Emergency contraception for individuals weighing 80 kg or greater: A randomized trial of 30 mg ulipristal acetate and 1.5 mg or 3.0 mg levonorgestrel.

OBJECTIVES: To compare the efficacy of emergency contraception (EC) regimens used within 72 hours of unprotected intercourse in individuals weighing ≥80 kg. STUDY DESIGN: We enrolled reproductive-aged healthy women in a multicenter, single-blind, randomized study of levonorgestrel 1.5 mg (LNG1X) and 3.0 mg (LNG2X) and ulipristal acetate 30 mg (UPA) (enrollment goal 1200). Key eligibility requirements included regular cycles, weight >/= 80kg, unprotected intercourse within 72 hours, no recent use of hormonal contraception, a negative urine pregnancy test (UPT), and willingness to abstain from intercourse until next menses. To assess our primary outcome of incidence of pregnancy, participants completed home UPTs; if no menses by 2-weeks post-treatment, or a positive UPT, they returned for an in-person visit with quantitative serum human chorionic gonadotropin and ultrasound. RESULTS: We enrolled and randomized 532; 44 were not dosed or not evaluable for primary end point, leaving an analyzable sample of 488 (173 LNG1X, 158 LNG2X, 157 UPA) with similar demographics between groups (mean age 29.6 years [5.74], body mass index 37.09 kg/m2 [6.95]). Five pregnancies occurred (LNG1X n = 1, LNG2X n = 1, UPA n = 3); none occurred during the highest at-risk window (day of ovulation and the 3 days prior). We closed the study before achieving our enrollment goal because the low pregnancy rate in all groups established futility based on an interim blinded analysis. CONCLUSIONS: Although slow enrollment limited our study power, we found no differences in pregnancy rates between EC regimens among women weighing 80 kg or more. Our results are not able to refute or support differences between the treatment arms. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clincialtrials.gov Clinical trials#: NCT03537768. IMPLICATIONS: Women weighing 80 kg or more experienced no differences in pregnancy rates between oral EC regimens but due to several significant study limitations including sample size and the lack of a study population at high risk of pregnancy, our results are not able to determine if differences in treatment effectiveness exist.

Estimating the cost of Rh testing and prophylaxis in early pregnancy: A time-driven activity-based costing study.

OBJECTIVE: To estimate the cost of Rhesus (Rh) testing and prophylaxis for first-trimester vaginal bleeding in the ambulatory setting. STUDY DESIGN: We used time-driven, activity-based costing to analyze tasks associated with Rh testing and prophylaxis of first-trimester vaginal bleeding at one hospital-based outpatient and two independent reproductive health clinics. At each site, we observed 10 patients undergoing Rh-typing and two patients undergoing Rh prophylaxis. We computed the costs of blood Rh-typing by both fingerstick and phlebotomy, cost of locating previous blood type in the electronic health record (available for 69.8% of hospital-based patients), and costs associated with Rh immune globulin prophylaxis. All costs are reported in 2021 US dollars. RESULTS: The hospital-based clinic reviewed the electronic health record to confirm Rh-status (cost, $26.18 per patient) and performed a phlebotomy, at $47.11 per patient, if none was recorded. The independent clinics typed blood by fingerstick, at a per-patient cost of $4.07. Rh-immune globulin administration costs, including the medication, were similar across facilities, at a mean of $145.66 per patient. Projected yearly costs for testing and prophylaxis were $55,831 for the hospital-based clinic, which was the lowest-volume site, $47,941 for Clinic A, which saw 150 patients/month, and $185,654 for Clinic B, which saw 600 patients/month. CONCLUSIONS: Rh testing and prophylaxis for first-trimester vaginal bleeding generates considerable costs for outpatient facilities, even for Rh-positive patients with a prior blood type on record. IMPLICATIONS: Rh testing and prophylaxis for first-trimester bleeding generate considerable costs even for Rh-positive patients and those with a previously known blood type. These findings highlight the need to reconsider this practice, which is no longer supported by evidence and already safely waived in multiple medical settings in the United States and around the world.

Menstrual cup use and intrauterine device expulsion in a copper intrauterine device randomized trial.

