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.

OBJECTIVE: 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 chemoluminescent assays to evaluate endogenous hormones [estradiol (E2), progesterone (P4), FSH, LH] and liquid chromatography-tandem triple quadrupole mass spectrometry (LC-MS/MS) to simultaneously analyze concentrations of ethinylestradiol (EE), dienogest (DNG), norelgestromin (NGMN), norethindrone (NET), gestodene (GSD), levonorgestrel (LNG), etonogestrel (ENG), segesterone acetate (NES), medroxyprogesterone acetate (MPA), and drospirenone (DRSP), in serum samples obtained at the time of enrollment in a recent study comparing oral ulipristal acetate and LNG EC in women with weight ≥ 80kg 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 a progestin [MPA (n=58, 11.2%), LNG (50, 9.6%), ENG (11, 2.1%), NET (5, 0.96%), NGMN (3, 0.06%), or DRSP (1, 0.02%)]. LNG was co-detected in all three participants with samples containing NGMN. Multiple progestins were detected in 8 other women: ENG/MPA (1); ENG/LNG (2); MPA/LNG (5). Samples from 55 (10.6%) had concentrations of one or more progestin considered above the minimum level for contraceptive [MPA ≥ 0.1ng/mL, n = 19; NGMN/LNG ≥ 0.2ng/mL, n = 31; ENG ≥ 0.09 ng/mL, n = 8; NET ≥ 0.35 ng/mL, n = 4]. We detected concentrations of serum P4 ≥ 3ng/mL, indicative of luteal phase (post-ovulation) status, in an additional 194 (37.3%) samples. CONCLUSIONS: More than one third of enrolled in our clinical trial of oral emergency contraception had evidence of prior ovulation at the time of enrollment. Additionally, about 23% had evidence of recent use of hormonal contraception recent use of hormonal contraception. This 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 non-inferiority designs or historical controls.

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.

A statement on abortion by 900 professors of obstetrics and gynecology after the reversal of Roe vWade.

In the American Journal of Obstetrics and Gynecology in 1972 and 2013, 100 leaders in obstetrics and gynecology wrote calls to action-in 1972 in anticipation of the Roe v Wade decision and in 2013 in concern over the increasing restrictions to abortion care. In this article, 900 professors support a call to action for reinstating federal protections for abortion. Over a year ago, the Supreme Court handed down the Dobbs decision, overturning nearly 50 years of precedent in retracting the constitutionally protected right to abortion. The medical community is already seeing the harms of this decision on the lives and health of our patients and on the ability to train upcoming physicians in this medically necessary evidence-based care. Further harms are anticipated, including negative effects on maternal mortality. The 900 professors of obstetrics and gynecology whose signatures appear at the conclusion of this article stand together in support of reproductive freedom, including the right to affordable, accessible, safe, and legal abortion care.

Over-the-Counter Oral Contraception as an Opportunity to Reduce Contraceptive Access Inequity.

This Viewpoint argues that making a progestin-only contraceptive pill available for sale as an over-the-counter product will help reduce logistic barriers to safe and effective birth control.

The effect of rifampin on serum etonogestrel concentrations and biomarkers of ovulation among contraceptive implant users: A pharmacokinetic and pharmacodynamic study.

