Julia V. Johnson

Efficacy and safety of single-dose systemic methotrexate in the treatment of ectopic pregnancy

OBJECTIVE To evaluate the safety and efficacy of single-dose systemic methotrexate (MTX) in the treatment of ectopic pregnancy (EP). DESIGN A database was started and continued prospectively for 35 patients meeting criteria for MTX therapy from June 1991 to October 1993. Follow-up was performed retrospectively on all patients with EPs (n = 82) by evaluating hospital and clinic records and by contacting affiliated physicians and individual patients. SETTING The University of Vermont Reproductive Endocrinology Service. INTERVENTIONS Methotrexate 50 mg/m2 was administered IM; blood samples were collected on days 0, 4, and 7 of MTX therapy and weekly thereafter until hCG titers became < 4 mIU/mL. RESULTS Thirty-five of 82 (42.7%) patients diagnosed with EP were treated with MTX. The mean hCG concentration on day of treatment was 1388.1 +/- 463.5 (+/- SE) mIU/mL, and mean time to complete resolution of hCG was 23.1 +/- 2.9 days. Thirty of 35 (85.7%) were successfully treated with a single dose of MTX. Five of 35 (14.3%) failed therapy and required laparoscopic surgery. Twelve of 35 (34.3%) experienced mild side effects that resolved spontaneously. Ten of 13 (76.9%) demonstrated tubal patency at follow-up hysterosalpingogram. Of the 15 patients seeking pregnancy, 3 of 15 (20.0%) conceived, resulting in 3 term deliveries and 2 spontaneous abortions. CONCLUSIONS Our results support the use of single-dose systemic MTX for the treatment of unruptured EP in carefully selected patients.

Effects of oral and transdermal hormonal contraception on vascular risk markers: a randomized controlled trial

OBJECTIVE: To compare the effects of oral and transdermal contraceptives containing similar hormone formulations on vascular risk markers. METHODS: We conducted a randomized, investigator-blinded, crossover, clinical trial with 24 healthy women, aged 18–35 years, who received 2 months of transdermal or oral contraceptive, 2 months washout, then 2 months of the alternative medication. The transdermal contraceptive contained 0.75 mg ethinyl estradiol and 6 mg norelgestromin. The oral contraceptive contained 35 mcg ethinyl estradiol and 250 mcg norgestimate. Blood samples taken before and after each treatment were analyzed in batch for D-dimer, von Willebrand factor, factor VIII, total and free protein S, antithrombin, fibrinogen, C-reactive protein, and normalized activated protein C sensitivity ratio (nAPCsr) determined with two thrombin generation-based assays, the &agr;2macroglobulin-thrombin end point method (&agr;2M-IIa) and calibrated automated thrombinography. Repeated measures analysis of variance was used for analysis. RESULTS: For both contraceptives (transdermal, oral) there were significant declines in free (19%, 11%) and total protein S (19%, 13%) and antithrombin (13%, 10%); increases in fibrinogen (8%, 10%), C-reactive protein (220%, 292%), nAPCsr &agr;2M-IIa (81%, 61%), and nAPCsr calibrated automated thrombinography (102%, 68%), all P<.05. Transdermal contraceptives had a greater effect than oral contraceptives on free protein S (P=.07), nAPCsr &agr;2M-IIa (P=.06), and nAPCsr calibrated automated thrombinography (P=.03). CONCLUSION: Oral and transdermal contraception with similar hormones had similar adverse effects on vascular risk markers. This suggests that this transdermal contraceptive has at least a similar thrombosis risk as its oral counterpart. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00554632 LEVEL OF EVIDENCE: I

Transvaginal ultrasonographic assessment of Hyskon or lactated Ringer's solution instillation after laparoscopy: randomized, controlled study.

We sought to evaluate two common fluids placed in the pelvis after pelvic surgery for their ability to remain in the pelvis for a time thought adequate for prevention of adhesions. Thirteen patients undergoing operative laparoscopy were randomized to receive 250 ml 32% dextran 70 (Hyskon), 250 ml lactated Ringers solution, or no fluid (control) at the end of surgery. Serial transvaginal ultrasonograms were obtained at 1 hr, 3 hr, 6 hr, 24 hr, 96 hr (4 days), and 168 hr (7 days) after surgery. Patients were asked about side effects of fluid instillation. The volume of lactated Ringers solution declined rapidly after instillation, with no significant difference from control at 24 hr (12 ml versus 7 ml). The volume of Hyskon did not decline rapidly by 24 hr and remained higher than the volume in controls or those receiving lactated Ringers solution (188 ml, P = 0.003). Although the volume of Hyskon remained higher than that of lactated Ringers solution or fluid volume in control patients by days 4 and 7, this difference did not reach statistical significance (45 ml versus 7 ml and 14 ml respectively, P = 0.39, on day 4). Patients in all groups noted abdominal pain. One patient who received Hyskon developed severe vulvar edema and another developed dyspnea. We conclude that the volume of Hyskon in the peritoneal cavity after laparoscopy does not decline as rapidly as does that of lactated Ringers solution; however, significant side effects may limit its usefulness. Transvaginal ultrasonography is useful in monitoring fluids placed in the pelvis for prevention of adhesions.

