Metabolic parameter, bleeding, and weight changes in U.S. women using progestin only contraceptives.

Our objective was to determine the effect of progestin-only contraceptives on metabolic parameters, bleeding patterns, and weight changes during the first year of use. Seventy-one women (> 95% Caucasian), who were advised regarding contraception alternatives, self-selected levonorgestrel implants (n = 44), depo-medroxyprogesterone acetate (n = 22), or oral norethindrone (n = 5). One year later, 11 levonorgestrel implant and five depomedroxyprogesterone acetate patients were randomly selected to compare (pre- and post-progestin use) levels of cholesterol, triglycerides, low density lipoprotein (LDL), high density lipoprotein (HDL), very low density lipoprotein (VLDL), apolipoproteins A-1 and B-100, bilirubin, and sex hormone binding globulin. Monthly bleeding and spotting records were kept in each group. Body weights were also monitored in each group. No statistically significant differences in metabolic parameters were found between pre- and post-progestin use in the levonorgestrel implant and depo-medroxyprogesterone acetate groups. Continued bleeding patterns were more prominent in the levonorgestrel implant and oral norethindrone groups than in patients receiving depo-medroxyprogesterone acetate. No significant weight gain was detected in any group. No changes in metabolic parameters or weight were noted over the one year of use of levonorgestrel implants or depo-medroxyprogesterone acetate. Depo-medroxyprogesterone acetate had the highest incidence of amenorrhea.

PIP: During March 1991-April 1992, health workers recruited 71 women aged 16-43 (98% Caucasian) attending the University of Utah Obstetrics and Gynecology Clinic for a clinical study examining metabolic parameters, menstruation disorders, and changes in weight after 12 months of use of a progestin-only contraceptive. The progestin-only contraceptives (number of women using each) included Norplant contraceptive implants (44), Depo-Provera (22), and a mini-pill (norethindrone) (5). Metabolic parameters were total cholesterol, triglycerides, high density lipoprotein (HDL), low density lipoprotein (LDL), very low density lipoprotein (VLDL), sex hormone binding globulin, apolipoprotein A-1, apolipoprotein B-100, and total and direct bilirubin. The only groups investigated for metabolic parameters were Norplant users and Depo-Provera users. Metabolic parameters did not change significantly after progestin use. No group experienced significant weight gain. However, one woman gained more than 60 pounds in the Norplant group and one woman gained more than 40 pounds in the Depo-Provera group. Depo-Provera users had significantly fewer total days of blood loss than Norplant users during months 5-12 (p 0.02) and mini-pill users during months 6-10 (p 0.04). Mini-pill users and Norplant users had similar bleeding patterns, except during months 11-12, when Norplant users had more bleeding than mini-pill users (e.g., month 12, 9 vs. 0 days). The total days of blood loss was 8.7 for Norplant users, 3.5 for Depo-Provera users, and 10.2 for mini-pill users. Less than 10% of Norplant users and mini-pill users experienced amenorrhea, while amenorrhea increased after 120 days in Depo-Provera users (p 0.001). After 1 year, the Norplant and mini-pill groups had more excessive prolonged (10 days) bleeding than the Depo-Provera group (29% and 50%, respectively, vs. 11%).

Comparison of the ClearView uterine manipulator with the Cohen cannula in laparoscopy.

The ClearView Uterine Manipulator was compared with the Cohen acorn-tipped cannula for efficacy and safety in patients undergoing laparoscopy at the University of Utah Medical Center. Fifty consecutive patients were randomized by computer to have either the ClearView instrument or the Cohen cannula used as a uterine manipulator (25 patients each). The ClearView manipulator was statistically superior to the Cohen cannula for range of motion in the anterior and posterior sagittal plane (p <0.0001). The Cohen cannula was consistently inserted in less time (p <0.02). There was no statistically significant difference between the instruments in ease of uterine manipulation, ease of dye instillation, percentage of dye leakage from the cervix, overall ease of use, ease of device insertion, and ease of device removal. Two cervical perforations occurred during cervical dilatation in the ClearView manipulator group in patients with cervical stenosis requiring dilatation with metal dilators (os <2 mm). No patients in the Cohen cannula group had cervical stenosis. In that group two cervical lacerations occurred requiring suture ligation. The ClearView instrument provides a greater range of motion, does not require an assistant to maintain uterine position, and allows manipulation without a cervical tenaculum. Its insertion occasionally (36%) required tenaculum placement, uterine sounding, and cervical dilatation, increasing the time of insertion compared with placement of the Cohen cannula. In patients with cervical stenosis, use of a uterine sound and cervical dilatation increase the risk of perforation.

