and RFC was determined by western blot. Folate transport capacity was assessed using radiolabeled methyl-tetrahydrofolate and rapid filtration techniques. Differences in expression and transport capacity were adjusted for gestational age and maternal age in multivariable regression models. P<.05 was considered statistically significant. Serum folate levels were not significantly different between groups. Placental MVM folate transporter expression did not change with gestational age. MVM RFC (-19%) and FR-α (-17%) expression was significantly reduced in placentas from obese women (P<.05). MVM folate transporter activity was reduced by-52% (P<.05) in obese women. These differences remained after adjustment for gestational age. There was no difference in mTOR signaling between groups. In conclusion, RFC and FR alpha expression and transporter activity in the placental MVM are significantly reduced in obese women in early pregnancy. These results may explain the higher incidence of NTDs in infants of obese women with adequate serum folate.

Predictors of Discontinuation of Long-Acting Reversible Contraception Before 30 Months of Use by Adolescents and Young Women.

PURPOSE: The purpose of the article was to describe adolescent and young women's rates of discontinuation of intrauterine devices (IUDs) and contraceptive implants, the extent to which discontinuation is predicted by baseline factors, reasons for discontinuation, and subsequent contraceptive initiation. METHODS: We recruited English-speaking women, aged 13-24 years, from a family planning clinic serving clients <25 years old. Participants completed surveys before and after contraceptive initiation visits. We reviewed medical records and contacted participants who initiated use of an IUD or contraceptive implant and assessed contraceptive discontinuation before 30 months of use. We collected follow-up data on duration of use, reasons for discontinuation, and new method selected. We used multivariable regression models to ascertain factors associated with method discontinuation. RESULTS: From 2011 to 2013, 775 young women completed surveys and initiated IUD or implant use. We determined 30-month discontinuation status of 633 women (81.7%). Among those with known outcome, fewer IUD than implant initiators had discontinued use (36.3% vs. 45.4%, p = .02). Mean duration of use was 733 days (95% confidence interval 702-763 days) for the IUD and 697 days (95% confidence interval 666-728 days) for the implant. Participants who stated at baseline that it was "very important" to avoid pregnancy were about half as likely to discontinue use. The most common reasons for discontinuation were pain (IUD) and bleeding (implant). Most participants initiated alternate contraception after discontinuing their original method. CONCLUSIONS: Adolescents and young women who initiate an IUD or implant make decisions for discontinuation based on weighing high contraceptive effectiveness with other reproductive health values and preferences.

Intrauterine Device Use and Ovarian Cancer Risk: A Systematic Review and Meta-analysis.

OBJECTIVE: To explore the relationship between intrauterine device (IUD) use and risk of ovarian cancer through systematic review of the literature and meta-analysis. DATA SOURCES: We searched MEDLINE, EMBASE, Cochrane Library, Web of Science Core Collection from inception to June 2018. For the MEDLINE search, we included the MeSH terms "intrauterine devices" AND "ovarian neoplasms," however also searching "intrauter*," "ovar*" and "fallopian tube," as well as "cancer" and "carcinoma" as keywords to include all possible variations. Similar search terms were used in the other databases. We also searched ClinicalTrials.gov. METHODS OF STUDY SELECTION: Case-control and cohort studies that collected individual level data on IUD use and ovarian cancer diagnosis were critically reviewed and data extracted. Review of abstracts from 399 articles through systematic database review and an additional 200 articles through Google Scholar identified a total of 15 studies with individual level data regarding IUD use and incident ovarian cancer. On critical review, 11 of these studies were used for meta-analysis. All case reports and reviews were excluded. TABULATION, INTEGRATION, AND RESULTS: The data were harmonized and weighted and summary odds ratios (ORs) were calculated. Covariates were identified evaluated separately. A random-effects meta-analysis was performed to confirm minimal bias. Harmonization and weighting of the data revealed an OR association between ever use of an IUD and incident ovarian cancer to be 0.68 (95% CI 0.62-0.75). There were no significant differences found between covariates. Heterogeneity among all studies was found to be I=68%. CONCLUSION: Intrauterine device use is associated with a reduced incidence of ovarian cancer based on a review of existing retrospective data. Unfortunately, prospective investigation into the role of IUDs in ovarian cancer prevention is limited.

