D R Mishell

University of Pittsburgh, Pittsburgh, PA, United States

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Publications (252)941.81 Total impact

  • Bryna Harwood, D R Mishell
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    ABSTRACT: Contraceptive vaginal rings (CVRs) contain sex steroids that diffuse through a plastic polymer ring at a constant rate and are absorbed directly through the vaginal epithelium into the systemic circulation. This delivery system provides many advantages over oral contraceptives (OCs), including avoidance of the first-pass effect through the liver, constant serum steroid levels, longer duration of use, and greater bioavailability of the hormones. CVRs containing progestin only are designed for continuous use for 3 to 6 months. Those containing progesterone alone are indicated for use in women who are breastfeeding. Large clinical trials of progestin-containing CVRs demonstrated good efficacy and safety of the CVR, with continuation rates similar to that of OCs. CVRs containing a combination of estrogen and progestin are designed to be used for 1 to 12 months in a cyclic manner similar to OCs, with withdrawal bleeding in the fourth week of each cycle. In clinical trials these CVRs have typical use efficacies similar to OCs, with an acceptable pattern of bleeding.
    Seminars in Reproductive Medicine 01/2002; 19(4):381-90. · 3.00 Impact Factor
  • Fertility and Sterility 01/2002; 77. · 4.30 Impact Factor
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    ABSTRACT: Serum levonorgestrel concentrations were assayed in a multicenter, 7-year study of 199 users of Jadelle rod implants. We examined drug levels, patterns of changes, factors affecting drug levels, and concentrations at which pregnancies occurred. Mean levonorgestrel concentrations declined from 435 pg/mL at 1 month of use to 64% of that value (280 pg/mL) at the end of 3 years. Between the end of the third and fifth years neither mean nor median serum levels varied markedly. At 5 years the mean concentration was again 64% of the first month's mean. Declining levels were observed thereafter through the end of 7 years when the mean, 224 pg/mL, was 52% of the 1-month value. Last measured drug concentrations of women who became pregnant during Jadelle use had mean and median values of 152 and 144 pg/mL, respectively, and a maximum value of 180 pg/mL. Analyses indicated ponderal index, body weight, duration of use, and a single clinical center were the most important variables affecting measured levonorgestrel levels. Approximately one-third of assays in the sixth and seventh years were found to be below 180 pg/mL, suggesting that Jadelle levonorgestrel implants would not maintain sufficiently high levels of effectiveness against pregnancy after 5 years and that heavier women would then be at greater risk of pregnancy.
    Contraception 08/2001; 64(1):43-9. · 2.93 Impact Factor
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    ABSTRACT: Contraceptive vaginal rings delivering various progestins alone or in combination with estrogen have been previously studied, showing adequate steroid vaginal absorption and acceptability by the users. Nestorone progestin (NES) is a potent 19-nor-progesterone derivative, inactive by the oral route, but an excellent option for vaginal delivery. The purpose of this study was to evaluate ovarian function during 6 months of continuous use of progestin-only vaginal rings delivering 3 different doses of NES: 50, 75, and 100 microg per day. Blood samples were taken twice a week for 5 consecutive weeks during a control cycle and on months 1, 3 and 6 of use, for the measurement of estradiol (E2), progesterone (P), and NES. A total of 87 volunteers randomly received each of the 3 doses. After an initial peak, NES serum levels remained fairly constant throughout the duration of the study at about 125, 200 and 250 pmol/L, respectively, decreasing slightly with time. Luteal activity occurred very rarely (1.2-2.6% of sampling periods) with no apparent difference between doses. Low E2 levels (< or =100 pmol/L) in all samples of a run were rare (5%) and only with the high dose ring (100 microg/day). E2 remained within normal levels (101-1500 pmol/L) in most of the segments studied. We conclude that the 50 and 75 microg/day NES rings provide adequate ovulation inhibition without hypoestrogenism, while the 100 microg/day ring may deliver an unnecessarily high dose.
