The Postmenopausal Vaginal Microbiome and Genitourinary Syndrome of Menopause.

This review summarizes our current understanding of associations of the postmenopausal vaginal microbiome with genitourinary syndrome of menopause. We review the normal postmenopausal microbiota, examine the association of the microbiome with vulvovaginal symptoms, describe microbial communities associated with physical and laboratory findings, and report the impact of different treatments for genitourinary syndrome of menopause on microbiota and symptom improvement. Postmenopausal vaginal symptoms have an underlying pathophysiology that has not been fully elucidated. Estrogen treatment may not be sufficient to relieve symptoms of vaginal discomfort in all postmenopausal individuals. In addition, other interventions targeted at changing the microbiota or pH do not consistently improve symptom severity.

Incidence, prevalence, and trends in polycystic ovary syndrome diagnosis: a United States population-based study from 2006 to 2019.

BACKGROUND: Polycystic ovary syndrome is the most common endocrine disorder in women of reproductive age, yet US incidence estimates do not exist, and prevalence estimates vary widely. OBJECTIVE: A population-based US study estimated the incidence, prevalence, and trends of polycystic ovary syndrome by age, race and ethnicity, and diagnosing provider type. STUDY DESIGN: A retrospective cohort study of patients enrolled in Kaiser Permanente Washington from 2006 to 2019 was conducted. All members identified as female, aged 16 to 40 years with at least 3 years of enrollment and at least 1 healthcare encounter during that time, were eligible for inclusion. Individuals were excluded if they had a history of oophorectomy or hysterectomy. Polycystic ovary syndrome cases were identified using the International Classification of Diseases diagnosis codes (International Classification of Diseases, Ninth Revision, 256.4 or International Classification of Diseases, Tenth Revision, E28.2). Individuals with a polycystic ovary syndrome diagnosis before study entry were excluded from incidence rate estimations. The incidence rates were adjusted by age using direct standardization to the 2010 US census data. Temporal trends in incidence were assessed using weighted linear regression (overall) and Poisson regression (by age, race and ethnicity, and provider type). Prevalent cases were defined as patients with a polycystic ovary syndrome diagnosis at any time before the end of 2019. Medical record review of 700 incident cases diagnosed in 2011-2019 was performed to validate incident cases identified by International Classification of Diseases codes using the Rotterdam criteria. RESULTS: Among 177,527 eligible patients who contributed 586,470 person-years, 2491 incident polycystic ovary syndrome cases were identified. The mean age at diagnosis was 26.9 years, and the mean body mass index was 31.6 kg/m2. Overall incidence was 42.5 per 10,000 person-years; the rates were similar over time but increased in individuals aged 16 to 20 years from 31.0 to 51.9 per 10,000 person-years (P=.01) and decreased among those aged 26 to 30 years from 82.8 to 45.0 per 10,000 person-years (P=.02). A small decreasing temporal trend in incidence rates was only observed among non-Hispanic White individuals (P=.01). The incidence rates by diagnosing provider type varied little over time. Among the 58,241 patients who contributed person-time in 2019, 3036 (5.2%) had a polycystic ovary syndrome International Classification of Diseases diagnosis code; the prevalence was the highest among the Hawaiian and Pacific Islander group (7.6%) followed by Native American and Hispanic groups. Medical record review classified 60% as definite or probable incident, 14% as possible incident, and 17% as prevalent polycystic ovary syndrome. The overall positive predictive value of polycystic ovary syndrome International Classification of Diseases diagnosis code for identifying definite, probable, or possible incident polycystic ovary syndrome was 76% (95% confidence interval, 72%-79%). CONCLUSION: Among a cohort of nonselected females in the United States, we observed stable rates of incident polycystic ovary syndrome diagnoses over time. The incidence of polycystic ovary syndrome was 4- to 5-fold greater than reported for the United Kingdom. The prevalence of polycystic ovary syndrome (5.2%) was almost double before the published US estimates (2.9%) based on the International Classification of Diseases codes. Race and ethnicity and provider type did not seem to have a major impact on temporal rates. Incident diagnoses increased over time in younger and decreased in older age groups, perhaps related to shifting practice patterns with greater awareness among practitioners of the impact of polycystic ovary syndrome on long-term health outcomes and improved prevention efforts. Moreover, increasing obesity rates may be a factor driving the earlier ages at diagnosis.

