Abstract
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.
Keywords: Humans; Contraception; Contraception/methods; Nonoxynol; Nonoxynol/administration & dosage; Randomized Controlled Trials as Topic; Spermatocidal Agents; Spermatocidal Agents/administration & dosage; Vaginal Creams, Foams, and Jellies; Vaginal Creams, Foams, and Jellies/administration & dosage; Vaginal Creams, Foams, and Jellies/chemistry
Plain language summary
Spermicide used alone for birth control
Spermicides have been used as birth control for thousands of years. Studies have recently looked at how well they work to prevent pregnancy and whether women like them. Spermicides contain an active ingredient (usually nonoxynol‐9) and something to disperse the product, such as foam or vaginal suppository (pessary). This review compared how well different spermicides worked for birth control when used alone.
In August 2013, we did computer searches for randomized trials of spermicides used for birth control. We have not found any new trials since the initial review. For the initial review, we also wrote to researchers to find other trials.
Trials had to focus on a spermicide used alone for birth control. The product could be compared to a different spermicide, the same spermicide used with a barrier method, another dose of the same spermicide, a different base for the same product, or another type of birth control. Each study must have had data on pregnancy.
We located reports from 14 trials for the initial review. We have not found any new trials since then. The largest trial compared five different spermicides. The gel with the smallest amount of nonoxynol‐9 did not prevent pregnancy as well as products with more of the same ingredient. Women liked the gel better than the film or suppository. Few differences were found in the other studies. These trials had problems recruiting women into the studies and then keeping them until the trial ended. Large losses to follow up can bias the results.
Background
Although vaginal spermicides have been used as contraceptives for millennia, only recently have these methods received scientific scrutiny. Spermicides are designed to prevent fertilization by killing or inactivating sperm as they ascend through the female genital tract. All spermicide products have two components: a chemical toxic to sperm and a formulation (also called a carrier or base) for its delivery (Cates 2011). The chemicals used in currently available spermicides are usually surfactants, the most common being nonoxynol‐9. 'Nonoxinol' is also a recognized spelling for this chemical. Other agents include octoxynol, menfegol, and benzalkonium chloride (Connell 2002; Speroff 2001). These agents dissolve the lipid components in the cell membrane of spermatozoa, resulting in their death or inactivation. Nonoxynol‐9 spermicides contain 52.5 to 230 mg (Embil 2005) of the active agent per application. The vehicles used to deliver the spermicide include foam, jelly, cream, melting suppository, foaming suppository, foaming tablet, and soluble film (Sherris 1984). A vaginal suppository may also be called a pessary. Unlike the melting suppository, the foaming suppository uses a chemical base that, when moistened, releases carbon dioxide bubbles to help distribute the spermicide. Instructions for use vary by product; tablets, suppositories, and film need time to melt to allow dispersal of the spermicide in the vagina. Users are advised to insert spermicides from 0 to 30 minutes before coitus. While some jellies, creams, and foams may protect for as long as eight hours, tablets and suppositories may be effective for only one hour (Speroff 2001). The scientific basis for these statements about duration of contraceptive activity is elusive.
Current spermicides have important advantages and disadvantages. These products are widely available 'over‐the‐counter' and generally cost less than hormonal contraceptives. No systemic absorption occurs (Sherris 1984). These products are simple to use and are under the control of the woman. Some women report that the lubrication provided by spermicide improved intercourse for them (Vandebosch 2004). Although protection against some sexually‐transmitted infections had been reported in the past, primarily with in vitro studies, more recent clinical trials have not confirmed this benefit (Cates 2011; Roddy 1998; Roddy 2002; Van Damme 2002). Spermicides with nonoxynol‐9 are not effective as microbicides, and may increase susceptibility to HIV if used more than twice a day (Cates 2011).
A central challenge for all spermicides is maintaining the balance between contraceptive protection and disturbing the vaginal environment (Zaneveld 1996). Spermicides act as cytotoxins and can injure vaginal and cervical epithelium. Frequent use may alter the vaginal flora, possibly leading to an increased risk of urinary tract infection (Scholes 2000). It can also damage the epithelium, possibly facilitating infection with HIV among female sex workers (WHO 2002). The World Health Organization considers spermicides a category 4 method (contraindicated) for women at high risk of HIV infection and category 3 for those already infected (WHO 2010). The probability of pregnancy with spermicide alone varies widely. In the first year of use, unintended pregnancies occur in 18% of women with perfect use and 28% of those with typical use (Trussell 2011). Allergy or sensitivity to the spermicide has been reported in 1% to 5% of users. Other users note irritation of genital tissues or a sensation of heat. Some couples find this method messy (Zaneveld 1996).
This review examined spermicides used alone for contraception, although spermicides are commonly used with barrier contraceptives, such as the condom, diaphragm, sponge, and cervical cap.
Objectives
To compare the probability of pregnancy among women using a spermicide alone versus any other contraceptive, including another spermicide.
Methods
Criteria for considering studies for this review
Types of studies
We included all randomized controlled trials in any language that compared any spermicide used alone for contraception with another method; pregnancy must have been reported as an outcome. The comparison method could have been a different spermicide, the same spermicide used with a barrier method, a different dose of the same spermicide, a different formulation for the same spermicide, or another type of contraceptive altogether.
Types of participants
All women included in the eligible trials were incorporated in this review.
Types of interventions
We included any commercially‐available spermicide used for prevention of pregnancy. Trials using spermicides for prevention of sexually‐transmitted infections were excluded. Any active agent was considered. No natural substances, such as lime juice, were included, because evaluations have not been completed. Formulations included foam, jelly, cream, suppository or pessary, tablet, and film. Most reports did not provide specific information about the composition of the vehicles in the products tested. At least one treatment arm in each included trial must have used spermicide alone for contraception.
Types of outcome measures
Primary outcomes
Each trial must have had reported pregnancies as an outcome.
Secondary outcomes
These measures included continuation rates, side effects, and acceptability. Changes to vaginal epithelium were included if reported. Reporting of side effects reflected definitions of outcomes used by investigators.
We excluded trials that only reported surrogate endpoints, such as in vitro effects on sperm motility.
Search methods for identification of studies
Electronic searches
In August 2013, we searched computerized databases for randomized controlled trials of spermicides for contraception: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, POPLINE, and LILACS. We also searched for trials via ClinicalTrials.gov and the search portal of the International Clinical Trials Registry Platform (ICTRP). Search strategies are shown in Appendix 1. Previous strategies can be found in Appendix 2. We did not use 'infection' in the search strategy, because microbicides were not the focus of this review.
Searching other resources
For the initial review, we examined the reference lists of trials found as well as those of review articles and textbook chapters. We wrote to the author of each published trial identified to solicit other published or unpublished trials that we may have missed. Discussions with an investigator revealed unpublished trial reports, which we then included.
Data collection and analysis
We assessed for inclusion all titles and abstracts that we found. We evaluated the methodological quality of the trials for potential biases by qualitatively assessing the study design, randomization method, allocation concealment, blinding, and rates for premature discontinuation and loss to follow up. One potentially relevant trial was published in Chinese (Xu 2003); we had this article translated into English. Correspondence with the author later revealed that it was not a randomized trial.
Two authors independently abstracted data from the studies identified to improve accuracy. Most studies had problems with recruitment and large losses to follow up. Therefore, we did not conduct a meta‐analysis. Most studies reported the 6‐month or 12‐month life‐table rates per 100 women or the probabilities. We entered those data into tables in RevMan. The results are presented descriptively. Information on statistical significance came from the individual trial reports.
Results
Description of studies
Results of the search
The 2013 search produced 20 unduplicated references. These included 17 citations from the main databases plus 1 from another source. We also identified two items from the searches of ClinicalTrials.gov and ICTRP but none were eligible.
