A prospective cohort study comparing expulsion after postplacental insertion: the levonorgestrel versus the copper intrauterine device.

OBJECTIVES: To compare the expulsion rate at 6 months after postplacental insertion by intrauterine device (IUD) type. STUDY DESIGN: This prospective cohort included participants with a postplacental IUD inserted after vaginal or cesarean delivery, aged 18-45 and ≥24 weeks' gestation. Study enrollment took place after IUD selection and insertion. Participants returned for a postpartum visit and received a short message service survey regarding IUD expulsion, removal, vaginal bleeding and breastfeeding weekly from weeks 0 to 5 and on weeks 12 and 24 postpartum. Multivariable logistic regression examined 6-month expulsion rate by IUD type adjusting for variables that differed between the groups at baseline and in the bivariate analyses. RESULTS: Of 114 participants, 75 (65.8%) chose a levonorgestrel 52-mg IUD and 39 (34.2%) chose a copper IUD; 58 (50.9%) had a vaginal delivery, and 56 (49.1%) had a cesarean delivery. Groups were similar except that copper IUD users had a higher median parity (3 vs. 2, p=.03) and a higher proportion of senior residents compared to junior residents had performed insertion (46.2% vs. 22.7%, p=.02). The expulsion rate at 6 months was similar between the levonorgestrel and copper groups (26.7% and 20.5%, respectively; p=.38). Multivariable logistic regression also demonstrated that the odds of expulsion did not differ by IUD type (adjusted odds ratio 0.98, 95% confidence interval 0.22-4.48). CONCLUSION: The expulsion rate at 6 months after postplacental insertion did not differ between the levonorgestrel and copper IUD type. IMPLICATIONS: Prior studies demonstrate a wide range of expulsion after postplacental insertion, and recent data suggest a higher expulsion rate for the levonorgestrel compared to the copper intrauterine device. However, many studies did not control for patient-level factors or delivery route. We found that when controlling for these confounding variables, the expulsion rate at 6 months postpartum did not differ by intrauterine device type.

Acceptability of the Woman's Condom in a phase III multicenter open-label study.

OBJECTIVE: This study aimed to evaluate the acceptability of the Woman's Condom (WC) over 6 months (183 days) and ≥6 menstrual cycles in a US-based multicenter open-label phase III contraceptive efficacy trial. STUDY DESIGN: We assessed acceptability via written questionnaire at visit 2 (after the third cycle) and visit 3 (after the sixth cycle or >183 days, or upon early discontinuation). Key domains included ease of use, comfort/lubrication, sexual satisfaction, male partner satisfaction and confidence in pregnancy and sexually transmitted infection (STI) prevention. We analyzed quantitative data using descriptive statistics. We conducted a content analysis to identify major themes from four open-ended questions. RESULTS: Most women [327/405 (81%)] had limited or no previous experience with female (internal) condoms. Of 405 evaluable women, 346 women completed questionnaires at visit 2 and 303 women at visit 3; 282 women attended both visits. Of women attending both visits, 165/282 (59%) reported at visit 2 that WC insertion was easy/very easy; this increased to 195/282 (69%) at visit 3 (p=.03). Many women [166/281 (59%)] preferred the WC [105/281 (37%)] or were neutral [61/281 (22%)], while 115/281 (41%) preferred male condoms. Women attending visit 3 felt confident that the WC could prevent pregnancy [246/303 (81%)] and STIs [217/303 (72%)]. Many women expressed empowerment with having control over their contraception; some disliked the design, esthetics and insertion process. Most women (254/299 (85%)] would recommend the WC to a friend. CONCLUSION: The WC's acceptability and ease of use is promising for wider dissemination as a female-controlled method that can protect against both pregnancy and STIs. IMPLICATIONS: The WC's overall acceptability and ease of use is promising for a new female-controlled barrier contraceptive option that can protect against both pregnancy and sexually transmitted infections.

Synthetic osmotic dilators in the induction of labour-An international multicentre observational study.

