Which of the following is a reason that diaphragms have a relatively high failure rate?

Contraceptive Technology Reports: An Analysis of the Today Sponge — Prepare for Its Return to the U.S.

Author:George Kovalevsky, MD, Assistant Professor, Department of Obstetrics and Gynecology, CONRAD, Eastern Virginia Medical School, Norfolk.

Peer Reviewer: Margaret Polaneczky, MD, Associate Professor of Obstetrics and Gynecology, Weill Medical College, Cornell University, New York City.

Introduction

The Today contraceptive sponge awaits the results of a Food and Drug Administration (FDA) review to return to the shelves in the United States. After being approved by the FDA in 1983, the sponge achieved considerable popularity before production was discontinued in 1995. At that time, production was halted due to the finding of too much bacteria in the factory’s water and other manufacturing concerns by the FDA. The makers decided that the cost of plant refurbishing would not be justified by estimated profits. Since then, Allendale (NJ) Pharmaceuticals has purchased rights to the Today sponge and has been working to bring the product back to the United States. The manufacturers have encountered numerous delays, but it appears that the product will be re-approved in the near future.1 Currently, the product is available in Canada and is being marketed on the Internet without FDA approval.

The Today sponge offers several advantages as a female-controlled, nonhormonal over-the-counter method of contraception. However, it has been shown to have relatively high pregnancy rates and does not offer any protection against transmission of HIV.

Description and Use

The Today sponge is a single-use device composed of soft polyurethane. It is round, measures 5.5 cm in diameter, and is approximately 2.5 cm thick. The device has an indentation on one side to better fit over the cervix. On the side opposite to the indentation, a polyester loop is attached to facilitate removal. The Today sponge contains 1 gm nonoxynol-9 and is estimated to release 125 mg over a 24-hour period of use.2 It also contains small amounts of preservatives such as citric, sorbic, and benzoic acids that lower its pH to about 4-5.3

The sponge is inserted into the vagina by the user prior to intercourse. It must be thoroughly moistened with tap water prior to insertion. The sponge can be used for as long as 24 hours and for more than one coital act during that time. Lastly, it should be left in place for at least six hours following intercourse. Thus, the total maximum time of wearing the sponge should not exceed 30 hours.1

The sponge is thought to prevent pregnancy through three modes. The most important is probably the spermicidal action of nonoxynol-9. The device also absorbs sperm and acts as a physical barrier covering the cervix.

Contraceptive Efficacy

The largest clinical trial of the Today sponge recruited women from 13 centers in the United States. One thousand four hundred fifty-four subjects randomly were assigned to use a sponge or a diaphragm (All-Flex, Ortho Pharmaceutical Corp.) used with a contraceptive cream containing 2% nonoxynol-9 (Ortho Creme, Ortho Pharmaceutical Corp.). Subjects were followed for one year. The 12-month cumulative life-table pregnancy rate among the sponge users was 17.0 per 100 women. This was significantly higher than in the diaphragm users, which was 12.5 per 100 women (p < 0.05).3

The other randomized controlled trial was conducted at a single center in London. Similarly, 249 women randomly were assigned to the Today sponge or diaphragm with contraceptive cream (All-Flex and Ortho Creme, Ortho Pharmaceutical Corp.). The study also found that the 12-month life-table failure rate was significantly higher for the sponge than the diaphragm: 24.5 and 10.9 per 100 women, respectively.4

Edelman and North reviewed and combined the results of all the Phase III clinical trials of the Today contraceptive sponge, including the two described above. They reported that a total of 2,245 women had been studied in 26 sites around the world. The overall cumulative 12-month life-table pregnancy rate was determined to be 13.3 per 100 women. The authors further categorized the failures as user failures (result of failure of the user to use the sponge as directed) or method failures (pregnancy occurred even though the sponge was used correctly). The cumulative method failure rate was 8.2 per 100 women, and user failure rate was 5.6 per 100 women.5

Trussell et al. performed a reanalysis of data from the U.S. trial discussed above. The authors calculated pregnancy rates according to quality and length of use. The analysis revealed that first-year probability of failure during typical use was 17% for the sponge and 13-17% for the diaphragm. In contrast, first-year probabilities of failure during perfect use were 11-12% for the sponge and 4-8% for the diaphragm. The authors attributed the large difference in failure rates between perfect and typical use of the diaphragm to the relatively higher complexity of its insertion. On the other hand, the sponge only needs to be moistened and therefore, consistent use nearly equates to perfect use.6 However, such secondary analyses need to be interpreted with caution since they were not planned in the study design and are open to multiple sources of error.

