Alternatives to mifepristone for early medical abortion.

OBJECTIVE: To review published reports of first-trimester medical abortion regimens that do not include mifepristone. METHODS: Reports listed in Pubmed and Medline on prospective and controlled trials of the efficacy of misoprostol, alone or associated with methotrexate, for first-trimester abortion were analyzed if they included more than 100 participants and were published since 1990. RESULTS: The efficacy of regimens using misoprostol alone ranged from 84% to 96%, and when misoprostol was used with methotrexate the efficacy ranged from 70% to 97%. Efficacy rates were influenced by follow-up interval. Treatment for infection, bleeding, and incomplete abortion were infrequent with both methods (0.3%-5%). CONCLUSION: Alone or in combination with methotrexate, misoprostol is an efficacious alternative to mifepristone for the medical termination of pregnancy.

Pelvic embolization for treatment of hemorrhage related to spontaneous and induced abortion.

OBJECTIVE: Presentation of outcomes of pelvic arterial embolization for hemorrhage after spontaneous or induced abortion. STUDY DESIGN: We collected case reports of embolization after spontaneous or induced abortion from oral presentations and from members of the National Abortion Federation. RESULTS: Pelvic arterial embolization was performed for 11 women who had hemorrhage after spontaneous or induced abortion, and it was initially successful for all women. One woman ultimately required a hysterectomy after unsuccessful repeated embolization. Prophylactic embolization was done for 8 women who were at risk for hemorrhage from placenta accreta; 4 of these women had subsequent hysterectomies. CONCLUSIONS: Selective pelvic arterial embolization may be a successful treatment for hemorrhage associated with spontaneous and induced abortion. Embolization can be considered before hysterectomy is undertaken for control of hemorrhage. There may be a role for prophylactic catheterization or embolization when there is a risk of severe hemorrhage.

Early medical abortion with methotrexate and misoprostol: outcomes and satisfaction among women aged 15-21 years.

STUDY OBJECTIVE: To compare the outcomes of women aged 15-21 yr to those of older women in a multicenter case series of early medical abortion. DESIGN, SETTING, PARTICIPANTS: We enrolled 1973 women at 34 outpatient Planned Parenthood sites in a case series for medical abortion in the first seven weeks of pregnancy. We used methotrexate (50 mg/m(2)) and misoprostol (800 mg vaginally, repeated as needed). We compared women who started the abortion prior to their 22(nd) birthday to older women. Outcomes of abortion were classified as documented or presumed complete medical abortion, and documented or presumed suction curettage. During the first half of the study, we did an exit interview assessing patient satisfaction. RESULTS: A total of 330 women were under 22 yr and 1641 women over 21 yr. Younger women presented for abortion at the same gestational ages. Overall, younger women had a higher rate of complete medical abortion than did older women (89.4% vs 83%). However, the multiple regression model demonstrated a significant adverse effect of prior live birth (P = 0.006), but not patient age, on outcome. Younger women were less likely to have had prior live births. Younger women were more likely to return for follow-up (96.4% vs 92.9%); the regression model demonstrated a significant effect (P = 0.001) of prior birth on rates of follow-up. Side effects and satisfaction were similar for older and younger women. CONCLUSIONS: Younger women having medical abortion with methotrexate and misoprostol have better outcomes and similar satisfaction levels as do older women.

Early medical abortion with methotrexate and misoprostol.

OBJECTIVE: To evaluate the introduction of an early medical abortion program with methotrexate and misoprostol, using a standardized protocol. METHODS: A total of 1973 women at 34 Planned Parenthood sites participated in a case series of early medical abortion. Ultrasound was used to confirm gestational age of less than 49 days from the first day of the last menstrual period. Women were given intramuscular methotrexate 50 mg/m(2) of body surface area on day 1, and then they inserted misoprostol 800 microg vaginally at home on day 5, 6, or 7. Women were advised to have a suction curettage if the pregnancy appeared viable 2 weeks after methotrexate or if any gestational sac persisted 4 weeks after methotrexate. Outcomes were complete medical abortion and suction curettage. RESULTS: Sixteen hundred fifty-nine women (84.1%) had a complete medical abortion, and 257 (13.0%) had suction curettage. The most common reason for curettage was patient option (8.9%). At 2 weeks after methotrexate use, 1.4% of women had curettage because of a viable pregnancy; at 4 weeks, 1.6% of women had curettage because of a persistent but nonviable pregnancy. One percent of women had curettage because of physician recommendation, most commonly for bleeding. Suction curettage rates decreased with site experience (P <.006) and were lower at early gestational ages (P <.004) and in nulliparous women (P <.004). CONCLUSION: Medical abortion with methotrexate and misoprostol is safe and effective and can be offered in a community setting.

