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Fully effective contraception in male and female guinea pigs immunized with the sperm protein PH-20.

Immunization of male and female animals with extracts of whole sperm cells is known to cause infertility. Also, men and women who spontaneously produce antisperm antibodies are infertile but otherwise healthy. Although the critical sperm antigens are unknown, these observations have led to the proposal that sperm proteins might be useful in the development of a contraceptive vaccine. The guinea pig sperm surface protein PH-20 is essential in sperm adhesion to the extracellular coat (zona pellucida) of the egg, a necessary initial step in fertilization. Here, we report that 100% effective contraception was obtained in male and female guinea pigs immunized with PH-20. Antisera from immunized females had high titres, specifically recognized PH-20 in sperm extracts, and blocked sperm adhesion to the egg zona pellucida in vitro. The contraceptive effect was long-lasting and reversible: immunized females, mated at intervals of six to fifteen months after immunization, progressively regained fertility.

Animals

Effect of "missed" pills on oral contraceptive effectiveness.

OBJECTIVE: The purpose of this study was to determine whether missing pills in an oral contraceptive (OC) cycle resulted in folliculogenesis and eventual ovulation. METHODS: Fifteen women selected from a population requesting tubal reanastomosis were randomized into three groups and issued pill packs missing four consecutive pills in specific sequences, as follows: group I, days 1-4; group II, days 3-6; and group III, days 6-9. Serum was drawn for assay of LH, FSH, estradiol (E2), and progesterone, and serial ovarian ultrasound examinations were done to study follicular development throughout the cycle at 4-day intervals. RESULTS: No subject ovulated, as suggested by serum progesterone concentrations (not exceeding 0.63 ng/mL for any woman) and ultrasound assessment of follicular development (no follicular diameter exceeding 13 mm). The highest (mean +/- standard deviation) serum concentrations of LH and FSH in any group (13.25 +/- 18.71 and 14.40 +/- 7.71 mIU/mL, respectively) and of E2 (44.35 +/- 26.79 pg/mL) were observed during or immediately after the pill-free interval. Ovarian ultrasound examinations suggested suppressed folliculogenesis in all groups. No functional ovarian cysts were detected. CONCLUSIONS: Oral contraceptives exerted a similar degree of pituitary and ovarian suppression even when the subjects missed four pills at varying times in a cycle. The anovulatory effect persisted when the OC pills were reinstituted and taken reliably after an interval of noncompliance.

Adult

A comparative evaluation of the safety and contraceptive effectiveness of 65 mg and 100 mg of 90-day norethindrone (NET) injectable microspheres: a multicenter study.

The first of a second generation of slow-release injectable contraceptives is the norethindrone (NET) microspheres with a 90-day duration of action. It was evaluated at 65-mg and 100-mg doses for safety and contraceptive effectiveness in two randomized, single-blind trials among 131 women: 94 women for 12 months and 37 women for 6 months. The 6-month trial included additional evaluations of ovarian function and serum NET values. In the 6-month trial, no indication of ovulation was detected in the 100-mg dose group, while 3 of the 19 women in the 65-mg group showed signs of ovulation (progesterone greater than 3 ng/ml). No pregnancies were reported in the 100-mg group and one pregnancy in the 65-mg group resulted in a life-table pregnancy rate for that dose of 2.6 per 100 woman-years (95% confidence interval, 0 to 7.5). Days of vaginal bleeding were analyzed for 30 days before treatment and in 90-day reference periods after treatment. The mean number of vaginal bleeding and spotting days increased initially after the first injection in both dose groups, but decreased to below baseline in both dose groups after 6 months. The two doses appear comparable in clinical safety, side effects, vaginal bleeding patterns, and laboratory measures. With the preliminary estimate of efficacy, the 65-mg dose would be the minimally effective dose for the NET 90-day injectable contraceptive.

Adult

The contraceptive effects of a new low-dose combination type oral contraceptive.