Ovulation induction with gonadotropins and intrauterine insemination compared with in vitro fertilization and no therapy: a prospective, nonrandomized, cohort study and meta-analysis.

OBJECTIVES: To determine whether one to four cycles of ovulation induction with hMG and IUI or one cycle of IVF results in the highest pregnancy rate and is least expensive and whether published pregnancy rates for one to four cycles of hMG and IUI results in a higher pregnancy rate than rates for one cycle of IVF, zygote intrafallopian transfer (ZIFT), or GIFT. DESIGN: Prospective, nonrandomized, cohort study. Patients were excluded who were infertile for < 18 months, had a significant male factor, had greater than mild endometriosis, or had bilateral nonpatency of the fallopian tubes. Cohort groups included 47 hMG and IUI patients (99 cycles), 19 IVF patients (19 cycles), and 21 patients (210 cycles) receiving no treatment. A meta-analysis on accumulated hMG and IUI data using similar entry criteria was also performed. Theoretical calculations were performed and stable fecundity assumed to compare with national data on IVF, ZIFT, and GIFT. SETTING: Fertility Center, Division of Reproductive Endocrinology, University of Utah, Salt Lake City, Utah. RESULTS: A course of therapy with one to four cycles of hMG and IUI was just as effective as one cycle of IVF in achieving pregnancy. No significant difference in pregnancy rates was found between one IVF cycle and one to four cycles of hMG and IUI in our population. In vitro fertilization was more expensive than four cycles of hMG and IUI. Both IVF and hMG and IUI were more effective than no therapy. Published data also suggest that four cycles of hMG and IUI theoretically result in higher pregnancy rates than one cycle of IVF, ZIFT, or GIFT. CONCLUSION: Cost-benefit analysis comparing hMG and IUI, IVF, and no therapy in infertility patients may favor a course of four cycles of hMG and IUI as the first line of therapy. Using meta-analysis and theoretical assumptions, the pregnancy rate for one cycle of hMG and IUI is inferior to IVF, GIFT, or ZIFT; two cycles are comparable to IVF or ZIFT and inferior to GIFT; three cycles are superior to IVF or ZIFT and comparable to GIFT; and four cycles are theoretically superior to all techniques.

Tumor necrosis factor-alpha inhibits ovulation and steroidogenesis, but not prostaglandin production in the perfused rat ovary.

OBJECTIVE: We tested the null hypothesis that tumor necrosis factor-alpha (TNF-alpha) does not decrease ovulation, estradiol and progesterone production, or prostaglandin (PG) E2, PGF2alpha, or 6 keto-PGF1alpha production in the open bursa rat ovarian perfusion model. METHODS: Experimental animals were controlled for age, weight, litter, and pregnant mare's serum gonadotropin (PMSG) aliquot. Female Sprague-Dawley rats, 26-27 days old, were injected with 25 IU PMSG. Forty-eight hours later, the right ovary was dissected, the bursa removed, and the specimen placed in the perfusion chamber with defined media. Luteinizing hormone and isobutylmethylxanthine were given as an ovulatory trigger. Test perfusions also received TNF-alpha in 0.8-nmol/L, -pmol/L, and -fmol/L doses. Samples were collected at 0, 1, 3, 5, 7, 10, and 20 hours. Ovulations were counted at 20 hours. Steroids and PGs were measured. RESULTS: The addition of TNF-alpha to the rat ovarian perfusion model resulted in a dose-dependent decrease in ovulations (mean +/- standard deviation): 16.14 +/- 6.2 in controls (n = 7) versus 2.38 +/- 3.4 with TNF-alpha 0.8 nmol/L (n = 7), and 4.3 +/- 1.5 with TNF-alpha 0.8 pmol/L (n = 3), both P < .001. Tumor necrosis factor-alpha also inhibited estradiol (P < .005) and progesterone production (P < .05) throughout, but produced no significant changes in PG production. CONCLUSIONS: Tumor necrosis factor-alpha inhibits ovulation in a dose-dependent fashion, and inhibits estradiol and progesterone production without altering PG production in the open bursa rat ovarian perfusion model.

GnRH agonist therapy in human ovarian epithelial carcinoma (OVCAR-3) heterotransplanted in the nude mouse is characterized by latency and transience.

