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.

Use of serum evaluation of contraceptive and ovarian hormones to assess reduced risk of pregnancy among women presenting for emergency contraception in a multicenter clinical trial.

OBJECTIVES: To evaluate ovulation risk among women enrolling in an emergency contraception (EC) study by measuring contraceptive steroids and ovarian hormones. STUDY DESIGN: We used standard chemiluminescent assays to evaluate endogenous hormones (estradiol, progesterone, follicle stimulating hormone, luteinizing hormone) and liquid chromatography-tandem triple quadrupole mass spectrometry to simultaneously analyze concentrations of ethinylestradiol, dienogest, norelgestromin (NGMN), norethindrone (NET), gestodene, levonorgestrel (LNG), etonogestrel (ENG), segesterone acetate, medroxyprogesterone acetate (MPA), and drospirenone in serum samples obtained at the time of enrollment in a recent study comparing oral ulipristal acetate and LNG EC in women with weight ≥80 kg reporting no recent use of hormonal contraception. RESULTS: We enrolled 532 and obtained a valid baseline blood sample from 520 women. Of these, 117 (22.5%) had detectable concentrations of progestin (MPA [n = 58, 11.2%], LNG [50, 9.6%], ENG [11, 2.1%], NET [5, 0.96%], NGMN [3, 0.06%], or drospirenone [1, 0.02%]). LNG was co-detected in all three participants with samples containing NGMN. Multiple progestins were detected in eight other women: ENG/MPA (1), ENG/LNG (2), and MPA/LNG (5). Samples from 55 (10.6%) had concentrations of one or more progestin considered above the minimum level for contraceptive (MPA ≥ 0.1 ng/mL, n = 19; NGMN/LNG ≥ 0.2 ng/mL, n = 31; ENG ≥ 0.09 ng/mL, n = 8; NET ≥ 0.35 ng/mL, n = 4). We detected concentrations of serum progesterone ≥ 3 ng/mL, indicative of luteal phase (postovulation) status, in an additional 194 (37.3%) samples. CONCLUSIONS: More than one-third of enrolled in our clinical trial of oral EC had evidence of prior ovulation at the time of enrollment. Additionally, about 23% had evidence of recent use of hormonal contraception. These results would have decreased the expected risk of pregnancy in the study. IMPLICATIONS: Many participants in a recent clinical trial of oral emergency contraception did not appear to be at risk for pregnancy or would not have benefited from intervention due to cycle timing. Investigators should consider the effects of these findings on expected pregnancy rates when determining sample size in future EC clinical trials, particularly when using noninferiority designs or historical controls.

Timing of Coronavirus Disease 2019 (COVID-19) Vaccination and Effects on Menstrual Cycle Changes.

OBJECTIVE: To assess whether menstrual cycle timing (follicular or luteal phase) of coronavirus disease 2019 (COVID-19) vaccine administration is associated with cycle length changes. METHODS: We used prospectively collected (2021-2022) menstrual cycle tracking data from 19,497 reproductive-aged users of the application "Natural Cycles." We identified whether vaccine was delivered in the follicular or luteal phase and also included an unvaccinated control group. Our primary outcome was the adjusted within-individual change in cycle length (in days) from the average of the three menstrual cycles before the first vaccination cycle (individuals in the unvaccinated control group were assigned a notional vaccine date). We also assessed cycle length changes in the second vaccination cycle and whether a clinically significant change in cycle length (8 days or more) occurred in either cycle. RESULTS: Most individuals were younger than age 35 years (80.1%) and from North America (28.6%), continental Europe (33.5%), or the United Kingdom (31.7%). In the vaccinated group, the majority received an mRNA vaccine (63.8% of the full sample). Individuals vaccinated in the follicular phase experienced an average 1-day longer adjusted cycle length with a first or second dose of COVID-19 vaccine compared with their prevaccination average (first dose: 1.00 day [98.75% CI, 0.88-1.13], second dose: 1.11 days [98.75% CI, 0.93-1.29]); those vaccinated in the luteal phase and those in the unvaccinated control group experienced no change in cycle length (respectively, first dose: -0.09 days [98.75% CI, -0.26 to 0.07], second dose: 0.06 days [98.75% CI, -0.16 to 0.29], unvaccinated notional first dose: 0.08 days [98.75% CI, -0.10 to 0.27], second dose: 0.17 days [98.75% CI, -0.04 to 0.38]). Those vaccinated during the follicular phase were also more likely to experience a clinically significant change in cycle length (8 days or more; first dose: 6.8%) than those vaccinated in the luteal phase or unvaccinated (3.3% and 5.0%, respectively; P <.001). CONCLUSION: COVID-19 vaccine-related cycle length increases are associated with receipt of vaccination in the first half of the menstrual cycle (follicular phase).

Local anaesthesia for pain control in first trimester surgical abortion.