Insulin Stimulates GLUT4 Trafficking to the Syncytiotrophoblast Basal Plasma Membrane in the Human Placenta.

CONTEXT: Placental transport capacity influences fetal glucose supply. The syncytiotrophoblast is the transporting epithelium in the human placenta, expressing glucose transporters (GLUTs) and insulin receptors (IRs) in its maternal-facing microvillous plasma membrane (MVM) and fetal-facing basal plasma membrane (BM). OBJECTIVE: The objectives of this study were to (i) determine the expression of the insulin-sensitive GLUT4 glucose transporter and IR in the syncytiotrophoblast plasma membranes across gestation in normal pregnancy and in pregnancies complicated by maternal obesity, and (ii) assess the effect of insulin on GLUT4 plasma membrane trafficking in human placental explants. DESIGN, SETTING, AND PARTICIPANTS: Placental tissue was collected across gestation from women with normal body mass index (BMI) and mothers with obesity with appropriate for gestational age and macrosomic infants. MVM and BM were isolated. MAIN OUTCOME MEASURES: Protein expression of GLUT4, GLUT1, and IR were determined by western blot. RESULTS: GLUT4 was exclusively expressed in the BM, and IR was predominantly expressed in the MVM, with increasing expression across gestation. BM GLUT1 expression was increased and BM GLUT4 expression was decreased in women with obesity delivering macrosomic babies. In placental villous explants, incubation with insulin stimulated Akt (S473) phosphorylation (+76%, P = 0.0003, n = 13) independent of maternal BMI and increased BM GLUT4 protein expression (+77%, P = 0.0013, n = 7) in placentas from lean women but not women with obesity. CONCLUSION: We propose that maternal insulin stimulates placental glucose transport by promoting GLUT4 trafficking to the BM, which may enhance glucose transfer to the fetus in response to postprandial hyperinsulinemia in women with normal BMI.

Patient Views on Religious Institutional Health Care.

Importance: Federal protections allow health facilities to limit options to patients on the basis of religious values. Little is known about whether US adults consider religious affiliation when selecting facilities and whether they agree with such limitations. Objective: To understand patient views on religious institutional care. Design, Setting, and Participants: This is a population-based, cross-sectional survey study of US adults recruited from the probability-based AmeriSpeak Omnibus panel available from NORC (formerly the National Opinion Research Center) at the University of Chicago. Surveys were administered via internet or telephone during a 3-day fielding period in November 2017. Data analysis was performed from January 2018 to October 2019. Exposures: Participant characteristics, including religiosity measures. Main Outcomes and Measures: Whether patients consider religious affiliation when selecting a health care facility and their views on whether an institution's religious values should take precedence over their health choices. Responses were compared by gender. When gender differences existed, regression models were performed, and thematic content analysis was applied to open-ended responses. Results: There were 1446 participants (745 [51.5%] male; mean [SD] age, 46 [17] years), for a survey completion rate of 24.5% and weighted cumulative response weight of 7.3%. Most respondents (62.6%) were white, and the most common religion was Protestant (28.2%). When specifically asked, only 6.4% reported that they considered religious affiliation when selecting a health care facility; most participants (71.3%) reported when selecting a health care facility that they did not care whether it is religiously affiliated, 13.4% preferred a religious affiliation, and 15.3% preferred no religious affiliation. There were no gender differences. Most participants (71.4%) believed that their health choices should take priority over an institution's religious affiliation in services offered, and this was more common for women than for men (74.9% vs 68.1%; difference, 6.8%; 95% CI, 5.6%-8.2%; P = .005), who more commonly endorsed concerns for personal choice and autonomy over one's own body. Conclusions and Relevance: This study suggests that most patients value their personal choices, yet do not consider an institution's religious affiliation when choosing their source of health care. Women placed greater emphasis on their autonomy in comparison with an institution's right to invoke religious restrictions to care. Given the growth in ownership of health care facilities by religious entities in the United States and increasing attention to conscientious objections, these findings point to a need for advocacy and legislation that effectively balances protections for religious institutions with protections for patients.