Changes in concentrations of cervicovaginal immune mediators across the menstrual cycle: a systematic review and meta-analysis of individual patient data.

BACKGROUND: Hormonal changes during the menstrual cycle play a key role in shaping immunity in the cervicovaginal tract. Cervicovaginal fluid contains cytokines, chemokines, immunoglobulins, and other immune mediators. Many studies have shown that the concentrations of these immune mediators change throughout the menstrual cycle, but the studies have often shown inconsistent results. Our understanding of immunological correlates of the menstrual cycle remains limited and could be improved by meta-analysis of the available evidence. METHODS: We performed a systematic review and meta-analysis of cervicovaginal immune mediator concentrations throughout the menstrual cycle using individual participant data. Study eligibility included strict definitions of the cycle phase (by progesterone or days since the last menstrual period) and no use of hormonal contraception or intrauterine devices. We performed random-effects meta-analyses using inverse-variance pooling to estimate concentration differences between the follicular and luteal phases. In addition, we performed a new laboratory study, measuring select immune mediators in cervicovaginal lavage samples. RESULTS: We screened 1570 abstracts and identified 71 eligible studies. We analyzed data from 31 studies, encompassing 39,589 concentration measurements of 77 immune mediators made on 2112 samples from 871 participants. Meta-analyses were performed on 53 immune mediators. Antibodies, CC-type chemokines, MMPs, IL-6, IL-16, IL-1RA, G-CSF, GNLY, and ICAM1 were lower in the luteal phase than the follicular phase. Only IL-1α, HBD-2, and HBD-3 were elevated in the luteal phase. There was minimal change between the phases for CXCL8, 9, and 10, interferons, TNF, SLPI, elafin, lysozyme, lactoferrin, and interleukins 1ß, 2, 10, 12, 13, and 17A. The GRADE strength of evidence was moderate to high for all immune mediators listed here. CONCLUSIONS: Despite the variability of cervicovaginal immune mediator measurements, our meta-analyses show clear and consistent changes during the menstrual cycle. Many immune mediators were lower in the luteal phase, including chemokines, antibodies, matrix metalloproteinases, and several interleukins. Only interleukin-1α and beta-defensins were higher in the luteal phase. These cyclical differences may have consequences for immunity, susceptibility to infection, and fertility. Our study emphasizes the need to control for the effect of the menstrual cycle on immune mediators in future studies.

Pharmacists' knowledge, perspectives, and experiences with mifepristone dispensing for medication abortion.

BACKGROUND: The U.S. Food and Drug Administration (FDA) restricts dispensing of mifepristone for medication abortion to certified health care providers at clinical facilities, thus prohibiting pharmacist dispensing. Allowing mifepristone dispensing by pharmacists could improve access to medication abortion. OBJECTIVE: To assess the feasibility of pharmacists dispensing mifepristone to patients who have undergone evaluation for eligibility and counseling for medication abortion by a clinician. METHODS: Before providing a study training on medication abortion, we administered baseline surveys to pharmacists who participated in a multisite mifepristone-dispensing intervention. The survey assessed medication abortion knowledge-using a 15-item score-and perceptions about the benefits and challenges of the model. We administered follow-up surveys in the study's final month that also assessed the pharmacists' satisfaction and experiences with mifepristone dispensing. To investigate the association of the study intervention with the pharmacists' knowledge, perceptions, and experiences dispensing mifepristone, we conducted multivariable linear regression analyses using generalized estimating equation models, accounting for clustering by individual. RESULTS: Among the 72 pharmacists invited from 6 pharmacies, 47 (65%) completed the baseline surveys, and 56 (78%) received training. At the study's end (mean 18 months later), 43 of the 56 pharmacists who received training (77%) completed the follow-up surveys. At follow-up, 36 (83%) respondents were very or somewhat satisfied with mifepristone dispensing, and 24 (56%) reported experiencing no challenges dispensing mifepristone. Four (6%) of the 72 pharmacists invited objected to participating in mifepristone dispensing. In regression analyses, average knowledge scores, perceived ease of implementation, and level of support for the pharmacist-dispensing model were higher at follow-up (P < 0.001). CONCLUSION: Most pharmacists were willing to be trained, dispensed mifepristone with few challenges when given the opportunity, were satisfied with the model, and had higher knowledge levels at follow-up. Our findings support removal of FDA's restriction on pharmacist dispensing of mifepristone.