BACKGROUND: Abortions prior to 14 weeks are among the most common outpatient surgical procedures performed on people capable of becoming pregnant. Various methods have been used to control pain; however, many people still experience pain with the procedure. OBJECTIVES: To evaluate the benefits and harms of local anaesthesia given for pain control during surgical abortion at less than 14 weeks' gestation. SEARCH METHODS: We searched CENTRAL (Ovid EBM Reviews), MEDLINE (Ovid), Embase, POPLINE, and Google Scholar to December 2022 for randomized controlled trials of pain control in surgical abortion at less than 14 weeks' gestation using suction aspiration. We searched the reference lists of related reviews and articles. SELECTION CRITERIA: We selected effectiveness and comparative effectiveness randomized controlled trials that studied local anaesthesia with common local anaesthetics and administration routes given for pain control in surgical abortion at less than 14 weeks' gestation using uterine aspiration. Outcomes included intraoperative pain, patient satisfaction, and adverse events. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. We computed mean differences (MD) with 95% confidence intervals (CI) for continuous variables reporting a mean. We assessed the certainty of evidence using GRADE. MAIN RESULTS: Thirteen studies with 1992 participants met the inclusion criteria. Due to heterogeneity of interventions, we could not pool more than two studies for any outcome. We used 13 mm improvement on a visual/verbal analogue scale to indicate a clinically meaningful difference in pain with surgical abortion (pain with dilation, aspiration, or during procedure). Based on type of pain control, we divided studies into three groups. Paracervical block (PCB) effectiveness trials A 20 mL 1% lidocaine PCB reduced pain with dilation (MD -37.00, 95% CI -45.64 to -28.36), and aspiration (MD -26.00, 95% CI -33.48 to -18.52) compared to a sham PCB (1 RCT, 120 participants; high-certainty evidence). A PCB with 14 mL of 1% chloroprocaine resulted in a slight reduction in pain with aspiration compared to a PCB with normal saline injected at two or four sites (MD -1.50, 95% CI -2.45 to -0.55; 1 RCT, 79 participants; high-certainty evidence). PCB comparative effectiveness trials An ultracaine PCB probably results in little to no clinically meaningful difference in pain during procedure compared to topical cervical lidocaine spray (median 1 point higher, interquartile range (IQR) 0 to 3; P < 0.001; 1 RCT, 48 participants; moderate-certainty evidence). A 1000 mg dose of intravenous paracetamol probably does not decrease pain as much as ultracaine PCB during procedure (median 2 points higher, IQR 1 to 3; P < 0.001; 1 RCT, 46 participants; moderate-certainty evidence). Various local anaesthetics in PCB comparative effectiveness trials A 10 mL buffered 2% lidocaine PCB probably does not result in a clinically meaningful difference in pain with dilation compared to a plain lidocaine PCB (MD -0.80, 95% CI -0.89 to -0.71; 1 RCT, 167 participants; moderate-certainty evidence). A buffered lidocaine PCB probably does not result in a clinically meaningful difference in pain with aspiration compared to plain lidocaine PCB (MD -0.57, 95% CI -1.01 to -0.06; 2 RCTs, 291 participants; moderate-certainty evidence). Non-PCB local anaesthesia or PCB technique effectiveness trials PCB: waiting versus no waiting Waiting three to five minutes between 1% lidocaine PCB injection and dilation probably does not result in a clinically meaningful difference in pain with dilation compared to not waiting (MD -0.70, 95% CI -1.23 to -0.17; 2 RCTs, 357 participants; moderate-certainty evidence). Topical cervical analgesia Topical 10 mL 2% lignocaine gel probably does not result in a clinically meaningful difference in pain with aspiration compared to KY Jelly (MD -0.87, 95% CI -1.60 to -0.14; 1 RCT, 131 participants; moderate-certainty evidence). In participants who also received a PCB, 20 mg topical cervical lidocaine spray probably does not result in a clinically meaningful difference in pain during the procedure compared to two pumps of normal saline spray (median -1 point, IQR -2 to -1; P < 0.001; 1 RCT, 55 participants; moderate-certainty evidence). Intravenous paracetamol 1000 mg compared to two pumps of cervical lidocaine spray probably does not results in a clinically meaningful difference in pain procedure (median 1 point, IQR -2 to 2; P < 0.001; 1 RCT, 48 participants; low-certainty evidence). Non-PCB local anaesthesia or PCB technique comparative effectiveness trials Depth of PCB The evidence suggests that a 3-cm deep PCB probably does not result in a clinically meaningful difference in pain with aspiration compared to a 1.5-cm deep PCB (MD -1.00, 95% CI -1.09 to -0.91; 2 RCTs, 229 participants; low-certainty evidence). PCB: four sites versus two sites A two-site (4-8 o'clock) 20 mL 1% lidocaine PCB does not result in a clinically meaningful difference in pain with dilation compared to a four-site (2-4-8-10 o'clock) PCB (MD 8.60, 95% CI 0.69 to 16.51; 1 RCT, 163 participants; high-certainty evidence). Overall, participants reported moderately high satisfaction with pain control and studies reported few adverse events. AUTHORS' CONCLUSIONS: Evidence from this updated review indicates that a 20 mL 1% plain lidocaine PCB decreases pain during an abortion procedure. Evidence supports forgoing buffering lidocaine and a wait time between PCB injection and cervical dilation. A 1.5-cm deep injection as opposed to a 3-cm deep injection is sufficient. A two-site PCB injection as opposed to a four-site injection has similar effectiveness. Topical cervical anaesthesia (10 mL 2% lignocaine gel or 20 mg topical cervical lidocaine spray) as compared to placebo did not decrease pain based on moderate-certainty evidence, but then when compared to PCB, pain control was similar. Due to this inconsistency in evidence regarding the effectiveness of topical anaesthesia, its routine use is presently not supported. This review did not include studies of pain management with conscious sedation but, based on the results of our prior Cochrane review and the 2022 WHO guidelines, we recommend that the option of combination of pain management using conscious sedation plus PCB and non-steroidal anti-inflammatory drugs should be offered where conscious sedation is available as it further decreases pain.

