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.

Associations between HIV, antiretroviral therapy and preterm birth in the US Women's Interagency HIV Study, 1995-2018: a prospective cohort.

OBJECTIVE: To evaluate the associations of HIV infection with preterm birth (PTB), and of HIV antiretroviral therapy (ART) with PTB. METHODS: We analysed singleton live-born pregnancies among women from 1995 to 2019 in the Women's Interagency HIV Study, a prospective cohort of US women with, or at risk for, HIV. The primary exposures were HIV status and ART use before delivery [none, monotherapy or dual therapy, or highly active antiretroviral therapy (HAART)]. The primary outcome was PTB < 34 weeks, and, secondarily, < 28 and < 37 weeks. We analysed self-reported birth data, and separately modelled the associations between HIV and PTB, and between ART and PTB, among women with HIV. We used modified Poisson regression, and adjusted for age, race, parity, tobacco use and delivery year, and, when modelling the impact of ART, duration from HIV diagnosis to delivery, nadir CD4 count, and pre-pregnancy viral load and CD4 count. RESULTS: We analysed 488 singleton deliveries (56% exposed to HIV) to 383 women. The risk of PTB < 34 weeks was similar among women with and without HIV, but the risk of PTB < 37 weeks was higher [32% vs. 23%; adjusted risk ratio (aRR) = 1.43; 95% confidence interval (CI): 1.07-1.91] among women with HIV. The risk of PTB < 34 weeks was lower among women with HIV receiving HAART than among those receiving no ART (7% vs. 26%; aRR:0.19; 95% CI: 0.08-0.44). The associations between HAART and PTB < 28 and < 37 weeks were similar. CONCLUSIONS: Antiretroviral therapy exposure was associated with a decreased risk of PTB among a US cohort of women with HIV. Given the growing concerns about ART and adverse pregnancy outcomes, this finding that ART may be protective for PTB is reassuring.

Perceived healthcare quality and contraception utilization among persons recently incarcerated.

Purpose: Previously incarcerated women have specific gender and physiologic needs that are poorly addressed on community re-entry. The objective of this study is to evaluate the relationship between contraception use and perceived healthcare quality post-incarceration. Additionally, we examine the association between social determinants of health and contraception use post-incarceration. Methods: A secondary analysis of a cross-sectional study of reproductive-aged women with a history of criminal-justice involvement in three cities (n = 383) was performed. Questions related to demographics, social determinants of health, sexual and reproductive health practices, health services use, and healthcare quality were analyzed. Bivariate analysis and logistic regression examined associations between these variables and contraception utilization among persons recently incarcerated. Results: 35% of the participants used a method to prevent pregnancy. There were no significant differences noted between contraceptive users and non-users in perceived healthcare quality. Participants who were not using a contraceptive method were more likely to lack health insurance and experience food insecurity when compared to contraceptive users. Conclusions: Although there was no difference in perceived healthcare quality between contraceptive users and non-users, significant barriers to contraceptive access on community re-entry exist. More studies are warranted to explore the sexual and reproductive health of previously incarcerated women.

Differences in Vaginal Microbiota, Host Transcriptome, and Proteins in Women With Bacterial Vaginosis Are Associated With Metronidazole Treatment Response.

BACKGROUND: Bacterial vaginosis (BV) treatment failures and recurrences are common. To identify features associated with treatment response, we compared vaginal microbiota and host ectocervical transcriptome before and after oral metronidazole therapy. METHODS: Women with BV (Bronx, New York and Thika, Kenya) received 7 days of oral metronidazole at enrollment (day 0) and underwent genital tract sampling of microbiome (16S ribosomal RNA gene sequencing), transcriptome (RNAseq), and immune mediator concentrations on day 0, 15, and 35. RESULTS: Bronx participants were more likely than Thika participants to clinically respond to metronidazole (19/20 vs 10/18, respectively, P = .0067) and by changes in microbiota composition and diversity. After dichotomizing the cohort into responders and nonresponders by change in α-diversity between day 35 and day 0, we identified that transcription differences associated with chemokine signaling (q = 0.002) and immune system process (q = 2.5 × 10-8) that differentiated responders from nonresponders were present at enrollment. Responders had significantly lower levels of CXCL9 in cervicovaginal lavage on day 0 (P < .007), and concentrations of CXCL9, CXCL10, and monocyte chemoattractant protein 1 increased significantly between day 0 and day 35 in responders vs nonresponders. CONCLUSIONS: Response to metronidazole is characterized by significant changes in chemokines and related transcripts, suggesting that treatments that promote these pathways may prove beneficial.

