Relationship between plasma concentration of 17-hydroxyprogesterone caproate and gestational age at preterm delivery.

BACKGROUND: The effectiveness of 17-hydroxyprogesterone caproate is unclear as trials have provided conflicting results. With the absence of fundamental pharmacologic studies addressing dosing or the relationship between drug concentration and gestational age at delivery, the effectiveness of the medication cannot be evaluated. OBJECTIVE: This study aimed to evaluate the relationship between plasma concentrations of 17-hydroxyprogesterone caproate and preterm birth rates and gestational age at preterm delivery and to assess the safety of the 500-mg dose. STUDY DESIGN: This study recruited 2 cohorts with previous spontaneous preterm birth; 1 cohort (n=143) was randomly assigned to either 250-mg or 500-mg 17-hydroxyprogesterone caproate, and the other cohort (n=16) was receiving the 250-mg dose for routine care. Steady-state trough plasma concentrations of 17-hydroxyprogesterone caproate obtained at 26 to 30 weeks of gestation were correlated to dose, spontaneous preterm birth rates, and measures of gestational length. Furthermore, maternal and neonatal safety outcomes were evaluated according to dose. RESULTS: There was a dose proportional increase in trough plasma concentrations with the 250-mg (median, 8.6 ng/m; n=66) and 500-mg (median, 16.2 ng/mL; n=55) doses. In 116 compliant participants with blood samples, drug concentration was not related to the spontaneous preterm birth rate (odds ratio, 1.00; 95% confidence interval, 0.93-1.08). However, there was a significant relationship between drug concentration and both the interval from the first administration to delivery (interval A: coefficient, 1.11; 95% confidence interval, 0.00-2.23; P=.05) and the interval from the 26- to 30-week blood draw to delivery (interval B: coefficient, 1.56; 95% confidence interval, 0.25-2.87; P=.02). The spontaneous preterm birth rate or measures of gestational length were not related to dose. Postenrollment cerclage adversely affected all pharmacodynamic assessments because it was a powerful predictor of spontaneous preterm birth (odds ratio, 4.03; 95% confidence interval, 1.24-13.19; P=.021) and both measures of gestational length (interval A [coefficient, -14.9; 95% confidence interval, -26.3 to -3.4; P=.011] and interval B [coefficient, -15.9; 95% confidence interval, -25.8 to -5.9; P=.002]). Initial cervical length was significantly related to the risk of postenrollment cerclage (odds ratio, 0.80; 95% confidence interval, 0.70-0.92; P=.001). Maternal and neonatal safety outcomes were similar in both dosing groups. CONCLUSION: In this pharmacodynamic study, trough plasma 17-hydroxyprogesterone caproate concentrations were significantly associated with gestational age at preterm birth but not with the preterm birth rate. Postenrollment cerclage was a powerful predictor of spontaneous preterm birth rate and gestational length. Initial cervical length predicted the risk of postenrollment cerclage. Adverse events were similar with the 500-mg and 250-mg doses of 17-hydroxyprogesterone caproate.

Contraception for Women With Psychiatric Disorders.

OBJECTIVE: Mental health care for women includes decision support to prepare for major life events, including preconception planning for treatment during pregnancy and the postpartum period. The authors discuss contraceptive choices and their effectiveness, side effects, and impact on psychiatric symptoms. The Centers for Disease Control and Prevention's recommendations, Medical Eligibility Criteria for Contraceptive Use, provided the structure for review of contraceptive choices. METHODS: A search of PsycINFO, PubMed, Embase, and Scopus was conducted for publications on the management of contraception for women with mental illness. Publications were selected if they included, based on the authors' consensus, data supporting evidence-based care important for psychiatrists who treat women desiring contraceptives. RESULTS: The majority of women choose combined oral contraceptives. Although long-acting reversible contraceptives (implants, intrauterine devices) are associated with low failure rates, favorable safety profiles, rapid return to fertility after removal, and few contraindications, they are chosen by only 14% of women. All methods are acceptable for women with depression, although medical comorbidities may dictate a specific type. The impact of hormonal contraceptives on the risk for depression is controversial; however, clinical studies and randomized placebo-controlled trials of women with psychiatric disorders have generally reported similar or lower rates of mood symptoms in hormonal contraceptive users compared with nonusers. Although interactions between psychotropic drugs and contraceptives are rare, clozapine, anticonvulsants, and St. John's Wort are exceptions. CONCLUSIONS: Proactive management of mental illness, contraception, and pregnancy improves a woman's capacity to function and optimizes her mental and reproductive health.

