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PubMed1997

Sperm antigens and their use in the development of an immunocontraceptive.

PROBLEM: Overpopulation is a global problem of significant magnitude, with grave implications for the future. World population is predicted to reach 10 billion people by the year 2050, an increase of more than 75% over the current population. Development of new contraceptives is necessary, since current forms of birth control are unavailable to many individuals due to sociological, financial, or educational limitations. METHODS: In an effort to identify new contraceptive alternatives, sperm-specific antigens are under the investigation as the basis for immunological regulation of fertility through contraceptive immunization. Anti-sperm antibodies (ASA) inhibit sperm function in vitro, induce infertility in experimental models, and have been implicated in some cases of clinical infertility. Furthermore, the development of ASA in vasectomized men does not lead to physiological complications despite the persistence of these antibodies for years; thus, ASA induced by immunization of men and women may be similarly harmless. Immunization has several conceptual advantages as a method of fertility regulation. Employment of non-pharmacologically active agents, convenience of administration, low cost, and the potential for relatively long-lasting yet reversible effects. RESULTS: Various approaches have been taken to identify candidate sperm antigens for immunocontraceptive development. Studies that utilized monoclonal antibodies and polyclonal antisera generated against sperm preparations have identified such promising candidates as PH-20, fertilin, SP-17, and SP-10. In animal model, 100% contraceptive effects were induced following PH-20 immunization and the effects were reversible. More recently, ASA from the sera of infertile patients were employed to identify several candidates as expressed by testis cDNA libraries. Perhaps the most extensively characterized and effective immunogen candidate identified thus far is lactate dehydrogenase-C4 (LDH-C4). Active immunization with LDH-C4 suppressed fertility in a variety of mammalian species, including primates, and the reversibility of these effects was demonstrated. CONCLUSION: The successful results obtained thus far support the feasibility of an effective immunocontraceptive and indicate the importance for continued investigation of additional sperm antigens as contraceptive immunogen candidates.

Contraception, Immunologic↗
PubMed1992

[Myocardial infarction in young women: apropos of 22 cases. Pathogenic and prognostic approach].

The authors report 22 cases of myocardial infarction documented by selective left ventriculography and coronary angiography in women under 45 years of age. The average age in this series was 36 +/- 6.8 years. Two patient groups were identified: Group I (n = 16) with the cardiovascular risk factor of oral contraception (mean age 33.9 +/- 5 years); and Group II (n = 6) comprising older patients (43.8 +/- 1.8 years) with a high prevalence of other risk factors (hyperlipidaemia, hypertension, diabetes). Myocardial infarction tended to be the inaugural event in Group I (9 out of 16 cases, 56.2%) whereas symptoms of effort angina were commonly observed in Group II (5 out of 6 cases, 83.3%). Coronary angiography showed more severe coronary lesions in Group II (score 1.5) than in Group I (score 0.75) in which isolated, single vessel disease mainly affecting the left anterior descending artery or normal coronary angiography was observed. Thrombolytic therapy was performed in 8 patients: percutaneous transluminal angioplasty was performed in 4 patients in the first month with a primary success in 3 cases. Coronary bypass surgery was performed in 1 case. The outcome during follow-up lasting 44.5 +/- 4.2 months was mainly favourable as 15 of the 20 patients had no secondary complications. Nevertheless, 2 patients died in the hospital period (1 from cardiogenic shock and 1 from complications of transluminal coronary angioplasty), 2 patients died less than 1 year after acute myocardial infarction (1 sudden death, 1 cardiogenic shock). Although oral contraception was withdrawn in all cases, many women continued to smoke.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

Contraceptive practice and trends in coital frequency.

Coital frequency among white, continuously married couples increased by 19 percent between 1965 and 1970, but by only five percent between 1970 and 1975. All of the increase in the latter five-year period is connected with a greater concentration of women in pregnancy-exposure and contraceptive-use categories associated with higher coital frequency. Over the five years, individual women who switched to more effective methods did not, on the average, experience as much of a decline in coital frequency as those who changed to less effective methods and those who did not change methods. (Some decline would be expected to be associated with the five-year increase in age.)

