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Research roundup: April 2023 edition

Perceived pain and sedation dosing during abortion procedures by demographics, PAPP-A as a novel screening for gestational age before medication abortion, patient experiences with progestin-only pills and attitudes towards OTC access.

by Colleen Denny, MD and Emma Gilmore, MD

published 04/28/23

1. Experiences of progestin-only pill users in the United States and attitudes toward over-the-counter access

Oral contraceptive pills are one of the most widely used forms of contraception in the United States, but for some individuals, obtaining access to a prescription can be prohibitive. An increasing body of evidence supports the provision of contraceptive pills without a prescription requirement, but less is known about patient perspectives on progestin-only pills, or POPs. While POPs are less frequently prescribed than combined oral contraceptives, they remain a feasible and safe option for numerous patients. The authors of this study led online focus group discussions for 36 POP users to better understand their perspectives regarding their chosen birth control method and the possibility of obtaining it over the counter (OTC). They found that the majority of POP users were happy with their method and found it easy to use, despite the need to take it at the same time every day. The vast majority of users expressed strong support for OTC access to POPs, particularly if pills were affordable and educational materials were available. The findings of this study indicate that POPs, if made available OTC, would be an acceptable and effective option for patients, adding to the existing literature on this topic. Learn more about the safety and efficacy of OTC pills and why we are ready for them now.

2. Combined Oral Contraceptive Adherence and Pregnancy Rates

Combined oral contraceptive pills (OCPs) are one of the most commonly used methods of contraception in the US and are typically reported as having a real-world failure rate of 7% in the first year of use. However, there is less detailed information about how pregnancy rates change with strict adherence to daily dosing as opposed to more frequently missed doses. In this secondary analysis of a multicenter Phase 3 trial, the authors pooled data from nearly 3,000 patients taking a new OCP containing 15mg estetrol and 3mg drospirenone in a 24 hormone and four placebo pill regimen. They collected detailed data regarding participants’ pill use, sexual activity, and use of alternative contraception. Patients who missed pills received detailed instructions about how to take future pills during that cycle to avoid pregnancy. The authors found that there was a significant difference in pregnancy rates depending on pill adherence, with pregnancy occurring in 0.09% of cycles where participants reported taking all hormone pills, up through 0.83% of cycles missing two hormone pills, and 1.6% missing more than two hormone pills. No pregnancies occurred when participants who missed pills followed missed-pill instructions. The authors suggest that these data provide a more accurate method-failure rate in patients using OCPs for contraception, as well as reassurance that patients using a 24-4 regimen are unlikely to conceive even if they miss up to two hormone pills, especially if they follow missed-pill instructions.

3. Combined and progestagen-only hormonal contraceptives and breast cancer risk: A UK nested case-control study and meta-analysis

Conflicting evidence exists on the link between hormonal birth control and breast cancer. The authors of this study sought to further explore this link by analyzing a primary care database within the United Kingdom, looking specifically at the association between breast cancer risk and prescriptions for hormonal contraceptives, particularly progestin-only methods. They found that progestin-only contraceptive use, regardless of mode of delivery, was associated with a small increase in breast cancer risk similar to the increase associated with combined hormonal contraceptives. Research has shown that the increased risk associated with combined pills returns to baseline within 10 years of discontinuation. However, long-term effects were not examined as a component of this study. It is important to interpret these results with caution. Little is known about all possible lifetime factors in subjects’ lives, particularly family history, which would have a large impact on breast cancer risk. The benefits of contraceptive use must be weighed against unclear, potential detrimental effects. Overall, this study is unlikely to change our overall understanding of cancer risks associated with contraception.