Instituting medical abortion services: changes in outcome and acceptability related to provider experience.

A prospective case series carried out at 34 Planned Parenthood sites studied the safety, efficacy, and acceptability of medical abortion with methotrexate and misoprostol in 1973 women. Women with pregnancies of 26 to 49 gestational days were given methotrexate followed by vaginal misoprostol. Eighty-one percent of women had documented complete medical abortions; abortion was not confirmed by examination in 6%, and 13% had documented suction curettage. The rate of suction curettage decreased with site experience, from 17% during the first 20 procedures to 10% at sites that had performed more than 50. Sites that had previous experience with either methotrexate or mifepristone medical abortion had a rate of 9% after they had performed at least 50 procedures. Exit interviews with 755 of the 902 women having abortions in the first year inquired about the level of comfort with the abortion and its overall acceptability. Women's satisfaction with the side effects did not directly correlate with site experience. Overall satisfaction with the abortion experience was related to whether the women had complete medical abortions or suction curettage.

Early medical abortion with methotrexate. Outcome and satisfaction among women aged 15-20 years

Background: We investigated the outcomes of women under age 21 who participated in a multi-center case series of early medical abortion using methotrexate and misoprostol.Methods: We enrolled 1973 women in a case series for medical abortion in the first seven weeks of pregnancy, using a standardized protocol and consent for methotrexate (50 mg/m(2)) and misoprostol (800 mg vaginally, repeated as needed).For this study, women who presented for abortion prior to their 21(st) birthday were compared to older women. Outcomes of abortion were classified as complete medical abortion (CMA) and suction curettage (SC). Secondary outcomes included symptoms. We did an exit interview assessing patient satisfaction during the first year of the study, and have exit interview data for approximately half of the women enrolled.We assessed the relationship of age and outcomes first by bivariate analysis using SAS (SAS Institute, Inc., Cary, NC). A multiple logistic regression model was constructed using age, gestational age, and measures of parity.Results: There were 219 women who were under 21 (18 under the age of 18). Compared to older women, adolescents presented for abortion at the same gestational ages. Compared to older women, younger women were less likely to have finished college (2.8% vs. 38. 7%), and were less likely to have had previous pregnancies (45.4% vs 76.6%) and live births (20.2% vs. 51.3%)The distribution of symptoms during abortion, such as bleeding and cramping, was the same across age groups; the only symptom which was more frequently found in younger women was headache.Overall younger women had a slightly higher rate of CMA as older women (90.2% vs. 86.5%). However, the multiple regression (MR) model did not show an effect of the woman's age on CMA. MR demonstrated an adverse effect of prior live birth, and advancing gestational age on rates of CMA; younger women were less likely to have had prior live births.Younger women were just as likely to report overall satisfaction (86.7% vs. 84.6%) with the abortion procedure and other questions of satisfaction, but were less likely to agree that the bleeding and cramping were acceptable. Conclusions: Younger women having medical abortion with methotrexate and misoprostol have similar outcomes and satisfaction levels as do older women. There is no reason to discourage adolescents who seek abortion from using a medical technique.

Low-dose oral contraceptives and bone mineral density: an evidence-based analysis.

We reviewed studies of the association of oral contraceptive (OC) use and bone mineral density (BMD). We limited the review to studies of women using low-dose oral contraceptives and that measured BMD by bone densitometry. A total of 13 studies met the inclusion criteria. Nine of these showed a positive effect of OC use on BMD, and four did not show an association. However, none of the studies showed a decrease in BMD with OC use. We classified the level of evidence from each study according to the guidelines of the US Preventive Services Task Force. The level of evidence supporting a positive association between OC use and increased BMD is II-1. There is fair evidence (Category B) to support the position that OC use has a favorable effect on BMD. We made suggestions for a study design that could yield Level I evidence.