Adolescent↗
PubMed2000

Do they, don't they, or why haven't they?. Contraceptive use patterns among inner-city sexually active female adolescents

Background: Female adolescents frequently practice unprotected vaginal intercourse leading to nearly 1 million unintended pregnancies and 3 million sexually transmitted diseases (STDs) a year. Qualitative reasons for three contraceptive use patterns were explored. Contraceptive use patterns were quantified and correlated with gynecologic history.Methods: A total of 146 predominantly non-white (81%) sexually active female adolescents with a mean age of 17.2 +/- 1.9 years (13-21 years), completed a 45-minute self-administered, computerized questionnaire as part of a larger project. The questionnaire assessed sexual, contraceptive, gynecologic and obstetric history. Nearly a third (32%) had ever been pregnant and 32% had ever had a STD. Subjects were asked to describe their contraceptive use patterns for condoms, pills, and Depo-Provera as either "never used," "have used, but stopped," or "used before and am still using." Adolescents typed in their qualitative reasons for never using, stopping, or still using each of the three methods of contraception.Results:None of the three condom use patterns were significantly correlated with ever having a STD or being pregnant. Of those who had ever been pregnant, 70% had stopped using Depo-Provera as compared to 38% who were still using Depo-Provera, p < 0.02; 47% had stopped using pills as compared to 25% who were still using pills, p = 0.04; 47% had stopped using pills as compared to 22% who had never used pills, p < 0.01. "Using another contraceptive" was the reason why one-third of subjects never used condoms. The most common reasons for never using pills were "on Depo-Provera," "would forget," and not liking to take pills. Reasons for never using Depo-Provera included using another contraceptive, not liking shots and "might make me fat." The top four reasons for discontinuing condom use were being in a trusting, monogamous relationship, using another form of contraception, abstinence, and "don't like the way condoms feel." Two of the main reasons for stopping pills and Depo-Provera were weight gain and altered menses. However, those subjects who stopped taking the pill reported "kept forgetting" and "they made me sick" as other reasons for stopping. "Prevent pregnancy" was by far the most common reason for still using pills and Depo-Provera, while for condoms "prevent STDs" was cited with equal frequency to "prevent pregnancy." Having regular or no periods were frequent reasons for ongoing use of pills and Depo-Provera, respectively. Depo-Provera users also reported "don't have to worry about missing a pill" as a major reason for continuing use.Conclusions: Understanding the reasons why adolescents never use, stop using, or continue to use a particular method of contraception may provide a focus for more effective counseling.

Journal Article↗
PubMed1997

A comparison of the clinical performance, contraceptive efficacy, reversibility and acceptability of Norplant implants and Ortho Gynae T380 intrauterine copper contraceptive device.

In this comparative study, the five-year continuity rate of 53.7% in the Norplant implants group was comparable to that of 52.7% in the copper IUD group. The difference was not statistically significant. Only one accidental pregnancy occurred during the five years of copper IUD use. Desire for future pregnancy was the main reason for removal in the Norplant implants group (35.9%) while expulsion of the IUD (13.2%) was the main reason for removal of the copper IUD. Menstrual disturbance was not a major side-effect in either group. The post-removal conception rates of 78.6% in the Norplant implants group and 75.0% in the copper IUD were good and comparable. Both the Norplant implants and copper IUD are acceptable and effective contraceptive methods in Singapore.

Adult↗
PubMed2001

Managing the transition from oral contraceptives to hormone replacement therapy.

Oral contraceptives provide multiple benefits for perimenopausal women; their use results in considerable economic savings by managing vasomotor symptoms, preventing pregnancy, and improving future outcomes. Hormone replacement therapy provides many health benefits for menopausal women; a recently introduced constant estrogen/intermittent progestin regimen takes advantage of receptor dynamics and the extended half-life of norgestimate to provide a continuous progestational effect on the endometrium. The lower progestin dose may also decrease progestin-related side effects and contribute to increased adherence and treatment continuation.

Climacteric↗
PubMed2004

A pilot study on the acceptability of levonorgestrel-releasing intrauterine device by young, single, nulliparous Chinese females following surgical abortion.

