1. Treatment of Early Pregnancy Loss With Mifepristone and Misoprostol Compared With Misoprostol Only
Early pregnancy loss (EPL) is common, affecting an estimated 15-20% of all early pregnancies. EPL is defined as early intrauterine pregnancies with finding that suggest the pregnancy will not progress. Approach to EPL management is driven by patient preference and clinical condition. When pregnancy tissue is retained within the uterus, options include expectant management, medication management, or procedural management via uterine aspiration. Patients who opt for medication management for EPL are typically offered either monotherapy with misoprostol alone or a combination of mifepristone and misoprostol. While the combination regimen has been shown to improve completion rates in terms of short term outcomes (passage of the gestational sac within a week), it is unclear how the regimens compare during longer follow up. In this retrospective cohort study of nearly 1,000 patients, the authors studied how the type of medical management influenced the need for future procedural management via uterine aspiration for treatment failure, including after subsequent menstruation (if ultrasound showed persistent retained products of conception). They found that treatment failure was significantly lower among patients who received both mifepristone and misoprostol compared to misoprostol alone, at 17.8% versus 25.1%, respectively, with a 34% reduction in the odds of treatment failure after combination therapy. Prior vaginal delivery and earlier gestational duration were both associated with lower odds of treatment failure. This study confirms the importance of mifepristone in successful medical management of EPL and helping patients to avoid undesired procedural management or prolonged care.
2. Contemporary Hormonal Contraception and Risk of Venous Thromboembolism
Hormonal contraception use has long been known to increase patients’ risk for venous thromboembolism (VTE), though absolute risk is still low and all contraceptive methods have a lower risk of VTE than pregnancy. However, there is less data about modern hormonal contraception, which uses lower doses of estrogen than historical formulations and/or may include novel progestins. In this large cohort study, the authors used Danish national registers to study VTE rates (either pulmonary embolism or lower limb deep venous thrombosis) among more than one million reproductive-aged females without known VTE risk factors between 2011 and 2021. In their analyses, the authors found that VTE rates increased with all forms of hormonal contraception use except IUDs, from 2.0 VTE per 10,000 person years at baseline for non-pregnant non-users to 10.0 for combined pills, 8.0 for vaginal rings, 8.1 for patches, 3.6 for progesterone-only pills, 3.4 for contraceptive implants, and 11.0 for contraceptive injections. Among pills users, risk for VTE also varied depending on the type of combined contraceptive pill used, at only 3.0 for patients taking a pill with 20mcg of ethinyl estradiol and levonorgestrel up to 14.2 for combined pills using novel progestins. This data can help providers tailor their contraception counseling based on patients’ individual risk factors and concerns, and highlights the importance of further investigation of novel progestins and bioidentical estrogens on VTE risk.
4. Evaluating the fidelity of AI-generated information on long-acting reversible contraceptive methods
Artificial intelligence is rapidly changing the medical field, from allowing providers and researchers to rapidly synthesize clinical data to widely accessible chatbots that allow patients to directly pose health questions. ChatGPT is a widely used chatbot that uses machine learning to provide users with answers on widely ranging topics, including reproductive health care. In this study, the authors presented ChatGPT with eight frequently asked questions about long-acting reversible contraception, repeating the questions over three different days with slightly varying terminology (“implant” versus “Nexplanon”) and analyzing the consistency and accuracy of responses. The authors found that approximately 70% of responses were both medically correct and answered the question posed. 16% of answers contained incorrect information, most commonly incorrect information of appropriate duration of use, and 14% of answers contained conflicting evidence without additional context. While the authors conclude that AI chatbots can already provide useful and accurate reproductive health guidance much of the time, they may still be a source of misinformation and confusion. Providers should continue to stay aware of AI’s capabilities and limitations to understand their patients’ decision-making processes around contraception methods and health care generally.
5. Double dosing ulipristal acetate emergency contraception for individuals with obesity: a randomised crossover trial
The two oral emergency contraception (EC) medications, levonorgestrel and ulipristal acetate, work by delaying or preventing ovulation. Over-the-counter EC with levonorgestrel (brand name Plan B) is known to be less effective for individuals with a body mass index (BMI) greater than 30kg/m22, and doubling its dose does not appear to improve efficacy. However, less is known about the relationship between ulipristal acetate (brand name ella) and BMI. For this study, the authors designed a crossover trial in which individuals with BMI ≥ 30 and weight ≥ 80kg took both single and double doses of ulipristal acetate in two separate cycles, thereby serving as their own controls. The aim of the trial was to determine whether the double dose of ulipristal acetate was more effective for delaying ovulation. Patients were monitored using labs and ultrasounds, and ulipristal acetate was dosed prior to each individual’s LH surge, which signals the start of ovulation. The authors found that a single dose of ulipristal acetate effectively delayed ovulation by 5 days in 100% of participants when taken prior to LH surge. These results suggest that the effectiveness of ulipristal acetate for EC is not impacted by weight or BMI, which is important information for all providers who discuss EC with patients.