PIP: The authors reviewed studies of the association of oral contraceptive (OC) use and bone mineral density (BMD). They limited the review to studies of women using low-dose OCs and that measured BMD by bone densitometry. A total of 13 studies met the inclusion criteria; 9 of these showed a positive effect of OC use on BMD, and 4 did not show an association. However, none of the studies showed a decrease in BMD with OC use. They classified the level of evidence from each study according to the guidelines of the US Preventive Services Task Force. There is evidence supporting a positive association between OC use and increased BMD. There is fair evidence to support the position that OC use has a favorable effect on BMD. The authors made suggestions for a study design that could yield level I evidence.

Managing clinical complexities of long-term contraception.

The 3 methods of long-term contraception (LTC) approved for use in the US are intrauterine devices (IUDs), levonorgestrel subdermal implants, and sustained-release medroxyprogesterone acetate injections. Women who use reversible LTC are likely to receive care from clinicians who did not prescribe the method of contraception originally. Fortunately, most concerns arising from the use of reversible LTC can be managed by clinicians regardless of their specialty. Problems associated with an IUD can include a missing string, partial expulsion of the device, change in menstrual pattern, vaginal discharge, or infection. Headaches, weight gain, dermatologic problems, changes in hair growth, and irregularities in menses are among the problems that clinicians may confront while caring for a woman who has had subdermal hormone implants or has been taking depot injections. Besides the problems caused by or complicating specific methods of LTC, a woman may seek clinical care for a variety of general concerns. These include a desire to terminate LTC in order to become pregnant, and physical changes that are suspected to indicate pregnancy or contraceptive failure. In addition, general health conditions such as concurrent medications, hypertension, and endocrine disorders may need special consideration in a woman using LTC. There are few medical indications for discontinuing or changing LTC, even when intercurrent illnesses arise.

Reflex human papillomavirus deoxyribonucleic acid testing in women with abnormal Papanicolaou smears.

OBJECTIVE: The study examined interrelationships between sensitivity and specificity of "reflex human papillomavirus deoxyribonucleic acid testing" from liquid-based cervical cytologic specimens by means of receiver operator characteristics curves. STUDY DESIGN: A cohort study was performed on 265 women evaluated by colposcopy because of atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion found on Papanicolaou smear. RESULTS: At a positive threshold of 0.2 pg/ml (1000 copies of human papillomavirus per test), human papillomavirus deoxyribonucleic acid testing detected 86% of women with cervical intraepithelial neoplasia and 93% of women with high-grade cervical intraepithelial neoplasia with a specificity of 30%. Decreasing the sensitivity of the human papillomavirus test to 1 pg/ml (5000 copies of human papillomavirus per test) improved the specificity of a positive result to 44% but decreased the clinical sensitivity to 78% for cervical intraepithelial neoplasia grade 2 or 3. Relationships between sensitivity and specificity were influenced by patient age and referral diagnosis. For example, limiting the analysis to only women with a referral for atypical squamous cells of undetermined significance found on Papanicolaou smear and a positive human papillomavirus test threshold of 0.5 pg/ml produced a sensitivity of 90% for cervical intraepithelial neoplasia grade 2 or 3 and a test specificity of 55%. CONCLUSION: Human papillomavirus deoxyribonucleic acid testing of residual cellular material from liquid cytologic specimens appears to be more appropriate for older women (>30 years old) and women with atypical squamous cells of undetermined significance, as opposed to low-grade squamous intraepithelial lesion, on their Papanicolaou smears.

Single dose methotrexate therapy: application to interstitial ectopic pregnancy.

A woman with a small (6-mm gestational sac) interstitial pregnancy had complete resolution after medical therapy alone. A single cycle of methotrexate 50 mg/m2 was used as outpatient treatment without any operative procedure either for diagnosis or intervention. The guidelines that have evolved for selection of women for single dose methotrexate treatment for both intrauterine and tubal ectopic pregnancies may be applicable to interstitial ectopic pregnancy as well. A suggested framework for treatment decisions is presented.

Triage of women with ASCUS and LSIL on Pap smear reports: management by repeat Pap smear, HPV DNA testing, or colposcopy?