Red blood cell capacity of modern menstrual products: considerations for assessing heavy menstrual bleeding.

BACKGROUND: Heavy menstrual bleeding affects up to one third of menstruating individuals and has a negative impact on quality of life. The diagnosis of heavy menstrual bleeding is based primarily on history taking, which is highly dependent on traditional disposable menstrual products such as pads and tampons. Only tampons undergo industry-regulated testing for absorption capacity. As use of alternative menstrual products is increasing, there is a need to understand how the capacity of these products compare to that of standard products. METHODS: A variety of commercially available menstrual products (tampons, pads, menstrual cups and discs, and period underwear) were tested in the laboratory to determine their maximal capacity to absorb or fill using expired human packed red blood cells. The volume of blood necessary for saturation or filling of the product was recorded. RESULTS: Of the 21 individual menstrual hygiene products tested, a menstrual disc (Ziggy, Jiangsu, China) held the most blood of any product (80 mL). The perineal ice-activated cold pack and period underwear held the least (<3 mL each). Of the product categories tested, on average, menstrual discs had the greatest capacity (61 mL) and period underwear held the least (2 mL). Tampons, pads (heavy/ultra), and menstrual cups held similar amounts of blood (approximately 20-50 mL). CONCLUSION: This study found considerable variability in red blood cell volume capacity of menstrual products. This emphasises the importance of asking individuals about the type of menstrual products they use and how they use them. Further understanding of capacity of newer menstrual products can help clinicians better quantify menstrual blood loss, identify individuals who may benefit from additional evaluation, and monitor treatment.

Helping patients choose between pain control options for outpatient procedural abortion at less than 12 weeks' gestation.

OBJECTIVES: This study aimed to identify predictors of patient satisfaction with their chosen pain control regimen for procedural abortion at <12 weeks' gestation in the outpatient setting. STUDY DESIGN: In this prospective cohort study, we developed an instrument to evaluate predictors of satisfaction with pain control regimens among patients choosing local anesthesia alone (paracervical block with 20 mL of 1% buffered lidocaine) or local anesthesia plus intravenous (IV) moderate sedation with 100 mcg of fentanyl and 2 mg of midazolam. Our primary outcome was to identify predictors of satisfaction with both anesthesia cohorts as measured on a 4-point Likert scale, but due to high satisfaction levels in the IV group, we focused our analysis on the local anesthesia group. RESULTS: We enrolled 149 patients in the local anesthesia group and 155 in the moderate IV sedation group. The mean procedure pain scores were 6.9 (±2.1) out of 10 in the local group and 4.0 (±2.7) in the IV group (p < 0.0001). More women in the IV group (92%) were satisfied or very satisfied with the amount of pain relief they experienced compared to the local group (66%; p < 0.0001). In the univariable model, only being afraid of a minor medical procedure was predictive of less satisfaction with local anesthesia for pain control (relative risk 0.8 [95% CI, 0.6-0.9]). Age, gestational age, anticipated pain, self-reported pain tolerance, self-reported anxiety, discomfort with the abortion decision, and history of prior vaginal or cesarean delivery or induced abortion did not predict satisfaction levels. CONCLUSIONS: Fear of minor medical procedures was the only variable that predicted decreased satisfaction with local anesthesia alone for procedural abortion under 12 weeks. IMPLICATIONS: Reliable predictors for satisfaction with local anesthesia alone for procedural abortion in the outpatient setting remain elusive. Fear of minor medical procedures may serve as an indicator of decreased satisfaction and could be incorporated into patient counseling. Moderate IV sedation is associated with high satisfaction levels.

Associations Among Menstrual Cycle Length, Coronavirus Disease 2019 (COVID-19), and Vaccination.