Kuyoh et al. conducted a Cochrane review comparing the contraceptive efficacy of the Today sponge to that of the diaphragm used with nonoxynol-9 as spermicide. Only the two clinical trials described above met the inclusion criteria for the analysis. After a rigorous review of the data and methods, the authors calculated the odds ratio for pregnancy for the sponge compared to the diaphragm to be 1.5 (95% CI 1.1-2.1) in the U.S. trial and 2.6 (95% CI 1.3-5.4) in the United Kingdom trial.2 This analysis confirmed the conclusion that the contraceptive efficacy of the Today sponge is significantly lower than that of the diaphragm with spermicide.

In an attempt to detect any sponge user characteristics that may lead to higher failure rate, subgroup analyses were performed in all trials. Of all user characteristics examined, only parity was shown to influence the contraceptive efficacy of the sponge. McIntyre and Higgins analyzed the data from the U.S. trial and found that for nulliparous women, the sponge was equally effective to the diaphragm (failure rate was 13.9 for sponge and 12.8 for diaphragm, p = 0.45); however, parous sponge users experienced a much higher failure rate (28.3 for sponge and 13.4 for diaphragm, p = .001). Notably, while the failure rate in sponge users was dramatically higher in parous than nulliparous women, parity had no significant effect on failure rates in diaphragm users.7 However, these results should be viewed with caution. These analyses were not planned in advance, and the discovered association could be due to chance or too confounding. For example, motivational levels for avoiding pregnancy may have been different in the subgroups. When women who experienced method failure were followed up, parous sponge users were found to be less likely to terminate the pregnancy than parous diaphragm users; rates of abortion were 37 and 55%, respectively.7 This suggests that parous women using the sponge may have had a lower motivation level for using the device consistently and correctly. Thus, the subgroup analysis was vulnerable to error. Furthermore, other studies of the sponge do not corroborate this relationship.5

Prevention of HIV and other Sexually Transmitted Diseases

In the face of a worldwide problem with the sexual transmission of HIV, as well as other sexually transmitted diseases, barrier contraceptives and spermicides were seen as a possible tool in the decrease of the risk of transmission. In vitro experiments and early clinical studies suggested that nonoxynol-9 was effective against transmission of HIV, chlamydia trachomatis, and Neisseria gonorrheae. However, a recent well-designed clinical trial of a low-dose, 52.5 mg nonoxynol-9 gel (COL-1492) has clearly shown that it did not offer any protection against transmission of any of these pathogens in a population of female sex workers and actually may increase risk of HIV infection. The hazard ratio for HIV infection in nonoxynol-9 users vs. placebo was 1.5 (95% CI 1.0-2.2, p = 0.047). No significant effect was observed on N. gonorrheae (HR = 1.2, 95% CI 0.9-1.6) or C. trachomatis (HR=1.2, 95%CI 0.8-1.6) infections. Subgroup analyses revealed that frequency of product use was an important predictor of HIV infection. Women who inserted the gel 3.5 times or more per day had an increased risk of infection (HR = 1.8, 95% CI 1.0-3.2, p = 0.03), while women using the gel less than 3.5 times per day had no difference in infection rate compared to placebo. Also, the investigators observed an increasing incidence of vaginal epithelial lesions with increasing frequency of product use, which in turn correlated with greater frequency of HIV infection.8 A Cochrane systematic review of clinical trials also found no reduction in risk of HIV and other sexually transmitted infections with use of various nonoxynol-9 preparations and an increase in frequency of genital lesions.9

In evaluating the effect of the Today sponge on sexual transmission of disease, Rosenberg et al. reported a significant protection for users against N. gonorrheae infection and a borderline significant reduction for C. trachomatis.10 Kreiss et al. also found that sponge use resulted in decreased risk of gonococcal infection compared to placebo (RR = 0.4, p < 0.001). However, they also reported an increased frequency of genital ulcers (RR = 3.3, p < 0.001) and vulvitis (RR = 3.3, p < 0.001). In addition, a nonstatistically significant increase in HIV seroconversion was observed in sponge users (HR = 1.7, 95% CI 0.9-3.0), and no significant difference in chlamydial infection frequency was seen.11

Based on available evidence, the World Health Organization/CONRAD meeting held in 2001 concluded that nonoxynol-9 use does not reduce the risk of sexually transmitted infections or HIV among sex workers, and no such studies have been conducted in other groups of women. Thus, nonoxynol-9 should not be used for the purpose of disease prevention.12 The physical barrier protection offered by the sponge appears to reduce the incidence of cervical gonococcal infection, but sponge users are equally vulnerable to genital lesions from nonoxynol-9, which are associated with increased risk of HIV transmission.