    Contraception 06/2001; 63(5):257-61. · 2.93 Impact Factor
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    ABSTRACT: To compare the rates of ovulation and pregnancy after tamoxifen citrate (TMX) or clomiphene citrate (CC) among anovulatory women with infertility. Prospective randomized trial. Infertility clinic in a university teaching hospital. Eighty-six anovulatory women under 40 years of age undergoing ovulation induction. The women were assigned randomly to receive either TMX or CC on cycle days 5-9. Rates of ovulation and pregnancy for the two treatment modalities. The overall rate of ovulation in the TMX group was 50 of 113 (44.2%) and in the CC group, 41 of 91 (45.1%). There were 10 pregnancies in the TMX group and 6 pregnancies in the CC group. The cycle fecundity per ovulatory cycle was 20.0% in the TMX group and 14.6% in the CC group. The overall rate of ovulation and pregnancy were similar with TMX and CC. TMX is a suitable alternative agent to CC in the management of anovulatory infertility.
    Fertility and Sterility 06/2001; 75(5):1024-6. · 4.30 Impact Factor
  • Source
    Contraception 06/2001; 63(5):255-6. · 2.93 Impact Factor
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    ABSTRACT: The objectives of this prospective non-concurrent cohort study were to confirm the efficacy of vaginal misoprostol for early pregnancy termination and to determine whether the incidence of side effects is lower with prophylactic loperamide and acetaminophen. Two-hundred women with an intrauterine pregnancy < or =56 days gestational age seeking medical pregnancy termination in an ambulatory research clinic were enrolled in the study. One-hundred participants (group 1) ingested 4 mg of loperamide and 500 mg of acetaminophen before the vaginal placement of 800 mirog of misoprostol moistened with 2 mL of saline. If abortion had not occurred, the same regimen was repeated every 24 h (maximum three doses). One-hundred participants (group 2) from the same clinic who previously underwent the same misoprostol regimen without prophylactic medication served as a control group for comparison with respect to abortion success and the incidence of side effects. The rate of successful abortion was not statistically significantly different between the two groups (group 1 93%, group 2 89%). The incidence of opiate analgesic use was significantly less in group 1 (4%) compared with group 2 (16%) (OR 0.22, 95% CI 0.06-0.73, p = 0.01). There was a significantly lower incidence of diarrhea in group 1 (23%) compared with group 2 (44%) (OR 0.38, 95% CI 0.20-0.73, p = 0.003). There was no difference in the incidence of fever/chills or the incidence of emesis between the two groups. Vaginal misoprostol is effective for termination of pregnancy < or = 56 days and the incidence of diarrhea and the use of opiate analgesia is significantly reduced with prophylactic loperamide and acetaminophen.
    Contraception 04/2001; 63(4):217-21. · 2.93 Impact Factor
  • J K Jain, D R Mishell
    Human Reproduction 03/2001; 16(2):393. · 4.59 Impact Factor
  • Source
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    ABSTRACT: We sought to determine the safety and acceptability of vaginal gel formulation PC-503 among low risk, abstinent women. The active ingredient was 2% pharmaceutical grade lambda carrageenan, a sulphated polymer that is generally recognised as safe by the US Food and Drug Administration. 35 women in five sites applied 5 ml of the PC-503 gel vaginally once a day for 7 days while abstaining from sexual intercourse. Visual vaginal examinations were performed on days 1, 4, and 8. STI testing and vaginal pool Gram stain preparations were done on days 1 and 8. Participants were asked about product acceptability. 34 of the 35 women enrolled completed 7 days' use. Following product use, five reported mild symptoms including "bladder fullness," "genital warmth," or discomfort, and lower abdominal pain, and one had moderate pale yellow cervical discharge. Using the Nugent criteria, three women had bacterial vaginosis (BV) before and after use; three had BV before but not after, and two had BV after but not before. Most of the women found PC-503 to be pleasant or neutral in feel and smell and considered extra lubrication to be an advantage; however, one third found it to be messy. Vaginal use of PC-503 gel did not cause significant adverse effects in a small number of low risk, sexually abstinent women. Further testing in larger numbers of sexually active women is planned. A smaller volume of gel may be more acceptable to some women.