A prospective pilot study to assess the impact of the etonogestrel implant on postpartum depression.

OBJECTIVES: To assess the feasibility of comparing the rates of positive depression screens at 6 weeks and 3 months postpartum in women using immediate postpartum etonogestrel implant (ENG-implant) and women using non-hormonal contraception or sterilisation. METHODS: This was a pilot prospective cohort study performed to test the design adequacy of comparing the rates of positive postpartum PHQ-9 screens (≥10) in women using immediate postpartum ENG-implant and women using non-hormonal contraception or sterilisation. Participants were recruited during the third trimester of pregnancy or during delivery hospitalisation. They self-allocated to one of the two comparison groups. PHQ-9 surveys were administered during the third trimester of pregnancy, immediately postpartum, and at 6 weeks and 3 months postpartum. RESULTS: Between June 2017 and March 2018, 91 patients were recruited. Of these patients, 11 were excluded and the remaining 80 were split evenly into each cohort. The women in the ENG-implant group were younger, less educated, and more often publicly insured. The percentage of participants with positive PHQ-9 screens were: 3% during the postpartum hospitalisation, 6.2% at 6 weeks postpartum, and 10.2% at 3 months postpartum. PHQ-9 scores were similar between groups at both postpartum time points. CONCLUSION: The rates of positive PHQ-9 screens at 6 weeks postpartum were similar between groups. These preliminary data suggest that immediate postpartum placement of the ENG-implant does not negatively impact the risk for a positive depression screen. Larger-scale, adequately powered studies are warranted to further investigate this finding.

Contraceptive Options Following Gestational Diabetes: Current Perspectives.

Gestational diabetes mellitus (GDM) complicates approximately 7% of pregnancies in the United States. Along with risk factors related to pregnancy, women with a history of GDM also have an increased risk of developing type 2 diabetes mellitus later in life. These women require special consideration when discussing contraception and other reproductive health issues. GDM carries a category 1 rating in the US Medical Eligibility Criteria for all contraceptive methods, which supports safety of the various methods but does not account for effectiveness. Contraceptive options differ in composition and mechanisms of action, and concerns have been raised about possible effects of contraception on metabolism. Clinical evidence is limited to suggest that hormonal contraception has significantly adverse effects on body weight, lipid, or glucose metabolism. In addition, the majority of evidence does not suggest a relationship between development of type 2 diabetes mellitus and use of hormonal contraception. Data are limited, so it is challenging to make a broad, general recommendation regarding contraception for women with a history of GDM. A woman's history of GDM should be considered during contraceptive counseling. Discussion should focus on potential medical comorbidities and the implications of GDM on future health, with special consideration of issues including bone health, obesity, cardiovascular disease, and thrombosis risk. Providers must emphasize the importance of reliable, highly effective contraception for women with GDM, to optimize the timing of future pregnancies. This approach to comprehensive counseling will guide optimal decision-making on contraceptive use, lifestyle changes, and planning of subsequent pregnancies.

Postpartum glucose tolerance in women with gestational diabetes using levonorgestrel intrauterine contraception.

OBJECTIVE: Postpartum contraception is critical in women with gestational diabetes mellitus (GDM). We evaluated the effect of the levonorgestrel intrauterine system (LNG-IUS) on glucose tolerance in postpartum women with GDM. STUDY DESIGN: The study is a descriptive analysis of 12-month glucose tolerance in women with recent GDM who used the LNG-IUS, the copper IUD or postpartum sterilization. RESULTS: Twelve months postpartum, 3 of 13 LNG-IUS users (23.1%) and 1 of 6 nonhormonal contraceptive users (16.6%) had prediabetes. No woman developed overt diabetes. CONCLUSIONS: This study is the first and only to measure the metabolic effects of the LNG-IUS women with GDM. Larger trials are necessary. IMPLICATIONS: Use of levonorgestrel intrauterine contraception does not appear to negatively affect glucose tolerance in postpartum women with a history of gestational diabetes. Additional appropriately powered clinical studies are needed to confirm these results.

