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Reproduction & Fertility Jan 2022To summarize the currently available phase I and II clinical trials of the effects of nonoxynol-9 (N-9) on human sperm structure and functions. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To summarize the currently available phase I and II clinical trials of the effects of nonoxynol-9 (N-9) on human sperm structure and functions.
METHODS
A systematic review and meta-analysis aiming to evaluate the spermicidal activity of N-9 on motility, was conducted in PubMed, EMBASE, and Cochrane databases by 10 March 2021. The counted numbers of progressive motile (PR) sperm in cervical mucus and the vanguard sperm penetration distances were analyzed. Other effects on sperm structures and physiological activities were reviewed as well.
RESULTS
In the pooled results, percentages or counted numbers of PR sperm decreased after the treatment of N-9. Vanguard sperm penetration distance was shortened in treated groups. N-9 has been confirmed to damage the structures of sperm, as well as other organelles like acrosome and mitochondria. The physiological activities such as generation of reactive oxygen species, superoxide dismutase activity, acrosin activity, and hemizona binding were all inhibited in the reviewed studies.
CONCLUSIONS
N-9 has several impacts on sperm owing to its potency in reducing sperm motility and cervical mucus penetration, as well as other functional competencies.
LAY SUMMARY
Nonoxynol-9 (N-9) has been used worldwide as a spermicide to kill sperm for more than 60 years but can cause side effects including vaginal irritation and can increase the rate of contraceptive failure. A detailed analysis of published literature aiming to evaluate the spermicidal activity of N-9 on sperm was carried out. In the pooled results, N-9 reduced the number of active sperm and the distance they traveled. It also caused damage to the structures of sperm and to the way the sperm acted and interacted with the egg. In conclusion, N-9 impacts on sperm in a number of ways that lead to sperm death and dysfunction.
Topics: Female; Humans; Male; Nonoxynol; Semen; Sperm Motility; Spermatocidal Agents; Spermatozoa
PubMed: 35350652
DOI: 10.1530/RAF-21-0024 -
Toxicology Mar 2022Tripterygium wilfordii Hook f. has a long history of use in Chinese medicine. Triptolide (TP), as its main pharmacological component, has been widely explored in various... (Review)
Review
Tripterygium wilfordii Hook f. has a long history of use in Chinese medicine. Triptolide (TP), as its main pharmacological component, has been widely explored in various diseases, including systemic lupus erythematosus, rheumatoid arthritis and cancer. However, due to its poor water solubility, limited therapeutic range and multi-organ toxicity, TP's clinical application has been greatly hampered. To improve its clinical potential, many attenuated drug combinations have been developed based on its toxicity mechanism and targeted delivery systems aimed at its water-solubility and structure. This review, conducted a systematic review of TP detoxification strategies including drug combination detoxification strategies from metabolic and toxic mechanisms, as well as drug delivery detoxification strategies from the prodrug strategy and nanotechnology. Many detoxification strategies have demonstrated promising potential in vitro and in vivo due to previous extensive studies on TP. Therefore, summarizing and discussing TP detoxification strategies for clinical problems can serve as a reference for developing novel TP detoxification strategies, and provide opportunities for future clinical applications.
Topics: Diterpenes; Drug Combinations; Epoxy Compounds; Phenanthrenes; Water
PubMed: 35202762
DOI: 10.1016/j.tox.2022.153134 -
BMJ Sexual & Reproductive Health Jul 2021Our primary objective was to evaluate whether new types of single-size diaphragms or cervical caps differ in prevention of pregnancy compared with older types of... (Review)
Review
INTRODUCTION
Our primary objective was to evaluate whether new types of single-size diaphragms or cervical caps differ in prevention of pregnancy compared with older types of diaphragms, and whether different types of gels differ in their ability to prevent pregnancy. A secondary aim was to evaluate method discontinuation and complications.
METHODS
A comprehensive search was conducted in PubMed, Embase and the Cochrane Library. The certainty of evidence was assessed according to the GRADE system.