We have previously documented the responsiveness of a cell line of human ovarian epithelial carcinoma (Bowman Gray 1) heterotransplanted in nude mice to treatment with the GnRH agonist Lupron-SR. In this study we used another human ovarian epithelial carcinoma cell line, OVCAR-3, and the human endometrial carcinoma cell line HEC-1A. After a latent period, OVCAR-3 tumors showed significant inhibition of growth on Days 17, 21, and 24 (P < 0.03) compared to controls. The effect was transient and did not persist beyond Day 24. HEC-1A tumors showed no inhibition of growth. Radioreceptor assay studies utilizing native radiolabeled GnRH and [D-Lys6]-GnRH revealed no specific GnRH receptors in any of the tumor samples (BG-1, OVCAR-3, HEC-1A, University of Nebraska cell line, and two fresh human ovarian epithelial tumor samples) compared to male rat anterior pituitary cells. Binding studies and the latency and transience of effect would suggest that the mechanism of action in this animal model may be indirect. This activity may be via altered circulating steroids, gonadotropins, cell-cycle regulatory events, or some other as-yet-undefined action related to GnRH agonist administration or indirectly via effects of the metabolic products of degraded GnRH agonist such as D-amino acids, which are incorporated into the cells by constitutive or adsorptive pinocytosis. This study confirms latency and transience of effect of GnRH agonist therapy on an in vivo model of ovarian cancer.

Photodynamic therapy of human ovarian epithelial carcinoma, OVCAR-3, heterotransplanted in the nude mouse.

OBJECTIVE: Our objective was to develop an animal model for the study of photodynamic therapy in the treatment of human ovarian epithelial carcinoma. STUDY DESIGN: The human ovarian carcinoma OVCAR-3 was heterotransplanted into nude, athymic mice and treated with photodynamic therapy consisting of the hematoporphyrin derivative Photofrin II 10 ng/kg and argon-pumped dye laser light at 630 nm (200 J/cm2). Growth of tumors on one side of seven mice (treated tumors, n = 7) was compared with contralateral tumors (control tumors, n = 8) not exposed to laser. Hematoporphyrin derivative uptake was determined in tumor and other tissues. RESULTS: Photodynamically treated tumors were completely ablated, and all remained absent. Hematoporphyrin derivative uptake was nonselective for tumor compared with other tissues. CONCLUSION: This model provides reproducible parameters for the study of photodynamic therapy in the treatment of gynecologic malignancies and demonstrates the need for methods to increase selective uptake of hematoporphyrin derivatives.

Argon laser therapy of endometriosis: a review of 92 consecutive patients.

The conception rate, relief of pain, and safety of argon laser photocoagulation of endometriosis were evaluated in 92 patients. All patients were treated at the time of diagnosis with the argon laser delivered through a flexible quartz fiber passed through the operating channel of a standard and unmodified laparoscope. The uncorrected pregnancy rate was 34% (19 of 56), with 64% of the pregnancies occurring within 6 months of therapy. The conception rate was slightly greater in women with infertility of 24 months or less and in women without other fertility factors. Ninety-two percent of 50 women with pelvic pain reported a reduction of their pain after treatment. The argon laser is an effective, simple, and safe alternative for the treatment of mild or moderate endometriosis.

Microsurgical ovarian transplantation in the primate.

We have developed a technique for orthotopic transplantation of ovaries by microsurgical reanastomosis of the ovarian blood vessels in rhesus monkeys. Four monkeys receiving autografts resumed cyclic menses and had postoperative circulating luteinizing hormone (LH) and progesterone concentrations consistent with developing follicles and corpus luteum function. Postoperative luteal phase ovarian biopsies were indicative of ovulation in three of the four animals. However, in a fifth recipient an ovarian allograft from an unrelated donor was rejected despite the use of a standard immunosuppressive regimen. This study suggests that ovarian transplantation by direct vascular anastomosis is a technically feasible surgical procedure in the human, where the vascular anatomy is similar and the caliber of the ovarian vessels if greater than in the rhesus monkey.

Dysmenorrhea: treatment with an antiprostaglandin.

Painful menses, one of the most frequent gynecologic complaints, is incapacitating for many women. It has recently been proposed that increased endometrial prostaglandin production and prostaglandin-induced myometrial contractility may be responsible for dysmenorrhea. In this prospective, double-blind, 3-way, crossover study, relief of pain by an antiprostaglanding drug, ibuprofen (400 mg), was compared with propoxyphene (64 mg) and placebo in 22 women with severe primary dysmenorrhea. Ibuprofen was significantly more effective in 18 patients when compared to the other 2 treatment regimens (P less than 0.001), while propoxyphene was superior to placebo in 13 patients (P less than 0.05). Prostaglandin E and F synthesis rates in endometrial biopsy specimens taken on the second day of treatment in 2 patients during each treatment cycle were lowest during ibuprofen in one case but showed no definite pattern in the second.