INTRODUCTION: To evaluate the effects of synthetic osmotic dilators (Dilapan-S/ Dilasoft) in women who required induction of labour in a large prospective multicentre international observational study. MATERIALS AND METHODS: Primary outcomes were duration of Dilapan-S/Dilasoft insertion (hours), total induction - delivery interval (hours) and the rate of vaginal deliveries within 24 h (%). Secondary outcomes were the number of dilators inserted, Bishop score increase after extraction of Dilapan-S/Dilasoft, complications during induction (uterine contractions, uterine tachysystole and hyperstimulation, effect on the fetus) and post induction (infections and neonatal outcomes), agents / procedures used for subsequent induction of labour, immediate rate of spontaneous labours following cervical ripening period, rate of spontaneous vaginal deliveries, rate of instrumental vaginal deliveries and caesarean sections. RESULTS: Total of 543 women were recruited across 11 study sites, of which, 444 women were eligible for analysis. With Dilapan-S/Dilasoft use of <12 h (n = 188) the overall vaginal delivery rate was 76.6% with 45.7% of these births occurring within 24 h, 66% within 36 h and 75.5% within 48 h from insertion of Dilapan-S/Dilasoft. The mean insertion-delivery interval for this group was 24.3(±10.4) hours. With Dilapan-S/Dilasoft use of >12 h (n = 256), the overall vaginal delivery rate was 64.8%, with 16% of these births occurring within 24 h, 48.4% within 36 h and 54.7% within 48 h from insertion of Dilapan-S/Dilasoft. The mean insertion-delivery interval for this group was 39.1(±29.2) hours. The mean gain in the Bishops score was +3.6(±2.3). The mean number of Dilapan-S/Dilasoft dilators used was 3.8 (±1.1). The overall rate of caesarean section was 30.1%. The overall complication rate was low including infection risk. No adverse neonatal outcome was attributable to the use of Dilapan-S/Dilasoft. CONCLUSION: Dilapan-S/Dilasoft are safe and effective methods for cervical ripening. Their use is associated with low maternal and neonatal complication rates. Future research should aim at level I clinical trials comparing Dilapan-S to other mechanical or pharmacological cervical ripening agents. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT02318173.

Pentoxifylline inhibits lipopolysaccharide-induced inflammatory mediators in human second trimester placenta explants.

BACKGROUND: Intrauterine infection and inflammation during pregnancy, which leads to up-regulation of inflammatory cytokines and prostaglandin synthesis, has been implicated in the pathogenesis of preterm delivery and other pregnancy complications. Effective preventive and therapeutic strategies to reduce these outcomes are lacking to date. Pentoxifylline (PTX) is a non-specific phosphodiesterase inhibitor which raises intracellular cyclic adenosine monophosphate and decreases production of pro-inflammatory mediators while enhancing anti-inflammatory cytokines. We hypothesized that pentoxifylline will decrease lipopolysaccharide (LPS)-induced pro-inflammatory cytokines production in human placental explants. METHODS: Placental explants derived from normal second trimester human placentas were treated with PTX, stimulated with LPS and cultured at 37 °C in 5% CO2. Conditioned media were assayed for pro- and anti-inflammatory mediators with multiplex immunoassays or ELISA, and explant tissues for mRNA with real time PCR. Means of PTX-treated and untreated samples were compared using paired t tests and Wilcoxon-signed rank tests. RESULTS: PTX preferentially inhibited placental expression and production of LPS-induced pro-inflammatory cytokines including TNF-α (25461 vs. 1908 pg/ml, p < 0.001), IL-1ß (2921 vs. 1067 pg/ml, p < 0.001) and IFN-γ (2190 vs 427 pg/ml, p < 0.001) with relative preservation of anti-inflammatory mediators. The suppressive effects on LPS-induced placental inflammation were independent of the timing of PTX administration in relation to LPS-induced stimulation. CONCLUSION: Our study suggests that PTX attenuates the LPS-induced pro-inflammatory milieu in human placental explants. We speculate that PTX may have utility as a candidate anti-inflammatory agent for prophylaxis and/or treatment of human placental inflammation.

Depo-Provera (depot medroxyprogesterone acetate) use after bariatric surgery.

In the US, obesity rates are increasing greatly. The Centers for Disease Control and Prevention estimates that 68.5% of Americans, including 63.9% of adult women older than 20 years, are overweight (body mass index between 25 kg/m2 and 29.9 kg/m2) or obese (body mass index >30 kg/m2). In light of this, it is not surprising that the rates of bariatric surgery have also been increasing. When considering the metabolic changes associated with both bariatric surgery and contraceptive use, in combination with the unique medical considerations of obese women, it is indisputable that clear guidelines are needed when counseling obese patients of reproductive age after bariatric surgery. In this literature review, we focus on depot medroxyprogesterone acetate (DMPA) and the implications of its use in obese women, preweight and postweight loss following bariatric surgery. Both DMPA use and bariatric surgery are known to cause bone loss, but it is still unclear whether there is an additive effect of the two factors on bone loss and whether either of these factors directly leads to an increased risk of bone fracture. The current consensus guidelines do not impose a restriction on the use of DMPA after bariatric surgery. DMPA use is associated with weight gain, and it is unclear whether weight loss blunting occurs with the use of DMPA after bariatric surgery. Prior studies had demonstrated an association with weight gain in adolescents, and therefore, those prescribing DMPA use after bariatric surgery in adolescents should proceed with caution. Adult women do not have a similar response to the use of DMPA. DMPA use has rarely been associated with increased risk of venous thromboembolism (VTE). The obesity-associated increase in VTE should be mitigated by surgically induced weight loss. The concurrent use of DMPA in the post bariatric surgical period should not further increase the risk of VTE.