Included studies
The spermicides tested in these studies are listed in Table 1.
1. Summary of spermicides tested.
| Brand name | Spermicide and dose | Trial |
| Neo Sampoon | Menfegol 60 mg | Abdelsalaam 1984 |
| Andolsek 1988 | ||
| Chi 1987 | ||
| Kazi 1992 | ||
| Lamptey 1985 | ||
| Youssef 1987 | ||
| Ortho menfegol foaming tablet | Menfegol 60 mg | Chompootaweep 1990 |
| Ghunney 1987 | ||
| Klufio 1988 | ||
| Ruoff 1988 | ||
| Collatex sponge | Nonoxynol‐9 1.15 g | Chi 1987 |
| Emko tablet | Nonoxynol‐9 100 mg | Abdelsalaam 1984 |
| Andolsek 1988 | ||
| Lamptey 1985 | ||
| Poindexter 1984 | ||
| Younis 1985 | ||
| Emko foam | Nonoxynol‐9 8% | Andolsek 1988 |
| Youssef 1987 | ||
| Ortho foaming tablet | Nonoxynol‐9 100 mg | Chompootaweep 1990 |
| Ghunney 1987 | ||
| Klufio 1988 | ||
| Ruoff 1988 | ||
| Ortho tablet | Nonoxynol‐9 100 mg | Kazi 1992 |
| Lamptey 1985 | ||
| Poindexter 1984 | ||
| Younis 1985 | ||
| Ortho tablet | Nonoxynol‐9 100 mg | Raymond 1999 |
| VCF film | Nonoxynol‐9 72 mg | Raymond 1999 |
| Advantage S gel | Nonoxynol‐9 52.5 mg | Raymond 2004 |
| Ortho Conceptrol gel | Nonoxynol‐9 100 mg | Raymond 2004 |
| Ortho Conceptrol gel | Nonoxynol‐9 150 mg | Raymond 2004 |
| Ortho Conceptrol film | Nonoxynol‐9 100 mg | Raymond 2004 |
| Encare suppository | Nonoxynol‐9 100 mg | Raymond 2004 |
Abdelsalaam 1984 compared the Neo Sampoon foaming tablet (menfegol 60 mg) and the Emko vaginal tablet (nonoxynol‐9 100 mg) among 200 women at a university hospital in Egypt. The duration of the trial was 12 months.
Andolsek 1988 conducted a similar trial comparing the Neo Sampoon tablets versus Emko vaginal foam among 271 women in Ljubljana (former Yugoslavia). The trial took place at a university medical center and followed women for 12 months.
Chi 1987 compared the Collatex vaginal sponge (the predecessor of the Today vaginal sponge) with the Neo Sampoon foaming tablet. The Collatex sponge contained 1.15 g of nonoxynol‐9 and was designed to provide 48 hours of protection. The Neo Sampoon foaming tablet contains menfegol 60 mg. A total of 1299 women participated at the four sites, which were Belgrade and Maribor (former Yugoslavia), Taiwan and Bangladesh. Follow up lasted 12 months.
Chompootaweep 1990 compared foaming vaginal tablets containing either nonoxynol‐9 (100 mg) or menfegol (60 mg). A total of 102 participants were recruited at three different sites: a factory clinic, a university clinic, and a health center. Observation continued for 12 months.
Ghunney 1987 compared two Ortho vaginal tablets in a clinic in Ghana. One contained nonoxynol‐9 100 mg, and the other contained menfegol 60 mg. Only 27 of the planned 150 women were enrolled, and the study was closed prematurely due to recruitment difficulties.
Kazi 1992 compared the Neo Sampoon tablet versus the Ortho Conceptrol tablet containing nonoxynol‐9 100 mg. The trial took place at nine sites in Pakistan and enrolled 172 women for 12 months of observation.
Based at a teaching hospital in Ghana, Klufio 1988 compared the Ortho vaginal tablets containing either nonoxynol‐9 100 mg or menfegol 60 mg in 150 women.
Lamptey 1985 compared the Neo Sampoon vaginal tablet (containing menfegol 60 mg) with two different brands of vaginal tablets (each containing nonoxynol‐9 100 mg). The trial included two sites in Ghana; one was a teaching hospital and the other was a polyclinic. Three hundred women were recruited; the observation period lasted 12 months.
In Texas, Poindexter 1984 randomized 110 women to either the Ortho vaginal tablet (nonoxynol‐9 100 mg) or the Emko vaginal tablet (nonoxynol‐9 100 mg). Recruitment took place at a university medical center and three family planning clinics. Follow up was 12 months.
A multicenter trial evaluated whether the vaginal contraceptive film should be distributed in commodities programs of the U.S. Agency for International Development (Raymond 1999). The spermicidal tablet was already being distributed, and evaluation was requested to inform a decision about whether to include the film. The VCF vaginal contraceptive film contains nonoxynol‐9 72 mg; the comparison was a foaming vaginal tablet containing 100 mg of the same active agent. The trial was conducted at eight sites in Mexico, Ecuador, Guatemala, Ghana, and the U.S. A total of 765 women were enrolled; observation lasted 28 weeks.
Another trial at 14 sites in the U.S. evaluated different doses of, and vehicles for, nonoxynol‐9 (Raymond 2004). By using five different treatments, the investigators were able to compare three different doses of nonoxynol‐9 (52.5 mg, 100 mg, and 150 mg) in gels and three different formulations (gel, film, and suppository) with the same dose of spermicide (100 mg). A total of 1536 women were enrolled; the observation period lasted 30 weeks.
Ruoff 1988 compared the Ortho foaming tablet containing either nonoxynol‐9 100 mg or menfegol 60 mg. The trial took place at clinics in three different U.S. states. Only 60 of the planned 150 participants were enrolled, and the trial was stopped prematurely because of recruitment difficulties.
At a university hospital in Egypt, Younis 1985 randomized 140 women to either the Ortho or Emko vaginal tablets (each containing nonoxynol‐9 100 mg) and followed them for 12 months.
Youssef 1987 compared the Neo Sampoon vaginal tablet with Emko vaginal foam. The dose of nonoxynol‐9 contained in one applicator of the latter was not specified in the report; the only information provided is that the concentration was 8%. The trial was conducted in one clinic in Egypt. The duration of the study was 12 months, and a total of 349 women participated.
Risk of bias in included studies
Chi 1987 featured high losses from the analysis by six months. Of 1299 participants enrolled at four sites, only 816 (63%) provided information at six months. The problem was most acute at the Bangladesh site, where only 39% returned at six months including just 12% of those randomized to the sponge. The study researchers did not present pregnancy rates for that site. Large losses of participants after randomization make the trial results suspect.
Chompootaweep 1990 had acceptable randomization and blinding of participants and clinicians as to treatment. Four participants were inappropriately dropped from analysis after randomization for non‐compliance. Losses from analysis were high; only 47% of participants (48 of 102) provided information at the final scheduled visit at 12 months. These losses undermine the interpretation of the results.
Lamptey 1985 also had an appropriate method of randomization, but there was no blinding of participants or researchers. The total losses of participants after randomization cannot be determined from the published report. Discontinuations were frequent; those who stopped use of the spermicide by 12 months included 33 of 99 assigned to Neo Sampoon, 47 of 101 assigned to the Ortho vaginal tablet, and 57 of 100 assigned to the Emko vaginal tablet.
Raymond 1999 featured excellent methods. A computer‐generated sequence was used to develop random‐permuted blocks of varying size. Allocation concealment was accomplished by sequentially‐numbered, sealed, opaque envelopes with method‐indicator cards. A formal sample size analysis was provided. Analysts were blinded as to treatment, although participants and investigators were not. When one planned interim analysis yielded higher failure rates than anticipated, all participants were advised and asked to sign a supplementary informed consent document. About 24% of participants discontinued the method early or were lost to follow up.