This study investigated the acceptability of the levonorgestrel-releasing intrauterine device (LNG-IUS) as contraception among young, single women after termination of pregnancy. Twenty subjects, with a median age of 21 years, had LNG-IUS inserted immediately after suction termination of first-trimester pregnancy. The subjects were followed-up at 6 weeks, 3 months, 6 months and 12 months. Fifteen subjects (75%) had other pregnancies terminated in the past. There were no serious complications or pregnancies. The acceptability of the LNG-IUS was generally above 86% during each follow-up visit. A total of seven (35%) subjects were lost to follow-up at different periods of the study. Overall, four subjects (22%) had the LNG-IUS removed. Nine subjects were seen at the end of the 1-year study period and all continued with the LNG-IUS for contraception. Side effects were commonly observed and irregular vaginal bleeding was the most common. We conclude that the LNG-IUS may be an acceptable method among selective young, single, nulliparous clients after termination of pregnancy and could be offered as an option of contraception to them. However, the small sample size and the high lost-to-follow-up rate are the major limitations of this study.

Abortion, Induced↗
PubMed1995

[Contraceptives, HIV, and other sexually transmitted diseases].

The large majority of women who acquire Human Immuno-Deficiency Virus (HIV) and other sexually transmitted diseases (STDs) are in their childbearing years and are current or potential users of contraceptive methods. Certain STDs augment women's risk for HIV due to damage which these diseases produce in the integrity of the epithelial lining of the vagina and the vulva. There also exists evidence that some contraceptive methods, such as the intrauterine device and certain hormonal products, may increase the risk of HIV and other STDs. Condoms and spermicides offer good levels of protection against these diseases, but are not highly effective contraceptives. The interrelations among these risks are important and create a great problem for women's reproductive health. Moreover, the high vulnerability of the female population for these diseases is also related to a variety of social factors which are referred to as gender relations (power of females in society relative to that of females). Among the gender-related inequalities which affect women are their lack of power to successfully control many aspects of sexual relations. Another problem has to do with the fact that there are no highly reliable female controlled methods for preventing infection by HIV and other STDs. Improvement in the reproductive health care of women depends on the development of new disease prevention products and structural changes in the delivery of care, as well as continued research efforts on the interrelations among contraceptive methods, HIV and other STD.

Contraceptive Agents↗
PubMed2004

Effectiveness and acceptability of progestogens in combined oral contraceptives - a systematic review.

BACKGROUND: The progestogen component of oral contraceptives (OCs) has undergone changes since it was recognized that their chemical structure can influence the spectrum of minor adverse and beneficial effects. METHODS: The objective of this review was to evaluate currently available low-dose OCs containing ethinylestradiol and different progestogens in terms of contraceptive effectiveness, cycle control, side effects and continuation rates. The Cochrane Controlled Trials Register, MEDLINE and EMBASE databases were searched. Randomized trials reporting clinical outcomes were considered for inclusion and were assessed for methodological quality and validity. RESULTS: Twenty-two trials were included in the review. Eighteen were sponsored by pharmaceutical companies and in only 5 there was an attempt for blinding. Most comparisons between different interventions included one to three trials, involving usually less than 500 women. Discontinuation was less with second-generation progestogens compared to first-generation (RR 0.79; 95% CI 0.69-0.91). Cycle control appeared to be better with second-compared to first-generation progestogens for both, mono-and triphasic preparations (RR 0.69; 95% CI 0.52-0.91) and (RR 0.61; 95% CI 0.43-0.85), respectively. Intermenstrual bleeding was less with third- compared to second-generation pills (RR 0.71; 95% CI 0.55-0.91).Contraceptive effectiveness of gestodene (GSD) was comparable to that of levonorgestrel (LNG), and had similar pattern of spotting, breakthrough bleeding and absence of withdrawal bleeding). Drospirenone (DRSP) was similar compared to desogestrel (DSG) regarding contraceptive effectiveness, cycle control and side effects. CONCLUSION: The third- and second-generation progestogens are preferred over first generation in all indices of acceptability. Current evidence suggests that GSD is comparable to LNG in terms of contraceptive effectiveness and for most cycle control indices. GSD is also comparable to DSG. DRSP is comparable to DSG. Future research should focus on independently conducted well designed randomized trials comparing particularly the third- with second-generation progestogens.