The effect of testosterone on ovulatory function in transmasculine individuals.

BACKGROUND: An estimated 1.4 million persons in the United States identify as transgender or nonbinary, signifying that their gender identity does not correspond with their assigned sex at birth. Individuals assigned female at birth may seek gender-affirming hormone therapy with testosterone. No studies have directly examined ovulatory function in transmasculine individuals using injectable testosterone. OBJECTIVES: Our primary objective was to determine the effect of testosterone on ovulatory suppression in transmasculine individuals. Secondary objectives were to determine predictors of ovulation in transmasculine individuals on testosterone, and to assess the effect of testosterone on antimüllerian hormone. MATERIALS AND METHODS: This prospective observational study recruited participants from a community clinic that provides gender-affirming hormone therapy. Enrolled individuals were assigned female at birth and were currently using or seeking to initiate masculinizing therapy with injectable testosterone esters (transmasculine individuals). Over a 12-week study period, participants collected daily urine samples for pregnanediol-3-glucoronide testing and completed daily electronic bleeding diaries. We assessed monthly serum mid-dosing interval testosterone, estradiol and sex hormone binding globulin, and antimüllerian hormone values at baseline and study end. Ovulation was defined as pregnanediol-3-glucoronide greater than 5 µg/mL for 3 consecutive days. The primary outcome was the proportion of participants who ovulated during the study period. We examined predictors of ovulation such as age, length of time on testosterone, serum testosterone levels, body mass index, and bleeding pattern. RESULTS: From July to November 2018, we enrolled 32 individuals; 20 completed the study (14 continuing testosterone users, 6 new users). Median age was 23 years (range 18-37 years). Bleeding or spotting during the study period was noted by 41% of participants (13/32). Among continuing users, median testosterone therapy duration was 11 months (range 1-60 months). A single ovulation was observed out of a total of 61 combined months of testosterone use; however, several transient rises in pregnanediol-3-glucoronide followed by bleeding episodes were suggestive of 7 dysfunctional ovulatory cycles among 7 individuals. There was no difference in antimüllerian hormone from baseline to 12 weeks between participants initiating testosterone and continuing users of testosterone. We did not have the power to examine our intended predictors given the low numbers of ovulatory events, but found that longer time on testosterone and presence of vaginal bleeding over 12 weeks were associated with transient rises in pregnanediol-3-glucoronide. CONCLUSION: This study suggests that testosterone rapidly induces hypothalamic-pituitary-gonadal suppression, resulting in anovulation in a proportion of new users. Importantly, these data also suggest that some long-term testosterone users break through the hormonal suppression and experience an ovulatory event, thereby raising concerns pertaining to the need for contraception in transmasculine individuals engaged in sexual intercourse with sperm-producing partners. Given the small number of overall participants, this work is hypothesis generating. Larger studies are needed to confirm and to clarify these findings.

Depression during perimenopause: the role of the obstetrician-gynecologist.

Depression in women is more common during perimenopause (the transition to menopause) than at other times in the life cycle. Symptoms of depression may be different in perimenopausal women compared to younger or older women, and are often dismissed as part of normal menopause. This is an expert narrative review. There are several evidence-based screening modalities which can be integrated into routine women's health visits, and can facilitate distinguishing between depression and normal perimenopausal symptoms. There is emerging evidence regarding the effect of hormonal changes on the development of perimenopausal depression and its optimal treatment, though critical research gaps remain. Obstetrician-gynecologists and other primary care providers play a vital role in the detection and management of depression in women. Providers caring for women during perimenopause have a unique opportunity to diagnose depression in their patients and identify appropriate treatment options.

Providing reproductive health services for women who inject drugs: a pilot program.