OBJECTIVE: To assess whether coronavirus disease 2019 (COVID-19) is associated with menstrual cycle length changes and, if so, how that compares with those undergoing vaccination or no event (control). METHODS: We conducted a retrospective cohort analysis in which we analyzed prospectively tracked cycle-length data from users of a period tracker application who also responded to a survey regarding COVID-19 symptoms and vaccination. We restricted our sample to users aged 16-45 years, with normal cycle lengths (24-38 days) and regular tracking behavior during the five cycles around COVID-19 symptoms or vaccination or a similar time period for those experiencing no event (control group). We calculated the within-user change in cycle length (days) from the three consecutive cycles preevent average (either vaccination, disease, or neither; cycles 1-3) to the event (cycle 4) and postevent (cycle 5) cycles. We used mixed-effects models to estimate the age- and country-adjusted difference in change in cycle length across the groups. RESULTS: We included 6,514 users from 110 countries representing 32,570 cycles (COVID-19 symptoms: 1,450; COVID-19 vaccination: 4,643; control: 421). The COVID-19 cohort experienced a 1.45-day adjusted increase in cycle length during cycle 4 (COVID-19) compared with their three preevent cycles (95% CI 0.86-2.04). The vaccinated group experienced a 1.14-day adjusted increase in cycle length during cycle 4 (COVID-19 vaccine) compared with their preevent average (95% CI 0.60-1.69). The control group (neither vaccine nor disease) experienced a 0.68-day decrease (95% CI -1.18 to -0.19) in a similar time period. Post hoc tests showed no significant differences in the magnitude of changes between the COVID-19 and vaccination cohorts. In both cohorts, cycle length changes disappeared in the postevent cycle. CONCLUSION: Experiencing COVID-19 is associated with a small change in cycle length similar to COVID-19 vaccination. These changes resolve quickly within the next cycle.

Society of Family Planning Clinical Recommendation: Medication abortion between 14 0/7 and 27 6/7 weeks of gestation.

OBJECTIVE: The objective of this Clinical Recommendation is to review relevant literature and provide evidence-based recommendations for medication abortion between 14 0/7-27 6/7 weeks of gestation, with focus on mifepristone-misoprostol and misoprostol-only regimens. METHODS: We systematically reviewed PubMed articles published between 2008 and 2022 and reviewed reference lists of included articles to identify additional publications. See Search Strategy for more details. RESULTS/CONCLUSIONS: Several randomized trials of medication abortion between 14 0/7-27 6/7 weeks of gestation demonstrate that mifepristone 200 mg orally before misoprostol increases effectiveness (complete abortion at 24 or 48 hours) compared to misoprostol only. Studies continue to evaluate different doses, routes, and dosing intervals for misoprostol. If mifepristone is unavailable, several misoprostol regimens with individual doses of at least 200 mcg or more are effective. Adjunctive osmotic dilators are of limited benefit. It is important to individualize care, with consideration to reducing misoprostol dose in low resources settings or at 24 0/7 weeks of gestation or later (or equivalent uterine size). Misoprostol in the setting of two or more previous cesarean sections is associated with increased risk of uterine rupture compared to one or none, but risk remains low. Most contraceptives can be started during or immediately following abortion. Appropriately trained and credentialed advanced practice clinicians can provide medication abortion between 14 0/7-27 6/7 weeks of gestation with appropriate backup within the confines of local regulations and licensure.

Society of Family Planning Clinical Recommendation: Medication abortion between 14 0/7 and 27 6/7 weeks of gestation: Jointly developed with the Society for Maternal-Fetal Medicine.

The objective of this Clinical Recommendation is to review relevant literature and provide evidence-based recommendations for medication abortion between 14 0/7 and 27 6/7 weeks of gestation, with a focus on mifepristone-misoprostol and misoprostol-only regimens. We systematically reviewed PubMed articles published between 2008 and 2022 and reviewed reference lists of included articles to identify additional publications. See Search Strategy for more details. Several randomized trials of medication abortion between 14 0/7 and 27 6/7 weeks of gestation demonstrate that mifepristone 200 mg orally before misoprostol increases effectiveness (complete abortion at 24 or 48 hours) compared to misoprostol only. Studies continue to evaluate different doses, routes, and dosing intervals for misoprostol. If mifepristone is unavailable, several misoprostol regimens with individual doses of at least 200 mcg or more are effective. Adjunctive osmotic dilators are of limited benefit. It is important to individualize care, with consideration to reducing misoprostol dose in low-resource settings or at 24 0/7 weeks of gestation or later (or equivalent uterine size). Misoprostol in the setting of two or more previous cesarean sections is associated with increased risk of uterine rupture compared to one or none, but risk remains low. Most contraceptives can be started during or immediately following abortion. Appropriately trained and credentialed advanced practice clinicians can provide medication abortion between 14 0/7 and 27 6/7 weeks of gestation with appropriate backup within the confines of local regulations and licensure.

