RESEARCH ROUNDUP /
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Research roundup: September 2022 edition

Pain management for medication abortion, support for eight years of use for a LNG 52mg IUD (Mirena and Liletta), IUD placement within 48 hours after medication abortion, and more.

by Colleen Denny, MD and Emma Gilmore, MD

published 09/30/22

1. Screening for High-Risk Human Papillomavirus Using Passive, Self-Collected Menstrual Blood

Cervical cancer is one of the leading causes of cancer-related mortality in individuals with a cervix, and the majority of cases are caused by human papillomavirus (HPV). However, many of these diagnoses could have been prevented with the use of routine cytology and treatment, such as colposcopy. Primary HPV screening is recognized as an evidence-based method of identifying high-risk patients, but a self-managed testing mechanism has not been widely accepted. The authors of this study used a novel menstrual pad, which stabilizes blood samples to compare whether menstrual blood yielded similar results to clinician-collected swabs for HPV screening. For menstrual samples collected within the previous two months, concordance between menstrual blood and clinician testing was almost 94%, which was higher than a self-collected HPV swab. Concordance was 100% in patients with high-grade lesions or high-risk strains of HPV. Menstrual pad analysis was also highly acceptable to patients. Overall, these results suggest that self-collected menstrual blood could be a viable and trustworthy option for primary HPV screening.

2. Mechanism of action of norgestrel 0.075 mg a progestogen-only pill. I. Effect on ovarian activity

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3. Mechanism of action of a 0.075 mg norgestrel progestogen-only pill II. Effect on cervical mucus and theoretical risk of conception

The Food and Drug Administration is currently evaluating an application to switch a prescription progesterone-only pill containing 0.075 of norgestrel (OPill) to over the counter. Progesterone-only oral contraceptives likely prevent pregnancy through a number of mechanisms but are thought to be potentially less effective than combined oral contraceptives containing both progesterone and estrogen due to less suppression of ovulation.

These two analyses examined the results from perfect use of the norgestrel pills by reproductive-aged women in a prospective, multicenter, randomized crossover study. They focused on two different mechanisms of pregnancy prevention: changes in cervical mucus and suppression of ovulation. The Han et al study evaluated more than 400 cervical mucus samples from 51 women taking norgestrel pills and graded them on whether they favored fertility, finding that 0% of samples were graded as favorable during a 28-day cycle. Glaiser et al analyzed the effect of norgestrel on ovarian function over the same 28-day period, monitoring follicular development and ovulation for participants taking norgestrel; a minority of participants (33%) ovulated during norgestrel use, though cervical mucus quality for these ovulating participants was not favorable for fertility. Taken together, these articles support the high effectiveness of a norgestrel-only pill in its ability to prevent pregnancy through multiple modalities, which may provide an important option for patients seeking contraception without a provider’s prescription.

4. Association of Progestogens and Venous Thromboembolism Among Women of Reproductive Age

It is well-established that estrogen-containing contraceptives are not recommended in individuals at high risk for venous thromboembolism (VTE), such as deep venous thrombosis (DVT) or pulmonary embolism (PE). These patients are typically guided towards non-hormonal or progestin-only contraceptives to diminish their risk. However, some evidence suggests that higher dose progestins, such as medroxyprogesterone acetate (DMPA) or non-contraceptive progestins, such as those given for heavy uterine bleeding, may increase clotting risk. The authors of this paper conducted a case-control study to assess the risk of VTE in patients using differing progestin-only medications. They found that higher-dose progestins, including norethindrone acetate, DMPA, and medroxyprogesterone acetate, were significantly associated with increased VTE risk, while lower-dose medications such as the levonorgestrel intrauterine device (LNG-IUD) and etonogestrel implant did not confer any increased risk. While further research is needed to better understand this link, this information can be used by providers when choosing appropriate medications for patients at risk for VTE.

5. Contraceptive efficacy and safety of 52mg LNG-IUS for up to 8 years: findings from the Mirena Extension Trial

The 52mg LNG-IUD is a highly-effective and reversible form of contraception and can be safely used by almost all patients. While the two 52mg LNG-IUDs available in the US, Liletta and Mirena, were previously FDA approved for 6 and 7 years, respectively, this multicenter single-arm study examined the risk of pregnancy for extended use for an additional year. Among 362 participants who entered a 6th year of IUD use (223 of whom completed 8 years of IUD use), only two pregnancies were noted, one in year six and one in year seven. Pearl indexes for years 6, 7, and 8 were very low and not statistically significant, at 0.34, 0.40, and 0.00, respectively. The authors also noted that extended use was associated with decreased bleeding and spotting days among users, with approximately 50% rates of amenorrhea or infrequent bleeding. For those who had their IUD removed to pursue pregnancy, the 12-month return-to-fertility rate was 77%. The authors concluded not only that 8-year use of the 52mg LNG-IUD was highly effective at preventing pregnancy, but that it did not appear to adversely affect bleeding profiles or long-term fertility outcomes. Providers who offer these 52mg LNG-IUDs in their practice can confidently offer patients the option of continued use of the IUD through 8 years without decreased effectiveness.