BACKGROUND: Needle syringe programs (NSPs), a proven harm reduction strategy for people who inject drugs, frequently offer limited healthcare services for their clients. Women who inject drugs face multiple barriers to accessing reproductive health care in traditional settings: personal histories of trauma, judgmental treatment from providers, and competing demands on their time. Our aim was to implement patient-centered reproductive healthcare services at a Seattle NSP. METHODS: We interviewed clients and staff of an NSP in Seattle and staff of other community-based organizations serving women who inject drugs, then used the Consolidated Framework for Implementation Research to code transcripts deductively. Based on our qualitative work, we implemented reproductive health care at the NSP program 1 day per week. We evaluated the implementation by surveying staff and clients and auditing charts over a 9-month period. RESULTS: Clients and staff (N = 15 for clients, N = 13 for staff) noted a high unmet need for trauma-informed, accessible reproductive health care. We successfully implemented reproductive health care services including short- and long-acting contraception, sexually transmitted disease testing, and cervical cancer screening. Survey data was limited but demonstrated client satisfaction with services. CONCLUSIONS: Integrating reproductive health care into an NSP's clinical services is feasible and can be a source of low-barrier preventive care for women unable to seek gynecologic care elsewhere.

Reproductive Health Care Utilization by Women Who Inject Drugs and Exchange Sex in the Seattle Area.

BACKGROUND: Few data exist regarding reproductive health needs of women who inject drugs (WWID) and exchange sex. This group is at increased risk of unintended pregnancy and sexually transmitted infections (STI). They also face stigma and other barriers to accessing reproductive health care. Purpose: To evaluate contraceptive usage, pregnancy intention, and uptake of general and reproductive health services among WWID and exchange sex. Methods: This analysis of the 2016 Seattle area National HIV Behavioral Surveillance survey included women aged 18-49 years who exchanged sex for money or drugs and injected drugs in the last year. We evaluated contraceptive utilization, pregnancy intention, and reproductive health care access. Results: Among 144 respondents meeting inclusion criteria, the median age was 39 (IQR 33-45), the median age at first injection was 22 (IQR 17-28), and the most commonly injected drug was heroin (62.0%). A minority (10.3%) desired pregnancy in the next year. Among women wanting to avoid pregnancy, 65.5% had not used any prescription contraception (pill/patch/ring, injection, intrauterine device, or implant) in the last year. In the last year, nearly all (92.4%) respondents had received health care and over half (59.0%) had had an STI test. Of women eligible for the HPV vaccine, 28.6% had received at least one dose. Conclusions: Most WWID and exchange sex want to avoid pregnancy. Despite accessing health care, a minority are using prescribed contraception. Health care tailored to these women's preferences may reduce unmet contraceptive need and improve access to well-woman care and preconception counseling.

The Effect of Hormonal Contraception and Menstrual Cycle Timing on Genital Herpes Simplex Virus-2 Shedding and Lesions.

BACKGROUND: The effect of female sex hormones on herpes simplex virus (HSV)-2 shedding and lesion frequency is poorly understood. Previous studies suggest that hormonal contraception may increase the frequency of HSV-2 shedding. METHODS: We studied HSV-2 seropositive women who performed daily genital swabbing for HSV DNA and completed diaries for genital lesions and menses. We used Poisson mixed effects models to determine if HSV detection varied throughout the menstrual cycle, or in response to hormonal contraception. We used the Wilcoxon signed-rank test and rank-sum test to determine if lesion frequency differed by cycle phase or hormonal contraceptive use. RESULTS: In 189 women aged 19 to 46 years who collected swabs on 10,715 days and were not using hormonal contraception, HSV-2 DNA was detected on 20.9% of days in the follicular phase and 17.8% of days in the luteal phase (rate ratio, 1.19; 95% confidence interval, 1.03-1.37, P = 0.02). Genital lesions did not differ in the follicular versus luteal phase (12.8% vs. 10.7%, P = 0.07). In analyses of hormonal contraception, including 244 women, HSV-2 DNA was detected on 19.0% of days for women not using hormonal contraception and 18.3% of days for those using hormonal contraception (P = 0.50). Lesions were present on 11.1% of days for women not using hormonal contraception, and 8.7% of days for those using hormonal contraception (P = 0.66). CONCLUSIONS: In women with genital HSV-2 infection who are not using hormonal contraception, the follicular phase of the cycle may be associated with a higher frequency of HSV-2 shedding compared to the luteal phase. Lesion frequency is similar during the 2 menstrual phases. Hormonal contraception use was not observed to affect genital HSV-2 DNA detection or lesions.

Use of the Levonorgestrel Intrauterine Device in Women With Type 2 Diabetes.

