Continuous dosing of a novel contraceptive vaginal ring releasing Nestorone® and estradiol: pharmacokinetics from a dose-finding study.

BACKGROUND: As part of a program to develop a novel estradiol-releasing contraceptive vaginal ring (CVR), we evaluated the pharmacokinetic (PK) profile of CVRs releasing segesterone acetate (Nestorone® (NES)) combined with one of three different estradiol (E2) doses. STUDY DESIGN: A prospective, double-blind, randomized, multi-centered study to evaluate a 90-day CVR releasing NES [200mcg/day] plus E2, either 10mcg/day, 20mcg/day, or 40mcg/day in healthy reproductive-age women with regular cycles. Participants provided blood samples twice weekly for NES and E2 levels during the first 60 days (ring 1) and the last 30 days (ring 2) of use. A subset underwent formal PK assessments at ring initiation, ring exchange (limited PK), and study completion. RESULTS: The main study enrolled 197 women; 22 participated in the PK substudy. Baseline characteristics between the main and PK participants were comparable, with an average BMI of 25.8 kg/m2 (SD 4.3). In the PK substudy, all three rings showed similar NES PK: mean area under the curve (AUC(0-72)) 34,181 pg*day/mL; concentration maximum (Cmax) 918 pg/mL; time to maximum concentration (Tmax) 3.5 h. For E2, the Cmax occurred at 2 h, and was significantly higher with the 20 mcg/day ring (mean 390 pg/mL); 10 mcg/day, 189 pg/mL, p=.003; 40 mcg/day, 189 pg/mL, p<.001), and declined rapidly to≤50 pg/mL for all doses by 24 h. For all subjects, the median E2 levels remained under 35 pg/mL during treatment. CONCLUSION: PK parameters of NES were not affected when paired with different doses of E2, but E2 levels from all three doses were lower than anticipated and no dose response was observed. IMPLICATIONS: While these novel estradiol-releasing combination contraceptive vaginal rings provided sustained release of contraceptive levels of Nestorone over 90 days, the E2 levels achieved were not consistent with bone protection, and a dose-response was not observed.

Cost-effectiveness of salpingotomy and salpingectomy in women with tubal pregnancy (a randomized controlled trial).

STUDY QUESTION: Is salpingotomy cost effective compared with salpingectomy in women with tubal pregnancy and a healthy contralateral tube? SUMMARY ANSWER: Salpingotomy is not cost effective over salpingectomy as a surgical procedure for tubal pregnancy, as its costs are higher without a better ongoing pregnancy rate while risks of persistent trophoblast are higher. WHAT IS KNOWN ALREADY: Women with a tubal pregnancy treated by salpingotomy or salpingectomy in the presence of a healthy contralateral tube have comparable ongoing pregnancy rates by natural conception. Salpingotomy bears the risk of persistent trophoblast necessitating additional medical or surgical treatment. Repeat ectopic pregnancy occurs slightly more often after salpingotomy compared with salpingectomy. Both consequences imply potentially higher costs after salpingotomy. STUDY DESIGN, SIZE, DURATION: We performed an economic evaluation of salpingotomy compared with salpingectomy in an international multicentre randomized controlled trial in women with a tubal pregnancy and a healthy contralateral tube. Between 24 September 2004 and 29 November 2011, women were allocated to salpingotomy (n = 215) or salpingectomy (n = 231). Fertility follow-up was done up to 36 months post-operatively. PARTICIPANTS/MATERIALS, SETTINGS, METHODS: We performed a cost-effectiveness analysis from a hospital perspective. We compared the direct medical costs of salpingotomy and salpingectomy until an ongoing pregnancy occurred by natural conception within a time horizon of 36 months. Direct medical costs included the surgical treatment of the initial tubal pregnancy, readmissions including reinterventions, treatment for persistent trophoblast and interventions for repeat ectopic pregnancy. The analysis was performed according to the intention-to-treat principle. MAIN RESULTS AND THE ROLE OF CHANCE: Mean direct medical costs per woman in the salpingotomy group and in the salpingectomy group were €3319 versus €2958, respectively, with a mean difference of €361 (95% confidence interval €217 to €515). Salpingotomy resulted in a marginally higher ongoing pregnancy rate by natural conception compared with salpingectomy leading to an incremental cost-effectiveness ratio €40 982 (95% confidence interval -€130 319 to €145 491) per ongoing pregnancy. Since salpingotomy resulted in more additional treatments for persistent trophoblast and interventions for repeat ectopic pregnancy, the incremental cost-effectiveness ratio was not informative. LIMITATIONS, REASONS FOR CAUTION: Costs of any subsequent IVF cycles were not included in this analysis. The analysis was limited to the perspective of the hospital. WIDER IMPLICATIONS OF THE FINDINGS: However, a small treatment benefit of salpingotomy might be enough to cover the costs of subsequent IVF. This uncertainty should be incorporated in shared decision-making. Whether salpingotomy should be offered depends on society's willingness to pay for an additional child. STUDY FUNDING/COMPETING INTERESTS: Netherlands Organisation for Health Research and Development, Region Västra Götaland Health & Medical Care Committee. TRIAL REGISTRATION NUMBER: ISRCTN37002267.