RESULTS
Four randomised controlled studies were included in the assessment. When comparing the new and old types of female barrier contraceptives the 6-month pregnancy rate varied between 11%-15% and 8%-12%, respectively. More women reported inability to insert or remove the FemCap device (1.1%) compared with the Ortho All-Flex diaphragm (0%) (p<0.0306). Urinary tract infections were lower when using the single-size Caya, a difference of -6.4% (95% CI -8.9 to -4.09) compared with the Ortho All-Flex diaphragm. The 6-month pregnancy rate for acid-buffering gel and spermicidal nonoxynol-9 gel varied between 10% and 12%. The discontinuation rate was lower in women who used acid-buffering gel compared with nonoxynol-9 gel (risk ratio (RR) 0.77, 95% CI 0.68 to 0.97).
CONCLUSIONS
Pregnancy rates were generally high in women using female barrier contraceptives. There was no difference in the efficacy for pregnancy prevention between the new types of diaphragms and cervical caps and the older diaphragms. The new types of diaphragms and cervical caps resulted in fewer urinary tract infections. Acid-buffering gels did not differ from spermicidal nonoxynol-9 gels regarding pregnancies but seemed to be better tolerated.
Topics: Contraception; Contraceptive Devices, Female; Diaphragm; Female; Gels; Humans; Pregnancy; Spermatocidal Agents
PubMed: 32868337
DOI: 10.1136/bmjsrh-2020-200632 -
Gynecologie, Obstetrique, Fertilite &... Dec 2018To develop clinical practice recommendations for the use of natural contraception and female and male barrier methods.
OBJECTIVE
To develop clinical practice recommendations for the use of natural contraception and female and male barrier methods.
MATERIALS AND METHODS
A systematic review of English and French literatures related to the safety and effectiveness of natural contraceptive methods based on PubMed, Cochrane Library, practice recommendations issued by international scientific societies and guidelines provided by the World Health Organization (WHO) as well as updates from the Center for Disease Control and Prevention (CDC).
RESULTS
Natural contraceptives methods include fertility awareness-based methods, lactational amenorrhea method (LAM) and withdrawal method. The prevalence is low (4.6% of users) and remains stable over the years. Identification of the fertile period can be symptom-based cervical mucus (Billings), two-day method, basal body temperature, symptom-thermal method or based on calendar calculation (Ogino-Knauss, standard day method). Pregnancy rate after one-year utilization varies from 0.4% to 5% in perfect use but 8% in common practice. Effectiveness increases with absence of vaginal sex and decreases when combined to barriers method inadequately implemented. Data is scarce on reliability and effectiveness of ovulation predictor kits readily available on internet. Lactational amenorrhea method (LAM) can be very effective (98%) provided three conditions are fulfilled: within 6 months after birth, amenorrhea is effective, and breastfeeding is exclusive or quasi exclusive (day/night). Withdrawal method is constraining and of limited effectiveness. Male and female condom, diaphragm, cervical cap and spermicides are mechanical and chemical barrier methods, preventing spermatozoids from passing through the cervix into the uterus and therefore preventing fecundation. Female and male condoms offer a double protection to avoid pregnancy and prevent STD's. They are effective provided strict conditions of use are fulfilled. Male condom is favored by teenagers (45.6% among 15 to 19 years old), sometimes in combination with contraceptive pill (16% of cases). Women on the pill decreases according to their age. Pregnancy rates within the first year of consistent and correct use of these methods vary between 5 to 26% and reach 20 to 32% in practical use. Diaphragm and cervical cap need to be used in combination with spermicides. Spermicides have limited effectiveness when used alone.
CONCLUSION
In common practice, natural and barrier contraceptive methods are more constraining and less effective than modern contraceptive method. They can be an alternative at given time and/or in situations where the women or the couple accept the possibility of an unexpected pregnancy which might be terminated or not. Women/couples need to be properly informed on how to use such methods, on their disadvantages and possible failures in common practice. Reminders are to be given on emergency contraceptive methods (IUD, hormonal) after unprotected sex.