4. Heavy Menstrual Bleeding Treatment With a Levonorgestrel 52-mg Intrauterine Device

While levonorgestrel (LNG)-IUDs provide excellent contraception, they also may be used off-label for menstrual regulation in patients with abnormal uterine bleeding, including menorrhagia. In this multicenter, phase 3, open-label clinical trial, the researchers recruited 105 patients with a documented menstrual blood loss of 80ml or more per cycle, without a known cause, for placement of a 52mg LNG-IUD (LILETTA). Participants were then asked to collect all menstrual products at three and six cycles after placement. Among the 82 patients who completed six months of follow-up with the LNG-IUD in place, the median decrease in menstrual blood loss was 97.6%, which did not differ by parity or BMI. Patients also reported improvement on several quality-of-life assessment questions over cycles three and six. This study demonstrates the rapid and dramatic improvement in menstrual blood loss for patients with heavy bleeding without a known cause. Providers caring for patients seeking medical management of heavy uterine bleeding, or otherwise considering LNG-IUDs for contraceptive purposes, can counsel on the safety and efficacy of these IUDs for improving bleeding profiles.

5. Extended use of levonorgestrel-releasing intrauterine system (LNG-IUS) 52 mg: A population pharmacokinetic approach to estimate in vivo levonorgestrel release rates and systemic exposure including comparison with two other LNG-IUSs

There are two 52mg LNG IUDs available, Mirena and LILETTA, that are both FDA-approved for eight years of use. Two other LNG-IUDs exist, the Skyla (13.5mg LNG) and the Kyleena (19.5mg LNG) and are FDA-approved for three and five years respectively. While extensive and reliable data is available regarding efficacy, less is known about the pharmacology of LNG IUDs over time. The authors of this study aimed to evaluate in vivo levels of levonorgestrel for the 52mg LNG-IUD and compare them to those of the 19.5mg and 13.5mg LNG-IUDs. Using data from existing clinical trials, they analyzed blood samples for patients using the 52mg LNG-IUD and compared it with established data regarding the other two LNG-IUDs. When reviewing in vivo levonorgestrel release rates, the serum level noted in patients using the 52mg LNG-IUD at eight years was similar to the serum level in patients using the 19.5mg LNG-IUD after five years, and 28% higher than the level in patients using the 13.5mg LNG-IUD after three years. The authors discuss but advise against concluding without additional data that 52mg LNG-IUDs could continue efficacy beyond the currently approved eight years. This information reaffirms previous knowledge about efficacy, while also providing clinicians with additional insight and data that can be used when counseling patients.

6. Early vs Interval Postpartum Intrauterine Device Placement: A Randomized Clinical Trial

For postpartum patients requesting an IUD after birth, postpartum visits, which are typically scheduled for six weeks after delivery, are frequently used for IUD placement. This timing is based on tradition, not evidence, and many patients have resumed sexual intercourse before their postpartum visit and may find it difficult to present for care during this timeline. Two to four weeks after delivery, when patients are often bringing their newborns to a health center, may be a more convenient time for IUD placement. However, there is conflicting evidence about expulsion rates of IUDs placed at varying times in the postpartum period. The authors of this study performed a randomized non-inferiority trial to evaluate expulsion rates for IUDs placed in the early postpartum period (two to four weeks after delivery) compared to interval placement (six to eight weeks after delivery). The study analysis ultimately included 254 postpartum patients who were followed for up to six months postpartum. IUDs placed in the early postpartum period were non-inferior to interval IUDs regarding complete expulsion, but not regarding partial expulsion. Odds of expulsion were higher in patients who were lactating or opted for copper IUDs, but these associations were not statistically significant. These results suggest that IUD placement at two to four weeks postpartum may be a useful option for patients as long as appropriate counseling and follow-up can be provided.

7. Mental Distress Among Female Individuals of Reproductive Age and Reported Barriers to Legal Abortion Following the US Supreme Court Decision to Overturn Roe v Wade

After the Supreme Court overturned Roe v. Wade on June 24, 2022, drastic restrictions were made to abortion access in the United States. Assuming these changes would have caused significant distress to reproductive-aged individuals, particularly females, the authors of this study performed a secondary analysis of a case-control survey study that had been performed from January to September 2022. The authors found that for more than 80,000 female individuals residing in states where abortion was restricted, there was a 10% increase in mental distress. As the survey respondents were not asked to disclose their own experiences with abortion, these results imply that legislative changes have an impact on emotional health across all females of reproductive age. The results of this analysis are further evidence that abortion restrictions are detrimental to the overall health of individuals in the United States.