Ectopic pregnancy prediction in women with a pregnancy of unknown location: data beyond 48 h are necessary.

STUDY QUESTION: Are there improvements in the accuracy of prediction of ectopic pregnancy (EP) in women with early symptomatic pregnancy using human chorionic gonadotrophin (hCG) curves when clinicians consider visits beyond the first 48 h after initial presentation? SUMMARY ANSWER: Two hCG values, measured 48 h (2 days) apart, are often not sufficient to accurately predict the outcome of a woman with a pregnancy of unknown location (PUL), but adding a third visit on Day 4 or 7 significantly improved the prediction for 1 in 15 women. WHAT IS KNOWN ALREADY: The use of serial hCG values is commonly used to aid in the prediction of the final diagnosis in women with a PUL. Initial outcome predictions based on two hCG values may often be incorrect. STUDY DESIGN, SIZE, DURATION: This retrospective multicenter cohort study included 646 women with a PUL, recruited over 2 years. Of these women, 146 were ultimately diagnosed with EP. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women presenting to the emergency room with first trimester pain or bleeding, with a PUL, at least 2 hCG values and a definitive final diagnosis from the University of Pennsylvania, University of Miami and University of Southern California, were recruited from 2007 to 2009. MAIN RESULTS AND THE ROLE OF CHANCE: Using currently recommended prediction rules, adding a third hCG evaluation on Day 4 after initial presentation significantly improved the accuracy of initial prediction from the first two values (48 h apart, or Day 2) by 9.3% (P = 0.015). Adding a third value on Day 7 improved prediction significantly by 6.7% (P = 0.031), compared with prediction based on first two values. The improvement in prediction by assessing four hCG values (Days 0, 2, 4 and 7) compared with three values (Days 0, 2 and 4) was 1.3% and not statistically significant. LIMITATIONS, REASONS FOR CAUTION: Missing data imputation likely biased results toward the null; predicted outcomes may not match those made by clinicians; and the study does not predict intrauterine pregnancy and spontaneous miscarriage separately. WIDER IMPLICATIONS OF THE FINDINGS: This study provides useful information for the prediction of outcomes for women with a symptomatic first trimester pregnancy of unknown location, but may not be generalizable to all pregnant women. STUDY FUNDING/COMPETING INTEREST(S): Supported by NIH grant numbers R01-HD036455 to Dr Barnhart and Dr Sammel, K24HD060687 to Dr Barnhart, and 5T32MH065218 to Ms. Zee. The authors have no conflicts of interest to declare.

Does a prediction model for pregnancy of unknown location developed in the UK validate on a US population?