Society of Family Planning Clinical Recommendation: Medication abortion between 14 0/7 and 27 6/7 weeks of gestation: Jointly developed with the Society for Maternal-Fetal Medicine.

The objective of this Clinical Recommendation is to review relevant literature and provide evidence-based recommendations for medication abortion between 14 0/7 and 27 6/7 weeks of gestation, with a focus on mifepristone-misoprostol and misoprostol-only regimens. We systematically reviewed PubMed articles published between 2008 and 2022 and reviewed reference lists of included articles to identify additional publications. See Search Strategy for more details. Several randomized trials of medication abortion between 14 0/7 and 27 6/7 weeks of gestation demonstrate that mifepristone 200 mg orally before misoprostol increases effectiveness (complete abortion at 24 or 48 hours) compared to misoprostol only. Studies continue to evaluate different doses, routes, and dosing intervals for misoprostol. If mifepristone is unavailable, several misoprostol regimens with individual doses of at least 200 mcg or more are effective. Adjunctive osmotic dilators are of limited benefit. It is important to individualize care, with consideration to reducing misoprostol dose in low-resource settings or at 24 0/7 weeks of gestation or later (or equivalent uterine size). Misoprostol in the setting of two or more previous cesarean sections is associated with increased risk of uterine rupture compared to one or none, but risk remains low. Most contraceptives can be started during or immediately following abortion. Appropriately trained and credentialed advanced practice clinicians can provide medication abortion between 14 0/7 and 27 6/7 weeks of gestation with appropriate backup within the confines of local regulations and licensure.

Risk of thromboembolism in patients with COVID-19 who are using hormonal contraception.

BACKGROUND: The novel coronavirus disease (COVID-19) has led to significant mortality and morbidity, including a high incidence of related thrombotic events. There has been concern regarding hormonal contraception use during the COVID-19 pandemic, as this is an independent risk factor for thrombosis, particularly with estrogen-containing formulations. However, higher estrogen levels may be protective against severe COVID-19 disease. Evidence for risks of hormonal contraception use during the COVID-19 pandemic is sparse. We conducted a living systematic review that will be updated as new data emerge on the risk of thromboembolism with hormonal contraception use in patients with COVID-19. OBJECTIVES: To determine if use of hormonal contraception increases risk of venous and arterial thromboembolism in women with COVID-19. To determine if use of hormonal contraception increases other markers of COVID-19 severity including hospitalization in the intensive care unit, acute respiratory distress syndrome, intubation, and mortality. A secondary objective is to maintain the currency of the evidence, using a living systematic review approach. SEARCH METHODS: ⁠⁠⁠⁠⁠⁠We searched CENTRAL, MEDLINE, Embase, CINAHL, Global Index Medicus, Global Health, and Scopus from inception on March 2023, and monitored the literature monthly. We updated the search strategies with new terms and added the database Global Index Medicus in lieu of LILACS. SELECTION CRITERIA: We included all published and ongoing studies of patients with COVID-19 comparing outcomes of those on hormonal contraception versus those not on hormonal contraception. This included case series and non-randomized studies of interventions (NRSI). DATA COLLECTION AND ANALYSIS: One review author extracted study data and this was checked by a second author. Two authors individually assessed risk of bias for the comparative studies using the ROBINS-I tool and a third helped reconcile differences. For the living systematic review, we will publish updates to our synthesis every six months. In the event that we identify a study with a more rigorous study design than the current included evidence prior to the planned six-month update, we will expedite the synthesis publication. MAIN RESULTS: We included three comparative NRSIs with 314,704 participants total and two case series describing 13 patients. The three NRSIs had serious to critical risk of bias in several domains and low study quality. Only one NRSI ascertained current use of contraceptives based on patient report; the other two used diagnostic codes within medical records to assess hormonal contraception use, but did not confirm current use nor indication for use. None of the NRSIs included thromboembolism as an outcome. Studies were not similar enough in terms of their outcomes, interventions, and study populations to combine with meta-analyses. We therefore narratively synthesized all included studies. Based on results from one NRSI, there may be little to no effect of combined hormonal contraception use on odds of mortality for COVID-19 positive patients (OR 1.00, 95% CI 0.41 to 2.40; 1 study, 18,892 participants; very low-certainty evidence). Two NRSIs examined hospitalization rates for hormonal contraception users versus non-users. Based on results from one NRSI, the odds of hospitalization for COVID-19 positive combined hormonal contraception users may be slightly decreased compared with non-users for patients with BMI under 35 kg/m2 (OR 0.79, 95% CI 0.64 to 0.97; 1 study, 295,689 participants; very low-certainty evidence). According to results of the other NRSI assessing use of any type of hormonal contraception, there may be little to no effect on hospitalization rates for COVID-19 positive individuals (OR 0.99, 95% CI 0.68 to 1.44; 1 study, 123 participants; very low-certainty evidence). We included two case series because no comparative studies directly assessed thromboembolism as an outcome. In a case series of six pediatric COVID-19 positive patients with pulmonary embolism, one (older than 15 years of age) was using combined hormonal contraception. In a second case series of seven COVID-19 positive patients with cerebral venous thrombosis, one was using oral contraceptives. One comparative study and one case series reported on intubation rates, but the evidence for both is very uncertain. In the comparative study of 123 COVID-19 positive patients (N = 44 using hormonal contraception and N = 79 not using hormonal contraception), no patients in either group required intubation. In the case series of seven individuals with cerebral venous thromboembolism, one oral contraceptive user and one non-user required intubation. AUTHORS' CONCLUSIONS: There are no comparative studies assessing risk of thromboembolism in COVID-19 patients who use hormonal contraception, which was the primary objective of this review. Very little evidence exists examining the risk of increased COVID-19 disease severity for combined hormonal contraception users compared to non-users of hormonal contraception, and the evidence that does exist is of very low certainty. The odds of hospitalization for COVID-19 positive users of combined hormonal contraceptives may be slightly decreased compared with those of hormonal contraceptive non-users, but the evidence is very uncertain as this is based on one study restricted to patients with BMI under 35 kg/m2. There may be little to no effect of combined hormonal contraception use on odds of intubation or mortality among COVID-19 positive patients, and little to no effect of using any type of hormonal contraception on odds of hospitalization and intubation for COVID-19 patients. We noted no large effect for risk of increased COVID-19 disease severity among hormonal contraception users. We specifically noted gaps in pertinent data collection regarding hormonal contraception use such as formulation, hormone doses, and duration or timing of contraceptive use. Differing estrogens may have different thrombogenic potential given differing potency, so it would be important to know if a formulation contained, for example, ethinyl estradiol versus estradiol valerate. Additionally, we downgraded several studies for risk of bias because information on the timing of contraceptive use relative to COVID-19 infection and method adherence were not ascertained. No studies reported indication for hormonal contraceptive use, which is important as individuals who use hormonal management for medical conditions like heavy menstrual bleeding might have different risk profiles compared to individuals using hormones for contraception. Future studies should focus on including pertinent confounders like age, obesity, history of prior venous thromboembolism, risk factors for venous thromboembolism, and recent pregnancy.