IN BRIEF Women with type 2 diabetes are less likely to receive prescriptions for contraceptives despite the fact that diabetes is associated with an increased risk of maternal and fetal complications. In the largest case series to date examining use of the levonorgestrel-releasing intrauterine device (LNG-IUD) in women with type 2 diabetes, we demonstrate that the LNG-IUD is safe and effective and does not affect glycemic control in women with type 2 diabetes. In this study of 115 women under the age of 55 years with type 2 diabetes who had an LNG-IUD placed between 2007 and 2012, we found low rates of pregnancies, expulsions, and other complications in every age category and disease stratification. Thirty-nine patients had A1C data before and up to 2 years after placement, and there was no significant change in A1C (mean A1C decrease of 0.17, 95% CI -0.76 to 0.43). This study will enable evidence-based contraceptive counseling for women with type 2 diabetes.

Continuous or extended cycle vs. cyclic use of combined hormonal contraceptives for contraception.

BACKGROUND: The avoidance of menstruation through continuous or extended (greater than 28 days) administration of combination hormonal contraceptives (CHCs) has gained legitimacy through its use in treating endometriosis, dysmenorrhea, and menstruation-associated symptoms. Avoidance of menstruation through extended or continuous use of CHCs for reasons of personal preference may have additional advantages to women, including improved compliance, greater satisfaction, fewer menstrual symptoms, and less menstruation-related absenteeism from work or school. OBJECTIVES: To determine the differences between continuous or extended-cycle CHCs (pills, patch, ring) in regimens of greater than 28 days of active hormone compared with traditional cyclic dosing (21 days of active hormone and 7 days of placebo, or 24 days of active hormones and 4 days of placebo). Our hypothesis was that continuous or extended-cycle CHCs have equivalent efficacy and safety but improved bleeding profiles, amenorrhea rates, adherence, continuation, participant satisfaction, and menstrual symptoms compared with standard cyclic CHCs. SEARCH METHODS: We searched computerized databases (Cochrane Central Register of Controlled Trials, PUBMED, EMBASE, POPLINE, LILACS) for trials using continuous or extended CHCs (oral contraceptives, contraceptive ring and patch) during the years 1966 to 2013. We also searched the references in review articles and publications identified for inclusion in the protocol. Investigators were contacted regarding additional references. SELECTION CRITERIA: All randomized controlled trials in any language comparing continuous or extended-cycle (greater than 28 days of active hormones) versus traditional cyclic administration (21 days of active hormones and 7 days of placebo, or 24 days of active hormones and 4 days of placebo) of CHCs for contraception. DATA COLLECTION AND ANALYSIS: Titles and abstracts identified from the literature searches were assessed for potential inclusion. Data were extracted onto data collection forms and then entered into RevMan 5. Peto odds ratios with 95% confidence intervals were calculated for all outcomes for dichotomous outcomes. Weighted mean difference was calculated for continuous outcomes. The trials were critically appraised by examining the following factors: study design, blinding, randomization method, group allocation concealment, exclusions after randomization, loss to follow-up, and early discontinuation. Because the included trials did not have a standard treatment (type of CHC formulation, route of delivery, or time length for continuous dosing), we could not aggregate data into meta-analysis. MAIN RESULTS: Twelve randomized controlled trials met our inclusion criteria. Study findings were similar between 28-day and extended or continuous regimens in regard to contraceptive efficacy (i.e., pregnancy rates) and safety profiles. When compliance was reported, no difference between 28-day and extended or continuous cycles was found. Participants reported high satisfaction with both dosing regimens, but this was not an outcome universally studied. Overall discontinuation and discontinuation for bleeding problems were not uniformly higher in either group. The studies that reported menstrual symptoms found that the extended or continuous group fared better in terms of headaches, genital irritation, tiredness, bloating, and menstrual pain. Eleven out of the twelve studies found that bleeding patterns were either equivalent between groups or improved with extended or continuous cycles over time. Endometrial lining assessments by ultrasound and/or endometrial biopsy were done in some participants and were all normal after cyclic or extended CHC use. AUTHORS' CONCLUSIONS: The 2014 update yielded four additional trials but unchanged conclusions. Evidence from existing randomized control trials comparing continuous or extended-cycle CHCs (greater than 28 days of active combined hormones) to traditional cyclic dosing (21 days of active hormone and 7 days of placebo, or 24 days of active hormone and 4 days of placebo) is of good quality. However, the variations in type of hormones and time length for extended-cycle dosing make a formal meta-analysis impossible. Future studies should choose a previously described type of CHC and dosing regimen. More attention needs to be directed towards participant satisfaction, continuation, and menstruation-associated symptoms.