Topics: Amenorrhea; Animals; Body Temperature; Breast Feeding; Cervix Mucus; Condoms; Contraception, Barrier; Contraception, Postcoital; Contraceptive Devices, Female; Female; Fertility; France; Humans; Lactation; Male; Natural Family Planning Methods; Ovulation Detection; Pregnancy; Spermatocidal Agents
PubMed: 30389545
DOI: 10.1016/j.gofs.2018.10.002 -
The Cochrane Database of Systematic... Mar 2014Vasectomy is an increasingly popular and effective family planning method. A variety of vasectomy techniques are used worldwide, including vas occlusion techniques... (Review)
Review
BACKGROUND
Vasectomy is an increasingly popular and effective family planning method. A variety of vasectomy techniques are used worldwide, including vas occlusion techniques (excision and ligation, thermal or electrocautery, and mechanical and chemical occlusion methods), as well as vasectomy with vas irrigation or with fascial interposition. Vasectomy guidelines largely rely on information from observational studies. Ideally, the choice of vasectomy techniques should be based on the evidence from randomized controlled trials (RCTs).
OBJECTIVES
The objective of this review was to compare the effectiveness, safety, acceptability and costs of vasectomy techniques for male sterilization.
SEARCH METHODS
In February 2014, we updated the searches of CENTRAL, MEDLINE, POPLINE and LILACS. We looked for recent clinical trials in ClinicalTrials.gov and the International Clinical Trials Registry Platform. Previous searches also included EMBASE. For the initial review, we searched the reference lists of relevant articles and book chapters.
SELECTION CRITERIA
We included RCTs comparing vasectomy techniques, which could include suture ligature, surgical clips, thermal or electrocautery, chemical occlusion, vas plugs, vas excision, open-ended vas, fascial interposition, or vas irrigation.
DATA COLLECTION AND ANALYSIS
We assessed all titles and abstracts located in the literature searches. Two reviewers independently extracted data from articles identified for inclusion. Outcome measures include contraceptive efficacy, safety, discontinuation, and acceptability. Peto odds ratios (OR) with 95% confidence intervals (CI) were used for dichotomous outcomes, such as azoospermia. The mean difference (MD) was used for the continuous variable of operating time.
MAIN RESULTS
Six studies met the inclusion criteria. One trial compared vas occlusion with clips versus a conventional vasectomy technique. No difference was found in failure to reach azoospermia (no sperm detected). Three trials examined vasectomy with vas irrigation. Two studies looked at irrigation with water versus no irrigation, while one examined irrigation with water versus the spermicide euflavine. None found a difference between the groups for time to azoospermia. However, one trial reported that the median number of ejaculations to azoospermia was lower in the euflavine group compared to the water irrigation group. One high-quality trial compared vasectomy with fascial interposition versus vasectomy without fascial interposition. The fascial interposition group was less likely to have vasectomy failure. Fascial interposition had more surgical difficulties, but the groups were similar in side effects. Lastly, one trial found that an intra-vas was less likely to produce azoospermia than was no-scalpel vasectomy. More men were satisfied with the intra-vas device, however.
AUTHORS' CONCLUSIONS
For vas occlusion with clips or vasectomy with vas irrigation, no conclusions can be made as those studies were of low quality and underpowered. Fascial interposition reduced vasectomy failure. An intra-vas device was less effective in reducing sperm count than was no-scalpel vasectomy. RCTs examining other vasectomy techniques were not available. More and better quality research is needed to examine vasectomy techniques.
Topics: Aminoacridines; Humans; Male; Oligospermia; Randomized Controlled Trials as Topic; Spermatocidal Agents; Surgical Instruments; Therapeutic Irrigation; Vas Deferens; Vasectomy
PubMed: 24683020
DOI: 10.1002/14651858.CD003991.pub4 -
The Cochrane Database of Systematic... Dec 2013Spermicides have been used as contraceptives for thousands of years. Despite this long use, only recently have studies examined the comparative efficacy and... (Review)
Review
BACKGROUND
Spermicides have been used as contraceptives for thousands of years. Despite this long use, only recently have studies examined the comparative efficacy and acceptability of these vaginal medications. Spermicides contain an active ingredient (most commonly nonoxynol-9) and a formulation used to disperse the product, such as foam or vaginal suppository.
OBJECTIVES
This review examined all known randomized controlled trials of a spermicide used alone for contraception.