Impact of coronavirus disease 2019 (COVID-19) vaccination on menstrual bleeding quantity: An observational cohort study.

OBJECTIVE: To assess whether coronavirus disease 2019 (COVID-19) vaccination impacts menstrual bleeding quantity. DESIGN: Retrospective cohort. SETTING: Five global regions. POPULATION: Vaccinated and unvaccinated individuals with regular menstrual cycles using the digital fertility-awareness application Natural Cycles°. METHODS: We used prospectively collected menstrual cycle data, multivariable longitudinal Poisson generalised estimating equation (GEE) models and multivariable multinomial logistic regression models to calculate the adjusted difference between vaccination groups. All regression models were adjusted for confounding factors. MAIN OUTCOME MEASURES: The mean number of heavy bleeding days (fewer, no change or more) and changes in bleeding quantity (less, no change or more) at three time points (first dose, second dose and post-exposure menses). RESULTS: We included 9555 individuals (7401 vaccinated and 2154 unvaccinated). About two-thirds of individuals reported no change in the number of heavy bleeding days, regardless of vaccination status. After adjusting for confounding factors, there were no significant differences in the number of heavy bleeding days by vaccination status. A larger proportion of vaccinated individuals experienced an increase in total bleeding quantity (34.5% unvaccinated, 38.4% vaccinated; adjusted difference 4.0%, 99.2% CI 0.7%-7.2%). This translates to an estimated 40 additional people per 1000 individuals with normal menstrual cycles who experience a greater total bleeding quantity following the first vaccine dose' suffice. Differences resolved in the cycle post-exposure. CONCLUSIONS: A small increase in the probability of greater total bleeding quantity occurred following the first COVID-19 vaccine dose, which resolved in the cycle after the post-vaccination cycle. The total number of heavy bleeding days did not differ by vaccination status. Our findings can reassure the public that any changes are small and transient.

Treatment of unfavorable bleeding patterns in contraceptive implant users: a randomized clinical trial of curcumin.