BACKGROUND: A logistic regression model (M4) was developed in the UK to predict the outcome for women with a pregnancy of unknown location (PUL) based on the initial two human chorionic gonadotrophin (hCG) values, 48 h apart. The purpose of this paper was to assess the utility of this model to predict the outcome for a woman (PUL) in a US population. METHODS: Diagnostic variables included log-transformed serum hCG average of two measurements, and linear and quadratic hCG ratios. Outcomes modeled were failing PUL, intrauterine pregnancy (IUP) and ectopic pregnancy (EP). This model was applied to a US cohort of 604 women presenting with symptomatic first-trimester pregnancies, who were followed until a definitive diagnosis was made. The model was applied before and after correcting for differences in terminology and diagnostic criteria. RESULTS: When retrospectively applied to the adjusted US population, the M4 model demonstrated lower areas under the curve compared with the UK population, 0.898 versus 0.988 for failing PUL/spontaneous miscarriage, 0.915 versus 0.981 for IUP and 0.831 versus 0.904 for EP. Whereas the model had 80% sensitivity for EP using UK data, this decreased to 49% for the US data, with similar specificities. Performance only improved slightly (55% sensitivity) when the US population was adjusted to better match the UK diagnostic criteria. CONCLUSIONS: A logistic regression model based on two hCG values performed with modest decreases in predictive ability in a US cohort for women at risk for EP compared with the original UK population. However, the sensitivity for EP was too low for the model to be used in clinical practice in its present form. Our data illustrate the difficulties of applying algorithms from one center to another, where the definitions of pathology may differ.

A moderately elevated day 3 FSH concentration has limited predictive value, especially in younger women.

BACKGROUND: A cycle day 3 FSH concentration is a popular screening tool for predicting success in achieving pregnancy after IVF. Difficulties interpreting this test have resulted from lack of consensus in defining an elevated FSH concentration, a change in the assays, and lack of controlling for factors which may confound the association between FSH concentration and pregnancy. METHODS: Assessment was made of the ability of a moderately elevated (10-11.4 mIU/ml, World Health Organization 2nd International Standard (IRP 78/549) and elevated FSH (>11.4 mIU/ml, conversion factor to SI units, 1.00) in predicting ability to achieve pregnancy through IVF and embryo transfer, both independently, and after controlling for confounding variables such as age, diagnosis, and response to gonadotrophins. RESULTS: A total of 293 IVF cycles were retrospectively reviewed. An FSH (>11.4) was strongly associated with inability to achieve pregnancy after IVF both independently (P < 0.01) and after multivariate analysis (P < 0.01), and had a strong predictive value (100%). A moderately elevated FSH (10-11.4) was not statistically associated with pregnancy outcome either independently or after multivariate analysis, and had a low predictive value (71%). CONCLUSIONS: Much of the predictive value of an elevated FSH is confounded by poor response to gonadotrophin stimulation, which may be overcome in younger women.

Noncontraceptive benefits and therapeutic uses of the oral contraceptive pill.

The oral contraceptive pill is one of the most extensively studied medications ever prescribed. The health benefits are numerous and outweigh the risks of their use. Definitive evidence exists for protection against ovarian and endometrial cancers, benign breast disease, pelvic inflammatory disease requiring hospitalization, ectopic pregnancy, and iron-deficiency anemia. It has also been suggested that oral contraceptives may provide a benefit on bone mineral density, uterine fibroids, toxic shock syndrome, and colorectal cancer. Minimal supportive evidence exists for oral contraceptives protecting against the development of functional ovarian cysts and rheumatoid arthritis. Treatment of medical disorders with oral contraceptives is an "off-label" practice. Dysmenorrhea, irregular or excessive bleeding, acne, hirsutism, and endometriosis-associated pain are common targets for oral contraceptive therapy. Most patients are unaware of these health benefits and therapeutic uses of oral contraceptives, and they tend to overestimate their risk. Counseling and education are necessary to help women make well-informed health-care decisions and improve compliance.

Prophylactic methotrexate after linear salpingostomy: a decision analysis.