Uncontrollable postpartum bleeding: a new approach to hemostasis through angiographic arterial embolization.

A case of severe postpartum hemorrhage is reported. Three separate surgical procedures failed to reveal the source of bleeding, and standard surgical techniques, including bilateral ligation of the hypogastric arteries, were unsuccessful in producing hemostasis. However, angiography successfully identified the specific bleeding vessel, and transcatheter embolization with Gelfoam fragments quickly and effectively stopped the hemorrhage. The authors consider angiographic embolization to be an effective alternative approach to the control of pelvic hemorrhage and recommend that the technique be considered prior to surgical intervention.

Detection of ovulation by a method of change in finger-finger electropotential readings.

The purpose of this study was to determine whether ovulation can be detected by using a device (OvultronR) that measures electropotential differences in finger-to-finger contact. Daily basal body temperatures and five consecutive readings on the OvultronR were obtained each morning in 34 women for a three-month period. During one cycle an endometrial biopsy was taken and dated to document the time of ovulation. Our results showed that in only five out of 104 cycles did the device show an isolated change at the time of ovulation. This device is not a reliable method either for prediction of or the detection of ovulation. Therefore, one cannot effectively use this device alone as a basis for a rhythm method of contraception.

PIP: To determine whether ovulation can be detected by an ovulometer (Ovultron), a device that measures changes in index finger - index finger electropotential, 34 women took basal body temperature and 5 consecutive reading on the ovulometer each morning for 3 months. The readings were plotted. Time of ovulation was determined by a rise in basal body temperature, confirmed by a finding of secretory endometrium in the biopsy each woman received during 1 cycle, and correlated with ovulometer readings. 31 of the 34 women had secretory endometrium, 21 had basal body temperature rises occurring at ovulation, and only 5 had changes in electropotential indicating ovulation (i.e., obvious changes at or 24 hours before ovulation and not on any other days in the cycle). The ovulometer is not a reliable method for prediction or detection of ovulation and cannot be effectively used as a basis for the rhythm method of contraception.

The obstetric complications of the infertility patient.

This study was undertaken to compare the outcome of pregnancy in patients treated for some type of infertility problem to that of a control group of patients from the same obstetric unit and also to the reported literature. Reported are the primary outcomes of 122 pregnancies in 104 patients treated for infertility and 106 pregnancies in patients of a control group delivered over the same period of time. Thirty-six percent of the treated patients had no pregnancy complications, whereas 54% of the control group had no pregnancy complications.

Teaching pelvic examination to second-year medical students using programmed patients.

A great deal of interest has been expressed in the use of the "programmed" patient during the past several years. This pilot study used programmed patients to teach medical students the techniques of pelvic examination. From the study, it was concluded that the experience with the programmed patient adds significantly to an undergraduate learning program, that this technique is well accepted by students and faculty, and that it adds realism to the study of obstetrics and gynecology early in a medical school curriculum.

Analysis of female sterilization technics.

PIP: To examine different female sterilization techniques, the cases of 846 women who were sterilized between July 1965 and December 1970 at the University of Utah Medical Center were compared for length of hospital stay, complications, and failure rates, and were followed up for at least 18 months. The most common sterilization technique was vaginal tubal ligation (365 cases). The average hospital stay for this procedure was 3.6 days with serious complications occurring at a rate of 2.6%. Postpartum tubal ligation was performed in 252 women and required an average of 1 day longer than the usual 3-day maternity hospital stay. The serious-complication rate was 2.1%. 115 patients underwent abdominal or caesarean-section tubal ligations, with their hospital stay lasting 6.0-6.8 days. Their complication rate was 4.2%. Hysterectomy was performed in 109 patients, whose average hospital stay was 8 days with a serious-complication rate of 8.0% including 1 death. There were 6 failures among the tubal ligations, 3 each with the Pomeroy and fimbriectomy techniques. The failure rates were 3% for the Pomeroy and 4.7% for the fimbriectomy. There was 1 failure among the hysterectomies. Choice of sterilization techniques depends on the individual physiological characteristics of the patient, but the Pomeroy technique through the vaginal route is suggested whenever possible.^ieng