BACKGROUND: Some users of the etonogestrel contraceptive implant experience bothersome bleeding, which can reduce contraceptive satisfaction and continuation. Few strategies exist to manage this bleeding. The exact mechanism of progestin-induced bleeding is unknown, but it is likely multifactorial (eg, impaired angiogenesis, "leaky" fragile vasculature, and inflammation). Curcumin, the active ingredient in turmeric, has anti-inflammatory, antiproliferative, and antiangiogenic properties, which may make it a useful agent for implant-associated bothersome bleeding. OBJECTIVE: This study aimed to evaluate whether curcumin decreases frequent or prolonged bleeding or spotting in contraceptive implant users. STUDY DESIGN: The study was a randomized, double-blind, placebo-controlled trial. Here, etonogestrel implant users with frequent or prolonged bleeding or spotting were enrolled and randomized to either 600-mg Theracurmin HP (Immunovites, Las Vegas, NV) or placebo daily for 30 days. The term "frequent" was defined as ≥2 independent bleeding or spotting episodes, and the term "prolonged" was defined as ≥7 consecutive days of bleeding or spotting in a 30-day interval. Implant use was confirmed by clinical examination and negative gonorrhea and chlamydia and pregnancy tests. Enrolled participants initiated study treatment after 3 consecutive days of bleeding or spotting; if no bleeding or spotting occurred within 30 days of enrollment, the participants were withdrawn from the study. Study treatments were encapsulated to maintain a similar appearance. Participants used text messages to record daily bleeding patterns and study drug compliance. Bleeding was defined as a day that required the use of protection with a pad, tampon, or liner, and spotting was defined as a day with minimal blood loss that did not require the use of any protection. Our primary outcome was the total number of days without bleeding or spotting during the 30 days of study drug or placebo exposure. The secondary outcomes included total number of bleeding-free days, bleeding episodes, and satisfaction. A sample size of 22 per group provided 80% power at an alpha level of .05 to demonstrate a 6-day difference between groups. RESULTS: From February 2021 to November 2022, 58 individuals enrolled in the study with 54 participants (93%) completing 30 days of treatment (26 in the curcumin group and 28 in the placebo group). Of note, 1 individual in the curcumin arm did not experience a qualifying bleeding event and, thus, never initiated treatment and, per protocol, was withdrawn from the study. Participant characteristics did not differ between groups, including length of implant use at study enrollment (placebo, 521±305 days; curcumin, 419±264 days). The study groups did not differ concerning any bleeding-related outcome (mean days without bleeding or spotting: curcumin, 16.7±6.9; placebo, 17.5±4.8; P=.62; mean bleeding-free days: curcumin, 23.4±4.9; placebo, 22.4±4.5; P=.44; bleeding episodes: curcumin, 2.0±0.8; placebo, 2.1±0.8; P=.63). In addition, satisfaction with the implant as contraception and acceptability of bleeding over the study period did not differ by study group (P=.54 and P=.30, respectively). CONCLUSION: Daily use of curcumin did not improve bleeding patterns in users of the etonogestrel contraceptive implant experiencing frequent or prolonged bleeding patterns.

Contraceptive services in Oregon's state-funded network during the COVID-19 pandemic.

OBJECTIVES: To understand how changes to in-person health care during the COVID pandemic impacted contraceptive use in Oregon's state-funded network. STUDY DESIGN: A retrospective cohort of 245,600 visits (virtual and in-person) among 70,295 women presenting to publicly funded family planning clinics in Oregon between January 2019 and June 2021. Data were abstracted from clinic records and restricted to visits of patients identifying as female, 12-51 years old, not using sterilization as a method. Contraception was grouped by effectiveness Tier (Tier 1: intrauterine device, implants; Tier 2: progestin injectable, pill/patch/ring). Multivariable logistic regression predicted the use of contraception by stage of the COVID pandemic which corresponded to service availability (prepandemic, acute: nonemergency services halted, subacute: restricted services), patient demographics, including insurance type, and clinic and geospatial characteristics. RESULTS: Overall during the acute stage, people with visits were more likely to leave with a method of contraception odds ratios (OR) 1.39 (95% confidence interval [CI] 1.24-1.57); however, it was significantly less likely to be a Tier 1 method (OR 0.82, 95% CI 0.74-0.91) as compared to prepandemic. This finding was particularly marked in rural areas (OR 0.69 [96% CI 0.58-0.83]) and among the publicly insured (OR 0.87 [95% CI 0.80-0.94]). CONCLUSIONS: Demand for contraception increased during the acute phase of the COVID pandemic, and shifts in method mix from Tier 1 to Tier 2 methods occurred. Disparities in contraceptive access persisted for those in rural locations or with public insurance. IMPLICATIONS: Lessons learned from the COVID-19 pandemic are critical to informing our future emergency response. The need for family planning services increased during the public health emergency.

Educational Intervention Among Adolescents and Young Adults on Emergency Contraception Options.

PURPOSE: Emergency contraception (EC), the 'last chance' contraceptive method, has gained significance post-Roe, but most young people do not know their options. METHODS: We conducted an educational intervention on EC among 1,053 students aged 18-25 years. We assessed changes in knowledge of key aspects of EC using generalized estimating equations. RESULTS: At baseline, virtually no one was aware of the intrauterine device for EC (4%), but postintervention, 89% correctly identified intrauterine devices as the most effective EC (adjusted odds ratio [aOR] = 116.6; 95% confidence interval [CI] 62.4, 217.8). Knowledge that levonorgestrel pills could be accessed without a prescription grew (60%-90%; aOR = 9.7, 95% CI 6.7-14.0), as did knowledge that pills work best when taken as soon as possible (75%-95%; aOR = 9.6, 95% CI 6.1-14.9). Multivariate results showed adolescent and young adult participants absorbed these key concepts across age, gender, and sexual orientation. DISCUSSION: Timely interventions are needed to empower youth with knowledge of EC options.

