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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.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%).

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.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.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.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.

PMSG-primed and hCG-triggered rat ovaries were exposed to nicotine and its major metabolite, cotinine, using in vitro and in vivo experimental approaches. In vivo, a dose-dependent reduction in oocytes within the fallopian tube was noted in nicotine treated rats (6.25 ng/g animal weight, P < 0.001). Serum estradiol concentrations were also reduced in rats receiving nicotine (P < 0.04). There were no significant differences in weight gain. Cotinine had no effects. In vitro, nicotine also caused a dose-dependent reduction in oocytes in the collection chamber (P < 0.0001). Estradiol levels in nicotine-treated perfusions were reduced and reached statistical significance at 7 h (P < 0.003). The in vitro fertilization rate was reduced for nicotine-treated perfusions exposed to 1.43 pg/mL of nicotine (P < 0.001). Cotinine had no effect in vitro. We conclude that nicotine inhibits ovulation, estradiol production, and fertilization both in vivo and in vitro in rat models of ovulation. Cotinine did not affect these parameters. These effects of nicotine are notably independent of nicotine's known effect on the midcycle gonadotropin surge.

In summary, we report a case of secondary infertility attributed to pseudomyxoma peritonei caused by ruptured appendiceal mucocele. Resection of the tumor and visible mucinous ascites resulted in spontaneous conception. We hypothesize secondary infertility was caused by significant peritoneal inflammation and inhibition of sperm-oocyte interaction from the ascites.

To our knowledge, this is the first report of documented growth regression of leiomyomatosis peritonei while the patient was receiving a gonadotropin-releasing hormone agonist. This further documents the role of gonadal steroids in the growth of this tumor.

The rat ovarian perfusion model with bursa removed and intact was used to further characterize the effects of interleukin-1 beta (IL-1 beta) and the natural IL-1 receptor anatagonist (IRAP) on ovulation, steroidogenesis, and prostaglandin production. Twenty-six- to 27-day-old female Sprague-Dawley rats were injected sc with 25 IU PMSG, and 48 h later, the right ovary was dissected (with bursa removed and intact for various experiments) and placed in the perfusion chamber. Ovaries were exposed to various doses of IL-1 beta alone, IL-1 beta with LH, and IL-1 beta with LH and isobutylmethylxanthine (IBMX). The natural IL-1 receptor antagonist was also added to the chambers with LH and IBMX. IL-1 beta at 0.8 (n = 3) and 8.0 (n = 4) nM did not induce LH-independent ovulation in PMSG-stimulated ovaries with bursa removed. In bursa-intact perfusions (n = 3), one ovulation was produced in each compared to control ovaries with bursa intact (n = 3) given an ovulatory trigger of LH alone [2.3 +/- 0.6 (+/- SD) ovulations; P < 0.02]. IL-1 beta enhanced, in a dose- and gonadotropin-dependent fashion, the production of prostaglandin E2 (PGE2) in PMSG-stimulated ovaries with bursa removed given an ovulatory trigger of LH and IBMX compared to that in controls. PGF2 alpha and 6-keto-PGF1 alpha were also modulated by IL-1 beta. Estradiol and progesterone production were not affected. The natural IRAP inhibited ovulation (7.8 +/- 3.9 ovulations vs. 12.4 +/- 1.5; P < 0.04) in PMSG-stimulated ovaries given LH and IBMX as the ovulatory trigger compared to that in controls. This inhibition of ovulation was not associated with reduced steroid or PG levels. IL-1 beta appears to play a potentially significant role in the process of ovulation. The functional importance of the bursa in this model is highlighted in this study. IL-1 beta modulates PG, but not steroid, production. IRAP inhibited ovulation without significantly affecting PG or steroid production.