OBJECTIVES: Rifampin, a strong CYP3A inducer, is the gold standard for evaluating CYP3A-mediated drug-drug interactions. We aimed to evaluate the pharmacokinetic and pharmacodynamic effects of a short course (2 weeks) of rifampin on serum etonogestrel (ENG) concentrations and serologic measures of ovarian activity (endogenous estradiol [E2] and progesterone [P4]) among ENG implant users. STUDY DESIGN: We enrolled healthy females using ENG implants for 12 to 36 months. We measured baseline serum ENG concentrations using a validated liquid chromatography mass-spectrometry assay and baseline E2 and P4 concentrations using chemiluminescent immunoassays. After 2 weeks of rifampin 600 mg daily, we repeated ENG, E2, and P4 measurements. We compared pre- and post-rifampin serum measurements using paired Wilcoxon signed-rank tests. RESULTS: Fifteen participants completed all study procedures. Participants' median age was 28.2 years (range 21.8-34.1), median body-mass index was 25.2 kg/m2 (range 18.9-37.3), and median duration of implant use was 22 months (range 12-32). All participants experienced significant decreases from baseline ENG concentrations (median 164.0 pg/mL [range 94.4-265.0]) to post-rifampin measurements (median 47.8 pg/mL [range 24.7-82.8]) (p < 0.001). Serum E2 concentrations also significantly increased with rifampin exposure (median 73 pg/mL vs 202 pg/mL, p = 0.003); increases in serum P4 concentrations were not statistically significant (p = 0.19). Three participants (20%) experienced increased luteal activity, with one presumptively ovulating post-rifampin (P4 = 15.8 ng/mL). CONCLUSIONS: With only short exposure to a strong CYP3A inducer, ENG implant users experienced clinically significant decreases in serum ENG concentrations that led to changes in biomarkers indicative of waning suppression of ovulation. IMPLICATIONS: Even a short, 2-week course of treatment with rifampin places etonogestrel contraceptive implant users at risk for decreased contraceptive efficacy. Clinicians should counsel patients using etonogestrel implants considering any duration of rifampin therapy on the need for backup nonhormonal contraception or the use of an intrauterine device to avoid unintended pregnancies.

A commentary on progestin-only pills and the "three-hour window" guidelines: Timing of ingestion and mechanisms of action.

Clinical guidelines for progestin-only pills (POPs) state that each pill should be taken at the same time each day, with only a "three-hour window" of tolerance before back-up contraception should be used. In this commentary, we summarize studies examining the timing of ingestion and mechanisms of action for various POP formulations and dosages. We found that different progestins have different properties that determine the effect of delayed or missed pills on effectiveness at preventing pregnancy. Our findings highlight that there is more margin for error for some POPs than guidelines suggest. The three-hour window recommendation should be re-evaluated in light of these findings. Since clinicians, potential POP users, and regulatory bodies rely on current guidelines to make decisions about POP use, a critical evaluation and update of these guidelines are urgently needed.

Telemedicine to improve reproductive health care for rural Coloradans: Perceptions of interest and access.

PURPOSE: To evaluate rural Colorado women's access to and preferences for receiving reproductive health care services. METHODS: We conducted an online survey of women ages 18-45 years old. We mailed recruitment postcards to a random sample of female, registered voters in rural Colorado zip codes. Survey questions assessed experiences, beliefs, and preferences regarding reproductive health care. We performed bivariate statistics and logistic regression for predictors of interest in telemedicine. FINDINGS: Respondents (n = 478) had a median age of 34 years (range 18-45). Most women identified as White (90.2%) and were insured (67.1% private; 20.5% public). Most (74.1%) noted barriers to obtaining reproductive care in their communities. Those who reported barriers cited a median of 3 barriers (range 1-8), most commonly too few community-based providers (81.4%) and long distance to care (69.5%). Among respondents, 51.0% had used telemedicine before and 52.5% were interested in using telemedicine for reproductive health services. Interest in telemedicine significantly differed by perceived difficulty accessing care, previous telemedicine use, traveling over 100 miles for medical care in the last year, and belief in the safety of abortion. Those interested in telemedicine were less likely to value having an established relationship with providers and face-to-face visits. CONCLUSIONS: Most reproductive-aged, rural Colorado women endorsed barriers to obtaining reproductive health care in their communities. Over half of rural women are interested in using telemedicine for reproductive health care; however, many are not. Both optimizing telemedicine and developing additional innovative solutions are needed to improve access to reproductive care in rural communities.

Medication Abortion.

This JAMA Patient Page describes medication abortion and its risks and effectiveness.

Continuation rates of two different-sized copper intrauterine devices among nulliparous women: Interim 12-month results of a single-blind, randomised, multicentre trial.