Risk of thromboembolism in patients with COVID-19 who are using hormonal contraception: a Cochrane systematic review.

BACKGROUND: The coronavirus disease COVID-19 is associated with an increased risk of thrombotic events. Individuals with COVID-19 using hormonal contraception could be at additional risk for thromboembolism, but evidence is sparse. METHODS: We conducted a systematic review on the risk of thromboembolism with hormonal contraception use in women aged 15-51 years with COVID-19. We searched multiple databases through March 2022, including all studies comparing outcomes of patients with COVID-19 using or not using hormonal contraception. We applied standard risk of bias tools to evaluate studies and GRADE methodology to assess certainty of evidence. Our primary outcomes were venous and arterial thromboembolism. Secondary outcomes included hospitalisation, acute respiratory distress syndrome, intubation, and mortality. RESULTS: Of 2119 studies screened, three comparative non-randomised studies of interventions (NRSIs) and two case series met the inclusion criteria. All studies had serious to critical risk of bias and low study quality. Overall, there may be little to no effect of combined hormonal contraception (CHC) use on odds of mortality for COVID-19-positive patients (OR 1.0, 95% CI 0.41 to 2.4). The odds of hospitalisation for COVID-19-positive CHC users may be slightly decreased compared with non-users for patients with body mass index <35 kg/m2 (OR 0.79, 95% CI 0.64 to 0.97). Use of any type of hormonal contraception may have little to no effect on hospitalisation rates for COVID-19-positive individuals (OR 0.99, 95% CI 0.68 to 1.44). CONCLUSIONS: Not enough evidence exists to draw conclusions regarding risk of thromboembolism in patients with COVID-19 using hormonal contraception. Evidence suggests there may be little to no or slightly decreased odds of hospitalisation, and little to no effect on odds of mortality for hormonal contraception users versus non-users with COVID-19.

Progestin intrauterine devices versus copper intrauterine devices for emergency contraception.

BACKGROUND: The copper intrauterine device (Cu-IUD) is a highly effective method of contraception that can also be used for emergency contraception (EC). It is the most effective form of EC, and is more effective than other existing oral regimens also used for EC. The Cu-IUD provides the unique benefit of providing ongoing contraception after it is inserted for EC; however, uptake of this intervention has been limited. Progestin IUDs are a popular method of long-acting, reversible contraception. If these devices were also found to be effective for EC, they would provide a critical additional option for women. These IUDs could not only provide EC and ongoing contraception, but additional non-contraceptive benefits, including a reduction in menstrual bleeding, cancer prevention, and pain management. OBJECTIVES: To examine the safety and effectiveness of progestin-containing IUDs for emergency contraception, compared with copper-containing IUDs, or compared with dedicated oral hormonal methods. SEARCH METHODS: We considered all randomized controlled trials and non-randomized studies of interventions that compared outcomes for individuals seeking a levonorgestrel IUD (LNG-IUD) for EC to a Cu-IUD or dedicated oral EC method. We considered full-text studies, conference abstracts, and unpublished data. We considered studies irrespective of their publication status and language of publication. SELECTION CRITERIA: We included studies comparing progestin IUDs with copper-containing IUDs, or oral EC methods for emergency contraception. DATA COLLECTION AND ANALYSIS: We systematically searched nine medical databases, two trials registries, and one gray literature site. We downloaded all titles and abstracts retrieved by electronic searching to a reference management database, and removed duplicates. Three review authors independently screened titles, abstracts, and full-text reports to determine studies eligible for inclusion. We followed standard Cochrane methodology to assess risk of bias, and analyze and interpret the data. We used GRADE methodology to assess the certainty of the evidence. MAIN RESULTS: We included only one relevant study (711 women); a randomized, controlled, non-inferiority trial comparing LNG-IUDs to Cu-IUDs for EC, with a one-month follow-up. With one study, the evidence was very uncertain for the difference in pregnancy rates, failed insertion rates, expulsion rates, removal rates and the difference in the acceptability of the IUDs. There was also uncertain evidence suggesting the Cu-IUD may slightly increase rates of cramping and the LNG-IUD may slightly increase bleeding and spotting days.  AUTHORS' CONCLUSIONS: This review is limited in its ability to provide definitive evidence regarding the LNG-IUD's equivalence, superiority, or inferiority to the Cu-IUD for EC. Only one study was identified in the review, which had possible risks of bias related to randomization and rare outcomes. Additional studies are needed to provide definitive evidence related to the effectiveness of the LNG-IUD for EC.