The CryoPop study: Screening for high-grade cervical dysplasia in Karnataka, India.

OBJECTIVE: To describe our experience of screening with visual inspection with acetic acid (VIA) and colposcopy to identify women with high-grade precancerous cervical lesions who were candidates for cryotherapy. Women were screened to determine eligibility for a clinical trial testing the safety and efficacy of a new, simple and inexpensive cryotherapy device (CryoPop®) targeted for use in low and middle-income countries (LMICs). DESIGN: Prospective cohort study. SETTING: Primary and urban health centres in Belagavi, Hubballi and Vijayapur, India. POPULATION: Women in the age-group 30-49 years, premenopausal, with no prior hysterectomy and no known HIV infection were eligible for screening. METHODS: Visual inspection with acetic acid was performed on eligible women following informed consent. VIA-positive women were referred for colposcopy and biopsy. Biopsies were read by two pathologists independently, with a third pathologist acting as tie-breaker if needed. MAIN OUTCOME MEASURES: The primary outcome measures were the number/proportion of women screening positive by VIA and the number/proportion of those women screening VIA-positive found to have high-grade cervical lesions on biopsy (cervical intraepithelial neoplasia 2/3 [CIN 2/3]). Demographic variables were compared between women who screened VIA-positive and those who screened VIA-negative; a separate comparison of demographic and limited reproductive variables was performed between women who had CIN 2/3 on biopsy and those without CIN 2/3 on biopsy. Chi-square or Fisher's exact tests for categorical data and t-tests or analysis of variance for numeric data were used with all tests two-sided and performed at an alpha 0.05 level of statistical significance. RESULTS: A total of 9130 women were screened with VIA between 4 July 2020 and 31 March 2021. The mean age of all women screened was 37 years (standard deviation = 5.6 years) with 6073 of the women (66.5%) in the 30-39 year range. Only 1% of women reported prior cervical cancer screening. A total of 501 women (5.5%) were VIA-positive; of these, 401 women underwent colposcopy. Of those who had colposcopy, 17 (4.2%) had high-grade lesions on biopsy, an additional 164 (40.9%) had low-grade cervical lesions on biopsy or endocervical curettage and one woman (0.2%) was found to have invasive cancer. VIA-positive women were younger and had higher levels of education and income; however, women who were VIA-positive and found to have CIN 2/3 were older, were more likely to be housewives and had higher household income than those without CIN 2/3. CONCLUSION: Despite the COVID-19 pandemic, over 9100 women were screened with VIA for precancerous lesions. However, only 17 (4.2%) were found to have biopsy-proven high-grade cervical lesions, underscoring the subjective performance of VIA as a screening method. Given that this is significantly lower than rates reported in the literature, it is possible that the prevalence of high-grade lesions in this population was impacted by screening a younger and more rural population. This study demonstrates that screening is feasible in an organised fashion and can be scaled up rapidly. However, while inexpensive and allowing for same-day treatment, VIA may be too subjective and have insufficient accuracy clearly to identify lesions requiring treatment, particularly in low-prevalence and low-risk populations, calling into question its overall cost-effectiveness.

Special ambulatory gynecologic considerations in the era of coronavirus disease 2019 (COVID-19) and implications for future practice.