OBJECTIVE: To evaluate menstrual cup use and intrauterine device (IUD) expulsion. STUDY DESIGN: We performed a secondary analysis of a 3-year contraceptive efficacy trial comparing two copper 380 mm2 IUDs. Investigators randomized participants approximately 1:4 to the TCu380A or NTCu380-Mini IUD. Approximately 12 months after enrollment began, we advised participants against menstrual cup use due to observed IUD expulsions in cup users. We evaluated IUD expulsion (including spontaneous partial and complete expulsion and accidental self-removal) at 12 and 36 months. We used multivariable logistic regression to evaluate IUD expulsion by age, baseline menstrual volume, body mass index, IUD type, menstrual cup use, parity, and uterine length. RESULTS: This analysis included 1046 participants (203 TCu380A and 843 NTCu380-Mini), with 879 (84.0%) nulliparas. Through 12 and 36 months, expulsion occurred in 74 (7.1%, 95% CI 5.5-8.6%) and 133 (12.7%, 95% CI 10.7-14.7%) participants, respectively. Overall, 250 (23.9%) reported menstrual cup use. More menstrual cup users than non-users experienced expulsion through 12 months (32/203 [15.8%] vs. 42/843 [5.0%]) and 36 months (58/250 [23.2%] vs. 75/796 [9.4%]). Through 36 months, NTCu380-Mini menstrual cup users had higher expulsion odds, while TCu380A cup users did not. Menstrual cup users more frequently experienced accidental self-removal than non-users in participants using the TCu380A (3/53 [5.7%] vs. 0/150 [0.0%]) and the NTCu380-Mini (20/197 [10.2%] vs. 7/646 [1.1%]). In multivariable regression, we found increased odds of expulsion through 36 months in participants using menstrual cups with the NTCu380-Mini (aOR 3.13, 95% CI 1.16-8.46) and <25 years (aOR 1.59, 95% CI 1.07-2.34). CONCLUSIONS: We found higher odds of IUD expulsion with menstrual cup and concurrent NTCu380-Mini IUD use over 36 months of use, but not with concurrent TCu380A IUD use. Menstrual cup users experienced higher likelihood of accidental self-removal regardless of IUD type. IMPLICATIONS: Menstrual cup and NTCu380-Mini use may increase IUD expulsion risk and may increase accidental self-removal risk with TCu380A and NTCu380-Mini use. Clinicians should advise patients of these risks and consider warning patients using an IUD shaped like the NTCu380-Mini (Nova-T frames) of expulsion risk with menstrual cup use.

Safety testing of Ovaprene: An investigational nonhormonal monthly vaginal contraceptive.

OBJECTIVES: Evaluate the safety of Ovaprene, an investigational nonhormonal vaginal contraceptive designed for monthly use. STUDY DESIGN: Open-label, multicenter study enrolling heterosexually-active women with previous permanent contraception who underwent assessments during five menstrual cycles: baseline postcoital test cycle, diaphragm postcoital test cycle, Ovaprene safety cycle, and two Ovaprene postcoital test cycles. Safety outcomes included treatment-emergent adverse events, systemic laboratory findings, pelvic examinations, colposcopies, Nugent scores, determination of community state types of vaginal microbiota, and anti-Escherichia coli activity and inflammatory markers in cervicovaginal fluids. RESULTS: We enrolled 38 participants. Of these, 33 used Ovaprene and completed 77 Ovaprene cycles. The most common product-related urogenital treatment-emergent adverse events were bacterial vaginosis and vaginal odor. The frequency of transitioning from Lactobacillus-dominated community state type to community state type IV (not Lactobacillus-dominated) was similar before Ovaprene use and afterwards. Mean Nugent scores were <4 at each visit without a discernible upward trend. Inflammatory markers showed wide variation but no upward trend, and E. coli inhibitory activity of cervical secretions did not change. We found no Staphylococcus aureus, the causative agent in toxic shock syndrome, on used Ovaprenes or in vaginal samples. No clinically important changes in systemic laboratory findings, pelvic examinations, or colposcopies occurred during Ovaprene use. CONCLUSIONS: Ovaprene use did not result in cervicovaginal irritation or adverse effects on resident vaginal microbiota and did not impact transitions from a Lactobacillus-dominated community state type to community state type IV. IMPLICATIONS: The finding that the use of Ovaprene, an investigational monthly user-controlled nonhormonal vaginal contraceptive, does not appear to result in adverse changes in vaginal health during short-term use supports further evaluation of the contraceptive potential of the device.