Ethiodol oil contrast medium inhibits macrophage phagocytosis and adherence by altering membrane electronegativity and microviscosity

OBJECTIVE To examine the effect of Ethiodol oil-soluble contrast medium and Sinografin aqueous-soluble contrast medium on macrophage function. After the observation that Ethiodol alters macrophage phagocytosis and adherence, we sought to determine the mechanism of action by which oil-soluble contrast medium alters the macrophage membrane. DESIGN The P388D1 cell line was used as a consistent source of macrophages for all experiments. The uptake of 3H-labeled candida albicans was determined in macrophages exposed to 1:100, 1:400, or 1:800 dilutions of Ethiodol, Sinografin (S.R. Squibb, Princeton, NJ) or untreated media. To evaluate the macrophage adherence, 51Cr-labeled macrophages were exposed to the same dilutions of the contrast media. Specific membrane properties, Fc receptor levels, electronegativity, and microviscosity were assessed by flow cytometry after exposure to 1:100 dilutions of Ethiodol or Sinografin. RESULTS Macrophage phagocytosis was decreased upon exposure to 1:100 and 1:400 dilutions of Ethiodol contrast medium, whereas adherence was reduced at the 1:100 dilution of Ethiodol. There was no effect of any dilution of Sinografin. There was a reduction in membrane electronegativity and microviscosity, but not Fc receptor levels, after exposure to a 1:100 dilution of Ethiodol. CONCLUSIONS This study establishes a decrease in macrophage phagocytosis and adherence after exposure to Ethiodol oil-soluble contrast medium. We established that this alteration in membrane function is caused by a reduction of membrane negative surface charge and microviscosity. This may suggest a mechanism of action for the therapeutic effect of oil-contrast hysterosalpingograms in women with unexplained infertility.

Correlation of serum androgens with anthropometric and metabolic indices in healthy, nonobese postmenopausal women.

OBJECTIVE The role of testosterone in the regulation of metabolic and physiological function in men is well defined, but its role in women remains enigmatic. Thus, the present study sought to assess the contribution of endogenous circulating androgens to the regulation of metabolic function, body morphometry, and physical function in normal naturally postmenopausal women. METHODS Using a cross-sectional design, we measured serum androgens in a cohort of 29 naturally postmenopausal women and correlated the results with metabolic, morphometric, and functional outcome parameters. These included insulin sensitivity, whole-body fat and lean body mass, visceral/abdominal fat areasm and aerobic capacity. RESULTS Higher serum testosterone levels were related to greater maximal aerobic capacity and reduced adiposity. Additionally, higher serum dihydrotestosterone, dehydroepiandrosterone sulfate, androstenedione, and androstenetriol glucuronidate levels were correlated to greater insulin sensitivity. CONCLUSION In naturally postmenopausal women, endogenous androgens may play a role in the maintenance of beneficial patterns of metabolic, morphometric, and functional parameters.

Postmenopausal uterine bleeding profiles with two forms of continuous combined hormone replacement therapy.

ObjectiveThis study was designed to compare the bleeding profiles of conjugated equine estrogens 0.625 mg in combination with 2.5 mg medroxyprogesterone acetate (Prempro; CEE/MPA group), the most widely prescribed continuous combined hormone replacement therapy (CCHRT) in the United States, with 17&bgr;-estradiol 1 mg combined with 0.5 mg norethindrone acetate (Activella; E 2 /NETA group), a newly available CCHRT preparation, over a 6-month period. DesignThis study was a prospective, randomized, multicenter, double-blind, controlled trial. A total of 438 healthy postmenopausal women were randomized and received treatment (Activella n = 217, Prempro n = 221). Each woman recorded bleeding diaries daily. Total cholesterol, triglycerides, and endometrial biopsies were obtained at screening and end-of-trial visits. ResultsThe more favorable bleeding profile was found in the E 2 /NETA (Activella) group. The differences in bleeding patterns were most marked in the first 3 months of treatment in women who were 1–2 years from last menses, with no bleeding in 71.4% vs. 40.0%; (p = 0.005) and with no bleeding and no spotting in 54.8% vs. 17.1%; (p = 0.001). Triglycerides fell by 8.5% in the E 2 /NETA group and increased by 11.7% in the CEE/MPA group (p < 0.001). Total cholesterol declined by 9.1% and 6.9%, respectively. ConclusionThe most important factor in the continuation of HRT is uterine bleeding. E 2 /NETA has significantly less bleeding than the most commonly prescribed CCHRT CEE/MPA, therefore; E 2 /NETA should be associated with improved continuation rates. The patient taking E 2 /NETA will receive effective treatment for her menopausal symptoms with less bleeding.