Journal Article↗
PubMed1976

Comparison of continuation rates of intrauterine devices.

The validation of reports of the performance of intrauterine contraceptive devices (IUDs) is fraught with confounding factors such as different protocols, populations, and clinic environments. Two-year life table continuation rates from a comparative study of the Lippes loop, TCu-200, and Dalkon shield are reported from a single clinic in which 1626 insertions were performed by two obstetrician/gynecologists. The difference between the highest and lowest parity-standardized continuation rates for the three devices was only 3.7 percentage points after 2 years of use. The TCu-200 and Dalkon shield yielded significantly lower expulson rates than the Lippes loop. The more recently developed IUDs do not appear to have higher continuation rates than the Lippes loop.

Adolescent↗
PubMed1993

One year contraception with a single subdermal implant containing nomegestrol acetate (Uniplant).

One single silastic capsule containing nomegestrol acetate, Uniplant, was inserted subcutaneously in 100 women of reproductive age who desired to avoid conception. Insertions and removals of the capsules were made in the gluteal region following intracutaneous local anesthesia with 2% procaine. Eighty women completed one year of use. Eleven women bore the implant for 6-11 months. A total of 1,085 women-months were recorded. One pregnancy occurred, resulting in a Pearl Index of 1.1. Bleeding episodes similar to menstruation occurred in all women but the degree of regularity varied from subject to subject. Amenorrhea developed in the range of 14-18% during the first six months of use but declined to less than 10% during the last six months. Menorrhagia likewise was higher in the first six months (18% in the first month) but fell to less than 10% during the last six months. Spotting was 5% or less. Of the twenty women who did not complete one year of use, nine discontinued because they found other methods were either more practical or less revealing. Three discontinued because of bleeding irregularities, three desired to become pregnant, one became pregnant. Other complaints included dizziness, headache, increased blood pressure, loss of libido, painful breasts and nausea. Over half of the women indicated their desire to continue using the single implant as a contraceptive.

Adult↗
PubMed2002

Ovarian function with a novel combined contraceptive vaginal ring.

BACKGROUND: NuvaRing is a combined contraceptive vaginal ring designed for 3 weeks continuous use followed by a 1 week ring-free period. The present study evaluated ovarian function in women who were instructed to either adhere to, or deviate from, the recommended regimen of use. METHODS: In this open-label, randomized study, 45 women aged between 18 and 35 years used NuvaRing for one cycle in which the ring was used according to the recommended regimen. Women in group A (n = 15) then continued with a 'normal' 3 week period of ring use after which the restoration of ovarian function-i.e. the time to ovulation-for each woman was determined by daily vaginal ultrasound and serum hormone levels. For women in group B (n = 15), the second cycle consisted of only 3 consecutive days of ring use, after which each woman was monitored until ovulation. Women in group C (n = 15) were not permitted to start a second 'normal' cycle until a follicle with a diameter of 13 mm was observed by vaginal ultrasound; subsequently, the development of these follicles during the second cycle of ring use was monitored daily. RESULTS: Irrespective of the length of the second cycle, 3 weeks (group A) versus 3 days (group B), a new cohort of follicles needed to be recruited and the time to ovulation after ring removal was similar (19 versus 17 days). The median time needed to develop a follicle up to 13 mm in diameter (group C) was 11 days (range 8-21 days); none of the women ovulated after insertion of the second ring. CONCLUSION: NuvaRing is a highly effective, reversible method of hormonal contraception. Ovulation, at least until the stage of a 13 mm dominant follicle, is prevented and as little as 3 consecutive days of NuvaRing use interferes with follicle growth.

Adolescent↗
PubMed1994

Comparison of adolescent and adult experiences with Norplant levonorgestrel contraceptive implants.