Health services provided at the time of abortion in the US: a scoping review of the qualitative and quantitative evidence.

Objectives: While it is well documented that abortion access is associated with improved health, pregnancy-related, and socioeconomic outcomes, the association between abortion access and other reproductive health outcomes is less well described. Abortion-providing clinics also offer preventative reproductive health services. We conducted a scoping review to ascertain the extent to which preventive reproductive healthcare services (contraception, sexually transmitted infection testing and treatment, cervical cancer screening) are affected by abortion access in the United States. Methods: Researchers screened articles and extracted data from PubMed, Embase, Scopus and CINAHL. We excluded articles that did not link abortion to contraception, sexually transmitted infection testing and treatment and cervical cancer screening; or took place outside the US. Results: 5,359 papers were screened, 74 were included for full text review. Sixty-five were about contraception, seven on STIs, one on cervical cancer screening, and one on other services. The association between policies that restrict or protect abortion access and preventative health services has not been studied on a national scale. Drivers of variation were: insurance and billing policies; regulatory requirements of abortion-providing facilities, lack of staff training in clinics that did not specialize in abortion care; and limited follow up after abortion. Conclusions: Abortion--providing clinics are a highly utilized access point for reproductive health services. More research is needed to determine the public health impact of constrained abortion access on contraceptive use, STI rates and cervical cancer in regions where many abortion-providing clinics have closed. Implications: Attention should be paid to changing trends in contraceptive use, STI rates and cervical cancer as abortion-providing clinics close, this may reduce access to reproductive health services broadly.

Geographic Access to Early Pregnancy Loss Management.

Early pregnancy loss (EPL) is common, but patients face barriers to the most effective medication (mifepristone followed by misoprostol) and procedural (uterine aspiration) management options. This cross-sectional geospatial analysis evaluated access in New Mexico to mifepristone and misoprostol and uterine aspiration in emergency departments (comprehensive) and to uterine aspiration anywhere in a hospital (aspiration) for EPL. Access was defined as a 60-minute car commute. We collected data from hospital key informants and public databases and performed logistical regression to evaluate associations between access and rurality, area deprivation, race, and ethnicity. Thirty-five of 42 (83.3%) hospitals responded between October 2020 and August 2021. Two hospitals (5.7%) provided comprehensive management; 24 (68.6%) provided aspiration. Rural and higher deprivation areas had statistically significantly lower adjusted odds ratios for comprehensive management (0.03-0.07 and 0.3-0.4, respectively) and aspiration (0.03-0.06 and 0.1-0.3, respectively) access. Mifepristone and uterine aspiration implementation would address disparate access to EPL treatment.

Successful postcoital testing of Ovaprene: An investigational non-hormonal monthly vaginal contraceptive.

OBJECTIVE: Evaluate reduction in progressively motile sperm per high power field (HPF) in midcycle cervical mucus after intercourse with Ovaprene: an investigational monthly non-hormonal vaginal contraceptive consisting of a vaginal ring and mechanical barrier, releasing spermiostatic ferrous gluconate. STUDY DESIGN: Open-label, multicenter study enrolling heterosexually-active women with previous permanent contraception. Participants underwent a baseline postcoital test cycle with no device to confirm the presence of sperm, followed by one diaphragm postcoital test cycle, one Ovaprene safety cycle, and two Ovaprene postcoital test cycles. In each postcoital test cycle, participants underwent a midcycle cervical mucus evaluation to confirm an Insler score ≥10 and absence of sperm, and then returned two to four hours after vaginal intercourse for repeat cervical mucus evaluation. We considered <5 progressively motile sperm/HPF indicative of preliminary contraceptive effectiveness. RESULTS: We enrolled 38 participants; 23 completed the study. All participants had ≥5 progressively motile sperm/HPF in the baseline cycle and <5 progressively motile sperm/HPF in all 49 Ovaprene cycles and all 35 diaphragm cycles, meeting the definition of a successful postcoital test. This was true regardless of examiner blinding, prior vaginal delivery or vaginal ring use, body mass index, or dislodgements noted by the participant or investigator. The mean of 27.2 (±17.9) progressively motile sperm/HPF in baseline postcoital test cycles was reduced to 0.5 (±1.1) and 0.5 (±1.3) progressively motile sperm/HPF in the first and second Ovaprene cycles, respectively. Ovaprene fit all participants and all could insert, position, and remove it. CONCLUSION: Use of Ovaprene resulted in meeting the prespecified criterion for contraceptive effect by all participants during all postcoital test cycles. IMPLICATIONS: The finding that use of Ovaprene, an investigational monthly non-hormonal vaginal contraceptive, resulted in postcoital testing of cervical mucus that met the pre-specified definition of success (<5 progressively motile sperm/HPF) supports further evaluation of contraceptive efficacy of the device in users at risk for pregnancy.