    Sexually Transmitted Infections 01/2001; 76(6):480-3. · 3.08 Impact Factor
  • B Harwood, D R Mishell
    Human Reproduction 01/2001; 15(12):2686-8. · 4.59 Impact Factor
  • D A Wing, M J Fassett, D R Mishell
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    ABSTRACT: To compare the effect of mifepristone with placebo on cervical ripening before labor induction in prolonged pregnancies. One hundred eighty women with pregnancies beyond 41 weeks and undilated, uneffaced cervices were assigned randomly to receive mifepristone 200 mg or placebo and observed for 24 hours. We then gave intravaginal misoprostol 25 microg every 4 hours or intravenous oxytocin. We expected 60% of placebo-treated and 80% of mifepristone-treated women to deliver vaginally within 48 hours. Among 180 subjects, 97 received mifepristone and 83 received placebo. The mean interval (+/- standard deviation [SD]) from start of induction to delivery was 2209 +/- 698 minutes for mifepristone-treated subjects and 2671 +/- 884 minutes for placebo-treated subjects (P <.001, log-transformed data). Twelve (13. 6%) mifepristone-treated women and seven (10.8%) placebo-treated women delivered vaginally on day 1 (P =.60). After 24 hours, the median Bishop score for both groups was 3 (0-11) (P =.51). One hundred thirty-one subjects required misoprostol, 65 (67.0%) were mifepristone-treated women, and 66 (79.5%) placebo-treated women (P =.06). The median (range) oxytocin dose was 871.5 (0-22,174) mU for mifepristone-treated women and 2021.0 (0-24,750) mU for placebo-treated women (P =.02). Seventy-seven (87.5%) mifepristone-treated women and 46 (70.8%) placebo-treated women delivered vaginally 48 hours after the start of treatment (P =.01). There were nine cesareans in the mifepristone group and 18 in the placebo group (P =.02). More nonreassuring fetal heart rate patterns and uterine contractile abnormalities occurred in mifepristone-treated subjects. There were no statistically significant differences in neonatal outcomes between groups. Mifepristone had a modest effect on cervical ripening when given 24 hours before labor induction, appearing to reduce the need for misoprostol and oxytocin compared with placebo.
    Obstetrics and Gynecology 11/2000; 96(4):543-8. · 4.37 Impact Factor
  • D R Mishell
    The Journal of reproductive medicine 11/2000; 45(10 Suppl):867-71. · 0.58 Impact Factor
  • Fertility and Sterility 09/2000; 74(3). · 4.30 Impact Factor
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    ABSTRACT: Soft tubing Norplant(R) contraceptive implants were studied in 1210 women for 7 years to measure the duration of effectiveness and the magnitude of the pregnancy rates over that time. Mean age at enrollment was 27.4 years. Of the enrollees, 42% were US residents. One-sixth (16.1%) weighed >/=70 kg at the time of implant placement. At the end of 5 years, the cumulative pregnancy rate was 1.1/100; at the end of 7 years, it was 1.9/100. No pregnancies occurred to any of the 400 women who enrolled in the study at age >/=30 years and who weighed <100 kg. Among women aged 18-33 years, the 7-year Norplant pregnancy rates are comparable to the median pregnancy rates of tubal sterilization methods for women of the same age and duration of use. For women aged >/=34 years, without regard to weight at admission, the 7-year effectiveness of soft tubing Norplant equals or surpasses that of tubal sterilization. For continuing implant users, annual pregnancy rates <1.0/100 in years 6 and 7, together with low cumulative pregnancy rates, testify that Norplant capsule implants remain highly effective for 7 years.