Raymond 2004 used similar rigorous methods. Computer‐generated random‐permuted blocks of randomly varied sizes were used for treatment assignment. Allocation concealment was assured by telephone calls to a central randomization center. A Data and Safety Monitoring Board oversaw the trial and performed one planned interim analysis, which did not influence the conduct of the trial. Blinding of participants and investigators was not done. The primary analysis included all participants who provided any follow‐up information until they no longer used the spermicide as their primary contraceptive method. In the intention‐to‐treat analysis, participants were kept in the analysis for the full seven months or until they were lost to follow up. After considering sample size and power issues and financial and time limitations, the investigators aimed for a total enrollment of 1800 women. Because recruitment proved difficult, enrollment was stopped at 1536. Fifty‐one women had no follow‐up information after admission, so the primary analysis included 1485 participants. Losses of participants after randomization were common. Approximately 39% of participants either discontinued the trial early or were deemed lost to follow up. No important disparities in these losses were seen among the five treatment groups, however. Overall, participants who dropped out had characteristics that suggested a higher risk of pregnancy than those who were retained.
The trials conducted by Family Health International in the 1980s had common methods. These trials included published (Youssef 1987) and unpublished reports (Abdelsalaam 1984; Andolsek 1988; Ghunney 1987; Kazi 1992; Klufio 1988; Poindexter 1984; Ruoff 1988; Younis 1985). Randomization was done centrally by random‐permuted blocks with a computer‐generated sequence of numbers. Allocation concealment was achieved by using method‐indicator cards in sealed, opaque, sequentially‐numbered envelopes distributed to the research sites. Data were transmitted to Family Health International, where the analyses were done. Exclusion of participants because of protocol violations occurred in several reports, and losses to follow up ranged widely. In addition, recruitment problems were serious at some sites (Ghunney 1987; Ruoff 1988), leading to premature closure of the trials.
Effects of interventions
Where available, the 12‐month life‐table rates per 100 women are presented for pregnancy and for discontinuation due to discomfort. Studies with shorter follow‐up periods reported the six‐month rates or probabilities. Some studies grouped discomfort with other personal reasons, so the outcome categories are described along with the results. A few trials reported the Pearl index, which represents the number of unintended pregnancies per 100 woman‐years of use. In these studies, the Pearl index was usually calculated with 12‐month data, but trials of shorter length used 6‐month data. The time frames are given with the specific results.
Chi 1987 compared the Collatex sponge (nonoxynol‐9 1.15 g) and Neo Sampoon tablet (menfegol 60 mg). Pregnancy rates varied widely by site, with rates five times higher in Taiwan than in Belgrade. Bangladesh was excluded from the pregnancy rates due to losses. Life‐table pregnancy rates at 12 months ranged from 3.8 to 18.2 per 100 women with the sponge and from 6.2 to 29.9 with the Neo Sampoon tablet. Results for the two methods were not significantly different. At all study sites, participants found the insertion of the sponge to be more difficult than insertion of the tablet. However, complaints of burning or stinging vaginal discharge were more common with the Neo Sampoon tablet than with the sponge; all four sites concurred. The study reported personal reasons for discontinuation, which included product‐related reasons, discomfort, and other reasons such as no confidence in the method. At six months, the discontinuation rates for these personal reasons were slightly higher for the sponge. At 12 months, two sites had slightly higher rates for the sponge than the tablet. These differences were not significant, however.
Four trials performed a blinded comparison of vaginal foaming tablets with either nonoxynol‐9 100 mg or menfegol 60 mg as the active agent (Chompootaweep 1990; Ghunney 1987; Klufio 1988; Ruoff 1988). Pregnancy rates among users of the two products were comparable over 6 and 12 months of use. Some trials had small numbers, e.g., 27 participants in a Ghana trial (Ghunney 1987), so pregnancy rates may be imprecise for single studies. Estimates for the Pearl index were also comparable for the two methods. Life‐table discontinuation rates for discomfort were available from the two larger trials in Thailand (Chompootaweep 1990) and Ghana (Klufio 1988). The rates ranged from 5.8 to 13.5 for nonoxynol‐9 and from 1.5 to 16.2 for menfegol, but they were not significantly different. In Klufio 1988, the 12‐month discontinuation rates for medical reasons were 9.0 for the menfegol and zero for the nonoxynol‐9. The difference was significant.
Three trials compared the Neo Sampoon tablet with either the Ortho vaginal tablet (Kazi 1992; Lamptey 1985) or the Emko vaginal tablet (Abdelsalaam 1984; Lamptey 1985). The Neo Sampoon tablet contained menfegol 60 mg and the Ortho and Emko tablets each had 100 mg of nonoxynol‐9. In Ghana (Lamptey 1985), the 12‐month life‐table pregnancy rates were similar for the Neo Sampoon, Ortho vaginal, and Emko tablets. In Pakistan (Kazi 1992), the 12‐month rates were 15.2 for menfegol and 22.5 for the Ortho tablet, but the study did not have the power to detect a significant difference. In Egypt (Abdelsalaam 1984), the six‐month pregnancy rates were also similar for menfegol and the Emko nonoxynol‐9. Only Lamptey 1985 provided the Pearl index, and the figures were 10.6 for menfegol, 13.8 for Ortho nonoxynol‐9, and 17.9 for Emko nonoxynol‐9.
The discontinuation rates for discomfort or medical reasons varied across these three studies. In Abdelsalaam 1984, the six‐month discontinuation rates for discomfort were similar for menfegol and the Emko tablet. Discontinuation rates were also similar for medical and product‐related reasons. In Kazi 1992, the 12‐month discontinuation rates for medical reasons (including discomfort) were similar for the two groups but somewhat higher overall. Lamptey 1985 noted significant differences in the 12‐month discontinuation rates for discomfort. The rates were zero for menfegol, 2.7 for the Ortho nonoxynol‐9, and 12.8 for the Emko tablet.
Three trials compared the Ortho vaginal tablet with the Emko vaginal tablet, each of which contained nonoxynol‐9 100 mg (Lamptey 1985; Poindexter 1984; Younis 1985). The 12‐month life‐table pregnancy rates were nearly identical in Lamptey 1985 and Younis 1985. The Pearl index results from Lamptey 1985 were given earlier. Discontinuations because of discomfort by 12 months were divergent, however. In Ghana (Lamptey 1985), Emko tablets had a discontinuation rate of 12.8 versus 2.7 for the Ortho tablet, and the difference was significant. In Egypt (Younis 1985), the rate was nearly twice as high for the Ortho tablet (11.6) as for the Emko (5.6), but the difference was not significant. The third trial (Poindexter 1984) compared the same two tablets, although the observation period was 6 months rather than 12. In this small U.S. study, discontinuation rates for pregnancy or discomfort were similar.
Two trials (Youssef 1987; Andolsek 1988) compared the Neo Sampoon tablet (menfegol 60 mg) with Emko foam (nonoxynol‐9 8%) over 12 months of use. Life‐table pregnancy rates were similar for the two methods in both trials. Discontinuation rates due to discomfort were also similar. Overall, rates were higher in Andolsek 1988 than in Youssef 1987.