The coronavirus disease 2019 pandemic has altered medical practice in unprecedented ways. Although much of the emphasis in obstetrics and gynecology to date has been on the as yet uncertain effects of coronavirus disease 2019 in pregnancy and on changes to surgical management, the pandemic has broad implications for ambulatory gynecologic care. In this article, we review important ambulatory gynecologic topics such as safety and mental health, reproductive life planning, sexually transmitted infections, and routine screening for breast and cervical cancer. For each topic, we review how care may be modified during the pandemic, provide recommendations when possible on how to ensure continued access to comprehensive healthcare at this time, and discuss ways that future practice may change. Social distancing requirements may place patients at higher risk for intimate partner violence and mental health concerns, threaten continued access to contraception and abortion services, affect prepregnancy planning, interrupt routine screening for breast and cervical cancer, increase risk of sexually transmitted infection acquisition and decrease access to treatment, and exacerbate already underlying racial and minority disparities in care and health outcomes. We advocate for increased use of telemedicine services with increased screening for intimate partner violence and depression using validated questionnaires. Appointments for long-acting contraceptive insertions can be prioritized. Easier access to patient-controlled injectable contraception and pharmacist-provided hormonal contraception can be facilitated. Reproductive healthcare access can be ensured through reducing needs for ultrasonography and laboratory testing for certain eligible patients desiring abortion and conducting phone follow-up for medication abortions. Priority for in-person appointments should be given to patients with sexually transmitted infection symptoms, particularly if at risk for complications, while also offering expedited partner therapy. Although routine mammography screening and cervical cancer screening may be safely delayed, we discuss society guideline recommendations for higher-risk populations. There may be an increasing role for patient-collected human papillomavirus self-samples using new cervical cancer screening guidelines that can be expanded considering the pandemic situation. Although the pandemic has strained our healthcare system, it also affords ambulatory clinicians with opportunities to expand care to vulnerable populations in ways that were previously underutilized to improve health equity.

Integrase inhibitors in late pregnancy and rapid HIV viral load reduction.

BACKGROUND: Minimizing time to HIV viral suppression is critical in pregnancy. Integrase strand transfer inhibitors (INSTIs), like raltegravir, are known to rapidly suppress plasma HIV RNA in nonpregnant adults. There are limited data in pregnant women. OBJECTIVE: We describe time to clinically relevant reduction in HIV RNA in pregnant women using INSTI-containing and non-INSTI-containing antiretroviral therapy (ART) options. STUDY DESIGN: We conducted a retrospective cohort study of pregnant HIV-infected women in the United States from 2009 through 2015. We included women who initiated ART, intensified their regimen, or switched to a new regimen due to detectable viremia (HIV RNA >40 copies/mL) at ≥20 weeks gestation. Among women with a baseline HIV RNA permitting 1-log reduction, we estimated time to 1-log RNA reduction using the Kaplan-Meier estimator comparing women starting/adding an INSTI in their regimen vs other ART. To compare groups with similar follow-up time, we also conducted a subgroup analysis limited to women with ≤14 days between baseline and follow-up RNA data. RESULTS: This study describes 101 HIV-infected pregnant women from 11 US clinics. In all, 75% (76/101) of women were not taking ART at baseline; 24 were taking non-INSTI containing ART, and 1 received zidovudine monotherapy. In all, 39% (39/101) of women started an INSTI-containing regimen or added an INSTI to their ART regimen. Among 90 women with a baseline HIV RNA permitting 1-log reduction, the median time to 1-log RNA reduction was 8 days (interquartile range [IQR], 7-14) in the INSTI group vs 35 days (IQR, 20-53) in the non-INSTI ART group (P < .01). In a subgroup of 39 women with first and last RNA measurements ≤14 days apart, median time to 1-log reduction was 7 days (IQR, 6-10) in the INSTI group vs 11 days (IQR, 10-14) in the non-INSTI group (P < .01). CONCLUSION: ART that includes INSTIs appears to induce more rapid viral suppression than other ART regimens in pregnancy. Inclusion of an INSTI may play a role in optimal reduction of HIV RNA for HIV-infected pregnant women presenting late to care or failing initial therapy. Larger studies are urgently needed to assess the safety and effectiveness of this approach.

The effect of gynecologic algorithm pathways on emergency department visit times.

BACKGROUND: The use of multidisciplinary algorithmic pathways is one strategy to improve efficiency and quality of care in Emergency Departments (EDs). To this end, in the fall of 2005, we implemented algorithmic pathways for evaluation of ED patients with common gynecologic complaints. OBJECTIVES: The goals of this initiative were to improve length of stay as a marker for operational efficiency and to reduce health care disparities by ensuring consistent management regimens for all patients. METHODS: A retrospective observational comparison study was performed through a review of consults in the year preceding and the year after implementation of the pathways. The length of stay was calculated based on time of initial triage until discharge. The length of stay from both groups was compared using an unpaired Student's t-test analysis. RESULTS: There was an 85-min decrease in the mean visit time between the pre-intervention group (108 patients, 610 min, SD 345.4) and the post-intervention group (105 patients, 525 min, SD 251.5), p=0.04. CONCLUSIONS: Algorithmic pathways had a positive impact on patient care as measured by the average amount of time our patients spent in the ED. Gynecologic care in the ED was standardized, and length of stay for patients with gynecologic complaints decreased. The implementation of algorithms resulted in more consistent care with earlier initiation of pertinent studies, while facilitating more rapid critical decision-making by providers from both departments. Further analysis is required to examine cost-effectiveness as well as patient safety and provider satisfaction issues.