Product Acceptability

The Today sponge offers several advantages that made it popular with users. It provides a mode of delivery of a spermicide that is not messy and easy to use. It doesn’t require a prescription and doesn’t have to be fitted by a physician. It can be inserted up to 24 hours prior to intercourse and thus does not interfere with spontaneity. Furthermore, it is effective for up to 24 hours without requiring application of additional spermicide.

Beckman et al. conducted a telephone survey of 385 current users of the Today sponge and 407 past users. The investigators found that the highest rated reasons in the decision to try the sponge were "effective," "comfortable," and "wouldn’t interfere with sexual pleasure." When asked for the most important reason, the most frequent responses were "effectiveness," "more convenient or easier to use than previous method," and "easy to use."13 Similarly, study participants were asked to rate importance of reasons in the decision to discontinue use of the sponge. The highest rated were "concern about effectiveness" and "preferred another method." When asked for a single most important reason they stopped using the device, the most common replies were "got pregnant," "wanted to get pregnant," and "preferred another method."13

In the Cochrane review by Kuyoh et al., the authors found that 12-month discontinuation rates were higher for the sponge than the diaphragm. The combined odds ratio for discontinuation in the two large trials was 1.3 (95% CI 1.1-1.6) for the sponge when compared with the diaphragm.2 Although this difference is statistically significant, the absolute rates are not dramatically different. On the other hand, the sponge has unique disadvantages. In the largest clinical trial, discontinuation rates for allergic-type reactions were significantly higher than for diaphragm users: 4.0 vs. 0.7 per 100 women at 12 months, p < 0.05. The same was true for discontinuation rates for discomfort: 6.1 vs. 2.8 per 100 women at 12 months, p < 0.05. 3 In summary, despite several apparent advantages, 12-month cumulative discontinuation rates for the sponge were found to be approximately 50 per 100 women, which was slightly higher than for diaphragm users.

Other Contraceptive Sponges

Two other contraceptive sponges are marketed outside the United States: the Pharmatex (Pharmalec, France) and the Protectaid (Gefar Pharma, Switzerland).Although these sponges are not approved by the Food and Drug Administration, the Protectaid sponge is available in Canada and also is being marketed on the Internet. Little information has been published on the Pharmartex sponge, which contains 60 mg benzalkonium chloride. On the other hand, several clinical trials of the Protectaid are available in the literature. The Protectaid sponge is composed of a polyurethane microalveolar foam matrix impregnated with 5g of F-5 gel. This gel contains low concentrations of three spermicides: 0.125% nonoxynol-9, 0.125% benzalkonium chloride, and 0.5% of sodium cholate. Thus, the amount on nonoxynol-9 released is much lower than that of the Today sponge. The F-5 gel also contains polydimethylsiloxane that acts as a dispersing agent. Finally, unlike the loop used for removal of the Today sponge, the Protectaid has slots to assist removal.14

The first study of the safety and efficacy of the Protectaid sponge involved 12 months of use by 20 young women. No pregnancies or significant adverse effects were recorded in this population.15 In 2001, Creatsas et al. reported the results of a multinational open-label uncontrolled trial of the product. One hundred and twenty-nine women in Canada, the Dominican Republic, France, and Greece were followed for 12 months, which generated 1,182 cycles of use. The contraceptive efficacy was found to be 77% with no significant effect of parity. Acceptability was found to be high, with no major adverse events and 85% reporting no adverse symptoms.14

In another paper by the same group, the safety and tolerability of the Protectaid sponge was investigated further. Thirty-five women were randomly assigned to use a sponge with F-5 gel containing 0.125% or 0.5% nonoxynol-9. The subjects were followed for 12 months and colposcopic examinations were performed before treatment and then two weeks and three, six, nine, and 12 months after start of use. Both groups demonstrated an equal efficacy rate of 91.4%, which again was not influenced by parity. Two mild cases of focal inflammation and irritation were noted on colposcopy in the higher concentration of nonoxynol-9 group, and no lesions were found in the lower concentration group. Subjects reported no complaints except seven women who had difficulty with sponge removal at the beginning of use.16

The Protectaid is not approved for use by the FDA.