Raymond 1999 found similar results with the vaginal contraceptive film and vaginal tablet, which contained nonoxynol‐9 72 mg and 100 mg, respectively. Conducted at eight international sites, the trial found the six‐month probabilities of pregnancy to be 28% for the tablet and 25% for the film. The Pearl index was calculated with the six‐month data, and the figures were 67.4 for the tablet and 59.8 for the film. Acceptability was addressed in a separate report; it revealed mixed results. Slightly more women assigned to the film liked their method "very much" (55%) as compared with those randomized to the tablet (50%). On the other hand, somewhat fewer participants assigned to the film reported having had no problems with the method (30%) compared with those assigned to the tablet (37%). The differences were not significant. Acceptability varied considerably by study site. In general, the film was more likely to stick to fingers and the tablet was easier to insert, although more women considered the tablet messy.
In Raymond 2004, the gel containing the lowest dose of nonoxynol‐9 (52.5 mg) was significantly less effective in preventing pregnancy than were the higher doses (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. The three different formulations (gel, film, and vaginal suppository) with 100 mg of nonoxynol‐9 had similar efficacy. The probabilities of pregnancy were 12% with the 100 mg film and 10% with the 100 mg suppository.
All the spermicide products were safe (Raymond 2004). Thirty‐four serious adverse events occurred during the trial, none of which was judged related to the spermicide. The seven‐month probability did not differ among the groups for vaginal candidiasis, bacterial vaginosis, irritation without infection, and urinary tract infection.
Gel was more acceptable to women than the Encare suppository (Raymond 2004). Significantly more women who used the 100 mg gel liked it "very much" compared to those who used the 100 mg film or the 100 mg suppository. The percentages were 49% for the gel, 41% for the film, and 34% for the suppository.
Discussion
A striking range of contraceptive efficacy with vaginal spermicides has been reported to date. Percentages for unintended pregnancy in the first year of use are 18% for perfect use and 28% for typical use (Trussell 2011). In the international trial of Raymond 1999, approximately a fifth of all participants became pregnant within six months with either the VCF film or the Conceptrol tablet. In contrast, in Egypt, the 12‐month life‐table rates of pregnancy were 2.8 for users of the Neo Sampoon tablet and 2.1 for Emko foam users (Youssef 1987). These wide variations presumably reflect important differences in fecundability as well as compliance and continuation with the assigned product. In addition, some studies reported more meticulous methods than others for follow up, which can affect the ascertainment of pregnancy data. However, poor trial quality was a generic problem.
The efficacy of spermicides may be dose‐related. The gel containing only 52.5 mg of nonoxynol‐9 was associated with a higher pregnancy risk than were gels containing higher doses of the same agent in Raymond 2004.
Several differences emerged in discontinuation rates due to discomfort or medical problems. For example, women using the Collatex sponge were slightly more likely to discontinue because of problems and personal reasons than were those using the Neo Sampoon tablet (Chi 1987). In another trial, those using the Neo Sampoon tablet were less likely to discontinue due to discomfort than were women using Emko tablets (Lamptey 1985).
In the five‐arm trial of Raymond 2004, clear differences emerged in the acceptability of different vehicles. A gel was more acceptable than the vaginal suppository. A higher proportion of women liked the gel "very much" compared with the Encare suppository and the Ortho Contraceptive film.
Losses of participants after randomization threaten trial validity (Schulz 2002). These trials were all hampered by retention problems. In some studies, many participants discontinued their method prematurely, and the investigators made no further attempts to track these women. Other participants were lost to follow‐up despite efforts to locate them and determine outcomes. Raymond 2004 examined characteristics of those who withdrew before the planned end of the observation period in the large U.S. trial of five products (Raymond 2004). About 40% of women did not complete the study for reasons other than pregnancy. Those more likely to discontinue early were younger, unmarried women with intercourse at least eight times per month and were enrolled at a university site or a site that had slow enrollment. However, many participants without these features also quit early. Hence, targeting retention efforts in future trials will be difficult. A '5‐and‐20' rule of thumb suggests that losses after randomization of 5% or less are unlikely to influence trial validity. In contrast, losses of 20% or more make results suspect (Strauss 2005).
Authors' conclusions
Implications for practice.
Most trials to date were so poorly done that drawing conclusions about the comparative efficacy of spermicides is not possible. The pregnancy probabilities varied widely in reported trials, but have been as high as 28% over six months of use (Raymond 1999). Few important differences emerged between products, although a gel containing nonoxynol‐9 52.5 mg was inferior to two other products tested in one trial (Raymond 2004). Aside from this one product, personal characteristics and behavior of users may be more important than characteristics of the spermicide products themselves in determining the likelihood of pregnancy. Gel may be a more acceptable spermicide formulation than film or vaginal suppository (Raymond 2004). In general use outside of research settings, spermicides fall into the bottom tier of contraceptive effectiveness (Steiner 2003). On the other hand, advantages of spermicides for women at low risk of HIV infection include easy availability, moderate cost, absence of systemic effects, and control by the woman.
Implications for research.
Randomized controlled trials of spermicides pose daunting challenges for investigators. Because of the limited appeal and effectiveness of spermicides, recruitment to recent trials has been difficult. In addition, many women discontinued their assigned method before the end of the trial (Raymond 2004). Women who discontinue their assigned method should be followed until the end of the trial; this often did not happen in published trials. In several studies, losses to follow up after randomization were high as well. As a result, many reports are difficult to interpret. Future trials need to address the dual challenges of recruitment and retention of participants. Shorter observation periods may enhance compliance with the assigned treatments. Innovative approaches may be needed to achieve high rates of follow up (Roddy 2002; Raymond 2004).
What's new
| Date | Event | Description |
|---|---|---|
| 5 August 2013 | New citation required but conclusions have not changed | Searches updated. No new trials were eligible. Two trials were excluded (Steiner 1998; Burke 2010). |
History
Protocol first published: Issue 2, 2005 Review first published: Issue 4, 2005
| Date | Event | Description |
|---|---|---|
| 20 September 2010 | New search has been performed | Searches were updated, but no new trials were found. Added searches of ClinicalTrials.gov and ICTRP. One ongoing trial was added (Blithe 2010a). |
| 25 April 2008 | Amended | Converted to new review format. |
| 15 April 2005 | New citation required and conclusions have changed | Substantive amendment |
Acknowledgements
Carol Manion of FHI assisted with the literature searches.
Appendices
Appendix 1. Search 2013
MEDLINE via PubMed (01 Jun 2010 to 05 Aug 201)
((spermicides OR spermatocidal agents) AND contracept*) NOT (stds/aids/hiv infection)
Filter: Clinical trial
CENTRAL (2010 to 01 Aug 2013)
spermicide in Title, Abstract, or Keywords
POPLINE (2010 to 01 Aug 2013)
(spermicidal contraceptive agents AND (contraception OR contraceptive agents)) NOT (sexually transmitted diseases OR HIV OR AIDS)
LILACS (2010 to 01 Aug 2013)
(spermicide or spermicides or spermatocidal agents or agentes espermatocidas or espermaticidas).
ClinicalTrials.gov (01 Jun 2010 to 01 Aug 2013)
Search terms: spermicide Condition: NOT cancer Intervention: contraceptive OR contraception Study type: interventional studies Gender: studies with female participants
ICTRP (01 Jun 2010 to 01 Aug 2013)
Condition: contraceptive OR contraception Intervention: spermicide
Appendix 2. Previous searches
2010
MEDLINE via PubMed (2008 to 20 Sep 2010)
(((spermicides OR spermatocidal agents) AND contracept*) AND (clinical trials OR comparative trials)) NOT (stds/aids/hiv infection)
CENTRAL (2008 to 20 Sep 2010)
spermicide in Title, Abstract, or Keywords
ClinicalTrials.gov (21 Sep 2010)
Search terms: spermicide Intervention: contraceptive OR contraception Study type: interventional studies Gender: studies with female participants
ICTRP (20 Sep 2010)
Condition: contraceptive OR contraception Intervention: spermicide
2005 (initial review) and 2008
These searches included the 2010 strategies listed for MEDLINE and CENTRAL plus the following:
POPLINE
(((spermicides/spermicidal contraceptive agents) & contracept*) & clinical trials) !(sexually transmitted disease*/hiv infection/acquired immune deficiency syndrome)
LILACS
(spermicide or spermicides or spermatocidal agents or agentes espermatocidas or espermaticidas)
EMBASE
(((Spermicide? or spermicidal agent) & contracept?) and (clinical trials or comparative studies)) not (HIV or AIDS or acquired( )immune( )deficiency( )syndrome or sexually( )transmitted( )disease? or STD?)