2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) enhances placental inflammation.

Preterm birth is a leading cause of perinatal morbidity and mortality that is often associated with ascending infections from the lower genital tract. Recent studies with animal models have suggested that developmental exposure to the environmental toxin 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) can increase the risk of preterm birth in the offspring. How TCDD may modify placental immunity to ascending infections is unclear. Therefore, we studied the effects of TCDD treatment on basal and Escherichia coli-stimulated cytokine production by placental explants. Cultures of second-trimester placentas were treated with up to 40 nM TCDD for 72 h and then stimulated with 10(7)CFU/ml E. coli for an additional 24h. Concentrations of cytokines and PGE2 were measured in conditioned medium by immunoassay. TCDD exposure increased mRNA levels of IL-1ß by unstimulated cultures, but no effects on protein levels of this cytokine were detected. TNF-α production was unaffected by TCDD for unstimulated cultures, but pre-treatment with 40 nM TCDD significantly increased E. coli-stimulated TNF-α production. Both basal and bacteria-stimulated PGE2 and COX-2 gene expression were enhanced by TCDD pretreatment. In contrast, production of the anti-inflammatory cytokine, IL-10, was reduced by TCDD pretreatment for both unstimulated and E. coli-stimulated cultures. No effect of TCDD on the viability of the cultures was detected. These results suggest that TCDD exposure may shift immunity to enhance a proinflammatory phenotype at the maternal-fetal interface that could increase the risk of infection-mediated preterm birth.

Effect of carbon monoxide on bacteria-stimulated cytokine production by placental explants.

PROBLEM: Preterm birth is frequently caused by an inflammatory response to ascending infections of the reproductive tract. Carbon monoxide (CO) has potent anti-inflammatory properties at subtoxic concentrations. Whether or not CO can modulate inflammatory responses by placental tissues is unclear. METHODS: Placental explant cultures were incubated with heat-killed Escherichia coli or Ureaplasma parvum in the presence or absence of 250 ppm CO for 24 hr. Concentrations of cytokines relative viability of the cultures were quantified. RESULTS: Escherichia coli- and U. parvum-stimulated IL-1ß production was significantly inhibited by CO supplementation. Escherichia coli-stimulated, but not U. parvum-stimulated, IFN-γ production was inhibited by CO. While CO inhibited PGE(2) production by unstimulated cells, no effects on bacteria-stimulated prostaglandin production were detected. CO had no effect on basal or E. coli-stimulated TNF-α production but enhanced TNF-α production by cultures stimulated with U. parvum. In addition, CO tended to improve the viability of the placental cultures. CONCLUSIONS: Low concentrations of CO tended to reduce proinflammatory cytokines and to promote the production of anti-inflammatory cytokines in a pathogen-specific manner. These properties suggest that CO may be useful for promoting a pro-pregnancy cytokine milieu by placental explants and may reduce the consequences of intrauterine infections.

Immediate postplacental IUD insertion at cesarean delivery: a prospective cohort study.

BACKGROUND: Immediate postplacental insertion of intrauterine devices (IUDs) during cesarean delivery could reduce a substantial barrier to access to long-term effective contraception. Initiating IUD use prior to discharge from the hospital postpartum eliminates a 6-week postpartum waiting period and an additional office visit. STUDY DESIGN: This was a prospective cohort study of 90 patients undergoing cesarean delivery. After delivery of the placenta, a copper T380A IUD was inserted into the endometrial cavity through the incision. The study participants were followed up at 6 weeks and 6 months postpartum. This study was conducted at the Weiler Division of the Montefiore Medical Center and at the Jacobi Medical Center in the Bronx, NY. RESULTS: Forty-three (48%) women returned for their 6-week follow-up visits, and among those, no expulsions were recorded. Forty-two (47%) women were reached for phone follow-up at 6 months postpartum, and 80% reported being "happy" or "very happy" with their IUD. CONCLUSIONS: Immediate postplacental IUD insertion at the time of cesarean delivery is safe and acceptable.

Can oxygen tension contribute to an abnormal placental cytokine milieu?