Comments

The sponge offers unique advantages as a female-controlled, easy to use, over-the-counter contraceptive. However, its relatively low contraceptive efficacy and failure to provide protection against HIV transmission make it a less-ideal option. Although some evidence exists that the Today sponge is as effective as the diaphragm for nulliparous women but has a high failure rate in parous women, these observations are based on unplanned secondary analyses. Further investigation is needed before a relationship between parity and efficacy can be safely concluded. Overall, the Today sponge has been found to have lower efficacy and higher discontinuation rates than the diaphragm. Thus, while the sponge may not be an appropriate choice for most women, it may be a good option for women at low risk for sexually transmitted infections and with lower fertility, such as those breast-feeding, or for women who wish to space their children. As new spermicides and microbicides become available, the sponge may offer an excellent method of delivery for these products in the future.

References

1. Today Sponge web site (www.todaysponge.com); 2003 (accessed Sept. 11, 2003).

2. Kuyoh MA, Toroitich-Ruto C, Grimes DA, Schulz KF, Gallo MF. Sponge versus diaphragm for contraception: A Cochrane review. Contraception 2003; 67:15-18.

3. Edelman DA, McIntyre SL, Harper J. A comparative trial of the Today contraceptive sponge and diaphragm. Am J Obstet Gynecol 1984; 150:869-876.

4. Bounds W GJ. Randomised comparison of the use-effectiveness and patients acceptability of the Collatex (Today) contraceptive sponge and the diaphragm. Br J Fam Plann 1984; 10:69-75.

5. Edelman DA, North BB. Updated pregnancy rates for the Today contraceptive sponge. Am J Obstet Gynecol 1987; 157:1,164-1,165.

6. Trussell J, Strickler J, Vaughan B. Contraceptive efficacy of the diaphragm, the sponge, and the cervical cap. Fam Plann Perspect 1993; 25:100-105,135.

7. McIntyre SL, Higgins JE. Parity and use-effectiveness with the contraceptive sponge. Am J Obstet Gynecol 1986; 155:796-801.

8. Van Damme L, Ramjee G, Alary M, et al. Effectiveness of COL-1492, a nonoxynol-9 vaginal gel, on HIV-1 transmission in female sex workers: A randomized controlled trial. Lancet 2002; 360:971-977.

9. Wilkinson D, Tholandi M, Ramjee G, et al. Nonoxynol-9 spermicide for prevention of vaginally acquired HIV and other sexually transmitted infections: Systematic review and meta-analysis of randomized controlled trials including more than 5000 women. Lancet Infect Dis 2002; 2:613-617.

10. Rosenberg MJ, Rojanapithayakorn W, Feldblum PH, et al. Effect of the contraceptive sponge on chlamydial infection, gonorrhea, and candidiasis. A comparative clinical trial. JAMA 1987; 257:2,308-2,312.

11. Kreiss J, Ngugi E, Holmes K, et al. Efficacy of nonoxynol 9 contraceptive sponge use in preventing heterosexual acquisition of HIV in Nairobi prostitutes. JAMA 1992; 268:477-482.

12. World Health Organization. WHO/CONRAD Technical Consultation on Nonoxynol-9. Summary report. Geneva, Oct. 9-10, 2001. Reprod Health Matter 2002; 10:175-181.

13. Beckman LJ, Murray J, Harvey SM. The contraceptive sponge: Factors in initiation and discontinuation of use. Contraception 1989; 40:481-496.

14. Creatsas G, Guerrero E, Guilbert E, et al. A multinational evaluation of the efficacy, safety, and acceptability of the Protectaid contraceptive sponge. Eur J Contracept Reprod Health Care 2001; 6:172-182.

15. Psychoyos A, Creatsas G, Hassan E, et al. Spermicidal and antiviral properties of cholic acid: Contraceptive efficacy of a new vaginal sponge (Protectaid) containing sodium cholate. Hum Reprod 1993; 8:866-869.

16. Creatsas G, Elsheikh A, Colin P. Safety and tolerability of the new contraceptive sponge Protectaid. Eur J Contracept Reprod Health Care 2002; 7:91-95.

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