Primary HPV and Molecular Cervical Cancer Screening in US Women Living With Human Immunodeficiency Virus.

BACKGROUND: Primary human papillomavirus (HPV) screening (PHS) utilizes oncogenic human papillomavirus (oncHPV) testing as the initial cervical cancer screening method and typically, if positive, additional reflex-triage (eg, HPV16/18-genotyping, Pap testing). While US guidelines support PHS usage in the general population, PHS has been little studied in women living with HIV (WLWH). METHODS: We enrolled n = 865 WLWH (323 from the Women's Interagency HIV Study [WIHS] and 542 from WIHS-affiliated colposcopy clinics). All participants underwent Pap and oncHPV testing, including HPV16/18-genotyping. WIHS WLWH who tested oncHPV[+] or had cytologic atypical squamous cells of undetermined significance or worse (ASC-US+) underwent colposcopy, as did a random 21% of WLWH who were oncHPV[-]/Pap[-] (controls). Most participants additionally underwent p16/Ki-67 immunocytochemistry. RESULTS: Mean age was 46 years, median CD4 was 592 cells/µL, 95% used antiretroviral therapy. Seventy WLWH had histologically-determined cervical intraepithelial neoplasia grade 2 or greater (CIN-2+), of which 33 were defined as precancer (ie, [i] CIN-3+ or [ii] CIN-2 if concurrent with cytologic high grade squamous intraepithelial lesions [HSILs]). PHS had 87% sensitivity (Se) for precancer, 9% positive predictive value (PPV), and a 35% colposcopy referral rate (Colpo). "PHS with reflex HPV16/18-genotyping and Pap testing" had 84% Se, 16% PPV, 30% Colpo. PHS with only HPV16/18-genotyping had 24% Colpo. "Concurrent oncHPV and Pap Testing" (Co-Testing) had 91% Se, 12% PPV, 40% Colpo. p16/Ki-67 immunochemistry had the highest PPV, 20%, but 13% specimen inadequacy. CONCLUSIONS: PHS with reflex HPV16/18-genotyping had fewer unnecessary colposcopies and (if confirmed) could be a potential alternative to Co-Testing in WLWH.

Mifepristone Pretreatment for the Medical Management of Early Pregnancy Loss.

BACKGROUND: Medical management of early pregnancy loss is an alternative to uterine aspiration, but standard medical treatment with misoprostol commonly results in treatment failure. We compared the efficacy and safety of pretreatment with mifepristone followed by treatment with misoprostol with the efficacy and safety of misoprostol use alone for the management of early pregnancy loss. METHODS: We randomly assigned 300 women who had an anembryonic gestation or in whom embryonic or fetal death was confirmed to receive pretreatment with 200 mg of mifepristone, administered orally, followed by 800 µg of misoprostol, administered vaginally (mifepristone-pretreatment group), or 800 µg of misoprostol alone, administered vaginally (misoprostol-alone group). Participants returned 1 to 4 days after misoprostol use for evaluation, including ultrasound examination, by an investigator who was unaware of the treatment-group assignments. Women in whom the gestational sac was not expelled were offered expectant management, a second dose of misoprostol, or uterine aspiration. We followed all participants for 30 days after randomization. Our primary outcome was gestational sac expulsion with one dose of misoprostol by the first follow-up visit and no additional intervention within 30 days after treatment. RESULTS: Complete expulsion after one dose of misoprostol occurred in 124 of 148 women (83.8%; 95% confidence interval [CI], 76.8 to 89.3) in the mifepristone-pretreatment group and in 100 of 149 women (67.1%; 95% CI, 59.0 to 74.6) in the misoprostol-alone group (relative risk, 1.25; 95% CI, 1.09 to 1.43). Uterine aspiration was performed less frequently in the mifepristone-pretreatment group than in the misoprostol-alone group (8.8% vs. 23.5%; relative risk, 0.37; 95% CI, 0.21 to 0.68). Bleeding that resulted in blood transfusion occurred in 2.0% of the women in the mifepristone-pretreatment group and in 0.7% of the women in the misoprostol-alone group (P=0.31); pelvic infection was diagnosed in 1.3% of the women in each group. CONCLUSIONS: Pretreatment with mifepristone followed by treatment with misoprostol resulted in a higher likelihood of successful management of first-trimester pregnancy loss than treatment with misoprostol alone. (Funded by the National Institute of Child Health and Human Development; PreFaiR ClinicalTrials.gov number, NCT02012491 .).