Data and analyses
Comparison 1. Collatex vaginal sponge (nonoxynol‐9 1.15 g) versus Neo Sampoon tablet (menfegol 60 mg).
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Life‐table rates per 100 women for pregnancy (12‐month) | Other data | No numeric data | ||
| 2 Life‐table rates per 100 women for discontinuation due to personal reasons (6‐month) | Other data | No numeric data | ||
| 3 Life‐table rates per 100 women for discontinuation due to personal reasons (12‐month) | Other data | No numeric data |
1.1. Analysis.
Comparison 1 Collatex vaginal sponge (nonoxynol‐9 1.15 g) versus Neo Sampoon tablet (menfegol 60 mg), Outcome 1 Life‐table rates per 100 women for pregnancy (12‐month).
| Life‐table rates per 100 women for pregnancy (12‐month) | |||
|---|---|---|---|
| Study | Site | Nonoxynol‐9 sponge | Menfegol tablet |
| Chi 1987 | Belgrade | 3.8 | 6.2 |
| Chi 1987 | Maribor | 11.7 | 12.7 |
| Chi 1987 | Taiwan | 18.2 | 29.9 |
1.2. Analysis.
Comparison 1 Collatex vaginal sponge (nonoxynol‐9 1.15 g) versus Neo Sampoon tablet (menfegol 60 mg), Outcome 2 Life‐table rates per 100 women for discontinuation due to personal reasons (6‐month).
| Life‐table rates per 100 women for discontinuation due to personal reasons (6‐month) | |||
|---|---|---|---|
| Study | Site | Nonoxynol‐9 sponge | Menfegol tablet |
| Chi 1987 | Begrade | 5.3 | 4.3 |
| Chi 1987 | Maribor | 9.1 | 7.7 |
| Chi 1987 | Taiwan | 44.9 | 32.6 |
| Chi 1987 | Bangladesh | 88.5 | 20.2 |
1.3. Analysis.
Comparison 1 Collatex vaginal sponge (nonoxynol‐9 1.15 g) versus Neo Sampoon tablet (menfegol 60 mg), Outcome 3 Life‐table rates per 100 women for discontinuation due to personal reasons (12‐month).
| Life‐table rates per 100 women for discontinuation due to personal reasons (12‐month) | |||
|---|---|---|---|
| Study | Site | Nonoxynol‐9 sponge | Menfegol tablet |
| Chi 1987 | Belgrade | 13.0 | 9.5 |
| Chi 1987 | Maribor | 14.8 | 15.6 |
| Chi 1987 | Taiwan | 48.9 | 49.5 |
| Chi 1987 | Bangladesh | 97.7 | 22.3 |
Comparison 2. Ortho vaginal tablets: nonoxynol‐9 100 mg versus menfegol 60 mg.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Life‐table rates per 100 women for pregnancy (6‐month) | Other data | No numeric data | ||
| 2 Life‐table rates per 100 women for pregnancy (12‐month) | Other data | No numeric data | ||
| 3 Pearl index per 100 woman‐years | Other data | No numeric data | ||
| 4 Life‐table rates per 100 women for discontinuation due to discomfort | Other data | No numeric data |
2.1. Analysis.
Comparison 2 Ortho vaginal tablets: nonoxynol‐9 100 mg versus menfegol 60 mg, Outcome 1 Life‐table rates per 100 women for pregnancy (6‐month).
| Life‐table rates per 100 women for pregnancy (6‐month) | ||
|---|---|---|
| Study | Nonoxynol‐9 tablet | Menfegol tablet |
| Chompootaweep 1990 | 15.2 | 13.3 |
| Ghunney 1987 | 11.8 | 0 |
| Klufio 1988 | 2.9 | 3.1 |
| Ruoff 1988 | 10.3 | 14.7 |
2.2. Analysis.
Comparison 2 Ortho vaginal tablets: nonoxynol‐9 100 mg versus menfegol 60 mg, Outcome 2 Life‐table rates per 100 women for pregnancy (12‐month).
| Life‐table rates per 100 women for pregnancy (12‐month) | ||
|---|---|---|
| Study | Nonoxynol‐9 tablet | Menfegol tablet |
| Chompootaweep 1990 | 31.7 | 25.3 |
| Klufio 1988 | 14.0 | 15.8 |
2.3. Analysis.
Comparison 2 Ortho vaginal tablets: nonoxynol‐9 100 mg versus menfegol 60 mg, Outcome 3 Pearl index per 100 woman‐years.
| Pearl index per 100 woman‐years | |||
|---|---|---|---|
| Study | Time frame | Nonoxynol‐9 tablet | Menfegol tablet |
| Chompootaweep 1990 | 12 months | 37.7 | 30.0 |
| Ghunney 1987 | 6 months | 13.4 | 0 |
| Klufio 1988 | 6 months | 16.2 | 15.9 |
| Ruoff 1988 | 12 months | 36.9 | 45.1 |
2.4. Analysis.
Comparison 2 Ortho vaginal tablets: nonoxynol‐9 100 mg versus menfegol 60 mg, Outcome 4 Life‐table rates per 100 women for discontinuation due to discomfort.
| Life‐table rates per 100 women for discontinuation due to discomfort | |||
|---|---|---|---|
| Study | Time frame | Nonoxynol‐9 tablet | Menfegol tablet |
| Chompootaweep 1990 | 6‐month | 10.1 | 13.4 |
| Chompootaweep 1990 | 12‐month | 13.5 | 16.2 |
| Klufio 1988 | 6‐month | 5.8 | 1.5 |
| Klufio 1988 | 12‐month | 5.8 | 1.5 |
Comparison 3. Ortho or Emko tablet (nonoxynol‐9 100 mg) versus Neo Sampoon tablet (menfegol 60 mg).
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Life‐table rates per 100 women for pregnancy | Other data | No numeric data | ||
| 2 Life‐table rates per 100 women for discontinuation due to discomfort and/or medical reasons | Other data | No numeric data |
3.1. Analysis.
Comparison 3 Ortho or Emko tablet (nonoxynol‐9 100 mg) versus Neo Sampoon tablet (menfegol 60 mg), Outcome 1 Life‐table rates per 100 women for pregnancy.
| Life‐table rates per 100 women for pregnancy | ||||
|---|---|---|---|---|
| Study | Time frame | Brand of nonoxynol‐9 | Nonoxynol‐9 100 mg | Menfegol 60 mg |
| Abdelsalaam 1984 | 6‐month | Emko | 10.6 | 6.7 |
| Kazi 1992 | 12‐month | Ortho | 22.5 | 15.2 |
| Lamptey 1985 | 12‐month 12‐month | Ortho Emko | 11.3 12.5 | 9.6 9.6 |
3.2. Analysis.
Comparison 3 Ortho or Emko tablet (nonoxynol‐9 100 mg) versus Neo Sampoon tablet (menfegol 60 mg), Outcome 2 Life‐table rates per 100 women for discontinuation due to discomfort and/or medical reasons.
| Life‐table rates per 100 women for discontinuation due to discomfort and/or medical reasons | |||||
|---|---|---|---|---|---|
| Study | Time frame | Nonoxynol‐9 brand | Nonoxynol‐9 100 mg | Menfegol 60 mg | Assessment |
| Abdelsalaam 1984 | 6‐month | Emko | 2.4 | 5.8 | discomfort |
| Kazi 1992 | 12‐month | Ortho Conceptrol | 23.9 | 17.4 | medical reasons including discomfort |
| Lamptey 1985 | 12‐month | Ortho Vaginal Emko | 2.7 12.8 | 0 0 | discomfort |
Comparison 4. Ortho tablet (nonoxynol‐9 100 mg) versus Emko tablet (nonoxynol‐9 100 mg).