Trends in the academic workforce of obstetrics and gynecology

OBJECTIVE: The objective was to report results from the seventh survey that monitored trends in numbers of full-time department faculty and from a first survey on the current and anticipated numbers of part-time faculty. METHODS: A faculty workforce survey, drafted in the same format as the prior published questionnaire, was sent electronically to chairs of obstetrics and gynecology at all 125 U.S. medical schools. Each chair was asked to provide the number of current full-time and part-time (0.5–0.9 full-time equivalent) faculty in each specialty and the projected department size in 5 years. When accuracy of data were questioned, we reviewed the department’s Web site and directly communicated with the chair. RESULTS: The mean number of full-time faculty per department increased from 25 in 1994 to 29 in 2008 (95% confidence interval 25–33). Most departments (84.0%) had part-time faculty, which constituted 21.2% of the total faculty. Growth was only substantial in the number of medical faculty. In 2008, half (50.1%) of all faculty were women. Private schools and research-oriented departments had the largest faculty sizes. Two-thirds of all chairs anticipated that the number of faculty will increase, especially for part-time faculty and entry-level assistant professors as generalists or maternal–fetal medicine specialists. CONCLUSION: Continued growth in department sizes was accompanied by considerably more women and more part-time faculty. The numbers of full-time and part-time faculty are anticipated to increase. LEVEL OF EVIDENCE: III

Spinal anesthesia versus intravenous sedation for transvaginal oocyte retrieval: Reproductive outcome, side-effects and recovery profiles

Transvaginal ultrasonically guided oocyte retrieval is commonly performed as part of in vitro fertilization efforts. The impact of anesthetic management on patient outcome from this procedure has not been well characterized. At our institution, patients are offered a choice of either heavy intravenous sedation or spinal anesthesia with minimal or no sedatives. In this pilot study, we retrospectively reviewed the anesthetic management, reproductive outcome and recovery room experience for all patients having oocyte retrieval during a 2-year interval (n = 95). Fifty-one oocyte retrievals were performed under spinal anesthesia, while 44 patients received solely intravenous sedatives. Both groups had similar reproductive outcomes. The intravenous sedation group required a significantly longer period until recovery room discharge criteria were met (P = 0.03), and were more likely to have postoperative emetic episodes (46% versus 6% in the spinal anesthesia group: P < 0.01). Two unplanned hospital admissions occurred in the intravenous sedation group: both were related to uncontrolled nausea and vomiting. We conclude that spinal anesthesia may have advantages over intravenous sedation for oocyte retrieval.

Surgically induced endometriosis does not alter peritoneal factors in the rabbit model

OBJECTIVE It was the purpose of this study to examine the cause and effect relationship between alterations in peritoneal factors and the presence of ectopic endometrium in the rabbit model. DESIGN Forty rabbits had autologous endometrial or omental (control) tissue surgically implanted. Peritoneal fluid (PF) volume, macrophage number, and macrophage activation, as well as the number of implants with adhesions, were compared with values obtained during the initial surgery. The effect of hormonal treatment on these factors was evaluated at a third laparotomy. RESULTS There was a significant increase (P less than 0.05) of adhesions in animals with endometrial implants. Peritoneal fluid volume, macrophage number, or macrophage activation were not increased in rabbits with endometrial implants as compared with controls, nor was there a response to hormonal manipulation. CONCLUSIONS These results demonstrate that PF volume, macrophage number, and macrophage activation are not altered by endometrial implants in the rabbit model. This suggests that the increase in these peritoneal factors in women with endometriosis may not be caused exclusively by the presence of ectopic endometrial tissue.

Executive Summary of the revitalize Initiative: Standardizing Gynecologic Data Definitions

Effective care coordination across the womens health continuum is critically important. Unlike obstetric care, which tends to be more episodic and limited to pregnant and postpartum women, women receive health care, whether around pregnancy or for nonobstetric issues, in a variety of care settings by members of multiple health disciplines. Having access to standardized clinical data is imperative to providing optimal patient care. The reVITALize Gynecology Data Definitions Initiative leads a national multidisciplinary movement to offer standard gynecologic data definitions for use in written and verbal clinical communication, electronic health record data capture, quality improvement, and clinical research.