Acceptability of a Tenofovir Disoproxil Fumarate Intravaginal Ring for HIV Pre-Exposure Prophylaxis Among Sexually Active Women.

INTRODUCTION: Vaginal ring delivery of antiretroviral drugs may provide protection against acquisition of HIV-1 when used as Pre-Exposure prophylaxis. As part of a randomized placebo-controlled safety trial of a tenofovir disoproxil fumarate (TDF) intravaginal ring (IVR), we assessed product acceptability through surveys of women after continuous ring use. METHODS: Sexually active, HIV-negative women were enrolled to investigate the safety and pharmacokinetics of 3 months of continuous TDF IVR use. The study was designed to include 40 US participants randomly assigned (3:1) to a TDF or placebo IVR. Twelve were randomized to TDF and 5 to the placebo group before the study was electively discontinued because of the development of vaginal ulcerations in 8 women in the TDF group. Acceptability data were gathered via self-administered, computer-based questionnaires. RESULTS: The average age of the 17 participants was 31 years (range, 18-42 years). Sixteen participants (94%) completed all questions at 2 study visits. When asked about ring likeability after 1 month of ring use, 12 (75%) of 16 reported overall liking the ring, including 6 (75%) of 8 who developed ulcerations. In addition, 10 (83%) of 12 who had their menses during the first month of ring use were not bothered by the ring, and 11 (69%) of 16 stated that the ring was not bothersome with use during sex. CONCLUSIONS: Despite unanticipated ulcers, TDF and placebo IVRs were acceptable to some women, even when used with menses and during sex, which is promising for continued development of IVRs for HIV prevention.

Management of early pregnancy loss with mifepristone and misoprostol: clinical predictors of treatment success from a randomized trial.

BACKGROUND: Early pregnancy loss is a common event in the first trimester, occurring in 15%-20% of confirmed pregnancies. A common evidence-based medical regimen for early pregnancy loss uses misoprostol, a prostaglandin E1 analog, with a dosage of 800 µg, self-administered vaginally. The clinical utility of this regimen is limited by suboptimal effectiveness in patients with a closed cervical os, with 29% of patients experiencing early pregnancy loss requiring a second dose after 3 days and 16% of patients eventually requiring a uterine aspiration procedure. OBJECTIVE: This study aimed to evaluate clinical predictors associated with treatment success in patients receiving medical management with mifepristone-misoprostol or misoprostol alone for early pregnancy loss. STUDY DESIGN: We performed a planned secondary analysis of a randomized trial comparing mifepristone-misoprostol with misoprostol alone for management of early pregnancy loss. The published prediction model for treatment success of single-dose misoprostol administered vaginally included the following variables: active bleeding, type of early pregnancy loss (anembryonic pregnancy or embryonic and/or fetal demise), parity, gestational age, and treatment site; previous significant predictors were vaginal bleeding within the past 24 hours and parity of 0 or 1 vs >1. To determine if these characteristics predicted differential proportions of patients with treatment success or failure, we performed bivariate analyses; given the small proportion of treatment failures in the combined treatment arm, both arms were combined for analysis. Thereafter, we performed a logistic regression analysis to assess the effect of these predictors collectively in each of the 2 treatment groups separately as well as in the full cohort as a proxy for the combined treatment arm. Finally, by using receiver operating characteristic curves, we tested the ability of these predictors in association with misoprostol treatment success to discriminate between treatment success and treatment failure. To quantify the ability of the score to discriminate between treatment success and treatment failure in each treatment arm as well as in the entire cohort, we calculated the area under the curve. Using multivariable logistic regression, we then assessed our study population for other predictors of treatment success in both treatment groups, with and without mifepristone pretreatment. RESULTS: Overall, 297 evaluable participants were included in the primary study, with 148 in the mifepristone-misoprostol combined treatment group and 149 in the misoprostol-alone treatment group. Among patients who had vaginal bleeding at the time of treatment, 15 of 17 (88%) in the mifepristone-misoprostol combined treatment group and 12 of 17 (71%) in the misoprostol-alone treatment group experienced expulsion of pregnancy tissue. Among patients with a parity of 0 or 1, 94 of 108 (87%) in the mifepristone-misoprostol treatment group and 66 of 95 (69%) in the misoprostol-alone treatment group experienced expulsion of pregnancy tissue. These clinical characteristics did not predict treatment success in the combined cohort alone (area under the curve=0.56; 95% confidence interval, 0.48-0.64). No other baseline clinical factors predicted treatment success in the misoprostol-alone treatment arm or mifepristone pretreatment arm. In the full cohort, the significant predictors of treatment success were pretreatment with mifepristone (adjusted odds ratio=2.51; 95% confidence interval, 1.43-4.43) and smoking (adjusted odds ratio=2.15; 95% confidence interval, 1.03-4.49). CONCLUSION: No baseline clinical factors predicted treatment success in women receiving medical management with misoprostol for early pregnancy loss. Adding mifepristone to the medical management regimen of early pregnancy loss improved treatment success; thus, mifepristone treatment should be considered for management of early pregnancy loss regardless of baseline clinical factors.