BACKGROUND: The purpose of this study was to determine the efficacy of a repeat Papanicolaou (Pap) smear and the Hybrid Capture tube-based (HCT) HPV DNA test for detecting cervical intraepithelial neoplasia (CIN) grade 2 or 3 in women with recent atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesion (LSIL) Pap smear reports. METHODS: Women with a recent Pap smear report of ASCUS (n = 169) or LSIL (n = 110) had a repeat Pap smear, sampling of the cervix for HCT HPV DNA assay and a colposcopy examination. Data were evaluated using three different triage thresholds for colposcopy examination: a repeat Pap smear of persistent ASCUS or more severe dysplasia, a finding of persistent LSIL or more severe dysplasia, and a carcinogenic HPV test result. RESULTS: The sensitivity, specificity, and positive and negative predictive values for detecting CIN 2/3 were 70%, 45%, 7%, and 96% for a repeat Pap smear using an ASCUS-positive threshold and 20%, 86%, 8%, and 94% for a repeat Pap smear using an LSIL-positive threshold, respectively, when women with an initial ASCUS Pap smear were considered. HPV testing for carcinogenic viruses alone or in combination with a repeat Pap smear (using ASCUS as a positive threshold) yielded results of 50%, 67%, 9%, and 96%, respectively, and 70%, 37%, 7%, and 95%, respectively, for detecting CIN 2/3. In women with an initial LSIL Pap smear, respective values for detecting CIN 2/3 by a repeat Pap smear with an ASCUS threshold were 92%, 26%, 14%, and 96%, and for an LSIL threshold 23%, 64%, 8%, and 86%, respectively. Hybrid Capture HPV testing alone or in combination with a repeat Pap smear yielded 69%, 43%, 14%, and 91%, respectively, and 100%, 21%, 14%, and 100%, respectively. CONCLUSIONS: A Pap smear triage threshold restricted to LSIL or more severe dysplasia for women with prior ASCUS or LSIL Pap smear results was clearly ineffective for detecting high-grade cervical precancerous lesions. In contrast, when the repeat Pap smear triage threshold was expanded to include persistent ASCUS as abnormal, 83% of the women with CIN 2/3 were detected. Detection of carcinogenic HPV DNA using the HCT test was almost as sensitive for detecting CIN 2/3 as a solitary repeat Pap smear using an ASCUS or more severe positive threshold. Combining the HPV test with a repeat Pap smear did not significantly improve the sensitivity of cytology for detecting high-grade CIN. This study suggests that women with ASCUS and particularly LSIL Pap smears should be referred for a colposcopy examination until better triage methods become available.

Overcoming unsatisfactory colposcopy. Use of osmotic dilators.

OBJECTIVE: To evaluate the usefulness of osmotic dilators as an alternative to diagnostic cone biopsy. STUDY DESIGN: Women who had an unsatisfactory colposcopic examination were offered repeat examination after use of osmotic dilators as part of an interventional, nonrandomized study. The physician selected the type, size and duration of use of the dilator. RESULTS: Twenty-nine of 32 women (91%) underwent a satisfactory repeat examination. Diagnostic cone biopsy was avoided in all women. Twenty-one women did not require further treatment, and four women had the lesion removed by the colposcopically directed biopsy. Six women underwent electrosurgery, and one woman underwent cryotherapy. CONCLUSION: The use of osmotic dilators can decrease the need for diagnostic cone biopsy.

Pain during early abortion.

OBJECTIVE: To determine which factors predict pain perception in women undergoing first-trimester abortion under local anesthesia. STUDY DESIGN: Women undergoing first-trimester abortion with local anesthesia were asked about their perception of pain during the procedure and at the time of discharge from the recovery room. They were also asked to compare the amount of pain experienced to their expected amount of pain. Additional data were abstracted from the patient record. RESULTS: During the study period, 1,055 women had abortions and had records suitable for analysis. Factors that were not found to be related to pain were the operating physician, maximal amount of cervical dilatation, size of the suction cannula, prior abortion and prior pelvic examination. Gestational age did not show a consistent relationship to pain, although there was a suggestion that pain perception increases at the highest gestational ages. Longer procedures and procedures following the use of osmotic dilators tended to have higher pain scores. Prior abdominal delivery did not have a significant relationship to pain score, but prior vaginal delivery correlated with decreased pain by any method of analysis. The difference in pain perception between women with and those without prior vaginal birth was most striking at the earliest gestational ages. CONCLUSION: Prior vaginal delivery was the most consistent predictor of decreased pain perception during first-trimester abortion. Future studies on discomfort during abortion should include gestational age, patient age and the route of prior deliveries.