6. Immediate postpartum contraceptive implant placement and breastfeeding success in postpartum people at risk for low milk supply: A randomized non-inferiority trial
There is theoretical concern that exposure to progestins may impact the establishment of milk supply during the immediate postpartum period. Currently, evidence supports the placement of the contraceptive etonogestrel implant (Nexplanon), during this time, without having a negative impact on lactogenesis. Unfortunately, less is known about the impact of contraceptive implant use on patients already at risk for low milk supply – such as those who had a premature delivery, have certain medical problems, or have had a low supply in the past. However, these patients and their providers may naturally have a specific interest in milk supply and contraception effects, and the authors of this study sought to increase what is known about this question. This three-armed trial enrolled patients at risk for low milk supply in three groups depending on timing of implant placement: within 30 minutes of delivery, 24-72 after delivery, or at their 6-week postpartum visit. Participants’ experiences with lactogenesis were evaluated through surveys about milk production and Nexplanon satisfaction. Unfortunately, study recruitment had to be terminated due to the Covid pandemic, and the authors were not able to establish non-inferiority with their results. However, their data still suggests that timing of implant placement does not seem to have an impact on milk supply. This information is helpful for providers and patients who have concerns about milk supply and the potential effects of contraception.
7. US Abortion Bans and Fertility & 8. US Abortion Bans and Infant Mortality
Since the Supreme Court ruling in Dobbs v. Jackson Women’s Health Organization in June 2022, the landscape of abortion access has changed dramatically in the US. Currently, 13 states ban abortion, and four other states restrict abortion after 6 weeks gestation. Furthermore, mounting restrictions and obstacles have made abortion inaccessible for patients due to financial, geographic or other barriers. The following investigations from JAMA focus on the impact of these restrictions on fertility and infant mortality by examining data from 2012 to 2023.
To understand the effect of Dobbs on individual fertility rates, the investigative team looked at US Census data on fertility rates for pregnancy-capable people 15-44 years old in states with abortion restrictions compared to states without restrictions. They also analyzed results according to risk factors that already place pregnant individuals at risk for adverse maternal and neonatal outcomes, such as being part of a minority group, having less education, and being unmarried. They found that abortion bans were associated with larger-than-expected increases in fertility rates for pregnancy-capable individuals in the South and for groups already facing healthcare disparities. Studies have already established that continuing an undesired pregnancy can lead to exacerbations of pre-existing obstacles such as economic instability. The results of this study suggest that abortion bans further increase these disparities by increasing fertility for individuals already grappling with inequity and leading to births in states that already lack infrastructure for maternal health. Historically, infant mortality in the US has been dropping, and was down to 5.6 deaths per 1000 live births in 2022. However, there is concern that abortion restrictions will lead to an increase in infant mortality for numerous reasons. Pregnancies affected by congenital anomalies are a frequent cause of infant death, and cannot be terminated in restrictive states. Furthermore, patients with undesired pregnancies who are already at risk for maternal complications may experience adverse events that negatively impact their fetuses. The study authors examined data on live births and infant deaths in 14 states with either complete or 6-week abortion bans and compared their outcomes to pre-Dobbs data and states without bans. Their findings were sobering. Black infants, who were already twice as likely to die in their first year when compared to white or Hispanic infants, experienced a disproportionate increase in infant mortality. Increases in infant mortality were also noted for infants in the south and those with and without congenital anomalies. Overall, these results suggest that abortion bans increase racial disparities in infant mortality while increasing infant mortality rates overall.
9. Proximity of Crisis Pregnancy Centers to Colleges and Universities in the United States, 2021
Crisis Pregnancy Centers, or CPCs, are faith-based facilities that offer pregnancy-related counseling and other services while attempting to dissuade pregnant individuals from having abortions. There are more than 2,500 CPCs in the United States, and most are centered in Midwestern or Southern states that are already in regions that lack the full range of reproductive health care options. CPCs are known to target younger people, often providing information or ultrasounds that are inaccurate or deceptive. Pregnancy-capable individuals between 18-24 years old are disproportionately likely to seek abortions in the US and are also within the age group targeted by CPCs. Many individuals within this age range attend a center of higher education (college, university) and CPCs often place informational packets around or near these centers to attract clientele. The authors of this study sought to evaluate the spatial relationship between CPCs and US colleges and universities, specifically the number of female students with a CPC within three driving miles. They found that more than 50% of pregnancy-capable college and university students live within three driving miles of a CPC, and in almost 70% of US states, a CPC was located less than one mile away from centers of higher education. This data suggests that CPCs are specifically targeting students at colleges and universities and highlights a need for unbiased and medically accurate information in these locations.
10. A Proof-of-Concept Study of Ulipristal Acetate for Early Medication Abortion
Medication abortion using a combination of mifepristone and misoprostol is the standard of care and represents a safe and highly effective form of abortion care, with published success rates of 95-96% overall. However, mifepristone may not be easily available in many regions due to cost, supply chain issues, and/or political restrictions. Misoprostol alone is an acceptable alternative regimen for medication abortion with similarly high efficacy. In this early phase, proof-of-concept, two-stage clinical study, the authors investigated whether higher doses of ulipristal, a selective progesterone receptor modulator, in combination with misoprostol could provide comparable rates of successful medication abortion. The authors combined a dose-finding study followed by an open-label study, with an ultimate total of 133 patients who received 60mg of oral ulipristal followed by 800mcg of buccal misoprostol. Successful pregnancy termination occurred in 97% of patients, with no serious adverse events and side effects similar to those observed with the mifepristone and misoprostol regimen. This study is limited by its small patient population size and lack of misoprostol alone comparison group.