SEARCH METHODS
In August 2013, we searched the following computerized databases for randomized controlled trials of spermicides for contraception: CENTRAL, MEDLINE, POPLINE, LILACS, EMBASE, ClinicalTrials.gov, and ICTRP. For the initial review, we examined the reference lists of trials found as well as those of review articles and textbook chapters.
SELECTION CRITERIA
We included any trial of a commercial product used alone for contraception. Each included trial must have provided sufficient information to determine pregnancy rates.
DATA COLLECTION AND ANALYSIS
Two authors independently extracted information from the trials identified. We did not conduct a meta-analysis, since most trials had large losses to follow up. We entered the data into tables and presented the results descriptively.
MAIN RESULTS
We located reports from 14 trials for the initial review, but have not identified any new trials since then. In the largest trial to date, the gel (Advantage S) containing the lowest dose of nonoxynol-9 (52.5 mg) was significantly less effective in preventing pregnancy than were gels with higher doses of the same agent (100 mg and 150 mg). Probabilities of pregnancy by six months were 22% for the 52.5 mg gel, 16% for the 100 mg dose, and 14% for the 150 mg dose. In the same trial, the three different vehicles with 100 mg of nonoxynol-9 had similar efficacy. Interpretation of these figures is limited, since 39% of participants discontinued the method or were lost from the trial. Few important differences in efficacy emerged in other trials.
AUTHORS' CONCLUSIONS
The probability of pregnancy varied widely in reported trials. A gel containing nonoxynol-9 52.5 mg was inferior to two other products tested in the largest trial. Aside from this finding, personal characteristics and behavior of users may be more important than characteristics of the spermicide products in determining the probability of pregnancy. Gel was liked more than the film or vaginal suppository in the largest trial. Spermicide trials have the dual challenges of difficult recruitment and high discontinuation rates; the latter threatens trial validity.
Topics: Contraception; Humans; Nonoxynol; Randomized Controlled Trials as Topic; Spermatocidal Agents; Vaginal Creams, Foams, and Jellies
PubMed: 24307556
DOI: 10.1002/14651858.CD005218.pub4 -
The Cochrane Database of Systematic... Sep 2013Spermicides have been used as contraceptives for thousands of years. Despite this long use, only recently have studies examined the comparative efficacy and... (Review)
Review
BACKGROUND
Spermicides have been used as contraceptives for thousands of years. Despite this long use, only recently have studies examined the comparative efficacy and acceptability of these vaginal medications. Spermicides contain an active ingredient (most commonly nonoxynol-9) and a formulation used to disperse the product, such as foam or vaginal suppository.
OBJECTIVES
This review examined all known randomized controlled trials of a spermicide used alone for contraception.
SEARCH METHODS
In August 2013, we searched the following computerized databases for randomized controlled trials of spermicides for contraception: CENTRAL, MEDLINE, POPLINE, LILACS, EMBASE, ClinicalTrials.gov, and ICTRP. For the initial review, we examined the reference lists of trials found as well as those of review articles and textbook chapters.
SELECTION CRITERIA
We included any trial of a commercial product used alone for contraception. Each included trial must have provided sufficient information to determine pregnancy rates.
DATA COLLECTION AND ANALYSIS
Two authors independently extracted information from the trials identified. We did not conduct a meta-analysis, since most trials had large losses to follow up. We entered the data into tables and presented the results descriptively.
MAIN RESULTS
We located reports from 14 trials for the initial review, but have not identified any new trials since then. In the largest trial to date, the gel (Advantage S) containing the lowest dose of nonoxynol-9 (52.5 mg) was significantly less effective in preventing pregnancy than were gels with higher doses of the same agent (100 mg and 150 mg). Probabilities of pregnancy by six months were 22% for the 52.5 mg gel, 16% for the 100 mg dose, and 14% for the 150 mg dose. In the same trial, the three different vehicles with 100 mg of nonoxynol-9 had similar efficacy. Interpretation of these figures is limited, since 39% of participants discontinued the method or were lost from the trial. Few important differences in efficacy emerged in other trials.