Background: The most widely used copper intrauterine device (IUD) in the world (the TCu380A), and the only product available in many countries, causes side effects and early removals for many users. These problems are exacerbated in nulliparous women, who have smaller uterine cavities compared to parous women. We compared first-year continuation rates and reasons/probabilities for early removal of the TCu380A versus a smaller Belgian copper IUD among nulliparous users. Methods: This 12-month interim report is derived from a pre-planned interim analysis of a sub population and focused on key secondary comparative endpoints. In this participant-blinded trial at 16 centres in the USA, we randomised participants aged 17-40 in a 4:1 ratio to the NT380-Mini or the TCu380A. In the first year, participants had follow-up visits at 6-weeks and 3, 6, and 12-months, and a phone contact at 9 months; we documented continued use, expulsions, and reasons for removal. Among participants with successful IUD placement, we compared probabilities of IUD continuation and specific reasons for discontinuation using log-rank tests. This trial is registered with ClinicalTrials.gov number NCT03124160 and is closed to recruitment. Findings: Between June 1, 2017, and February 25, 2019, we assigned 927 nulliparous women to either the NT380-Mini (n = 744) or the TCu380A (n = 183); the analysis population was 732 (NT380-Mini) and 176 (TCu380A). Participants using the NT380-Mini, compared to the TCu380A, had higher 12-month continuation rates (78·7% [95% CI: 72·9-84·5%] vs. 70·2% [95% CI: 59·7-80·7], p = 0·014), lower rates of removal for bleeding and/or pain (8·1% vs. 16·2%, p = 0·003) and lower IUD expulsion rates (4·8% vs. 8·9%, p = 0·023), respectively. Interpretation: The NT380-Mini offers important benefits for a nulliparous population compared to the TCu380A in the first twelve months, when pivotal experiences typically occur. Higher continuation rates with the NT380-Mini may avert disruptions in contraceptive use and help users avoid unintended pregnancy. Funding: Bill & Melinda Gates Foundation, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and Mona Lisa, N.V. (Belgium).

Effect of Topiramate on Serum Etonogestrel Concentrations Among Contraceptive Implant Users.

OBJECTIVE: To evaluate topiramate and etonogestrel pharmacokinetic interactions in contraceptive implant users. METHODS: We conducted a prospective, noninferiority study with healthy women using etonogestrel implants continuously for 12-36 months. We measured baseline serum etonogestrel concentrations and then began a 6-week titrated topiramate regimen to standard migraine (100 mg/day) and epilepsy (400 mg/day) dosages. We repeated serum etonogestrel concentrations at 3 weeks (100 mg/day), 4 weeks (200 mg/day), and 6 weeks (400 mg/day) of topiramate therapy. We measured etonogestrel using a validated liquid chromatography-tandem, mass-spectrometry assay and tested for noninferiority (less than 30% decrease) in serum etonogestrel concentrations from baseline. RESULTS: We enrolled 48 total participants; 32 completed 3 weeks, 31 completed 4 weeks, and 27 completed all follow-up visits. Participants' median age was 25.3 years (range 18.3-37.2), median body mass index (BMI) was 25.5 kg/m2 (range 18.7-42.2), and median duration of implant use was 24 months (range 12-36). Median etonogestrel concentrations were 142 pg/mL (range 76.2-771) at baseline, 126 pg/mL (range 72.4-585) at 3 weeks, 119 pg/mL (range 65.6-542) at 4 weeks, and 105 pg/mL (46.2-859) at 6 weeks. The 95% CIs for mean percent change in serum etonogestrel concentrations from baseline were [-37.3%+16.9%], [-45.4%+5.2%], and [-66.8%+24.8%] at 3 weeks, 4 weeks, and 6 weeks, respectively. Excluding one participant who had a serum etonogestrel concentration less than 90 pg/mL at baseline, 30.8% of participants (8/26, 95% CI 14.3-51.8%) had a serum etonogestrel concentration less than 90 pg/mL at 6 weeks. CONCLUSION: Though only a mild enzyme-inducing antiepileptic drug, concomitant topiramate use led to inferior serum etonogestrel concentrations among implant users, with a significant proportion reaching etonogestrel concentrations below the threshold for ovulatory suppression when taking antiepileptic dosages of topiramate. FUNDING SOURCE: This study was primarily funded through an Investigator-Initiated Study grant from Merck Sharp & Dohme Corp [MISP#57073]. This work was also supported by NIH/NCATS CTSA Grant Number UL1 TR001082 and NICHD K12 Women's Reproductive Health Research Scholar Program (grant number 5K12HD001271-18). CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT03335163.