OBJECTIVE The aim of this study was to determine whether culturing human placental explants under different oxygen tensions will alter expression of pro- and anti-inflammatory mediators. METHODS Placental explant cultures from second-trimester, elective, terminations-of-pregnancy were incubated under 21, 5, or 1% O(2) concentrations for 24 hr in the presence or absence of IL-10. Cytokine concentrations in the conditioned medium were quantified by immunoassay. RESULTS Culture of placental explants under 21, 5, or 1% O(2) concentrations produced hyperoxic (143 ± 1.6 mmHg), normoxic (37 ± 1.6 mmHg), and hypoxic (18.2 ± 1.6 mmHg) pO(2) levels for the maternal-fetal interface in the medium. Oxygen tension had profound effects on basal placental cytokine levels as well as on IL-10-stimulated cytokine production. IL-1ß and TNF-α, but not IFN-γ production, was reduced by 21% O(2) . Moreover, 21% O(2) levels increased the anti-inflammatory cytokines IL-10 and IL-13 while 1% O(2) tended to decrease the production of these cytokines. CONCLUSIONS Five percent- O(2) incubation more accurately represents in vivo pO(2) conditions at the maternal-fetal interface. Routine culture of placental explants in room air produces a superphysiologic oxygen tension that tended to increase the production of anti-inflammatory and decrease the production of pro-inflammatory cytokines. In addition, low pO(2) may reduce responsiveness of the placenta to the anti-inflammatory actions of IL-10.

Obesity and contraception: emerging issues.

Obesity is increasing in prevalence worldwide. Obese women are at similar risk of unintended pregnancy as normal weight women, although limited data are available on the effects of obesity on the efficacy of contraception. Conflicting data exist regarding efficacy of oral contraceptives in obese women, although trends of oral contraceptive failure are no higher than compared with those of normal weight women. The risk of venous thromboembolism is increased with obesity, and this risk may be additive when using a combined hormonal method. Bariatric surgery can lead to increased fertility; postoperative recommendations include avoiding pregnancy in the first year. Contraceptive use patterns in these women are largely unknown. Surgeons need greater awareness of the need for use of effective long-acting methods, and consensus guidelines need to be established.

Same-day initiation of the transdermal hormonal delivery system (contraceptive patch) versus traditional initiation methods.

INTRODUCTION: Published comparisons of oral contraceptive pill (OCP) initiation methods demonstrate that OCP initiation at the office visit ("Quick Start") resulted in higher continuation rates into the second cycle. This trial was performed to investigate whether Quick Start with the contraceptive patch would provide similar results. MATERIALS AND METHODS: Sixty women were randomized to initiate use of the contraceptive patch using Quick Start (Group 1, n=30) or on the first day of their next menses (Group 2, n=30). Telephone contact at 6 weeks occurred to ensure that the second cycle had been initiated. A single follow-up visit was scheduled after completion of the third patch cycle. RESULTS: Continuation rates for Groups 1 and 2 were 97% and 93% (p=1.0), respectively, into the second cycle, and 93% and 90%, respectively, into the third cycle (p=1.0). Only approximately half of the subjects planned to continue using the patch after the study. CONCLUSION: Quick Start for the contraceptive patch did not improve continuation rates into the second or third cycle.

A pilot study of mifepristone and misoprostol administered at the same time for abortion in women with gestation from 50 to 63 days.

INTRODUCTION: In the interest of decreasing the amount of time it takes to achieve a medical abortion, we performed a pilot study to evaluate the simultaneous administration of mifepristone and vaginal misoprostol for women with gestation from 50 to 63 days. MATERIALS AND METHODS: Forty women were enrolled with undesired pregnancies from 50 to 56 days' gestation (group 1) and 40 from 57 to 63 days' gestation (group 2). All women used misoprostol 800 mug vaginally immediately after having swallowed the 200 mg mifepristone tablet. Follow-up evaluations with transvaginal ultrasonography occurred at 24 h and 2 weeks after treatment. RESULTS: The 24-h expulsion rates were 88% (95% CI, 77-98) and 83% (95% CI, 7-94) in groups 1 and 2, respectively. The complete abortion rates at 2 weeks were 93% (95% CI, 84-100) and 90% (95% CI, 81-99), respectively. DISCUSSION: Simultaneous administration of oral mifepristone and vaginal misoprostol provides 24-h expulsion rates in women with gestation from 50 to 63 days, comparable to those reported in the medical literature for standard treatment regimens. Further study of this regimen in a large randomized trial is warranted.

A pilot study of mifepristone and misoprostol administered at the same time for abortion up to 49 days gestation.