OBJECTIVE: To compare two strategies for managing women after linear salpingostomy for treatment of tubal pregnancy: observation and prophylactic methotrexate. DESIGN: Decision analysis. SETTING: Outpatient tertiary-care center. PATIENT(S): One thousand hypothetical women treated with a linear salpingostomy for ectopic pregnancy. INTERVENTION(S): Observation after salpingostomy and treatment of persistent ectopic pregnancy with a single dose of methotrexate (current standard of care) versus treatment with prophylactic methotrexate at the time of salpingostomy. MAIN OUTCOME MEASURE(S): Number of ruptured ectopic pregnancies, surgical procedures, complications, and cost for each group (observation vs. prophylaxis). RESULT(S): Prophylactic methotrexate results in fewer cases of tubal rupture (0.4% vs. 3.7%) and fewer procedures (1.9% vs. 4.7%) at a lower cost ($67.55 less/patient) compared with observation alone. Methotrexate-associated complications occur more frequently with prophylaxis (5.5% vs. 0.8%). Certain conditions change which strategy is preferable. Observation is the best strategy when the persistent ectopic pregnancy rate is <9%, the success of prophylaxis is <95%, the complication rate associated with methotrexate is >18%, or the rupture rate of persistent ectopic pregnancies is <7.3%. CONCLUSION(S): Prophylactic methotrexate at the time of linear salpingostomy for the treatment of ectopic pregnancy is preferable to observation as long as certain conditions exist.

Exposure to soy-based formula in infancy and endocrinological and reproductive outcomes in young adulthood.

CONTEXT: A large body of evidence documents the role of phytoestrogens in influencing hormone-dependent states. Infants fed soy formula receive high levels of phytoestrogens, in the form of soy isoflavones, during a stage of development at which permanent effects are theoretically possible. However, a paucity of data exists on the long-term effects of infant soy formulas. OBJECTIVE: To examine the association between infant exposure to soy formula and health in young adulthood, with an emphasis on reproductive health. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study conducted from March to August 1999 among adults aged 20 to 34 years who, as infants, participated during 1965-1978 in controlled feeding studies conducted at the University of Iowa, Iowa City (248 were fed soy formula and 563 were fed cow milk formula during infancy). MAIN OUTCOME MEASURES: Self-reported pubertal maturation, menstrual and reproductive history, height and usual weight, and current health, compared based on type of formula exposure during infancy. RESULTS: No statistically significant differences were observed between groups in either women or men for more than 30 outcomes. However, women who had been fed soy formula reported slightly longer duration of menstrual bleeding (adjusted mean difference, 0.37 days; 95% confidence interval [CI], 0.06-0.68), with no difference in severity of menstrual flow. They also reported greater discomfort with menstruation (unadjusted relative risk for extreme discomfort vs no or mild pain, 1.77; 95% CI, 1.04-3.00). CONCLUSIONS: Exposure to soy formula does not appear to lead to different general health or reproductive outcomes than exposure to cow milk formula. Although the few positive findings should be explored in future studies, our findings are reassuring about the safety of infant soy formula.

Distribution of a spermicide containing Nonoxynol-9 in the vaginal canal and the upper female reproductive tract.

Topical, intravaginal microbicides and spermicides are greatly needed to prevent transmission of sexually transmitted diseases and/or unwanted pregnancies. The development of such compounds is a high research priority. The presumed method of action of existing, or novel, microbicides/spermicides is to provide a chemical barrier to the vaginal epithelium preventing exposure to micro-organisms. Other intravaginal products are used to treat vaginal bacteria of fungal infections. Little is known, however, about the actual or optimal initial distribution and subsequent spread of medications placed in the vagina. We describe a sensitive new technique to quantify the spread of a gel placed in the vagina using magnetic resonance imaging (MRI). Five millilitres of an over-the-counter spermicide containing Nonoxynol-9 was mixed with Gadolinium. MRI was used to quantify spread of the mixture 10 min after insertion with a standard applicator. We demonstrated contiguous spread of gel throughout the vagina. The coverage of material was thicker in the upper vagina than in the lower vagina. We also demonstrated, for the first time, that spermicidal compounds may migrate from the vaginal canal into the endocervix within 10 min of insertion. This finding suggests that topical microbicides/spermicides may act both in the vaginal canal and in the upper female genital tract.