Plan A: postabortion contraception.

More than 1 million abortions are performed annually in the United States. Women presenting for abortion care are often motivated by the pregnancy to use effective contraception; they are also at high risk for repeat unintended pregnancy. For these reasons, abortion represents an optimal time to initiate effective contraception. There is strong evidence that most methods of contraception, including intrauterine devices and the contraceptive implant, should be initiated at the time of the abortion procedure. Most women ovulate within the first month after an abortion. If provision of contraception is delayed, women are less likely to use effective contraception and more likely to have a repeat unintended pregnancy. Although some methods of permanent contraception can be safely performed at the time of abortion, federal and state laws often restrict these procedures being performed concurrently. Contraceptive counseling and provision at the time of abortion are important strategies to decrease rates of unintended pregnancy.

Sexually transmitted infections in midlife women.

Rates of sexually transmitted infections (STIs) are increasing in all age groups. Although STI incidence decreases with age, midlife women have risk factors that may lead to STI acquisition and underdiagnosis. Clinicians may assume that older women are not sexually active. Although many STIs are asymptomatic, when midlife women do experience vaginal symptoms, they may be erroneously attributed to menopause changes. Clinicians should follow evidence-based screening recommendations provided by the US Preventive Services Task Force and consider STIs in the differential diagnosis of vaginal symptoms. Treatment of STIs in midlife women are guided by the Centers for Disease Control and Prevention's STI Treatment Guidelines.

Risk Factors for Incident Polycystic Ovary Syndrome Diagnosis.

Objective: While highly prevalent, risk factors for incident polycystic ovary syndrome (PCOS) are poorly delineated. Using a population-based cohort, we sought to identify predictors of incident PCOS diagnosis. Materials and Methods: A matched case-control analysis was completed utilizing patients enrolled in Kaiser Permanente Washington from 2006 to 2019. Inclusion criteria included female sex, age 16-40 years, and ≥3 years of prior enrollment with ≥1 health care encounter. PCOS cases were identified using International Classification of Diseases codes. For each incident case (n = 2,491), 5 patients without PCOS (n = 12,455) were matched based on birth year and enrollment status. Potential risk factors preceding diagnosis included family history of PCOS, premature menarche, parity, race, weight gain, obesity, valproate use, metabolic syndrome, epilepsy, prediabetes, and types 1 and 2 diabetes. Potential risk factors for incident PCOS diagnosis were assessed with univariate and multivariable conditional logistic regressions. Results: Mean age of PCOS cases was 26.9 years (SD 6.8). PCOS cases, compared with non-PCOS, were more frequently nulliparous (70.9% versus 62.4%) and in the 3 years prior to index date were more likely to have obesity (53.8% versus 20.7%), metabolic syndrome (14.5% versus 4.3%), prediabetes (7.4% versus 1.6%), and type 2 diabetes (4.1% versus 1.7%) (p < 0.001 for all comparisons). In multivariable models, factors associated with higher risk for incident PCOS included the following: obesity (compared with nonobese) Class I-II (body-mass index [BMI], 30-40 kg/m2; odds ratio [OR], 3.8; 95% confidence interval [CI], 3.4-4.2), Class III (BMI > 40 kg/m2; OR, 7.5, 95% CI, 6.5-8.7), weight gain (compared with weight loss or maintenance) of 1-10% (OR, 1.7, 95% CI, 1.3-2.1), 10-20% (OR, 1.9; 95% CI, 1.5-2.4), and >20% (OR, 2.6; 95% CI, 1.9-3.6), prediabetes (OR, 2.7; 95% CI, 2.1-3.4), and metabolic syndrome (OR, 1.8: 95% CI, 1.5-2.1). Conclusion: Excess weight gain, obesity, and metabolic dysfunction may play a key role in the ensuing phenotypic expression of PCOS. Treatment and prevention strategies targeted at preventing weight gain in early reproductive years may help reduce the risk of this syndrome.

Medical termination of pregnancy in cynomolgus macaques.