HYPOTHESIS: Simultaneous administration of mifepristone and misoprostol for medical abortion in women up to 49 days gestation will result in complete abortion in 90% of women within 24 h of treatment. MATERIALS AND METHODS: Forty women with pregnancies up to 49 days gestation inserted 800 mug vaginal misoprostol in our office immediately after taking mifepristone 200 mg orally. Follow-up visits, which included vaginal ultrasonography, occurred 24+/-1 h and 2 weeks after treatment. If a gestational sac was still present at the first follow-up visit, the misoprostol dose was repeated. Suction abortion was performed for a viable gestation at the second follow-up visit, presence of a nonviable gestation within 5 weeks of treatment and when clinically indicated. RESULTS: Expulsion occurred in 36/40 (90%, 95% CI 80-99) and 39/40 (98%, 95% CI 93-100) women by the first and second follow-up visits, respectively. One woman who had initially expelled the gestational sac after a single dose of misoprostol later required a suction curettage for an incomplete abortion. CONCLUSION: Simultaneous administration of mifepristone and vaginal misoprostol is a promising regimen for medical abortion up to 49 days gestation.

Feasibility study of the use of a daily electronic mail reminder to improve oral contraceptive compliance.

Women who ingest their oral contraceptive pill (OCP) as part of a daily routine are more likely use their OCPs correctly. This trial examines the feasibility of an electronic-mail (e-mail) reminder system to improve OCP compliance. An e-mail reminder was sent to 50 new OCP users daily for 3 months. Subjects sent an e-mail reply to confirm receipt. OCP compliance was recorded on diaries. Four subjects were discontinued for not checking their e-mail. Active participants missed a median of 18% of the e-mail reminders (range: 0-65%). A follow-up visit was scheduled after completion of three OCP cycles. Of the 40 subjects returning completed diaries, 50% missed no active pills at all and 20% missed at least one in each cycle. Most found the daily e-mail somewhat (65%) or very helpful (19%) for OCP compliance. Of those continuing OCPs, 64% wanted to continue receiving e-mail reminders at the completion of the study. Because inconsistent OCP use is a significant cause of unplanned conception, the use of e-mail to improve OCP compliance has the potential to decrease unintended pregnancies.

Pharmacoeconomics of medical abortion: a review of cost in the United States, Europe and Asia.

Procedures for the termination of pregnancy have existed for many years. Vacuum aspiration, otherwise referred to as 'surgical' abortion, is a very common and safe procedure. Its efficacy and acceptability has been established and its complication rate is low. Medical abortion is a much more recent phenomenon. It is defined as early pregnancy termination with the use of abortion inducing medications, without surgery [1]. In contrast to surgical abortion, medical abortion is not as routinely offered, nor are many providers comfortable with its use. Medical abortion regimens currently available throughout the world include mifepristone (Mifeprex trade mark, Aventis Pharma AG) and a prostaglandin analogue (usually misoprostol), methotrexate and misoprostol and misoprostol (Cytotec trade mark, CD Searle & Co.) alone. In the US, minimal information exists directly comparing medical to surgical abortion. Most abortion surveillance data was collected by the Centers for Disease Control prior to the approval of mifepristone. In contrast, there is over a decade's worth of experience from Europe with both the use and provision of medical abortion. A complete review of these issues must include background information on the history and incidence of abortion, who chooses to get an abortion, who provides that service and at what cost. The cost issue is discussed using three different viewpoints: cost to the patient, cost to the provider, cost to society - mainly in the form of government expenditure and savings. Following the cost analysis, there is a summary of relevant information from countries in Europe, primarily the UK, France, Sweden and countries in Asia, mainly China and India.

Pregnancies diagnosed during Depo-Provera use.

We conducted a review of contraceptive failures among women using Depo-Provera (depot medroxyprogesterone acetate), using reports to the Insurance Division of Planned Parenthood Federation of America, Inc. Cases were included if the Depo-Provera had been given at a Planned Parenthood center and pregnancy had either been diagnosed by, or reported to, a Planned Parenthood center. There were 402 reports of pregnancy from 1994 through 1998. The crude rate of reported pregnancies was 0.42 pregnancies per 1000 women using Depo-Provera each year. Pregnancy was diagnosed after the first trimester in 46% of women. Seventy-seven women (19.1%) received additional Depo-Provera injections while pregnant. Of the women whose date of conception could be estimated, 113 of 258 (45%) became pregnant after the injection. There was no observed increase in ectopic pregnancy rate, and no fetal anomalies were reported. Although pregnancy during Depo-Provera use is rare, it does occur. These pregnancies are frequently unrecognized until beyond first trimester.