Trust in provider and stigma during second-trimester abortion.

OBJECTIVE: To determine whether trust in the provider and sociodemographics are associated with individual-level abortion stigma. METHODS: We performed a cross sectional and exploratory study design using secondary analysis of a randomized trial that enrolled participants undergoing second trimester abortion. We collected baseline survey data from 70 trial participants to assess stigma (Individual Level of Abortion Stigma scale, ILAS; range 0-4), trust in provider (Trust in Physician scale; range 1-5), anxiety, depression, and sociodemographics. We performed multiple linear regression, for which ILAS score was the outcome of interest. Univariate associations were used to inform the regression model. RESULTS: The mean abortion stigma score was at the low end of the ILAS at 1.21 (range 0.2-2.8, SD 0.66). Age, race, income, BMI, parity, gestational age at time of abortion, and reasons for ending the pregnancy were not significantly associated with the ILAS score. Higher trust in provider scores were (m 4.0, SD 0.49) and inversely related to the ILAS score, even after adjustment for confounders (ß -0.02, CI -0.03 to -0.004, p = 0.013). Screening positive for anxiety or depression was associated with a higher ILAS score ((ß 0.48, CI 0.10, 0.90, p = 0.015); (ß = 0.27 CI -0.097, 0.643)), while cohabitation was associated with lower ILAS score (ß -0.44, CI -0.82 to -0.57, p = 0.025). CONCLUSIONS: Trust in an abortion provider, anxiety, depression, and cohabitation are associated with abortion stigma among people seeking second trimester abortion care. Interventions that improve trust in a provider may be an area of focus for addressing abortion stigma. Future research should confirm these findings in larger populations and across diverse locations and demographics and to conduct qualitative research to understand what patients perceive as trust-promoting behaviors and words during abortion encounters.

Induced Abortion and the Risk of Rh Sensitization.

Importance: While population-level data suggest Rh immunoglobulin is unnecessary before 12 weeks' gestation, clinical evidence is limited. Thus, guidelines vary, creating confusion surrounding risks and benefits of Rh testing and treatment. As abortion care in traditional clinical settings becomes harder to access, many people are choosing to self-manage and need to know if ancillary blood type testing is necessary. Objective: To determine how frequently maternal exposure to fetal red blood cells (fRBCs) exceeds the most conservative published threshold for Rh sensitization in induced first-trimester abortion. Design, Setting, and Participants: Multicenter, observational, prospective cohort study using high-throughput flow cytometry to detect circulating fRBCs in paired maternal blood samples before and after induced first-trimester abortion (medication or procedural). Individuals undergoing induced first-trimester abortion before 12 weeks 0 days' gestation were included. Paired blood samples were available from 506 participants who underwent either medical (n = 319 [63.0%]) or procedural (n = 187 [37.0%]) abortion. Exposure: Induced first-trimester abortion. Main Outcomes and Measures: The primary outcome was the proportion of participants with fRBC counts above the sensitization threshold (125 fRBCs/5 million total RBCs) after induced first-trimester abortion. Results: Among the 506 participants, the mean (SD) age was 27.4 (5.5) years, 313 (61.9%) were Black, and 123 (24.3%) were White. Three of the 506 participants had elevated fRBC counts at baseline; 1 of these patients had an elevated fRBC count following the abortion (0.2% [95% CI, 0%-0.93%]). No other participants had elevated fRBC counts above the sensitization threshold after induced first-trimester abortion. The median change from baseline was 0 fRBCs, with upper 95th and 99th percentiles of 24 and 35.6 fRBCs, respectively. Although there was a strong association between the preabortion and postabortion fRBC counts, no other baseline characteristic was significantly associated with postabortion fRBC count. Conclusions and Relevance: Induced first-trimester abortion is not a risk factor for Rh sensitization, indicating that Rh testing and treatment are unnecessary before 12 weeks' gestation. This evidence may be used to inform international guidelines for Rh immunoglobulin administration following first-trimester induced abortion.