AUTHORS' CONCLUSIONS
The probability of pregnancy varied widely in reported trials. A gel containing nonoxynol-9 52.5 mg was inferior to two other products tested in the largest trial. Aside from this finding, personal characteristics and behavior of users may be more important than characteristics of the spermicide products in determining the probability of pregnancy. Gel was liked more than the film or vaginal suppository in the largest trial. Spermicide trials have the dual challenges of difficult recruitment and high discontinuation rates; the latter threatens trial validity.
Topics: Administration, Intravaginal; Contraception; Female; Humans; Pregnancy; Pregnancy Rate; Randomized Controlled Trials as Topic; Spermatocidal Agents
PubMed: 24085632
DOI: 10.1002/14651858.CD005218.pub3 -
The Cochrane Database of Systematic... Jul 2002The contraceptive vaginal sponge was developed as an alternative to the contraceptive diaphragm. The sponge, made of polyurethane impregnated with nonoxynol-9 (1g),... (Comparative Study)
Comparative Study Review
BACKGROUND
The contraceptive vaginal sponge was developed as an alternative to the contraceptive diaphragm. The sponge, made of polyurethane impregnated with nonoxynol-9 (1g), releases 125 mg of the spermicide over 24 hours of use. Unlike the diaphragm, the sponge can be used for more than one coital act within 24 hours without the insertion of additional spermicide, and the sponge does not require fitting or a prescription from a physician. How the sponge compares with the diaphragm in terms of efficacy and continuation is not clear.
OBJECTIVES
To compare the efficacy and continuation rates of the sponge with the diaphragm (used with nonoxynol-9). Our a priori hypothesis was that the sponge would have higher rates for failure and discontinuation than the diaphragm.
SEARCH METHODS
In April 2013, we searched the computerized databases MEDLINE, POPLINE, LILACS, CENTRAL, ClinicalTrials.gov and ICTRP.Earlier searches also included EMBASE. For the initial review, we searched the reference lists of relevant articles and book chapters.We also contacted investigators involved with the identified trials for other published or unpublished trials.
SELECTION CRITERIA
We included randomized controlled trials comparing the vaginal contraceptive sponge (Today; Collatex) with any diaphragm used with nonoxynol-9 to prevent pregnancy.
DATA COLLECTION AND ANALYSIS
We examined the studies identified through the literature searches for possible inclusion and evaluated their methodological quality using the Cochrane guidelines. We entered data into RevMan and calculated Peto odds ratios for overall pregnancy and 12-month discontinuation using numbers of women as the denominator. We also abstracted 12-month cumulative life-table ratios for these same outcomes but were unable to aggregate these data.
MAIN RESULTS
Two trials met the inclusion criteria. The sponge was significantly less effective in both trials in preventing overall pregnancy than was the diaphragm. In the larger USA trial, the 12-month cumulative life-table termination rates per 100 women for overall pregnancy were 17.4 for the sponge and 12.8 for the diaphragm. The rates were 24.5 for the sponge and 10.9 for the diaphragm in the UK trial.Similarly, discontinuation rates at 12 months were higher with the sponge than with the diaphragm (Odds ratio 1.31; 95% CI 1.07 to 1.59). Allergic-type reactions were more common with the sponge, although discontinuation for discomfort differed in the two trials.No new trials have been identified since the initial review.
AUTHORS' CONCLUSIONS
The sponge was less effective than the diaphragm in preventing pregnancy.Discontinuation rates were higher at 12 months as well.Other randomized controlled trials will be needed to resolve the potential role of spermicides in preventing sexually transmitted infections or in causing adverse effects
Topics: Contraceptive Devices, Female; Female; Humans; Nonoxynol; Pregnancy; Pregnancy Rate; Randomized Controlled Trials as Topic; Spermatocidal Agents
PubMed: 23866318
DOI: 10.1002/14651858.CD003172 -
The Cochrane Database of Systematic... Oct 2005Spermicides have been used as contraceptives for thousands of years. Despite this long use, only recently have studies examined the comparative efficacy and... (Review)
Review
BACKGROUND
Spermicides have been used as contraceptives for thousands of years. Despite this long use, only recently have studies examined the comparative efficacy and acceptability of these vaginal medications. Spermicides contain an active ingredient (most commonly nonoxynol-9) and a formulation used to disperse the product, such as foam or vaginal suppository.