Women Living with Human Immunodeficiency Virus with Intended and Unintended Pregnancy: Characteristics and Patient Outcomes.

Background: Rates of unintended pregnancy may be higher in women living with human immunodeficiency virus (WLWH) than in the general population, and it is unclear how populations of WLWH with intended and unintended pregnancy differ. We compared baseline characteristics and outcomes between WLWH with intended and unintended pregnancy. Materials and Methods: We conducted a retrospective analysis of WLWH enrolled in a human immunodeficiency virus (HIV) and Pregnancy clinic from 2003 to 2014. Data were analyzed using descriptive statistics, chi-square test, Student's t-test, one-way analysis of variance, and linear and logistic regression analysis. Two-tailed p-value <0.05 was considered significant. The study was approved by the Johns Hopkins University School of Medicine Institutional Review Board. Results: Sixty-nine (27.1%) of 255 women reported an intended pregnancy. Women with intended pregnancy (WWIP) were more likely to be older, White, married, privately insured, and college educated. WWIP were less likely to use tobacco (15.9% vs. 44.2%, p < 0.001), alcohol (2.9% vs. 11.1%, p = 0.041), opiates (0.0% vs. 19.3%, p < 0.001), or cocaine (2.9% vs. 21.0%, p < 0.001) during pregnancy, more likely to disclose their HIV status to the father of the baby by delivery (100.0% vs. 15.8%, p < 0.001), and more likely to receive less effective contraception at delivery (condoms 14.9% vs. 4.8%, p = 0.024; sterilization 11.9% vs. 22.1%, p = 0.028). In multivariate regression analysis, pregnancy intendedness was an important predictor of nondetectable viral load at pregnancy entry but not at delivery. Conclusions: WLWH vary in their baseline characteristics and pregnancy outcomes depending on pregnancy intendedness, highlighting the need to improve pregnancy timing in WLWH and intensify interventions for women with unintended pregnancy.

Childbearing motivations, pregnancy desires, and perceived partner response to a pregnancy among urban female youth: does HIV-infection status make a difference?

Despite a growing literature assessing pregnancy desires among HIV-infected women enrolled in clinical care, little attention has been paid to HIV-infected youth for whom pregnancy is a very relevant issue. In urban areas with high rates of teen pregnancy and HIV infection, further understanding of childbearing motivations and relationship dynamics influencing pregnancy desires among female youth is needed. This study compares the childbearing motivations, pregnancy desires, and perceived partner desire for a pregnancy among predominately African-American HIV-infected (n=46) and HIV-uninfected (n=355) female youth (15-24 years). An HIV-infected status was not significantly associated with childbearing motivations or the desire for a future pregnancy, p>0.10. HIV-infection was, however, associated with an increased likelihood to perceive that one's partner would have a positive response to a pregnancy (adjusted odds ratio [aOR] 3.5, 95% confidence interval [CI] 1.2-10.4, p=0.02) compared to uninfected peers. While race was not associated with participants' own desire for a child, white youth were significantly less likely to perceive a positive partner response to becoming pregnant than their African-American peers (aOR 0.23, 95% CI 0.09-0.56, p=0.001). These data suggest that the desire for childbearing is not diminished by HIV infection among urban female youth, highlighting the need for routine, provider-initiated discussions about childbearing with urban youth to minimized unintended pregnancies and HIV transmission.

Update on trends for inpatient surgical management of tubal ectopic pregnancy in Maryland.