Application of a Multiplex Platform to Identify Novel Biomarkers for Pregnancy Location and Viability.

Determining early pregnancy location and viability can be cumbersome, often requiring serial evaluations. This study aimed to identify novel biomarker candidates for pregnancy location and viability using a pseudodiscovery high-throughput technique. This was a case-control study among patients presenting for early pregnancy assessment, including ectopic pregnancies, early pregnancy losses, and viable intrauterine pregnancies. For pregnancy location, ectopic pregnancy was considered "case" and non-ectopic considered "control." For pregnancy viability, viable intrauterine pregnancy was considered "case" and early pregnancy loss + ectopic pregnancy were considered "control." Using Proximity Extension Assay technology from Olink Proteomics, serum levels of 1012 proteins were compared separately for pregnancy location and viability. Receiver operator characteristic curves were generated to determine a biomarker's discriminative abilities. Analysis included 13 ectopic pregnancies, 76 early pregnancy losses, and 27 viable intrauterine pregnancies. For pregnancy location, 18 markers had an area under the curve (AUC) ≥0.80, with three being expressed more in ectopic compared to non-ectopic pregnancies: thyrotropin subunit beta, carbonic anhydrase 3, and DEAD (Asp-Glu-Ala-Asp) box polypeptide 58. For pregnancy viability, two markers had an AUC ≥0.80: lutropin subunit beta and serpin B8. While some of the markers had previously been implicated in early pregnancy physiology, others were from pathways not previously explored. Using a high-throughput platform, a large number of proteins were screened as potential biomarkers for pregnancy location and viability, and twenty candidate biomarkers were identified. Further exploration of these proteins may facilitate validation as diagnostic tools for establishing early pregnancy diagnoses.

Feasibility and acceptability of virtual group contraceptive counseling prior to abortion care.

OBJECTIVES: This study aimed to evaluate the feasibility and acceptability of virtual group contraceptive counseling in the abortion care setting. STUDY DESIGN: Patients seeking abortion care at an urban university hospital were invited to participate in this cohort study. Prior to their clinical appointments, groups of two to six patients participated in 45-minute virtual contraceptive counseling visits facilitated by study staff. Contraceptive method use, effectiveness, and side effects were reviewed according to group interest. Participant satisfaction scores were collected immediately following the sessions. After their appointments, providers estimated the time spent on contraceptive counseling during the clinical visit. RESULTS: Of 195 patients approached, 86 (44%) were enrolled. Fifty-seven (66%) enrolled patients completed a session. The most common reason for declining enrollment was concern about the time commitment. Most (93%) participants reported being "satisfied" or "very satisfied" overall, and 96% would recommend group contraceptive counseling to a friend. Providers reported that compared to typical counseling, participants required a shorter amount of time during the clinical visit than nonparticipants (time spent <5 minutes: 74% vs 54%). CONCLUSIONS: Virtual group contraceptive counseling for patients seeking abortion was feasible and acceptable in this study. Group virtual visits may reduce provider time burden, add value when virtual care delivery is desired or required, and deserve further study. IMPLICATIONS: Family planning clinics can consider incorporating virtual group counseling as a person-centered and efficient approach to contraceptive counseling at the time of abortion care.

Evaluation of a decision aid for early pregnancy loss: A pilot randomized controlled trial in Philadelphia, Pennsylvania.