    Contraception 03/2000; 61(3):187-94. · 2.93 Impact Factor
  • Contraception 03/2000; 61(3). · 2.93 Impact Factor
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    ABSTRACT: Vaginal inspections using colposcopy before insertion of contraceptive vaginal rings and at 2-month intervals during ring use were conducted on 169 users of four different formulations. The rings studied released Nestorone alone (50, 75, 100 g daily over 6 months); ethinyl estradiol: Nestorone (30:100 and 15:150 g daily over 6 months); ethinylestradiol:norethindrone acetate (20:1000 and 15:1000 g daily over 4 months); and ethinyl estradiol:norethindrone acetate (20:1000 g daily over 12 months). A total of 88 altered or atypical conditions of the vaginal surface appearance were recorded in 507 inspections (17.4% of inspections). Many of these atypical appearances were quite subtle. The incidence was significantly higher (p <0.01) than in the single pretreatment examinations (11 in 158 inspections; 7.0%), but closely matched that of a "control group" of sexually active women who were the subject of an earlier study by the same investigators. In that study, the incidence was 18% (57 atypical conditions in 317 inspections). In all, 83% of atypical conditions identified in the vagina during ring use had disappeared by the next scheduled colposcopy despite continued ring use. Findings of potential significance were conservatively defined as all ulcerations, those abrasions and ecchymoses that were >0.5 cm in any direction, and fields of five or more petechiae. Findings fitting those criteria comprised 30% of atypical conditions in ring users, 33% in the control group, and 27% pretreatment. The corresponding incidence as a percentage of inspections were 5.3%, 6. 0%, and 2.5% in the ring users, control groups, and pretreatment groups, respectively. These differences were not statistically significant. The findings suggest that the vaginal rings included in the studies contributed little, if at all, to clinically significant lesions or to total lesion incidence. Further definition would require a larger and longer-term study with matched controls.
    Contraception 03/2000; 61(2):131-8. · 2.93 Impact Factor
  • D R Mishell
    Contraception 02/2000; 61(1):1. · 2.93 Impact Factor
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    ABSTRACT: Several progestin-only long acting contraceptives are currently available in the form of implants or injectables. Vaginal rings are another contraceptive option in the final stages of development. These steroid-containing polymer rings are placed in the vagina, providing relatively constant drug release, thus allowing for lower effective doses. Vaginal rings have the advantage of being user-controlled and non-provider dependent, and their use is non-coital related. The first clinical study with medroxyprogesterone acetate vaginal rings was published in 1970. Since then numerous clinical trials testing different steroids and doses have followed. A large Phase III multicenter clinical trial with a levonorgestrel ring, releasing 20 microg/day, was coordinated and sponsored by WHO. The cumulative one-year pregnancy rate was 4. 5%. The principal reasons for discontinuation were menstrual disturbances (17.2%), followed by frequent expulsion of the ring (7. 1%), and vaginal symptoms (6.0%). The finding of erythematous lesions in the vagina in some women has led to the development of a more flexible device. Collaboration with industry should facilitate the manufacture of a redesigned levonorgestrel ring with a higher release rate. The Population Council is also developing a vaginal ring containing Nestorone for 6 months of continuous use. Ovulation inhibition was achieved in over 97% of the segments studied, with rings releasing either 50, 75, or 100 microg/day. No pregnancies occurred in women using the low-dose ring, while one pregnancy each occurred in the intermediate- and high-dose ring groups for a 6-month cumulative pregnancy rate of 0.0, 1.9, and 2.1%. Bleeding irregularities were common. Nestorone is orally inactive; therefore this ring is also excellent for use in lactating women.