OBJECTIVES
This review examined all known randomized controlled trials of a spermicide used alone for contraception.
SEARCH STRATEGY
We searched the following computerized databases from inception to July 2004 for randomized controlled trials of spermicides for contraception: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, POPLINE, LILACS, and EMBASE. We examined the reference list of each trial found as well as that of review articles and textbook chapters.
SELECTION CRITERIA
We included any trial of a commercial product used alone for contraception. Each included trial must have provided sufficient information to determine pregnancy rates. We located reports from 14 trials.
DATA COLLECTION AND ANALYSIS
Two reviewers independently extracted information from the trials identified. We did not conduct a meta-analysis, since most trials had large losses to follow-up. We entered the data into tables and presented the results descriptively.
MAIN RESULTS
In the largest trial to date, the gel (Advantage S) containing the lowest dose of nonoxynol-9 (52.5 mg) was significantly less effective in preventing pregnancy than were gels with higher doses of the same agent (100 mg and 150 mg). Probabilities of pregnancy by six months were 22% for the 52.5 mg gel, 16% for the 100 mg dose, and 14% for the 150 mg dose. In the same trial, the three different vehicles with 100 mg of nonoxynol-9 had similar efficacy. Interpretation of these figures is limited, since 39% of participants discontinued the method or were lost from the trial. Few important differences in efficacy emerged in other trials.
AUTHORS' CONCLUSIONS
The probability of pregnancy varied widely in reported trials. A gel containing nonoxynol-9 52.5 mg was inferior to two other products tested in the largest trial. Aside from this finding, personal characteristics and behavior of users may be more important than characteristics of the spermicide products in determining the probability of pregnancy. Gel was liked more than the film or vaginal suppository in the largest trial. Spermicide trials have the dual challenges of difficult recruitment and high discontinuation rates; the latter threatens trial validity.
Topics: Contraception; Humans; Randomized Controlled Trials as Topic; Spermatocidal Agents
PubMed: 16235396
DOI: 10.1002/14651858.CD005218.pub2 -
The Cochrane Database of Systematic... 2003The diaphragm is usually used with a spermicide. However, some practitioners have suggested that spermicides offer no additional contraceptive protection and have... (Review)
Review
BACKGROUND
The diaphragm is usually used with a spermicide. However, some practitioners have suggested that spermicides offer no additional contraceptive protection and have advocated alternative guidelines for the use of diaphragms.
OBJECTIVES
The objective of this review was to compare the effectiveness, safety and acceptability of the diaphragm with and without spermicide.
SEARCH STRATEGY
We searched MEDLINE, EMBASE, POPLINE, CINAHL, the Cochrane Controlled Trials Register, and reference lists of relevant articles. In addition, we contacted experts in the field to identify unpublished studies.
SELECTION CRITERIA
Randomized controlled trials comparing women of reproductive age using the diaphragm with and without spermicide as the sole contraceptive method that reported clinical outcomes.
DATA COLLECTION AND ANALYSIS
Two reviewers independently extracted data on outcomes and trial characteristics and any discrepancies were resolved by consensus or by consultation with the third reviewer. The results of the one identified study are presented descriptively.
MAIN RESULTS
We identified only one study. No significant difference was found in the pregnancy rates (with typical use or consistent use) or discontinuation rates between the diaphragm-with-spermicide and diaphragm-without-spermicide groups. There was a trend towards higher pregnancy rates in the diaphragm-without-spermicide group. However, this study failed to recruit the planned number of participants and was consequently underpowered.
REVIEWER'S CONCLUSIONS
As only one underpowered study was identified, we cannot distinguish between the contraceptive effectiveness of the diaphragm with and without spermicide. We cannot draw any conclusion at this point, further research is needed. However, the study provides no evidence to change the commonly recommended practice of using the diaphragm with spermicide.
Topics: Contraception; Contraceptive Devices, Female; Female; Humans; Intrauterine Devices, Medicated; Randomized Controlled Trials as Topic; Spermatocidal Agents
PubMed: 12535422
DOI: 10.1002/14651858.CD002031