OBJECTIVES: To evaluate the effect of a decision aid on decisional conflict scale in patients choosing management for early pregnancy loss. STUDY DESIGN: We conducted a pilot randomized control trial to assess the effect of the Healthwise patient decision aid on decisional conflict scale in patients with early pregnancy loss as compared with a control website. Patients 18years and older were eligible if they had an early pregnancy loss between 5 and 12 completed weeks of gestation. Participants completed surveys at baseline, poststudy intervention, after consultation, and 1week postconsultation. Surveys assessed participant scores on the decisional conflict scale (scale 0-100), knowledge, assessment of shared decision-making, satisfaction, and decision regret. Our primary outcome was the poststudy-intervention decisional conflict scale score. RESULTS: From July 2020 through March 2021 we randomized 60 participants. After the intervention, the median decisional conflict scale score for the control group was 10 [0-30] and 0 [0-20] for the intervention group (p = 0.17). When assessing the decisional conflict scale subscales postintervention, the informed subscale for the control group was 16.7 [0-33.3] as opposed to 0 [0] for the patient decision aid group (p = 0.003). Knowledge remained significantly higher in the experimental arm from the postintervention to the 1-week follow-up. We found no differences between groups when assessing our other metrics. CONCLUSIONS: Use of a validated decision aid did not result in statistically significant differences in the total decisional conflict scale scores as compared with the control. Participants allocated to the intervention were more informed postintervention and had consistently higher knowledge scores. IMPLICATIONS: Use of a validated decision aid prior to early pregnancy loss management consultation did not affect overall decisional conflict but resulted in improved knowledge.

Application of a Multiplex Platform to Identify Novel Biomarkers for Pregnancy Location and Viability.

Determining early pregnancy location and viability can be cumbersome, often requiring serial evaluations. This study aimed to identify novel biomarker candidates for pregnancy location and viability using a pseudodiscovery high through-put technique. This was a case-control study among patients presenting for early pregnancy assessment, including ectopic pregnancies, early pregnancy losses, and viable intrauterine pregnancies. For pregnancy location, ectopic pregnancy was considered "case" and non-ectopic considered "control." For pregnancy viability, viable intrauterine pregnancy was considered "case" and early pregnancy loss + ectopic pregnancy were considered "control." Using Proximity Extension Assay technology from Olink Proteomics, serum levels of 1012 proteins were compared separately for pregnancy location and viability. Receiver operator characteristic curves were generated to determine a biomarker's discriminative abilities. Analysis included 13 ectopic pregnancies, 76 early pregnancy losses, and 27 viable intrauterine pregnancies. For pregnancy location, 18 markers had an area under the curve (AUC) ≥ 0.80, with three being expressed more in ectopic compared to non-ectopic pregnancies: thyrotropin subunit beta, carbonic anhydrase 3, and DEAD (Asp-Glu-Ala-Asp) box polypeptide 58. For pregnancy viability, two markers had an AUC ≥ 0.80: lutropin subunit beta and serpin B8. While some of the markers were previously identified as implicated in early pregnancy physiology, others were from pathways not previously explored. Using a high through-put platform, a large number of proteins were screened as potential biomarkers for pregnancy location and viability, and twenty candidate biomarkers were identified. Further exploration of these proteins may facilitate validation as diagnostic tools for establishing early pregnancy diagnoses.

State restrictions on abortion are associated with fewer abortions in patients with high-risk cardiovascular conditions.

OBJECTIVES: Patients with modified World Health Organization (mWHO) class IV cardiovascular conditions are at high risk of severe maternal morbidity and mortality in pregnancy and are advised to avoid pregnancy or consider abortion if they become pregnant. We aimed to determine if state-level abortion policy is associated with receiving an abortion in this high-risk population. STUDY DESIGN: We conducted a descriptive retrospective cross-sectional study of abortion among people 15-44 years of age with mWHO class IV cardiovascular conditionsstate policy on abortion using US claims data from United health Group from 2017 to 2020. RESULTS: There was a statistically significant association between restrictive abortion policy at that state level and lower number of pregnancies ending in abortions in this high-risk group. CONCLUSIONS: States with the most restrictive abortion policy have the lowest proportion of pregnancies ending in abortion among patients with mWHO class IV cardiovascular conditions. IMPLICATIONS: Variation in receiving abortion by state of residence among patients with mWHO class IV cardiovascular conditions may indicate an impending rise in severe maternal morbidity and mortality related to cardiovascular disease in pregnancy, and the risk factor is where a person lives. This trend may be exacerbated by the Supreme Court Decision Dobbs v Jackson Women's Health.

The Dobbs v Jackson Women's Health Organization Supreme Court Decision-Concerns, Challenges, and Consequences for Health Care.

This Viewpoint discusses potential consequences that the US Supreme Court ruling in Dobbs v Jackson Women's Health Organization may have for patient outcomes, public health, training and legal challenges for health care professionals, and the patient-practitioner relationship.