Role of periovulatory luteinizing hormone concentrations during assisted reproductive technology cycles stimulated exclusively with recombinant follicle-stimulating hormone.

OBJECTIVE: To study the effect of endogenous luteinizing hormone (LH) concentration on fertilization, pregnancy, and early pregnancy loss rates. DESIGN: Retrospective cohort study. SETTING: Tertiary-care university center. PATIENT(S): One hundred sixty-six normogonadotropic patients undergoing IVF. INTERVENTION(S): Luteal phase pituitary down-regulation and recombinant FSH (Gonal-F) were used for ovarian stimulation. The mean of 4-5 serum LH concentrations, from stimulation days 5-12, was computed for analysis. MAIN OUTCOME MEASURE(S): Fertilization, pregnancy, and early pregnancy loss rates according to periovulatory levels of LH. RESULT(S): Data were analyzed by stratifying patients according to a mean periovulatory LH value of 3 mIU/mL. After controlling for confounding variables with logistic regression, results showed that the fertilization rate was significantly lower in patients with a periovulatory LH <3 mIU/mL versus > or = 3 mIU/mL (52% and 58%, respectively; P=.03). Pregnancy rates and spontaneous abortion rates were similar in both groups. There were seven biochemical pregnancies, all in patients with an LH <3 mIU/mL (P=.07). CONCLUSION(S): Low endogenous LH concentrations (<3 mIU/mL) in the late follicular phase of an IVF cycle are associated with significantly lower fertilization rates and a trend toward higher biochemical pregnancy rates. It may be of clinical benefit, when exclusively using r-hFSH in ART cycles, to add LH in the late follicular phase or to further reduce the dose of GnRH agonist.

Diagnosing ectopic pregnancy: decision analysis comparing six strategies.

OBJECTIVE: To compare six published methods of diagnosing ectopic pregnancy. METHODS: Decision analysis compared six diagnostic algorithms involving combinations of clinical examination, transvaginal ultrasound, serum progesterone, serum hCG, and D&C. The population was composed of hemodynamically stable women who presented to a tertiary care university emergency department with abdominal pain or bleeding in their first trimesters. Outcome measures included number of missed ectopic pregnancies, potentially interrupted intrauterine pregnancies, surgical and diagnostic procedures, time until diagnosis, and cost. RESULTS: Ultrasound followed by serum hCG in women with nondiagnostic scans yielded the most favorable outcomes; no ectopic pregnancy was missed, only 1% of all potential intrauterine pregnancies were interrupted, and time to diagnosis averaged 1.46 days. Quantitative hCG measurement followed by ultrasound only in women with hCG levels above the discriminatory zone was optimal if sensitivity of ultrasound to diagnose intrauterine pregnancy was less than 93%. Serum progesterone measurement was not favored because it was associated with missed ectopic pregnancies (2.6%). CONCLUSION: Given the current accuracy of tests for diagnosing ectopic pregnancy, algorithms using a combination of ultrasound and hCG resulted in the best outcomes. Ultrasound as the first step was the most efficient and accurate method of diagnosing ectopic pregnancies.

Comparability of perioperative morbidity between abdominal myomectomy and hysterectomy for women with uterine leiomyomas.