OBJECTIVE: To compare acceptability, tolerance of side effects, and continuation rates among adolescent and adult Norplant accepters. METHODS: An 18-month observational study was conducted of 136 adolescents and 542 adults who received Norplant at the Francis Scott Key Medical Center in Baltimore, Maryland. Data were collected from the following: a self-administered history form completed at the preinsertion visit, a self-administered follow-up form completed at routine follow-up visits, problem-visit chart review, and telephone contact for patients noncompliant with follow-up appointments. RESULTS: The adolescents ranged in age from 13-18 years (mean 16.4), and adults ranged in age from 19-46 (mean 24.7). The mean parity among teenagers was 1.4; among adults, 3.2. Thirty-nine percent of teenagers and 64% of adults had had one or more therapeutic abortions. Forty percent of adolescents and 47% of adults reported at least one contraceptive failure in the past. Both adolescent and adult Norplant accepters made few telephone calls or problem visits because of complaints or side effects. Compliance with routine annual follow-up was poor for adolescents (24 of 136, 18%) and adults (72 of 542, 13%). Follow-up of noncompliant patients revealed low rates of implant removal. Fifteen adolescents (11%) and 60 adults (11%) had Norplant removed. The most common reasons for removal included irregular bleeding, weight gain, headaches, and desire for pregnancy. CONCLUSIONS: Implant acceptability, continuation, and tolerance of side effects were high and comparable among adolescent and adult accepters. Initial implant users were primarily adolescents or adults who had experienced problems with other forms of reversible contraception. Adherence to scheduled follow-up appointments was poor, regardless of age.

Adolescent↗
PubMed1983

Antifertility actions of alpha-chlorohydrin in the male.

Non-steroidal chemicals that affect male fertility have been known for over 25 years but only one compound, alpha-chlorohydrin, possesses most of the attributes of an ideal male contraceptive. In the male rat, for example, continuous daily oral administration of low doses produces an almost immediate and continuous antifertility response that ceases when treatment is withdrawn. Such a dose regime does not interfere with libido, is apparently not toxic and the action is specific towards mature sperm. Furthermore, the action of the compound is species-specific: it is effective in the rat, ram, boar, guinea pig, hamster, rhesus monkey and upon ejaculated human sperm but it is ineffective in the mouse and the rabbit. High doses of alpha-chlorohydrin can be neurotoxic, nephrotoxic and, in rats, lead to prolonged or permanent infertility. However, the antifertility response and the toxicity of racemic alpha-chlorohydrin may be due, respectively, to the separate enantiomers. No other antifertility chemical has been investigated to such an extent as alpha-chlorohydrin; this article reviews the progress that has been achieved with alpha-chlorohydrin during the past six years.

Animals↗
PubMed2006

Triphasic versus monophasic oral contraceptives for contraception.

BACKGROUND: Side effects of oral contraceptive pills (OCs) discourage adherence to and continuation of OC regimens. Strategies to decrease adverse effects led to the introduction of the triphasic OC in the 1980s. Whether triphasic OCs have higher accidental pregnancy rates than monophasic pills is unknown. Nor is it known if triphasic pills give better cycle control and fewer side effects than the monophasic pills. OBJECTIVES: To compare triphasic OCs with monophasic OCs in terms of efficacy, cycle control, and discontinuation due to side effects. SEARCH STRATEGY: We searched the computerized databases of MEDLINE, EMBASE, POPLINE, LILACS and CENTRAL. Additionally, we searched the reference lists of relevant articles and book chapters. We also contacted researchers and pharmaceutical companies in Europe and the U.S. to identify other trials not found in our search. SELECTION CRITERIA: We included randomized controlled trials (RCTs) comparing any triphasic OC with any monophasic pill used to prevent pregnancy. Interventions had to include at least three treatment cycles. DATA COLLECTION AND ANALYSIS: We assessed the studies found in the literature searches for possible inclusion and for their methodological quality. We contacted the authors of all included studies and of possibly randomized trials for supplemental information about the methods and outcomes studied. We entered the data into RevMan 4.2 and calculated odds ratios for the outcome measures of efficacy, breakthrough bleeding, spotting, withdrawal bleeding and discontinuation. MAIN RESULTS: Of 21 trials included, 18 examined contraceptive effectiveness: the triphasic and monophasic preparations did not differ significantly. Several trials reported favorable bleeding patterns, i.e. less spotting, breakthrough bleeding or amenorrhea, in triphasic versus monophasic OC users. However, meta-analysis was generally not possible due to differences in measuring and reporting the cycle disturbance data as well as differences in progestogen type and hormone dosages. No significant differences were found in the numbers of women who discontinued due to medical reasons, cycle disturbances, intermenstrual bleeding or adverse events. AUTHORS' CONCLUSIONS: The available evidence is insufficient to determine whether triphasic OCs differ from monophasic OCs in effectiveness, bleeding patterns or discontinuation rates. Therefore, we recommend monophasic pills as a first choice for women starting OC use. Large, high-quality RCTs that compare triphasic and monophasic OCs with identical progestogens are needed to determine whether triphasic pills differ from monophasic OCs. Future studies should follow the WHO recommendations on recording menstrual bleeding patterns and the CONSORT reporting guidelines.