Labor induction outcomes in third-trimester stillbirths.

OBJECTIVE: To describe the management of third-trimester stillbirth at a single institution, stratifying induction intervals and adverse outcomes by method. METHODS: Women diagnosed with fetal demise at 28weeks or later and admitted to an academic hospital between January 2007 and September 2010 were identified. A chart review extracted demographics, history, induction method, delivery interval, and adverse outcomes. RESULTS: Seventy-four women were included, with a median gestational age of 35.5weeks (range, 28-40weeks). Ten women had undergone at least 1 prior cesarean. Induction methods included misoprostol alone or for cervical ripening; oxytocin and amniotomy; transcervical Foley catheter; and mifepristone. Overall, 88% of patients delivered within 24hours; median time to fetal delivery was 11hours 20minutes (range, 7minutes to 57hours 12minutes). Adverse outcomes included intrapartum fever and postpartum hemorrhage. In total, 98% of patients, including those with prior cesarean, had a successful vaginal delivery. CONCLUSION: Regardless of third-trimester induction method for management of stillbirth, the majority of women experience safe delivery within 24hours. The descriptive data imply that misoprostol-only inductions might confer the shortest induction intervals; however, further prospective trials are needed to identify the optimal misoprostol regimen for women with third-trimester stillbirth.

Estradiol valerate and dienogest: a new approach to oral contraception.

Most combination oral contraceptives contain ethinyl estradiol and a progestin. A new and novel oral contraceptive formulation combines estradiol valerate (E2V) with dienogest (DNG) in a four-phase dosing regimen. 17ß-estradiol is a naturally-occurring estrogen, and a contraceptive pill containing such an estrogen offers potential benefits with regard to metabolic side effects and adverse events. Dienogest is derived from 19-nortestosterone and exerts profound progestational effects on the endometrium, but it differs from other progestins in its class by its antiandrogenic activity. Estradiol valerate plus dienogest (E2V/DNG) is now available in a four-phasic regimen that integrates an estrogen stepdown and progestin stepup dosing approach along with a short two-day hormone-free interval. This regimen offers safe, reliable contraception and has been shown to be an effective treatment for heavy menstrual bleeding. Metabolic effects and adverse events appear similar to those reported with oral contraceptives containing ethinyl estradiol.

Delays in request for pregnancy termination: comparison of patients in the first and second trimesters.

BACKGROUND: Despite the availability of first trimester abortion services in urban settings, many women request abortion in the second trimester. We identified protective and risk factors associated with women who delay requesting abortions until the second trimester. STUDY DESIGN: The study was a cross-sectional survey of 247 patients requesting surgical abortion at an urban family planning clinic. Survey and medical records data were analyzed for associations between 18 risk factors and incidence of second trimester request. RESULTS: Thirty-two percent of subjects presented in the second trimester. Chi-square analyses revealed that first trimester participants were more often employed (p<.0001), privately insured (p=.01), or had previous abortions (p=.04). Second trimester patients were younger (p<.0001), more often primigravid (p=.04), experienced more difficulty financing the procedure (p<.0001) and finding a surgeon (p<.0001), traveled longer distances (p=.005), and more often feared the procedure (p=.03). Using multiple logistic regression, women requesting second trimester abortions were more likely to report: obstacles financing the abortion (OR 2.34, 95% CI 1.28-4.28); traveling long distances (OR 2.88, 95% CI 1.31-6.31); and fear (OR 2.45, 95% CI 1.17-5.17). These women were less often employed outside the home (OR 0.35, 95% CI 0.19-0.64). CONCLUSIONS: Physicians and advocates must strive to reduce abortion costs, increase access to trained surgeons, and allay women's fears of abortion procedures.