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Life‐table rates per 100 women for pregnancy | Other data | No numeric data | ||
| 2 Life‐table rates per 100 women for discontinuation due to discomfort | Other data | No numeric data |
4.1. Analysis.
Comparison 4 Ortho tablet (nonoxynol‐9 100 mg) versus Emko tablet (nonoxynol‐9 100 mg), Outcome 1 Life‐table rates per 100 women for pregnancy.
| Life‐table rates per 100 women for pregnancy | |||
|---|---|---|---|
| Study | Time frame | Nonoxynol‐9 Ortho | Nonoxynol‐9 Emko |
| Lamptey 1985 | 12‐month | 11.3 | 12.5 |
| Poindexter 1984 | 6‐month | 12.4 | 13.2 |
| Younis 1985 | 12‐month | 19.0 | 18.7 |
4.2. Analysis.
Comparison 4 Ortho tablet (nonoxynol‐9 100 mg) versus Emko tablet (nonoxynol‐9 100 mg), Outcome 2 Life‐table rates per 100 women for discontinuation due to discomfort.
| Life‐table rates per 100 women for discontinuation due to discomfort | |||
|---|---|---|---|
| Study | Time frame | Nonoxynol‐9 Ortho | Nonoxynol‐9 Emko |
| Lamptey 1985 | 12‐month | 2.7 | 12.8 |
| Poindexter 1984 | 6‐month | 5.9 | 15.6 |
| Younis 1985 | 12‐month | 11.6 | 5.8 |
Comparison 5. Emko foam (nonoxynol‐9 8% concentration) versus Neo Sampoon tablet (menfegol 60 mg).
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Life‐table rates per 100 women for pregnancy (12‐month) | Other data | No numeric data | ||
| 2 Life‐table rates per 100 women for discontinuation due to discomfort (12‐month) | Other data | No numeric data |
5.1. Analysis.
Comparison 5 Emko foam (nonoxynol‐9 8% concentration) versus Neo Sampoon tablet (menfegol 60 mg), Outcome 1 Life‐table rates per 100 women for pregnancy (12‐month).
| Life‐table rates per 100 women for pregnancy (12‐month) | ||
|---|---|---|
| Study | Nonoxynol‐9 8% foam | Menfegol tablet |
| Andolsek 1988 | 19.3 | 12.8 |
| Youssef 1987 | 2.1 | 2.8 |
5.2. Analysis.
Comparison 5 Emko foam (nonoxynol‐9 8% concentration) versus Neo Sampoon tablet (menfegol 60 mg), Outcome 2 Life‐table rates per 100 women for discontinuation due to discomfort (12‐month).
| Life‐table rates per 100 women for discontinuation due to discomfort (12‐month) | ||
|---|---|---|
| Study | Nonoxynol‐9 8% foam | Menfegol tablet |
| Andolsek 1988 | 32.1 | 24.0 |
| Youssef 1987 | 2.6 | 2.6 |
Comparison 6. Ortho tablet (nonoxynol‐9 100 mg) versus VCF film (nonoxynol‐9 72 mg).
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Probability of pregnancy through six months of typical use | Other data | No numeric data |
6.1. Analysis.
Comparison 6 Ortho tablet (nonoxynol‐9 100 mg) versus VCF film (nonoxynol‐9 72 mg), Outcome 1 Probability of pregnancy through six months of typical use.
| Probability of pregnancy through six months of typical use | ||
|---|---|---|
| Study | Tablet 100 mg | VCF film 72 mg |
| Raymond 1999 | 28.0 | 24.9 |
Comparison 7. Nonoxynol‐9 gels (52.5 mg, 100 mg, 150 mg); Nonoxynol‐9 film 100 mg; Nonoxynol‐9 suppository 100 mg.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Probability of pregnancy through six months of typical use | Other data | No numeric data | ||
| 2 Discontinued method early | Other data | No numeric data | ||
| 3 Liked the method "very much" | Other data | No numeric data |
7.1. Analysis.
Comparison 7 Nonoxynol‐9 gels (52.5 mg, 100 mg, 150 mg); Nonoxynol‐9 film 100 mg; Nonoxynol‐9 suppository 100 mg, Outcome 1 Probability of pregnancy through six months of typical use.
| Probability of pregnancy through six months of typical use | |||
|---|---|---|---|
| Study | Brand name | Dose | Pregnancy probability |
| Raymond 2004 | Advantage S gel | 52.5 mg | 22.2% |
| Raymond 2004 | Ortho Conceptrol gel | 100 mg | 15.5% |
| Raymond 2004 | Ortho Conceptrol gel | 150 mg | 14.0% |
| Raymond 2004 | Ortho Conceptrol film | 100 mg | 11.9% |
| Raymond 2004 | Encare suppository | 100 mg | 10.0% |
7.2. Analysis.
Comparison 7 Nonoxynol‐9 gels (52.5 mg, 100 mg, 150 mg); Nonoxynol‐9 film 100 mg; Nonoxynol‐9 suppository 100 mg, Outcome 2 Discontinued method early.
| Discontinued method early | |||
|---|---|---|---|
| Study | Brand name | Dose | Discontinued |
| Raymond 2004 | Advantage S gel | 52.5 mg | 15% |
| Raymond 2004 | Ortho Conceptrol gel | 100 mg | 17% |
| Raymond 2004 | Ortho Conceptrol gel | 150 mg | 18% |
| Raymond 2004 | Ortho Conceptrol film | 100 mg | 18% |
| Raymond 2004 | Encare suppository | 100 mg | 17% |
7.3. Analysis.
Comparison 7 Nonoxynol‐9 gels (52.5 mg, 100 mg, 150 mg); Nonoxynol‐9 film 100 mg; Nonoxynol‐9 suppository 100 mg, Outcome 3 Liked the method "very much".
| Liked the method "very much" | |||
|---|---|---|---|
| Study | Brand name | Dose | Liked "very much" |
| Raymond 2004 | Advantage S gel | 52.5 mg | 46% |
| Raymond 2004 | Ortho Conceptrol gel | 100 mg | 49% |
| Raymond 2004 | Ortho Conceptrol gel | 150 mg | 43% |
| Raymond 2004 | Ortho Conceptrol film | 100 mg | 41% |
| Raymond 2004 | Encare suppository | 100 mg | 34% |
Characteristics of studies
Characteristics of included studies [ordered by study ID]
Abdelsalaam 1984.
| Methods | Randomized controlled trial in Zagazig, Egypt. Randomization by computer‐generated sequence | |
| Participants | 200 women aged 18 to 40 years, not pregnant or infertile and without anatomical abnormalities of the lower genital tract. Recruitment from January to April 1982. | |
| Interventions | Neo Sampoon foaming vaginal tablet (menfegol 60 mg; Eisai Company, Tokyo, Japan) versus Emko vaginal tablet (nonoxynol‐9 100 mg; Schering Corporation, Kenilworth, NJ). | |
| Outcomes | Pregnancy, acceptability, and safety measured by interview and physical examination at 1, 3, 6, and 12 months. | |
| Notes | Number of women returning for 12‐month visit 'low' in both groups, so data provided only through 6 months. Unpublished report from Family Health International, study 786, site 365. No sample size calculation provided. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Allocation concealment (selection bias) | Low risk | sequentially numbered, sealed opaque envelopes |
Andolsek 1988.