A study was carried out in 9 women volunteers to investigate the centron of 0.75 mg lynestrenol plus 0.0375 mg ethinyl oestradiol given for 22 days per cycle over a period of 6 cycles. The results of assessments of a number of hormonal, vaginal and cervical parameters showed that this combination has a two-fold effect: a central effect on the pituitary and a peripheral effect on the ovaries and on endometrial development. The findings of an effect on cervical mucus, as with higher dose combinations, were not sufficiently consistent to warrant a claim for a cervical barrier. The preparation appeared to be well tolerated but there was a high incidence of irregular bleeding in the first treatment cycle. In most of the women, however, this had corrected itself by the second cycle.

Adult

Is the contraceptive effect of 300 micrograms of norethisterone mainly peripheral or central?

The effect of norethisterone (NET) on pituitary function was evaluated by measuring circulating follicle stimulating hormone (FSH) and luteinizing hormone (LH) during the mid follicular phase as well as before and after removal of the corpus luteum (CL) in 30 untreated women and 43 women treated with 300 micrograms of NET daily for three months. All untreated women exhibited significantly elevated FSH levels after removal of the CL irrespective of the stage of the luteal phase. In the NET-treated women, the levels of FSH were significantly raised in women with luteal activity but these levels were not influenced by the operative procedure in those women without luteal activity. The LH levels remained unchanged after removal of the CL in both untreated and NET-treated women. The results suggest that a low dose of gestagen exerts variable effects on pituitary function. The main contraceptive effect seems to be through direct interference with ovarian function.

Adult

Problem-solving skills, locus of control, and the contraceptive effectiveness of young women.

It was proposed that the lack of insight into the risk-taking behavior of many sexually active women who do not want to get pregnant may reflect the lack of an adequate framework from which to investigate the problem. The purpose of this study was to examine the relationships between contraceptive effectiveness and several cognitive factors. The sample consisted of 155 single women, 15.3-25.7 years of age, from a Planned Parenthood clinic and an abortion clinic. Contraceptive effectiveness, operationally defined as the number of unplanned pregnancies in a woman's history, was significantly and negatively related to means-ends problem-solving ability and a belief in internal control and significantly and positively related to a belief in chance control. It was suggested that these results support the utility of a cognitive, problem-solving approach to the study of contraceptive behavior.

Abortion, Induced

Development of a polymeric releasing device for 2'-carbomethoxyphenyl 4-guanidinobenzoate (a proteinase inhibitor): release rate, in vitro antifibrinolytic activity and in utero contraceptive effect.

A polymeric delivery system consisting of ethylene-vinyl acetate copolymer (EVAc) was developed for 2'-carbomethoxyphenyl 4-guanidinobenzoate (MSGB), a potent inhibitor of the sperm enzyme acrosin. The optimal device consists of copolymer with 40% vinyl acetate by weight (EVAc/40), 65% drug loading and MSGB with a particle size of 250-499 micron. This formulation yields a device that is highly flexible and can be shaped to many forms and sizes. Construction of the device does not alter the properties of MSGB. Well controlled release of MSGB from the device occurs in vitro and in the uteri of rats. The in vitro release rate under "infinite sink" conditions is essentially the same as the in vivo release rate. The contraceptive effect of the MSGB-releasing device was tested in rabbits by placing a blank (control) device in one uterine horn and an MSGB-releasing device in the contralateral horn. In contrast to blank devices, MSGB-releasing devices completely prevent pregnancy, not only by inhibiting fertilization but also by decreasing implantation. MSGB possesses high in vitro antifibrinolytic activity. These results indicate that a very flexible device can be constructed for uterine application which retains its contraceptive effect by release of MSGB. The antifibrinolytic activity of MSGB may further decrease the menorrhagia that can be associated with IUD use.

Animals

Contraceptive effects of extended lactational amenorrhoea: beyond the Bellagio Consensus.