OBJECTIVES: In Maryland, an analysis from 1994-1999 found that most hospitalized patients with tubal pregnancy underwent extirpative operations. The objective of this study was to determine whether practice patterns had changed over time. METHODS: Using the Maryland Health Service Cost Review Commission (HSCRC) database from January 1, 2000-December 31, 2004, subjects were identified by ICD-9 code 633.1, tubal pregnancy. The incidence of hospitalization was estimated based on state census data. Cases were analyzed by demographics, presentation, surgeon volume for ectopics, surgical treatment, length of stay, and charges. RESULTS: There were 2292 cases of tubal pregnancy identified, yielding an incidence for hospitalization of 4.81 per 10,000 women. The mean age of subjects was 29.6. Most were admitted through the emergency department (76.8%). Extirpative procedures were used in 88.01%. ER admission and increasing age were associated with extirpative surgery. Mean length of stay was 1.86 days; mean total charges were $5480.11. CONCLUSIONS: A greater percentage of hospitalized ectopics were treated radically than prior. This may be due to acuity of presentation or regional surgical practices and preferences. Continued surveillance and a move toward improvement of Maryland's outcomes for ectopic pregnancy is needed. We propose an algorithm for emergency triage and management of pregnancy in an unknown location toward this end.

Pregnant Individuals' Views on Fetal Tissue Research in the United States.

OBJECTIVE: Fetal tissue research has driven significant medical advances but remains publicly contentious in the United States. The views of pregnant individuals in the United States regarding the donation of fetal tissue offer an important and previously unexplored perspective on this issue. METHODS: We conducted a secondary analysis of data from two separate, broader qualitative studies. Pregnant and recently pregnant individuals (N=79) from clinical sites at the University of North Carolina at Chapel Hill, Johns Hopkins University, and Massachusetts General Hospital were interviewed individually using a semi-structured guide addressing a range of issues related to infectious disease research and pregnancy, including the acceptability of fetal tissue research. Interviews were transcribed, coded, and analyzed for emergent themes. RESULTS: Among this sample of predominantly Black (61%), reproductive-aged pregnant and recently pregnant participants, the majority (72%) generally supported fetal tissue research. The following three themes were identified: choice, respect, and meaning. Respondents discussed the deeply personal nature of decisions surrounding fetal tissue research, emphasizing the importance of informed consent and respect for the person's emotional state when approaching for consent. The ways in which participants regarded how to respectfully handle fetal tissue also shaped views about the acceptability of donation, both for and against. For many participants, fetal tissue donation to research represented one way of ascribing meaning to pregnancy termination or loss. CONCLUSION: Among this diverse sample of pregnant and recently pregnant individuals, most were supportive of fetal tissue donation for research. A better understanding of pregnant individuals' views on this topic may lead to policies and practices that are congruent with the needs and values of people facing decisions regarding the disposition of fetal remains.

Understanding high fertility desires and intentions among a sample of urban women living with HIV in the United States.

To assess childbearing motivations, fertility desires and intentions, and their relationship with key factors, we conducted a cross-sectional survey among 181 HIV-infected women of reproductive age (15-44 years) receiving clinical care at two urban health clinics. Fertility desires (59%) and intentions (66% of those who desired a child) were high among this predominately African American sample of women, while the proportion with accurate knowledge of mother-to-child transmission (MTCT) was low (15%). Multivariate regression analyses identified factors significantly associated with the intention to have a child. Notably, age and parity did not remain significant in the adjusted model. The discrepancies between expressed desires and intentions for future childbearing, and the strong role of perceived partner desire for childbearing emphasize the need for universal reproductive counseling to help women living with HIV navigate their reproductive decisions and facilitate safe pregnancies and healthy children.

Primary care guidelines for the management of persons infected with human immunodeficiency virus: 2009 update by the HIV medicine Association of the Infectious Diseases Society of America.

Evidence-based guidelines for the management of persons infected with human immunodeficiency virus (HIV) were prepared by an expert panel of the HIV Medicine Association of the Infectious Diseases Society of America. These updated guidelines replace those published in 2004. The guidelines are intended for use by health care providers who care for HIV-infected patients or patients who may be at risk for acquiring HIV infection. Since 2004, new antiretroviral drugs and classes have become available, and the prognosis of persons with HIV infection continues to improve. However, with fewer complications and increased survival, HIV-infected persons are increasingly developing common health problems that also affect the general population. Some of these conditions may be related to HIV infection itself and its treatment. HIV-infected persons should be managed and monitored for all relevant age- and gender-specific health problems. New information based on publications from the period 2003-2008 has been incorporated into this document.