Evaluation of ovulation and safety outcomes in a multi-center randomized trial of three 84 day ulipristal acetate regimens.

OBJECTIVES: To describe ovulation inhibition and safety of daily oral ulipristal acetate (UPA) over 84 days. STUDY DESIGN: This multi-center phase 1 and/or 2 trial randomized participants to use oral ulipristal 10 mg or 5 mg daily or a 3 cycle regimen of 5 mg for 24 days followed by four placebo days. We stratified randomization by body mass index (BMI) <32 or 32-40 kg/m2. To estimate ovulation inhibition, the primary outcome, participants underwent transvaginal ultrasound and blood sampling twice weekly; we analyzed compliant participants who completed the 84 day study. Safety endpoints included 3 endometrial biopsies and liver chemistry tests. RESULTS: We enrolled 180 participants and included 137 in the ovulation inhibition analyses. Progesterone values that remained below 3ng/mL throughout treatment suggested consistent ovulation inhibition in 52 of 137 (38%) participants; 25 of 47(53%), 20 of 44(45%), and 7 of 46(15%) among participants randomized to the 10 mg, 5 mg, and cyclic treatments, respectively (p < 0.01). Progesterone values consistently <3 ng/mL were more frequent in participants with a BMI > 32kg/m2 (25/50(50%) vs 27/87(31%), p = 0.01). Average ulipristal concentrations were higher among participants with low progesterone concentrations (p < 0.01). Endometrial biopsies during treatment showed progesterone-receptor-modulator-associated endometrial changes in 52 of 164 participants (32%); 22 of 49(40%), 16 of 48(29%), and 14 of 51(26%) in women randomized to the 10 mg, 5 mg, and the cyclic treatments, respectively (p = 0.07, test-for-trend); these changes resolved after treatment cessation. Liver transaminase changes were rare. CONCLUSIONS: Oral ulipristal acetate over 12 weeks did not reliably suppress ovulation, particularly in the 5 mg cyclic-dose group. Ovulation inhibition and endometrial changes were dose dependent. Reversible endometrial changes occurred during treatment. IMPLICATIONS: Progesterone-receptor modulators have been suggested for daily oral contraception. Since progesterone concentrations suggest that ovulation occurred during treatment, further studies would be necessary to assess whether these were functional ovulations and to evaluate other possible mechanisms of contraception.

Discontinuation rates of intrauterine contraception due to unfavourable bleeding: a systematic review.

OBJECTIVE: Levonorgestrel-releasing intrauterine devices (LNG-IUDs) and copper intrauterine devices (Cu-IUDs) offer long-acting contraception; however, some women may discontinue use within the first year due to bleeding pattern changes, limiting their potential. This systematic literature review investigated whether differences in bleeding profiles influence continuation rates in women in America, Europe and Australia. METHODS: Searches performed in PubMed and Embase were screened to identify publications describing bleeding patterns and rates of early IUC removal/discontinuation or continuation, descriptions of bleeding patterns, reasons for discontinuation, and patient satisfaction, acceptability and tolerability for LNG-IUDs and Cu-IUDs published between January 2010 and December 2019. The results were further restricted to capture citations related to 'Humans' and 'Females'. The review was limited to studies published from 2010 onwards, as changing attitudes over time mean that results of studies performed before this date may not be generalizable to current practice. RESULTS: Forty-eight publications describing 41 studies performed principally in the USA (n = 17) and Europe (n = 13) were identified. Publications describing bleeding patterns in LNG-IUD users (n = 11) consistently observed a reduction in bleeding in most women, whereas two of three studies in Cu-IUD users reported heavy bleeding in approximately 40% of patients. Rates of discontinuation for both devices ranged widely and may be as high as 50% but were lower for LNG-IUDs versus Cu-IUDs. Discontinuation rates due to bleeding were consistently higher for Cu-IUDs versus LNG-IUDs. CONCLUSIONS: Bleeding is a common reason for discontinuation of Cu-IUDs and LNG-IUDs. The more favourable bleeding pattern observed in LNG-IUD users may be associated with a lower rate of early discontinuation of LNG-IUDs versus Cu-IUDs.

Association of Obesity With Longer Time to Pregnancy.