8. PAPP-A as a screening tool for assessment of gestational age before medication abortion in an intended-use population

Medication abortion is a safe and effective option for abortion care and is now used in the majority of abortions in the United States. Regimens using a combination of mifepristone and misoprostol or misoprostol alone, are best studied and recommended for use through 11 weeks’ gestation. However, determining the gestational age of a pregnancy, and accordingly, a patient’s eligibility for medication abortion, might be challenging in patients with irregular or unknown menstrual dating and/or for whom ultrasound dating is not feasible or convenient. In this study, the authors sought to determine whether levels of PAPP-A, a common serum biomarker assessed in pregnancy, could be used to determine eligibility for medication abortion. The authors collected serum PAPP-A samples and ultrasound dating information from 286 patients seeking abortion care. In analyzing different PAPP-A thresholds from two different laboratories and comparing them to gestational age, the authors concluded that PAPP-A levels had high sensitivity in determining whether a patient was more than 71 days gestational age. While more research is needed to determine how this serum biomarker could best be used for abortion care, this could be an exciting tool for safely caring for abortion patients without accessing an in-clinic ultrasound.

9. The association of patient age, race, and demographic features on reported pain and sedation dosing during procedural abortion: A retrospective cohort study

Patients’ experience of pain during procedural abortion varies widely among patients and is a complicated intersection of patient and procedural factors. Previous research has shown that factors such as age, parity, and race all influence patients’ perception of pain during abortion. While moderate sedation is a recognized safe and effective method of managing pain during procedural abortions, there are no formal guidelines regarding sedation dosing. In this retrospective chart review of 225 patients receiving fentanyl and midazolam for sedation during a procedural abortion, the authors sought to identify which factors were associated with sedation medication dosing. They found an association between race and reason for abortion with medication dosing, with white patients receiving higher doses of midazolam than Black patients and patients terminating for fetal anomalies receiving higher fentanyl doses despite no difference in patient pain scores between in these groups. They did not find a difference in dosing or pain scores across different age groups. The authors suggest that their findings demonstrate that explicit and implicit clinician bias may significantly impact sedation dosing during procedural abortions and encourage providers to recognize these trends to better address these biases and more equitably manage patients’ pain.

10. Sexually Transmitted Disease Surveillance 2021

The CDC has released its most recent STI surveillance data report, consolidating reported data on cases of chlamydia, gonorrhea, and syphilis from 2021. Cases of all three infections increased from 2020, with an approximate 4% increase in both reported chlamydia and gonorrhea cases and a dramatic 32% increase in both syphilis and congenital syphilis cases. While absolute numbers of reported chlamydia cases in 2021 still are below pre-pandemic levels, the authors discuss whether cases are underreported, impacted by disruptions in screening for an often asymptomatic STI. Younger patients, gay and bisexual men, and Black and American Indian/Alaska Native patient groups continue to be disproportionately affected by STIs. Given the continued rise in STI cases across the board, the CDC calls for continuing rebuilding of STI screening and treatment institutions in the wake of the pandemic, facilitating STI testing with more rapid and point-of-care testing, and increased support for STI prevention, including pre-exposure prophylaxis. Learn more about PrEP and nPEP.

Colleen Denny, MD, is an attending ObGyn at Bellevue Hospital in New York City, where she is the Medical Director of the Women's Clinic, and a clinical assistant professor with the NYU School of Medicine. She enjoys providing care for patients in all phases of life and is especially interested in issues related to contraception access and public health. Outside of work, she’s a runner, a dancer, and a bit of a crossword puzzle nerd.
Emma Gilmore is a fellow in Complex Family Planning at the University of Pennsylvania. She completed her residency in Obstetrics and Gynecology at New York University. She's passionate about reproductive rights, medical education, and combating health care disparities, particularly in sexual and reproductive health. In her free time, she can be found taking her dog on walks around the beautiful parks in and around Philadelphia.
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