Access to Fertility Treatment for Mixed-Status Couples With Human Immunodeficiency Virus.

In an effort to place the recent Centers for Disease Control and Prevention Morbidity and Mortality Weekly Report publications regarding conception options for mixed-status couples with human immunodeficiency virus (HIV) in perspective, we review the historical evolution of conception options for mixed-status couples with HIV with particular focus on the potential need for fertility treatment and the feasibility of accessing such treatment.

Missed Opportunities for Repeat HIV Testing in Pregnancy: Implications for Elimination of Mother-to-Child Transmission in the United States.

HIV testing is an effective intervention that is used for reducing perinatal HIV transmission. Centers for Disease Control and Prevention recommends a second HIV test during the third trimester of pregnancy for women in settings with an elevated HIV incidence (≥17 cases per 100,000 person-years). We conducted a retrospective cohort study at a single hospital in Baltimore, Maryland, to determine whether a second HIV test was done and to compare HIV retesting with mandated syphilis retesting. Of women who delivered at this hospital, 98.8% received prenatal care. Descriptive, bivariate, and multivariable analyses were performed. Among 1632 women, mean age was 27.6 years (standard deviation: 6.3), 59.6% were black, and 55.5% were single. HIV retesting was done in 28.4% of women, which was significantly less often compared with the state-mandated syphilis retesting (78.7%, p < 0.001). The odds of having an HIV retest were 15 times higher among women who received prenatal care at a teaching clinic [adjusted odds ratio (aOR): 15.58; 95% confidence interval (CI): 11.12-21.81], and they were lower among women with private insurance (aOR: 0.54, 95% CI: 0.34-0.86). The odds of having a syphilis retest were twice as high among women who received prenatal care at a faculty practice (aOR: 2.17; 95% CI: 1.53-3.09), and they were lower among women with private insurance (aOR: 0.61, 95% CI: 0.43-0.88). Emphasizing an "opt-out" HIV retesting approach through state laws may minimize risk perception, and this is one strategy that can be considered in areas of high HIV incidence to reach the goal of eliminating perinatal HIV transmission in the United States.

Safety of Tenofovir Disoproxil Fumarate-Based Antiretroviral Therapy Regimens in Pregnancy for HIV-Infected Women and Their Infants: A Systematic Review and Meta-Analysis.

BACKGROUND: There are limited data on adverse effects of tenofovir disoproxil fumarate (TDF)-based antiretroviral therapy (ART) on pregnant women and their infants. METHODS: We conducted a systematic review of studies published between January 1980 and January 2017 that compared adverse outcomes in HIV-infected women receiving TDF- vs. non-TDF-based ART during pregnancy. The risk ratio (RR) for associations was pooled using a fixed-effects model. RESULTS: Seventeen studies met the study inclusion criteria. We found that the rate of preterm (<37 weeks gestation) delivery (RR = 0.90, 95% confidence interval [CI]: 0.81 to 0.99, I = 59%) and stillbirth (RR = 0.60, 95% CI: 0.43 to 0.84, I = 72.0%) were significantly lower in women exposed (vs. not) to TDF-based ART regimen. We found no increased risk in maternal severe (grade 3) or potentially life-threatening (grade 4) adverse events (RR = 0.62; 95% CI: 0.30 to 1.29), miscarriage (RR = 1.09; 95% CI: 0.80 to 1.48), very preterm (<34 weeks gestation) delivery (RR = 1.08, 95% CI: 0.72 to 1.62), small for gestational age (RR = 0.87, 95% CI: 0.67 to 1.13), low birth weight (RR = 0.91; 95% CI: 0.80 to 1.04), very low birth weight (RR = 3.18; 95% CI: 0.65 to 15.63), congenital anomalies (RR = 1.03; 95% CI: 0.83 to 1.28), infant adverse outcomes or infant mortality (age >14 days) (RR = 0.65; 95% CI: 0.23 to 1.85), but increased neonatal mortality (age <14 days) risk (RR = 5.64, 95% CI: 1.70 to 18.79) with TDR-based ART exposure. No differences were found for anthropomorphic parameters at birth; one study reported minor differences in z-scores for length and head circumference at age 1 year. CONCLUSIONS: TDF-based ART in pregnancy seems generally safe for women and their infants. However, data remain limited and further studies are needed, particularly to assess neonatal mortality and infant growth/bone effects.