OBJECTIVE: To assess whether obesity is associated with increased time to pregnancy in a cohort of participants who were stopping their contraceptive method to attempt pregnancy. METHODS: We performed a secondary analysis of the FACT (Fertility After Contraceptive Termination) study. This prospective analysis included 432 participants, aged 18-35 years, who discontinued contraception to become pregnant, were sexually active with a male partner, and provided pregnancy status data within the first 12 months in the study. The primary outcome, time to pregnancy, was measured beginning with discontinuation of contraception to estimated pregnancy date. We used Cox proportional hazard models to assess associations of normal (lower than 25.0), overweight (25.0-29.9), and obese (30 or higher) body mass index (BMI) and time to pregnancy while controlling for potential confounding factors. RESULTS: After adjusting for confounders, participants with BMIs 30 or higher were noted to have prolonged time to pregnancy compared with those with BMIs lower than 25 (adjusted hazard ratio [aHR] 0.62; 95% CI 0.44-0.89). The median time to pregnancy for participants with normal BMIs was 5.3 months (95% CI 3.8-6.4) compared with 8.2 months (95% CI 6.8-10.8) for participants with obesity. Pregnancy rates at 1 year were 76.4% (95% CI 69.7-82.6%), 69.5% (95% CI 60.5-78.1%), and 59.1% (95% CI 51.0-67.4%) for participants with BMIs lower than 25, 25-29.9, and 30 or higher, respectively. Menstrual irregularity was also associated with decreased fertility (aHR 0.67; 95% CI 0.46-0.97). CONCLUSION: Compared with participants with normal BMIs, we observed increased time to pregnancy for participants with obesity stopping contraception with the intention to become pregnant. Understanding the reasons for this association will be helpful to inform patients and guide clinical practice. FUNDING SOURCE: The FACT Study was funded, in part, by Bayer, CooperSurgical, and the Society of Family Planning.

Variability in repeat serum etonogestrel concentrations among contraceptive implant users during the steady-release pharmacokinetic period.

OBJECTIVE: To assess the variability of repeated measurements of serum etonogestrel concentration among contraceptive implant users. STUDY DESIGN: We measured 3 consecutive serum etonogestrel concentrations, drawn weekly, in women using etonogestrel implants for 12 to 36 months. We used a repeated measures test to evaluate differences. RESULTS: Among 20 participants, repeat serum etonogestrel concentrations did not differ from initial measurements (Friedman's test, p = 0.95). Mean serum etonogestrel concentrations had similar 95% confidence intervals at each time point: (134.09, 201.46), (135.08, 237.46), and (132.66, 192.45). CONCLUSION: We confirm that single-time measurements of serum etonogestrel concentration are acceptable pharmacokinetic outcomes for etonogestrel implant studies. IMPLICATIONS: Pharmacokinetic studies of the etonogestrel contraceptive implant assume single-time measurements are stable steady-state estimates based on small studies using older analysis methods. Our repeated measures study using modern liquid-chromatography mass-spectrometry analysis methods provides updated support for single-time pharmacokinetic measurements among etonogestrel implant users.

Maternal morbidity after preterm premature rupture of membranes at <24 weeks' gestation.