We have recorded the duration of lactational anovulation and amenorrhoea in a well-nourished group of Australian women who breastfed their babies throughout the study. The data enabled us to compare the theoretical cumulative probability of conception among breastfeeding women who had unprotected intercourse irrespective of their menstrual status with that of those who had unprotected intercourse only during lactational amenorrhoea. Breastfeeding alone is not an effective form of contraception, since all the women in our study resumed normal ovulation while still breastfeeding. However, among women who have unprotected intercourse only during lactational amenorrhoea but adopt other contraceptive measures when they resume menstruation, only 1.7% would have become pregnant during the first 6 months of amenorrhoea, only 7% after 12 months, and only 13% after 24 months. Thus for our women it would be possible to extend the Bellagio Consensus Conference guidelines which stated that lactational amenorrhoea can only be relied on as a contraceptive for the first 6 months post-partum in women who are fully or almost fully breastfeeding. The lactational amenorrhoea method can be relied on for excellent contraceptive protection in the first 6 months of breastfeeding, irrespective of when supplements are introduced into the baby's diet; for women who continue to breastfeed the method can also give good protection for up to 12 months post partum. Once menstruation has returned, other forms of contraception are essential to prevent pregnancy.

Amenorrhea

Effective contraception with the levonorgestrel-releasing intrauterine device: 12-month report of a European multicenter study.

The use-effectiveness of an intrauterine contraceptive device releasing 20 mcg of levonorgestrel daily (Lng-IUD), and of a Nova T copper-releasing IUD, were studied in a randomized, comparative multicenter trial. The Lng-IUD was inserted in 1821, and the Nova T in 937 women. The 12-month net pregnancy rate with the Lng-IUD (0.1 per hundred women) was significantly lower than that with the Nova T (0.9 per hundred). Removal rates for menstrual problems and/or pain were similar for the two methods (net rates 7.5 and 8.7, respectively). The 12-month continuation rates were 82.2 for the Nova T and 79.7 for the Lng-IUD. The reduction of the bleeding led to oligomenorrhea and amenorrhea in users of the Lng-IUD; the removal rate for these reasons was 1.4. The removal rate for hormonal side effects with the Lng-IUD was 2.4. Blood hemoglobin concentrations increased among users of the Lng-IUD and decreased among users of the Nova T. The results show that the Lng-IUD was a highly effective contraceptive method which reduced menstrual bleeding. It is a promising alternative for women desiring a highly effective method for long-term use.

Adult

Oral contraceptives: effects on plasma insulin response to glucose and on the response to insulin and 2-deoxyglucose uptake by peripheral tissue.

Oral contraceptive steroids, norethynodrel and mestranol, were fed to 11-wk-old female Sprague-Dawley rats, in combination and in quantities proportional to those used by women for contraceptive purposes. Three experiments were performed. The first experiment, demonstrated that 10 wk of treatment, impaired the animal's glucose tolerance, but not its insulin response to glucose. The second experiment demonstrated that 6 wk of steroid feeding, decreased the in vivo conversion of blood U-14C-labeled glucose into adipose tissue fatty acids and into diaphragm glycogen, although the effect on the diaphragm was not statistically significant. In the third experiment, it was found that the uptake of 2-deoxyglucose-1-14C by the adipose tissue removed from rats after 6 wk of treatment, was not different from that of control tissue, but the uptake by the hemidiaphragms was slightly lower.

Adipose Tissue

Contraceptive effects of intravaginal application of acrosin and hyaluronidase inhibitors in rabbit.

Eight single-drug and combinations of two-drug treatments were used to study the contraceptive efficacy of the intravaginal application of acrosin inhibitors (TLCK; NPGB) and hyaluronidase inhibitors (Compound 53D/k; Phosphorylated hesperidin) in the rabbit. Drug concentrations were selected so that they did not inhibit rabbit sperm motility upon incubation at 37 degrees C for 30 minutes. In the first series, the drugs were added to semen before artificial insemination; in the second series, the drugs were administered intravaginally before artificial insemination with untreated rabbit semen. The data show that these drugs are highly effective intravaginal contraceptives in the rabbit. The data suggest that this is a specific inhibitory effect on fertilization since the drug concentrations used did not affect sperm motility.

Amino Acid Chloromethyl Ketones