BACKGROUND: Although pregnancy is expected during studies of novel contraceptives in non-human primates, gestation, delivery, and lactation remove females from groups for prolonged intervals. As the macaque cervix does not facilitate transcervical surgical termination of pregnancy, we sought to establish a medical termination protocol. METHODS: A descriptive case series of outcomes of medical termination of pregnancy up to 32 days gestation in cynomolgus monkeys. Efficacy and time to uterine resolution were determined according to medication, dose, and route of administration. RESULTS: Thirty-seven macaques underwent 65 medical terminations. Over 80% of animals terminated after initial treatment with mifepristone 20 mg intramuscularly (IM). Intrafetal methotrexate was effective for salvage treatment. Medical termination regimens were less effective for animals receiving investigational contraceptive agents. CONCLUSIONS: Medical termination for macaques is safe and effective. We recommend a protocol with mifepristone 20 mg IM and misoprostol 200 µg buccally as initial treatment.

Contraceptive use among cisgender women with bacterial sexually transmitted infections: A cross-sectional study.

BACKGROUND: Data on contraceptive use among women with bacterial sexually transmitted infections (STIs) are sparse, despite this population's high risk for unplanned pregnancy. METHODS: This cross-sectional study included 1623 cisgender women recently diagnosed with a bacterial STI who completed a public health Partner Services interview between January 2017 and December 2019 in King County, WA, USA. Contraceptive methods were categorized as: (1) highly or moderately effective and (2) least effective or no method. Poisson regression models were used to assess associations between individual characteristics and contraceptive method. RESULTS: Almost two thirds of the women (62.6%) reported using highly or moderately effective contraception, with 30.3% of women using long-acting contraception (LARC). More than one in three women (37.4%) reported using least effective methods or no method. Black women were less likely to report using a highly or moderately effective method compared to White women (aRR 0.58, 95% CI 0.43-0.80) and women with private insurance were more likely to report using a highly or moderately effective method compared to those with public insurance (aRR 1.67, 95% CI 1.28-2.19). CONCLUSIONS: Given that many women with bacterial STIs are not desiring pregnancy, this study highlights the need for additional reproductive health services for women with recent STI diagnoses.

Society of Family Planning Clinical Recommendations: Contraceptive Care in the Context of Pandemic Response.

The coronavirus disease 2019 (COVID-19) pandemic has posed a burden to healthcare systems around the world and has changed the way people access health services, including contraception. This document sets forth guidance from the Society of Family Planning for providing contraceptive care in the context of the COVID-19 pandemic, including when access to healthcare is restricted due to pandemic response. It also outlines the role of telehealth for providing contraceptive care beyond the pandemic. Clinicians can use synchronous telemedicine visits and other forms of telehealth to provide many aspects of contraceptive care. Both audio-video and audio-only visits are acceptable forms of telemedicine. Access to permanent contraception should be maintained, especially in the postpartum period. Combined hormonal contraceptive (CHC) users who have asymptomatic or mild COVID-19 infection may continue their contraceptive method, while those admitted to the hospital with severe infection should suspend CHC use until they are clinically recovered. CHC users who take Paxlovid for mild-moderate COVID-19 infection can consider a back-up contraceptive method for the duration of therapy, but clinically relevant drug interactions are unlikely. Future research should examine contraceptive outcomes in people who receive care via telemedicine; and access to telemedicine among historically excluded populations such as adolescents, people of color, people of low socioeconomic status, disabled people, or people who do not speak English as a primary language.

Same-day mifepristone prior to second-trimester induction termination with misoprostol: A retrospective cohort study.

OBJECTIVE: To evaluate whether same-day administration of mifepristone and misoprostol, compared with misoprostol alone, reduces the duration of second-trimester induction of labor for termination of pregnancy or increases the rate of fetal expulsion within 24 hours. STUDY DESIGN: We conducted a retrospective analysis of patients undergoing induction of labor for pregnancy termination in the second trimester between 2009 and 2018. We compared patients who received mifepristone on the same day as the first dose of misoprostol to those who received misoprostol alone. The primary outcome was expulsion within 24 hours after the first dose of misoprostol. RESULTS: Two hundred ninety-eight patients met criteria for inclusion, of whom 94 (31.5%) received same-day mifepristone. Expulsion within 24 hours occurred in 93.6% of the mifepristone-plus-misoprostol group and 79.9% of the misoprostol-only group (RR 1.17, 95%CI 1.07-1.28). Expulsion within 12 hours occurred in 56.4% of the mifepristone-plus-misoprostol group and 34.0% of the misoprostol-only group (RR 1.66, 95%CI 1.28-2.16). After adjusting for demographic and clinical characteristics, the rate of expulsion within 24 hours was similar between groups (RR 1.07, 95%CI 0.92-1.26), while the rate of expulsion within 12 hours remained different (RR 1.69, 95%CI 1.01-2.83). Median time to expulsion was shorter in the mifepristone-plus-misoprostol group than the misoprostol-only group (689 minutes vs 901 minutes, p < 0.001). CONCLUSION(S): Patients who received mifepristone on the same day as misoprostol had a shorter duration of induction termination and higher rate of success within 12 hours.