    Steroids 01/2000; 65(10-11):687-91. · 2.72 Impact Factor
  • John K. Jain, Karen R. Meckstroth, Daniel R. Mishell
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    ABSTRACT: The purpose of this study was to compare the abortifacient effect of intravaginally administered moistened misoprostol tablets with that of the combination regimen of mifepristone and oral misoprostol. One hundred women at </=56 days' gestation received 800 microg misoprostol intravaginally in the form of sodium chloride solution-moistened tablets. The dose was repeated 24 hours later if a gestational sac persisted on ultrasonographic examination. These 100 subjects (group 1) were then matched with 100 subjects who had received 600 mg mifepristone followed by 400 microg misoprostol orally as part of a large multicenter American trial (group 2). Subjects were monitored for abortion success, adverse side effects, and bleeding characteristics. Abortion failure was defined as persistence of an intrauterine sac or the need to perform a surgical evacuation of the uterus for hemorrhage, for incomplete abortion, or at the subject's request. In 88 of the 100 women in group 1 and 94 of the 100 women in group 2, abortion occurred and a surgical procedure was not required. Abortion rates were not influenced by gestational age in either group. Prostaglandin-related side effects of fever and chills, vomiting, diarrhea, and uterine pain were all significantly higher in group 1. Excessive uterine bleeding was uncommon in both groups, and no subjects received blood transfusions. The abortion rate with intravaginally administered moistened misoprostol tablets is similar to that with the combination of mifepristone and oral misoprostol. However, intravaginal administration of misoprostol is associated with significantly more prostaglandin-related side effects.
    American Journal of Obstetrics and Gynecology 12/1999; 181(6):1386-91. · 3.97 Impact Factor
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    ABSTRACT: A total of 107 sexually active women, aged 18-35 years, was recruited through family planning clinics in four centres in different countries. Each woman underwent two or three gentle but thorough and systematic vaginal inspections using a consistent technique with colposcopic magnification over a 4-6 month period to look for changes in vaginal and cervical appearance which might be related to sexual intercourse, tampon use, contraceptive method used, cigarette smoking or other environmental factors. Obvious changes in appearance were photographed at x10 magnification. These 'appearances' or 'conditions' were classified according to a modification of the recommendations of a workshop sponsored by the World Health Organization, the Population Council and the Conrad Program. Most of these alterations in the appearance of the vaginal epithelium were judged to be of such minor clinical importance that they have been termed 'conditions' or 'changes in appearance' rather than 'lesions'. In all, 56 'conditions' or 'appearances' were noted in 314 inspections, the commonest being petechiae (53.6%). Potentially significant conditions justifying the term 'lesions' (three microulcerations, two ecchymoses, five abrasions and one mucosal tear; 3.5% of inspections) usually healed spontaneously and disappeared rapidly. The incidence of these conditions was highest when the inspections followed intercourse in the previous 24 h (25.2 versus 14.2%; P < 0.0008), or tampon use (32.4 versus 15.9%; P < 0. 0001). These processes may be regarded as a reflection of regular minor trauma to the vaginal epithelium.
    Human Reproduction 09/1999; 14(8):1974-8. · 4.59 Impact Factor

Publication Stats

4k Citations
941.81 Total Impact Points

Institutions

  • 2002
    • University of Pittsburgh
      • Department of Obstetrics, Gynecology and Reproductive Sciences
      Pittsburgh, PA, United States
  • 1972–2001
    • University of California, Los Angeles
      • Department of Obstetrics and Gynecology
      Los Angeles, California, United States
  • 2000
    • Keck School of Medicine USC
      Los Angeles, California, United States
    • University of Sydney
      • Discipline in Obstetrics and Gynaecology
      Sydney, New South Wales, Australia
  • 1975–2000
    • University of Southern California
      • Department of Obstetrics and Gynecology
      Los Angeles, CA, United States
  • 1989–1990
    • Population Council
      • Center for Biomedical Research
      New York City, NY, United States
  • 1968
    • Harbor-UCLA Medical Center
      Torrance, California, United States