Accuracy of Papanicolaou test among HIV-infected women.

OBJECTIVE: We examined the accuracy of the Papanicolaou (Pap) test among women with and women at high risk for human immunodeficiency virus (HIV) infection. METHODS: Pap test results and colposcopy findings were compared for 189 HIV-infected women and 95 HIV-uninfected women from the Baltimore HIV Epidemiology Research (HER) study site who were followed up semiannually from 1993 through 1999. Correlations were examined using data from individual visits that were analyzed using generalized estimating equation methods. RESULTS: Among women with normal results of Pap tests who underwent biopsy, the likelihood of cervical intraepithelial neoplasia was significantly greater for HIV-infected women (14.3%) than for HIV-uninfected women (1.2%) (P < .01). The specificity and negative predictive value of Pap testing were higher among HIV-uninfected women, regardless of whether detection of atypical squamous cells of undetermined significance was considered to be abnormal. Independent predictors of discordant cytologic and histologic findings included detection of human papillomavirus (adjusted odds ratio [OR], 3.1; 95% confidence interval [CI], 1.0-9.8) and a CD4 cell count of < 500 cells/microL (adjusted OR, 6.5; 95% CI, 1.5-29.2). Of the 19 HIV-infected women with normal cytologic findings and cervical intraepithelial neoplasia, 18 had abnormal Pap test findings (most often atypical squamous cells of undetermined significance) within 1 year of discordant cytologic and histologic findings. CONCLUSION: In this well-described cohort of women with and women at high risk for HIV infection, agreement between cytologic findings and colposcopic and histologic findings was high. A small number of HIV-infected women had cervical intraepithelial neoplasia, despite having normal cytologic findings; 95% of these women would have had cytologic abnormalities detected within 1 year of the discordant results by use of current guidelines for Pap test screening. These data fail to support the need for routine colposcopy in all HIV-infected women.

Effect of HIV infection on atypical squamous cells of undetermined significance.

BACKGROUND: Detection of atypical squamous cells of undetermined significance (ASCUS) is a cervical cytologic finding that is suggestive but not definitive of squamous intraepithelial lesions (SILs). METHODS: We examined the risk, characteristics, and progression of ASCUS in women with and without human immunodeficiency virus (HIV) infection. Cervical Papanicolou (Pap) test and colposcopy data were obtained at the first 10 semiannual visits for the HIV Epidemiology Research study of 774 HIV-infected and 480 demographically similar, HIV-uninfected women in the United States. Multiple logistic regression models and Cox proportional hazards models were utilized. RESULTS: ASCUS was more common among HIV-infected women (odds ratio [OR], 1.6 [95% confidence interval {CI}, 1.3-2.0] to 2.6 [95% CI, 1.9-3.6]) after adjustment for human papillomavirus (HPV) infection and other risk factors (e.g., race, condyloma, and prior Pap test result). Among women with normal Pap test results at enrollment, the cumulative incidence of ASCUS was 78% among HIV-infected women and 38% among HIV-uninfected women. HIV-infected and HIV-uninfected women with ASCUS did not differ by prevalence of indices of inflammation (inflammation on Pap test and leukocytes on cervical gram stain). HPV infection, including high risk types, was more common among HIV-infected women with ASCUS. Among women with ASCUS, 60% of HIV-infected and 25% of HIV-uninfected women developed SILs (P < .01). Compared with HIV-infected women with higher CD4+ lymphocyte counts, HIV-infected women with CD4+ lymphocyte counts < 200 cells/microL were more likely to present subsequently with a SIL detected by Pap test (OR, 1.7; 95% CI, 0.8-3.6). CONCLUSIONS: Higher risk of SIL following the appearance of ASCUS among HIV-infected women, especially women with low CD4+ lymphocyte counts, supports the need for follow up with colposcopy and histologic examination, as indicated, to allow early detection and treatment of SIL.