6. Lactogenesis and breastfeeding after immediate versus delayed birth-hospitalization insertion of etonogestrel contraceptive implant: A non-inferiority trial

There is well-established utility of placing IUDs and subdermal implants during postpartum hospitalization. Patients leave the hospital with a reliable form of birth control and are protected even if they are unable to attend their postpartum visit. However, some providers may have hesitations about using levonorgestrel-containing devices immediately after delivery, to avoid interfering with the initiation of breastfeeding. Overall, this concern is mostly theoretical, with clear evidence that immediate levonorgestrel IUD placement doesn’t negatively impact breastfeeding. However, less is known about the effect of the implant. For this study, the authors assessed lactogenesis stage II (copious milk secretion) in patients who had an implant placed within 2 hours of delivery and 24-48 hours from delivery. They found no significant differences in lactogenesis stage II between groups, and breastfeeding was not negatively impacted in the immediate placement group. This study adds to existing research supporting immediate post-delivery initiation of progestin-only contraception. Delivery-room insertion of the subdermal contraceptive implant could be offered to patients as a convenient and safe option for postpartum contraception.

7. PAIN management for medical abortion before 14 weeks' gestation: A systematic review

Medication abortion in the first trimester is highly effective and safe and is an increasingly popular choice for patients seeking pregnancy termination. However, the optimal method for managing pain during a medication abortion is less clear. In this systematic review, the authors analyzed five studies (four randomized control trials and one observational study) involving more than 500 patients to understand which pain control regimens had a significant effect on maximum pain score in the 24 hours after misoprostol dosing. They concluded that the heterogeneity of the study designs in the five selected studies precluded any meta-analysis. However, in a review of study findings, the authors suggested that ibuprofen appeared superior for pain control than either paracetamol or placebo, that there appeared to be no benefit for prophylactic ibuprofen dosing in comparison with therapeutic dosing, and that pregabalin and ambulation did not appear to affect pain scores. While more research is needed to address pain management, these findings underscore the common practice of providing ibuprofen to patients undergoing a medication abortion.

8. Using Prophylactic Antihemorrhagic Medications in Second-Trimester Surgical Abortions

Second-trimester surgical abortion via dilation and evacuation (D&E) is a safe and effective form of pregnancy termination. However, as approximately up to 1% of these procedures are complicated by hemorrhage, defined as an estimated blood loss of more than 500ml. Techniques to reduce hemorrhage risk are important to further improve the safety of abortion. In this retrospective review of nearly 150 surgical abortions between 14- and 22-week’s gestation, the authors determined that prophylactic antihemorrhage medications, including lidocaine with epinephrine or vasopressin, methylergonovine, carboprost, oxytocin, and/or misoprostol is given before hemorrhage, were used in 72% of procedures. Patients who received prophylactic uterotonics were significantly less likely to have a hemorrhage, had significantly lower procedural blood loss, and were less likely to require intervention for hemorrhage. However, these differences were not noted for patients who received prophylactic vasoconstrictors only. While the authors caution that this hospital-based retrospective study may not be reflective of all patient populations undergoing an abortion, these findings indicate the need for more research on the potential benefits of prophylactic antihemorrhage medication use.

9. Placement of an intrauterine device within 48 hours after early medical abortion - a randomized controlled trial

Immediate IUD placement is safe and acceptable to patients after surgical abortion and vaginal or cesarean delivery. However, patients undergoing medication abortion typically have delays of two to four weeks before they are eligible for IUD placement, with varying requirements in order to ensure that the abortion is “complete.” The authors of this paper hypothesized that immediate IUD placement—within 48 hours of completed medication abortion—would increase long-term IUD use and be acceptable to patients. The authors designed a randomized controlled trial comparing standard IUD placement, (within two to four weeks) to immediate IUD placement (within 48 hours of completed abortion) and measured user rates at six months after abortion. Completed medication abortion was determined through an assessment of the patient’s symptoms, such as the passage of blood clots, and the IUD was placed within 48 hours of this determination. Immediate IUD placement was found to be safe and resulted in lower pain scores for patients, who also preferred this timing of IUD placement. However, six-month user rates did not differ between the two groups. This study suggests that an immediate IUD may be a desirable and safe option for patients and should warrant more consideration and research.

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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