OBJECTIVE: The aim of this study was to compare the perioperative morbidity associated with abdominal myomectomy with that of hysterectomy. STUDY DESIGN: This was a retrospective cohort study of 394 women at an academic medical center. Main outcome measured was perioperative morbidity, with the following secondary outcomes: febrile morbidity, hemorrhage, unintended major surgical procedures, life-threatening events, and rehospitalization. RESULTS: Morbidity was associated with myomectomy and hysterectomy in 39% and 40% of cases, respectively. The crude odds ratio for morbidity of myomectomy with respect to hysterectomy was 0.93 (95% confidence interval, 0.63-1.40). Women who underwent myomectomy were significantly younger, weighed less, and had a smaller preoperative uterine size. In a multivariable analysis that accounted for these differences the odds ratio increased to 1.46 (95% confidence interval, 0.77-2.77) but still was not statistically elevated. The study had >90% power to detect a clinically relevant 15% absolute difference in overall morbidity between the 2 groups. CONCLUSION: No clinically significant difference in perioperative morbidity between myomectomy and hysterectomy was detected. Myomectomy should be considered a safe alternative to hysterectomy.

Meclizine for prevention of nausea associated with use of emergency contraceptive pills: a randomized trial.

OBJECTIVE: We conducted a randomized trial to determine whether pretreatment with meclizine reduces the incidence of nausea and vomiting associated with the Yuzpe regimen of emergency contraception. METHODS: We randomly assigned 343 women aged 18-45 years who were not at risk for pregnancy to pretreatment with 50 mg of meclizine, placebo, or no drug 1 hour before the first of two doses of emergency contraceptive pills. We asked participants to complete three questionnaires over the following 48 hours. RESULTS: The incidence of nausea was 47% in the group pretreated with meclizine and 64% in the other two groups (relative risk adjusted for center 0.7, 95% confidence intervals 0.6, 0.9 for comparisons of meclizine with both placebo and no drug). The severity of nausea and the incidence of vomiting were also significantly lower in the meclizine pretreatment group than in the other two groups. Drowsiness was reported by about twice as many women in the meclizine pretreatment group (31%) than in the other two groups (13% in the placebo group, 16% in the no-pretreatment group; P < .01 for both comparisons). CONCLUSION: Meclizine is effective for preventing nausea and vomiting associated with the Yuzpe regimen of emergency contraceptive pills. Women using this drug should be cautioned to anticipate drowsiness.

The effect of dehydroepiandrosterone supplementation to symptomatic perimenopausal women on serum endocrine profiles, lipid parameters, and health-related quality of life.

Dehydroepiandrosterone (DHEA), an androgenic steroid hormone, exhibits an age-related decline. Perimenopausal women have only approximately 50% of peak DHEA levels. Despite limited scientific data, DHEA has gained recognition as a dietary supplement to reduce the symptoms of aging and improve well-being. This randomized, double-blind placebo-controlled trial examined the effects of 50 mg/day of oral DHEA supplementation, for 3 months, on 60 perimenopausal women with complaints of altered mood and well-being. Changes in the serum endocrine profile of women in the DHEA group were significantly greater than the placebo group, including a 242% [95% confidence interval (CI) +60.1, +423.9] increase in DHEAS, a 94.8% (95% CI +34.2, +155.4) increase in testosterone, and a 13.2% (95% CI -27.88, +0.5) decline in cortisol compared to baseline. Women receiving DHEA had a 10.1% (95% CI -15.0, -5.1) decline in high-density lipoprotein and an 18.1% (95% CI -32.2, -3.9) decline in Lp(a) from baseline, but these declines did not significantly differ from women who received placebo. Women receiving DHEA did not have any improvements significantly greater than placebo in the severity of perimenopausal symptoms, mood, dysphoria, libido, cognition, memory, or well-being. DHEA supplementation significantly effects the endocrine profile, may affect the lipid profile, but does not improve perimenopausal symptoms or well-being compared to placebo.

Diagnostic accuracy of ultrasound above and below the beta-hCG discriminatory zone.