| Methods | Randomized controlled trial in Ljubljana (former Yugoslavia). Randomization by computer‐generated sequence | |
| Participants | 271 women aged 18 to 40 years, not pregnant or infertile and without anatomical abnormalities of lower genital tract. Recruitment from April 1982 to March 1985. | |
| Interventions | Neo Sampoon foaming vaginal tablet (menfegol 60 mg; Eisai Company, Tokyo, Japan) versus Emko vaginal foam (nonoxynol‐9 8%; Schering Corporation, Kenilworth, NJ) | |
| Outcomes | Pregnancy, acceptability, and safety measured at 1, 3, 6, and 12 months. | |
| Notes | Only 46% of participants completed 12 months of observation. Seven participants excluded from analysis because they never used the assigned method. Unpublished report from Family Health International study 785, site 20. No sample size calculation provided. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Allocation concealment (selection bias) | Low risk | sequentially numbered, sealed opaque envelopes |
Chi 1987.
| Methods | Randomized controlled trial in Belgrade and Maribor (former Yugoslavia) and one center each in Taiwan and Bangladesh. Randomization by computer‐generated sequence | |
| Participants | 1299 women aged 18 to 40 years, not infertile and with normal vaginal anatomy. A minimum of two menses since last pregnancy ended. Recruitment from 1979 to 1981. | |
| Interventions | Collatex vaginal contraceptive sponge (nonoxynol‐9 1.15 g) versus Neo Sampoon foaming tablets (menfegol 60 mg; Eisai Company, Tokyo, Japan). Collatex sponge could be used for up to 48 hours; Neo Sampoon could be used for a single coitus. | |
| Outcomes | Clinical acceptability, use patterns, and use effectiveness measured at 1 and 6 months of use | |
| Notes | 63% of participants completed 6‐month trial. No sample size calculation provided. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Allocation concealment (selection bias) | Low risk | sequentially numbered, sealed opaque envelopes |
Chompootaweep 1990.
| Methods | Randomized controlled trial at three sites in Bangkok, Thailand. Randomization by computer‐generated sequence | |
| Participants | 122 women aged 18 to 40 years, not pregnant or infertile and with normal vaginal anatomy. Must have had one menses since last pregnancy. Recruitment from July to November 1986. | |
| Interventions | Vaginal foaming tablets containing either nonoxynol‐9 100 mg or menfegol 60 mg (Ortho Pharmaceutical Corporation, Raritan, NJ). | |
| Outcomes | Pregnancy, acceptability, and continuation rates measured at 1, 3, 6, and 12 months. | |
| Notes | 47% completed 12‐month trial. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Allocation concealment (selection bias) | Low risk | sealed, opaque, sequentially‐numbered envelopes |
Ghunney 1987.
| Methods | Randomized controlled trial at one site in Accra, Ghana. Randomization by computer‐generated sequence | |
| Participants | 27 women aged 18 to 40 years, not pregnant or infertile and with no anatomical abnormalities of the lower genital tract. Recruitment from January 1985 to February 1987. | |
| Interventions | Vaginal foaming tablets containing either nonoxynol‐9 100 mg or menfegol 60 mg (Ortho Pharmaceutical Corp., Raritan, NJ). | |
| Outcomes | Pregnancy, acceptability, and continuation rates measured at 1, 3, 6, and 12 months. | |
| Notes | Difficulty in recruitment of planned 150 participants led to discontinuation of enrollment at only 27. 85% of participants completed 12 months of observation. No sample size calculation provided. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Allocation concealment (selection bias) | Low risk | sealed, opaque, sequentially‐numbered envelopes |
Kazi 1992.
| Methods | Randomized controlled trial at 9 sites in Pakistan. Randomization by computer‐generated sequence | |
| Participants | 172 women aged 18 to 40 years, not pregnant or infertile and without serious gynecological problems. | |
| Interventions | Neo Sampoon (menfegol 60 mg; Eisai Company, Tokyo, Japan) versus Conceptrol vaginal tablet (nonoxynol‐9 100 mg; Ortho Pharmaceutical Corporation, Raritan, NJ). Recruitment from July 1989 to February 1991. | |
| Outcomes | Pregnancy, acceptability, and continuation rates measured at 1, 3, 6, 9, and 12 months. | |
| Notes | Only 28% of participants completed 12 months of observation. Unpublished report of Family Health International study 7805. No sample size calculation provided. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Allocation concealment (selection bias) | Low risk | sealed, opaque, sequentially‐numbered envelopes |
Klufio 1988.
| Methods | Randomized controlled trial at one site in Accra, Ghana. Randomization by computer‐generated sequence | |
| Participants | 150 women aged 18 to 40 years, not pregnant or infertile with no anatomical abnormalities of the lower genital tract. Recruitment from December 1984 to January 1986. | |
| Interventions | Vaginal foaming tablets containing either nonoxynol‐9 100 mg or menfegol 60 mg (Ortho Pharmaceutical Corporation, Raritan, NJ). | |
| Outcomes | Pregnancy, acceptability, and continuation rates measured at 1, 3, 6, and 12 months. | |
| Notes | Only 59% of participants completed 12 months of observation. Unpublished report of Family Health International study 7798, site 0044. No sample size calculation provided. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Allocation concealment (selection bias) | Low risk | sealed, opaque, sequentially‐numbered envelopes |
Lamptey 1985.
| Methods | Randomized controlled trial at two sites in Accra, Ghana. Randomization by computer‐generated sequence. | |
| Participants | 300 women aged 18 to 40 years, not pregnant or infertile and with normal vaginal anatomy. Recruitment interval not specified. | |
| Interventions | Neo‐Sampoon vaginal tablet (menfegol 60 mg; Eisai Company, Tokyo, Japan) versus Ortho vaginal tablet (nonoxynol‐9 100 mg; Ortho Pharmaceutical Corporation, Raritan, NJ) versus Emko vaginal tablet (nonoxynol‐9 100 mg; Schering Corporation, Kenilworth, NJ). | |
| Outcomes | Pregnancy, acceptability, and continuation rates measured at 1, 3, 6, and 12 months. | |
| Notes | Proportion completing 12‐month trial unclear. No sample size calculation provided. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Allocation concealment (selection bias) | Low risk | sealed, opaque, sequentially‐numbered envelopes |
Poindexter 1984.
| Methods | Randomized controlled trial at several sites in Houston, Texas. Randomization by computer‐generated sequence. | |
| Participants | 110 women aged 18 to 40 years, not pregnant or infertile and without anatomical abnormalities of the lower genital tract. Recruitment from May 1982 to October 1983. | |
| Interventions | Ortho vaginal tablet (nonoxynol‐9 100 mg; Ortho Pharmaceutical Corporation, Raritan, NJ) versus Emko vaginal tablet (nonoxynol‐9 100 mg; Schering Corporation, Kenilworth, NJ). | |
| Outcomes | Pregnancy, acceptability, and continuation measured at 1, 3, 6, and 12 months. | |
| Notes | Improper exclusions of 3 participants after randomization. High losses after randomization; only 26% of participants completed 6 months of observation, and only 11% completed 12 months. Unpublished report of Family Health International study 793, site 225. No sample size calculation provided. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Allocation concealment (selection bias) | Low risk | sequentially‐numbered, opaque sealed envelopes |
Raymond 1999.