Clinical significance of methohexital, meperidine, and diazepam in breast milk.

Concentrations in breast milk of medications used during general anesthesia were measured to determine whether interruption of breast-feeding was indicated. Breast milk and maternal blood samples were obtained from nine women undergoing tubal sterilization under general anesthesia. Concentrations of methohexital, meperidine, diazepam, and nordiazepam were determined for each sample by gas chromatography. Methohexital levels declined rapidly after the first hour and were undetectable at 24 hours. Meperidine was present in both milk and blood during the recovery period but not at 24 hours. Infant-exposure indices for methohexital were less than 1% and ranged from 1.2% to 3.5% for meperidine. The maximum doses of methohexital and meperidine to an infant, in a 100 mL feeding 1 hour after induction of anesthesia were estimated to be 0.04 mg and 0.06 mg, respectively. Diazepam and nordiazepam were not detectable in any sample of milk or blood. The maximum possible infant-exposure index for diazepam would be 3%. The amounts of methohexital, meperidine and diazepam excreted into breast milk do not warrant interruption of breast-feeding.

Prolonged retention of laminaria fragments: an unusual complication of laminaria usage.

A single laminaria japonica was placed the day before an abortion requested by a 32-year-old nulliparous woman. On the day of the procedure, the laminaria was found to be tightly wedged in the cervix, and attempts at removal resulted in pushing the laminaria into the uterine cavity. The abortion was completed, and 3 days later, after placement of additional osmotic dilators, the intrauterine laminaria was crushed and removed. Fifteen months later, a small fragment of laminaria passed spontaneously. Hysteroscopy was performed, and approximately 30 fragments of laminaria were removed.

Regional differences in calcium-release channels from heart.

The heart is a heterogeneous tissue composed of several cell types tailored for specialized functions. We found that intracellular channels also exhibit regional specialization. In cardiac and skeletal muscle these channels are called the calcium-release channel and are identified by activation with either calcium or caffeine and inhibition by the hexavalent cation ruthenium red. The calcium-release channel of the sarcoplasmic reticulum from the interventricular septum has a smaller conductance (31 pS vs. 100 pS) and has longer open and closed times when compared with the channel from left-ventricular free wall. An additional calcium-permeable channel with an even smaller conductance (17 pS) was found in the septum, and this channel is similar to the inositol 1,4,5-trisphosphate-gated channel from smooth muscle and different from the calcium-release channel (ryanodine receptor) from skeletal and cardiac muscle. The inositol 1,4,5-trisphosphate-activated channel may be derived from specialized conducting tissue that is relatively abundant in the septum, whereas the other calcium-release channels may be derived from regionally specialized myocardial cells in the septum and free wall.

Biphasic effects of doxorubicin on the calcium release channel from sarcoplasmic reticulum of cardiac muscle.

To define the mechanism of doxorubicin cardiotoxicity, the effects of doxorubicin and caffeine were examined on calcium release channels from cardiac sarcoplasmic reticulum. We found that calcium release from cardiac sarcoplasmic reticulum vesicles was induced by both compounds. When sarcoplasmic reticulum vesicles were incorporated into planar lipid bilayers, calcium-permeable channels were observed. Addition of caffeine (2.5-10 mM) increased channel open probability from less than 0.1% to 40%, and this effect persisted for a mean of 44 minutes. In contrast, doxorubicin (2.5-10 microM) had a biphasic effect; initially, doxorubicin activated the channel, whereas after a mean of 8 minutes, the channel became irreversibly inhibited. Although the degree of channel activation by doxorubicin was concentration dependent, the time needed to inactivate the channel was concentration independent. Pretreatment with dithiothreitol (0.2 mM) prevented doxorubicin-induced channel inactivation, and channel activity persisted for an average of 58 minutes. Dithiothreitol alone did not alter channel open probability. Our results support the hypotheses that 1) the integrity of sulfhydryl groups is important for some aspects of calcium release channel function and 2) activation and inactivation of the channel are separable processes. The biphasic effect of doxorubicin on channel function may also correspond to the clinically observed adverse effects of doxorubicin, a widely used chemotherapeutic agent that, after prolonged usage, causes a dilated cardiomyopathy.