Contraception↗
PubMed1985

Who's to blame: adolescent sexual activity.

Fifty case studies of adolescent women seeking contraceptives for the first time suggest no direct relationship between the initiation of sexual activity and the availability of contraceptives at family planning clinics. However, the persistence of sexual activity, once initiated, may be influenced by the availability of contraceptives when the adolescent realizes she wants to continue sexual activity and does not want to become pregnant. Five characteristics of the adolescents which support the above finding are discussed.

Adolescent↗
PubMed1981

Inhibitors of acrosomal proteinase as antifertility agents. A problem of acrosomal membrane permeability.

In vitro studies were performed to investigate the accessibility of acrosin to various proteinase inhibitors inside the intact acrosome of testicular, ejaculated, and uterine human spermatozoa. As test system the gelatin plate assay was used. For this assay it was shown formerly that a correlation exists between the size of the digested lysis areas (halo formation) and acrosin activity estimated with synthetic substrates. In addition, saturation of the gelatin substrate membranes with acrosin inhibitors including highly specific ones before application of spermatozoa completely prevented halo formation indicating that the gelatinolytic activity of human spermatozoa is caused exclusively by acrosin. When human spermatozoa were incubated with various acrosin inhibitors (concentration: 1 mmol/l) prior to application to the gelatin membrane, reduction of halo formation could not be observed, however. This result indicates that most of the tested acrosin inhibitors (9 naturally occurring protein inhibitors, 2 microbial peptide inhibitors, 19 synthetic inhibitors) were unable to penetrate the acrosomal membranes of testicular, ejaculated, and uterine human spermatozoa. Only 2 inhibitors caused moderate up to complete inhibition of the gelatinolytic activity of the spermatozoa if applied in concentrations between 1 and 10 mmol/l: the proteinase inhibitor aprotinin and the synthetic inhibitor NPGB (4-nitrophenyl 4-guanidinobenzoate). Obviously, human acrosomal membranes seem to be especially impenetrable to proteins, polypeptides, and synthetic agents. Those acrosin inhibitors penetrating the human sperm head membranes are either too toxic or the local concentration necessary for effective acrosin inhibition in vivo cannot be achieved within the male or female genital tract secretions. Therefore, acrosin inhibitors cannot be used for human contraception at present. Thus it is mandatory to continue the search for suitable acrosin inhibitors with low toxicity easily penetrating into the intact sperm acrosome.

Acrosome↗
PubMed2005

Novel testis/sperm-specific contraceptive targets identified using gene knockout studies.

The population explosion and unintended pregnancies resulting in elective abortions continue to be the major public health issues in spite of availability of current methods of contraception. There is an urgent need for a better method of contraception that is accepted, effective, and available. Various targets are being investigated that can be used for contraception. The gene knockout technology is a powerful approach to identify such novel targets. Using search in the database, at least 93 genes were identified in the literature whose deletion demonstrated an effect on fertility in male mice. However, majority of these knockouts also demonstrated an effect on non-reproductive organs concomitant with an effect on fertility. The knockouts of only a few genes/proteins induced a specific effect on fertility without a serious side effect. The potential role of these novel genes/proteins in contraception/contraceptive vaccine development is discussed.

Animals↗