| Methods | Randomized controlled trial at 8 sites in Mexico, Ecuador, Guatemala, Ghana, and the U.S. Stratified (by center) randomization by computer‐generated sequence with random permuted blocks of 4 and 6. Sample size determined by requirements of the U.S. Food and Drug Administration (at least 200 women who either became pregnant or completed 6 months of use). Sample size was estimated to have 81% power to show significance with a one‐sided test (alpha 0.10) if the rates in the tablet and film groups were 12% and 19% at 6 months. | |
| Participants | 765 women aged 18 to 35 years, not infertile and at low risk of sexually‐transmitted diseases, >6 weeks from last pregnancy, not breastfeeding, and without symptoms of vaginitis. Trial conducted between 1995 and 1997. | |
| Interventions | VCF Vaginal Contraceptive Film (nonoxynol‐9 72 mg; Apothecus, Inc., Oyster Bay, NY) versus Conceptrol foaming tablets (nonoxynol‐9 100 mg; Ortho Pharmaceutical Corporation, Raritan, NJ). | |
| Outcomes | Pregnancy rates measured at 4, 12, 20, and 28 weeks. Acceptability measured by questionnaire at 4 weeks and at discontinuation. | |
| Notes | 94% of participants provided information at 28 weeks. 95% completed at least one questionnaire. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Allocation concealment (selection bias) | Low risk | sealed, sequentially‐numbered opaque envelopes |
Raymond 2004.
| Methods | Randomized controlled trial at 14 sites in the U.S. | |
| Participants | 1536 women aged 18 to 40 years, not infertile and at low risk of sexually‐transmitted disease. Trial conducted between 1998 and 2002. | |
| Interventions | Advantage S (nonoxynol‐9 52.5 mg; Columbia Laboratories, Inc., Miami, FL) versus Ortho Options Conceptrol Vaginal Contraceptive Gel (nonoxynol‐9 100 mg; Advanced Care Products, Skillman, NJ) versus Ortho Options Conceptrol Vaginal Contraceptive Gel (nonoxynol‐9 150 mg; Advanced Care Products) versus Ortho Options Contraceptive Film (nonoxynol‐9 100 mg; Advanced Care Products) versus Encare suppository (nonoxynol‐9 100 mg; Thompson Medical Co., Inc., West Palm Beach, FL). | |
| Outcomes | Pregnancy rates measured at 4, 17, and 30 weeks; safety measured through 7 months. Discontinuation from trial. Acceptability measured by questionnaire at 4 weeks and at final visit. | |
| Notes | Stratified randomization by computer‐generated sequence, using randomly varied block sizes. Sample size based on logistical and financial considerations; estimated power not described. Recruitment stopped short of goal of 1800 participants. 88% of participants provided information at 30 weeks. Characteristics of participants were correlated with discontinuation. 90% of participants completed at least one questionnaire. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Allocation concealment (selection bias) | Low risk | randomization by telephone call to central randomization center |
Ruoff 1988.
| Methods | Randomized controlled trial at 3 sites in the U.S. Randomization by computer‐generated sequence | |
| Participants | 61 women aged 18 to 40 years, not pregnant or infertile and without anatomical abnormalities of the lower genital tract. Recruitment from July 1984 to November 1986. | |
| Interventions | Vaginal foaming tablets containing either nonoxynol‐9 100 mg or menfegol 60 mg (Ortho Pharmaceutical Corp., Raritan, NJ). | |
| Outcomes | Pregnancy, acceptability, and continuation measured at 1, 3, 6, and 12 months. | |
| Notes | Difficulty in recruitment at all sites led to stopping enrollment at 61 instead of intended 150 participants. Four participants were improperly excluded after randomization. Only 11% of participants completed 12 months of observation. Unpublished report of Family Health International study 7799, sites 0220, 0930, and 0909. Sample size calculation not provided. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Allocation concealment (selection bias) | Low risk | sealed, opaque, sequentially‐numbered envelopes |
Younis 1985.
| Methods | Randomized controlled trial in Cairo, Egypt. Randomization by computer‐generated sequence | |
| Participants | 140 women aged 18 to 40 years, not infertile and without abnormalities of the lower genital tract. Recruitment from January to April 1983. | |
| Interventions | Ortho vaginal tablet (nonoxynol‐9 100 mg; Ortho Pharmaceutical Corporation, Raritan, NJ) versus Emko vaginal tablet (nonoxynol‐9 100 mg; Schering Corporation, Kenilworth, NJ). | |
| Outcomes | Pregnancy, acceptability, and continuation measured at 1, 3, 6, and 12 mo. | |
| Notes | Improper exclusion of two participants after randomization. Only 56% of participants completed 12 months of observation. Unpublished report of Family Health International study 793, site 314. Sample size calculation not provided. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Allocation concealment (selection bias) | Low risk | sealed, opaque, sequentially‐numbered envelopes |
Youssef 1987.
| Methods | Randomized controlled trial at one clinic in Alexandria, Egypt. Randomization by computer‐generated sequence. Sample size based on anticipated difference in pregnancy rates of 10% (not further specified). | |
| Participants | 349 women aged 18 to 40 years, not infertile, without abnormal vaginal anatomy, and with at least one menses since last pregnancy. | |
| Interventions | Neo‐Sampoon (menfegol 60 mg; Eisai Company, Tokyo, Japan) versus Emko foam (nonoxynol‐9 8%; Schering Corporation, Kenilworth, NJ) | |
| Outcomes | Pregnancy and discontinuation rates measured at 1, 3, 6, and 12 month. | |
| Notes | Proportion of participants providing information at 12 months is unclear. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Allocation concealment (selection bias) | Low risk | sealed, opaque, sequentially‐numbered envelopes |
Characteristics of excluded studies [ordered by study ID]
| Study | Reason for exclusion |
|---|---|
| Borko 1985 | Data from the clinical site (Maribor, Yugoslavia) are included in Chi 1987. |
| Burke 2010 | Phase III trial of spermicide that is not yet commercially available. Therefore, study did not meet the eligibility criteria. |
| Steiner 1998 | Feasibility study. Participants had been trying to get pregnant for <= 3 months and were willing to postpone pregnancy for one month. Restricted frequency and timing of intercourse; assessed pregnancy risk after one act of intercourse on day of ovulation. Ovulation assessed by home test. Participants at one site had difficulty reading test results; other two sites used a different test kit. |
| Xu 2003 | Not a randomized controlled trial. Communication with authors revealed alternate assignment to methods at each site. |
| Xu 2006 | Not a randomized controlled trial. Communication with author indicated alternate assignment to study groups. |
Contributions of authors
DA Grimes developed the concept and registered the title. He performed the literature search, and he did the primary data entry into RevMan. LM Lopez did the secondary data abstraction and edited the review. The other authors read, edited, and approved the review. LM Lopez also conducted the updates from 2008 to 2013.
Sources of support
Internal sources
No sources of support supplied
External sources
U. S. Agency for International Development, USA.
National Institute of Child Health and Human Development, USA.
Declarations of interest
DA Grimes has consulted with the pharmaceutical companies Bayer Healthcare Pharmaceuticals and Merck & Co, Inc.
EG Raymond conducted two of the included trials.
Edited (no change to conclusions)
References
References to studies included in this review
Abdelsalaam 1984 {unpublished data only}
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Andolsek 1988 {unpublished data only}
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Chi 1987 {published and unpublished data}
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Kazi 1992 {unpublished data only}
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Klufio 1988 {unpublished data only}
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Lamptey 1985 {published and unpublished data}
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Raymond 1999 {published and unpublished data}
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Younis 1985 {unpublished data only}
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Youssef 1987 {published data only}
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Xu 2003 {published data only}
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