Contraceptive Use Among Women in the United States Aged 18-44 Years with Selected Medical Contraindications to Estrogen.

Objective: Medical contraindications to estrogen limit women's contraceptive options. This study assessed the association between selected medical contraindications to estrogen on contraceptive use and examined whether contraindications serve as a barrier to the prevention of unintended pregnancy. Materials and Methods: We analyzed women aged 18-44 at risk of unintended pregnancy participating in the 2017 Behavioral Risk Factor Surveillance System. Survey questions queried women regarding contraceptive use and contraindications to estrogen use. We assessed the most recently used contraceptive method and compared the odds of women using each category of contraception (no methods, less effective methods, pill/patch/ring, injection, intrauterine device, implant, permanent contraception) between those with and without potential contraindications to estrogen using multinomial logistic regression models. Results: This study included 32,098 women, of whom 16% had one or more potential contraindications to estrogen. There were significant differences in contraceptive choice by potential contraindication status (p < 0.01). Fifteen percent of women with potential contraindications reported using estrogen-containing methods (pill, patch, or ring) compared with 20% of women with no potential contraindication. Women with potential contraindications to estrogen more frequently used permanent contraception (odds ratio [OR] vs. pill/patch/ring: 1.48 95% confidence interval [CI]: 1.17-1.88) or no contraceptive method (OR vs. pill/patch/ring: 1.37 95% CI: 1.07-1.75) after adjustment for race, age, marital status, and income. Conclusions: Potential medical contraindications to estrogen are associated with permanent contraception and the use of no contraception. These results portray a complicated relationship but could suggest a lack of access to other contraceptive options.

Ketamine Compared With Fentanyl for Surgical Abortion: A Randomized Controlled Trial.

OBJECTIVE: To compare patient satisfaction with anesthesia after first-trimester surgical abortion among patients receiving intravenous (IV) ketamine compared with IV fentanyl for procedural sedation. METHODS: This was a randomized noninferiority trial comparing IV ketamine to IV fentanyl for first-trimester surgical abortion up to 13 6/7 weeks of gestation. Patients were randomized to receive either ketamine 200-500 micrograms/kg IV over 2 minutes, repeated every 5 minutes until appropriate analgesia was achieved, or fentanyl 0.5-1 micrograms/kg IV over 2 minutes, repeated every 5 minutes until appropriate analgesia was achieved. All patients received midazolam 2 mg IV. The primary outcome, patient satisfaction, was measured using the Iowa Satisfaction with Anesthesia Scale immediately postprocedure. Secondary outcomes included postoperative pain, additional pain medication necessary during the procedure and on discharge, physician satisfaction, and time to discharge. We calculated a sample size of 84 with a noninferiority margin of 0.6 on the Iowa Satisfaction with Anesthesia Scale with 80% power, one-sided type 1 error of 0.025, and further increased this number to 110 to account for potential dropout. RESULTS: From April to October 2021, 184 patients were screened and 110 were randomized (57 to ketamine and 53 to fentanyl). Demographics were similar between groups. The primary outcome, patient satisfaction with anesthesia, was noninferior in the ketamine group (mean score 2.4, SD 0.8) as compared with the fentanyl group (mean score 2.2, SD 0.9) with a risk difference of 0.20 (95% CI 0.11-0.52). More hallucinations were reported in the ketamine group. Otherwise, secondary outcomes were similar between the groups. CONCLUSION: Compared with IV fentanyl, IV ketamine is noninferior for patient satisfaction with anesthesia when used for procedural sedation for first-trimester outpatient surgical abortion. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT04871425.