OBJECTIVE: To evaluate clinical use and accuracy of transvaginal ultrasound for diagnosing intrauterine pregnancies, spontaneous miscarriages, and ectopic pregnancies in women who present with beta-hCG concentrations above or below an established discriminatory zone. METHODS: Ultrasound diagnosis at presentation was compared with final clinical diagnosis in 333 consecutive pregnant women who presented to an emergency department with vaginal bleeding or abdominal pain. The sensitivity, specificity, predictive value, and overall diagnostic accuracy of ultrasound were calculated. RESULTS: Transvaginal ultrasound was nondiagnostic in 59 (17.7%) of 333 subjects and 43 (67.2%) of 64 subjects with beta-hCG levels below 1500 mIU/mL at presentation. Preliminary ultrasound diagnoses were reported significantly more frequently when presenting beta-hCG levels were above 1500 mIU/mL (253 [94.1%] of 269 subjects) compared with levels below 1500 mIU/mL (21 [32.8%] of 64 subjects: P < .001; relative risk (RR) 3.4 [95% confidence interval (CI) 2.23, 5.18]). The proportion of accurate preliminary ultrasound diagnoses was significantly higher in subjects who presented with beta-hCG levels above 1500 mIU/mL (227 [91.5%] of 248 subjects) compared with levels below 1500 mIU/mL (18 [28.6%] of 63 subjects: P < .001; RR 2.9 [95% CI 2.04, 4.15]). Sensitivity of transvaginal ultrasound diagnosis of intrauterine pregnancy, spontaneous miscarriage, and ectopic pregnancy in women who presented with beta-hCG levels below 1500 mIU/mL was 33.3%, 28.2%, and 25.0%, respectively. CONCLUSION: The sensitivity, predictive value, and accuracy of transvaginal ultrasound for diagnosing complications of early pregnancy were poor when beta-hCG levels were below the discriminatory zone at presentation. Ultrasound impressions should be correlated with beta-hCG concentrations.

Postoperative day 1 serum human chorionic gonadotropin level as a predictor of persistent ectopic pregnancy after conservative surgical management.

OBJECTIVE: To determine characteristics predictive of persistent ectopic pregnancy (EP). DESIGN: Retrospective cohort study. SETTING: Tertiary care, university hospital. PATIENT(S): All women treated surgically for an EP whose postoperative hCG levels were followed until complete resolution or determination of a persistent EP over a 54-month period. MAIN OUTCOME MEASURE(S): Final outcome defined as successful treatment or persistent EP. RESULT(S): Twenty-six (17.7%) of 147 patients were diagnosed with a persistent EP. An inverse relationship was noted between the percent decrease in hCG at postoperative day 1 and the incidence of persistent EP. A significantly greater percentage of persistent EPs were noted when the postoperative day 1 hCG fell < 50% from the initial preoperative hCG level (relative risk = 3.51 [1.25 to 6.68]). No case of persistent EP was noted if the postoperative day 1 hCG declined by > or = 77%. Surgical time differed significantly (129 minutes versus 101 minutes) between cases treated successfully as compared with cases in which conservative treatment failed. No other preoperative or intraoperative variables were found to be significantly different. CONCLUSION(S): Although no single postoperative hCG value is predictive of conservative surgical treatment for EP, a day-1 postoperative hCG value may be used as a predictor of persistent EP.

Changes in the menstrual bleeding of users of a subdermal contraceptive implant of nomegestrol acetate (Uniplant) do not influence sexual frequency, sexual desire, or sexual enjoyment.

OBJECTIVE: To evaluate the effect of menstrual changes induced by a nomegestrol acetate subdermal contraceptive implant (Uniplant; Thermex, Bahia, Brazil) on users' sexuality. DESIGN: Prospective observational survey. SETTING: San Borja-Arriarán Hospital, University of Chile, School of Medicine. PATIENT(S): Normally cycling healthy women and their partners. INTERVENTION(S): Structured interview before and during use of the contraceptive. MAIN OUTCOMES MEASURE(S): Sexual frequency, desire, and enjoyment; perception of health; and contraceptive satisfaction. RESULT(S): During the use of the implant more women reported irregular cycles (32% versus 11%) and vaginal spotting (38% versus 19%). Frequency of sexual relations was unchanged (2.3 versus 2.5/wk) but the percent of couples engaging in sexual relations during vaginal spotting increased (28% versus 11%). There was no significant difference in the percent of men or women who reported an increase, or decrease, in perceived sexual desire, sexual enjoyment, or perception of health during the use of Uniplant. CONCLUSION(S): Despite the alterations in menstrual cyclicity and the occurrence of spotting, the use of a contraceptive subdermal implant of nomegestrol acetate did not effect desire for, enjoyment of, or frequency of sexual relations in users.