Patient-controlled tissue collection for genetic testing after early pregnancy loss: A pilot study.

OBJECTIVE: To determine how frequently and effectively products of conception can be obtained among women pursuing medical management of early pregnancy loss. METHODS: This pilot study was conducted to assess products of conception recovery outcomes for participants opting for medical management compared with women opting for surgical aspiration A tissue-collection kit was provided to women opting for medical management. Outcome measures included successful collection of products of conception, quantity and integrity of DNA, and participant satisfaction with the process. RESULTS: Tissue was collected from 19 of 22 participants in the medical management group (84%) and 39 participants (100%) in the surgical management group (P = .02). DNA yield and integrity were similar among both groups (P = .03 and P = .003, respectively). Participants in the medical group reported a high comfort level with the kit and the process of tissue collection. CONCLUSIONS: Medical management of a missed abortion followed by patient-controlled collection of products of conception for subsequent cytogenetic analysis is well tolerated and highly effective. This methodology may reduce the need for surgical management, empower women to have more agency in their medical decisions, and increase access to genetic testing.

The Cervicovaginal Microbiota and Its Associations With Human Papillomavirus Detection in HIV-Infected and HIV-Uninfected Women.

BACKGROUND: Bacterial vaginosis (BV) is characterized by low abundance of Lactobacillus species, high pH, and immune cell infiltration and has been associated with an increased risk of human papillomavirus (HPV) infection. We molecularly assessed the cervicovaginal microbiota over time in human immunodeficiency virus (HIV)-infected and HIV-uninfected women to more comprehensively study the HPV-microbiota relationship, controlling for immune status. METHODS: 16S ribosomal RNA gene amplicon pyrosequencing and HPV DNA testing were conducted annually in serial cervicovaginal lavage specimens obtained over 8-10 years from African American women from Chicago, of whom 22 were HIV uninfected, 22 were HIV infected with a stable CD4+ T-cell count of > 500 cells/mm3, and 20 were HIV infected with progressive immunosuppression. Vaginal pH was serially measured. RESULTS: The relative abundances of Lactobacillus crispatus and other Lactobacillus species were inversely associated with vaginal pH (all P < .001). High (vs low) L. crispatus relative abundance was associated with decreased HPV detection (odds ratio, 0.48; 95% confidence interval, .24-.96; Ptrend = .03) after adjustment for repeated observation and multiple covariates, including pH and study group. However, there were no associations between HPV and the relative abundance of Lactobacillus species as a group, nor with Lactobacillus gasseri, Lactobacillus iners, and Lactobacillus jensenii individually. CONCLUSIONS: L. crispatus may have a beneficial effect on the burden of HPV in both HIV-infected and HIV-uninfected women (independent of pH).