BACKGROUND: After preterm premature rupture of membranes at <24 weeks' gestation, pregnant women may choose continuation (expectant management) or termination of pregnancy, via either dilation and evacuation or labor induction. Neonatal outcomes after expectant management are well described. In contrast, limited research addresses maternal outcomes associated with expectant management compared to termination of pregnancy. OBJECTIVE: This study aimed to compare maternal morbidity after preterm premature rupture of membranes at <24 weeks' gestation in women who choose either expectant management or termination of pregnancy. STUDY DESIGN: This retrospective cohort study included women with preterm premature rupture of membranes between 14 0/7 and 23 6/7 weeks' gestation with singleton or twin pregnancies at 3 institutions from 2011 to 2018. We excluded pregnancies complicated by fetal anomalies, rupture of membranes immediately after obstetrical procedures (chorionic villus sampling, amniocentesis, cerclage placement, fetal reduction), spontaneous delivery <24 hours after membrane rupture, and contraindications to expectant management. Our primary outcome was the difference in composite maternal morbidity between women choosing expectant management and women choosing termination of pregnancy. We defined composite maternal morbidity as at least 1 of the following: chorioamnionitis, endometritis, sepsis, unplanned operative procedure after delivery (dilation and curettage, laparoscopy, or laparotomy), injury requiring repair, unplanned hysterectomy, unplanned hysterotomy (excluding cesarean delivery), uterine rupture, hemorrhage of >1000 mL, transfusion, admission to the maternal intensive care unit, acute renal insufficiency, venous thromboembolism, pulmonary embolism, and readmission to the hospital within 6 weeks. We compared the demographic and antenatal characteristics of women choosing expectant management with that of women choosing termination of pregnancy and used logistic regression to quantify the association between initial management decision and composite maternal morbidity. RESULTS: We identified 350 women with pregnancies complicated by preterm premature rupture of membranes at <24 weeks' gestation, and 208 women were eligible for the study. Of the 208 women, 108 (51.9%) chose expectant management as initial management, and 100 (48.1%) chose termination of pregnancy as initial management. Among women selecting termination of pregnancy, 67.0% underwent labor induction, and 33.0% underwent dilation and evacuation. Compared to women who chose termination of pregnancy, women who chose expectant management had 4.1 times the odds of developing chorioamnionitis (38.0% vs 13.0%; 95% confidence interval, 2.03-8.26) and 2.44 times the odds of postpartum hemorrhage (23.1% vs 11.0%; 95% confidence interval, 1.13-5.26). Admissions to the intensive care unit and unplanned hysterectomy only occurred after expectant management (2.8% vs 0.0% and 0.9% vs 0.0%). Of women who chose expectant management, 36.2% delivered via cesarean delivery with 56.4% non-low transverse uterine incisions. Composite maternal morbidity rates were 60.2% in the expectant management group and 33.0% in the termination of pregnancy group. After adjusting for gestational age at rupture, site, race and ethnicity, gestational age at entry to prenatal care, preterm premature rupture of membranes in a previous pregnancy, twin pregnancy, smoking, cerclage, and cervical examination at the time of presentation, expectant management was associated with 3.47 times the odds of composite maternal morbidity (95% confidence interval, 1.52-7.93), corresponding to an adjusted relative risk of 1.91 (95% confidence interval, 1.35-2.73). Among women who chose expectant management, 15.7% avoided morbidity and had a neonate who survived to discharge. CONCLUSION: Expectant management for preterm premature rupture of membranes at <24 weeks' gestation was associated with a significantly increased risk of maternal morbidity when compared to termination of pregnancy.

Contraception Selection, Effectiveness, and Adverse Effects: A Review.

IMPORTANCE: Many women spend a substantial proportion of their lives preventing or planning for pregnancy, and approximately 87% of US women use contraception during their lifetime. OBSERVATIONS: Contraceptive effectiveness is determined by a combination of drug or device efficacy, individual fecundability, coital frequency, and user adherence and continuation. In the US, oral contraceptive pills are the most commonly used reversible method of contraception and comprise 21.9% of all contraception in current use. Pregnancy rates of women using oral contraceptives are 4% to 7% per year. Use of long-acting methods, such as intrauterine devices and subdermal implants, has increased substantially, from 6% of all contraceptive users in 2008 to 17.8% in 2016; these methods have failure rates of less than 1% per year. Estrogen-containing methods, such as combined oral contraceptive pills, increase the risk of venous thrombosis from 2 to 10 venous thrombotic events per 10 000 women-years to 7 to 10 venous thrombotic events per 10 000 women-years, whereas progestin-only and nonhormonal methods, such as implants and condoms, are associated with rare serious risks. Hormonal contraceptives can improve medical conditions associated with hormonal changes related to the menstrual cycle, such as acne, endometriosis, and premenstrual dysphoric disorder. Optimal contraceptive selection requires patient and clinician discussion of the patient's tolerance for risk of pregnancy, menstrual bleeding changes, other risks, and personal values and preferences. CONCLUSIONS AND RELEVANCE: Oral contraceptive pills are the most commonly used reversible contraceptives, intrauterine devices and subdermal implants have the highest effectiveness, and progestin-only and nonhormonal methods have the lowest risks. Optimal contraceptive selection incorporates patient values and preferences.