PIP: Findings are presented from a study evaluating the effect of menstrual changes induced by a nomegestrol acetate subdermal contraceptive implant (Uniplant) on users' sexuality. The Uniplant implant evaluated is manufactured by Thermex of Bahia, Brazil. New subjects enrolled in a phase III clinical trial of the implant at San Borja-Arriaran Hospital, University of Chile, School of Medicine were observed prospectively. The participants were 118 normally cycling healthy women of median age 28 years and 60 male partners of median age 31 years. A structured interview was held before and during use of the contraceptive. Before insertion of the implant, 11% of the women reported irregular menstrual cycles, 19% reported vaginal spotting, and 11% of the couples reported engaging in sexual relations during vaginal spotting. During use of the implant, 32% of the women reported irregular cycles, 38% reported vaginal spotting, and 28% of the couples reported engaging in sexual relations during vaginal spotting. The frequency of sexual relations remained unchanged at 2.3-2.5 acts of coitus per weeks. There was no significant difference in the percentage of men or women who reported an increase or decrease in perceived sexual desire, sexual enjoyment, or perception of health during the use of Uniplant.

Efficacy of frozen-section evaluation of uterine curettings in the diagnosis of ectopic pregnancy.

OBJECTIVE: This study was undertaken to examine the accuracy of frozen section for the identification of products of conception on curettage of patients undergoing surgery for suspected ectopic pregnancy. STUDY DESIGN: A retrospective analysis of 87 consecutive cases in which frozen-section assessment of an endometrial curettage specimen to identify products of conception was undertaken. A frozen-section diagnosis was considered correct if the final diagnosis concurred with the findings at frozen section. RESULTS: Eighty-one of 87 (93.1%) specimens were correctly identified at frozen section. Frozen section had a sensitivity of 78.3% and a specificity of 98.4%. The positive predictive value of frozen section in this population was 94.7% and the negative predictive value was 92.6%. No significant correlation was found regarding the attending pathologist at frozen section, preoperative human chorionic gonadotropin, or time of day at frozen section. CONCLUSIONS: Frozen section is accurate for the identification of products of conception on endometrial curettage in the evaluation of a suspected ectopic pregnancy.

Endometrial stripe thickness as a predictor of ectopic pregnancy.

OBJECTIVE: To evaluate the potential utility of endometrial stripe thickness in predicting pregnancy outcome in women with an hCG less than a discriminatory zone. DESIGN: Retrospective case review. SETTING: University emergency department. PATIENTS: Women who presented with symptomatic early pregnancies after a spontaneous conception with an hCG level less than a discriminatory zone evaluated to rule out an ectopic pregnancy (EP). INTERVENTIONS: Measure endometrial stripe thickness by transvaginal ultrasound. MAIN OUTCOME MEASURES: Initial endometrial stripe thickness was correlated to eventual pregnancy outcomes. RESULTS: The mean initial endometrial stripe thickness of patients eventually diagnosed with an intrauterine pregnancy (13.42 +/- 0.68 mm), spontaneous abortion (9.28 +/- 0.88 mm), and an EP (5.95 +/- 0.35 mm) were all statistically different from each other. Ninety-seven percent of pregnancies found to have an endometrial stripe thickness < or = 8 mm were abnormal (EP or spontaneous abortion). CONCLUSIONS: This study suggest a role of the evaluation of the endometrial stripe thickness in the detection of abnormal pregnancies in patients presenting for evaluation of a symptomatic early pregnancy with an hCG below a discriminatory zone. Initial endometrial stripe thickness measured in patients with an EP is significantly thinner than in those with an intrauterine pregnancy.