An Update on Emergency Contraception – Effectiveness How it works, how effective it

(Published March 2022)

The published literature on progestin-only emergency contraception pills (ECPs) (Next Choice^® and Plan B One-Step^®) estimates a range of effectiveness between 52% and 94% in reducing pregnancy risk based on nine studies of nearly 10,500 women.^1-9  The package inserts for Next Choice and Plan B state that the expected pregnancy rate of 8% (with no contraceptive use) was reduced to approximately 1% in clinical trials; for every eight expected pregnancies, seven are prevented with the use of progestin-only ECPs.

Two randomized trials compared the efficacy of levonorgestrel with the second-generation antiprogestin ulipristal acetate (UPA), one up to 72 hours after unprotected intercourse¹⁰ and the second up to 120 hours after.¹¹ When these two studies were combined, UPA was found to have a pregnancy rate 42% lower than levonorgestrel up to 72 hours and 65% lower in the first 24 hours.¹¹ In the second randomized study, 30 mg UPA prevented significantly more pregnancies than did levonorgestrel in the 72-120 hour subgroup.

Data clearly show that the progestin-only EC and UPA regimens are more effective than the Yuzpe method. All EC regimens are more effective than using no method of contraception.¹²

The published literature on combined progestin–estrogen ECPs estimates a range of effectiveness between 56% and 89% in reducing pregnancy risk. A meta-analysis of eight studies concluded that the effectiveness of the combined regimen is 74%.¹³

The Copper T IUD used as EC is more than 99% effective in reducing pregnancy risk.^14,15

Most published efficacy data likely overestimate the effectiveness of progestin-only ECPs. For progestin-only ECPs, efficacy was demonstrated initially in noncomparative observational studies; thereafter, use of a placebo was believed to be unethical. Therefore, the chance that pregnancy would occur in the absence of EC is estimated indirectly using published data on the probability of pregnancy on each day of the menstrual cycle.^16,17 This estimate is compared with the actual number of pregnancies observed after treatment in observational treatment trials. Effectiveness is calculated as 1 – (O/E), where O and E are the observed and expected number of pregnancies, respectively.¹⁸

Calculation of effectiveness involves many assumptions that are difficult to validate. Accurate estimates of efficacy depend on accurate recording of timing of intercourse and cycle day (to estimate timing of ovulation).¹⁸ One study comparing self-report of cycle day with urinary pregnanediol concentrations demonstrated that more than 30% of women presenting for progestin-only ECPs had inaccurately dated their menstrual cycles, believing themselves to be in the fertile phase of their cycle when they were not. In the same study, 60% reported more than one act of intercourse in the cycle, indicating that pregnancies attributed to progestin-only ECP failure might actually be the result of unprotected intercourse earlier in the cycle.¹⁹ Another study found that 99 women were between days –5 and +1 when the day of ovulation (day 0) was estimated as usual cycle length minus 13 days. However, hormonal data indicated that only 51 of these 99 (56%) were between days –5 and +1.²⁰ In another study, cervical smears showed that more than one-third of women requesting progestin-only ECPs had no sperm present in the vagina and that those with sperm present had fewer sperm than women attempting to become pregnant.²¹ For a variety of reasons, many women do not accurately understand when they are at risk for pregnancy.

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The efficacy of progestin-only EC may be enhanced by adding a nonsteroidal anti-inflammatory agent that is specific for a cyclooxygenase-2 (COX-2) inhibitor. A pilot study of 41 women found that adding a COX-2 inhibitor (meloxicam 15 mg) to levonorgestrel 1.5 mg significantly increased the proportion of cycles with no follicular rupture or ovulatory dysfunction (88% versus 66%, P = 0.012). Adding a COX-2 inhibitor can disturb the ovulatory process after the onset of the luteinizing hormone surge.²² Generic meloxicam is covered by many community pharmacy generic plans. A trial regarding optimal dosing is under way.

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References:

1. von Hertzen H, Piaggio G, Ding J, et al. Low dose mifepristone and two regimens of levonorgestrel for emergency contraception: a WHO multicentre randomised trial. Lancet. 2002;360:1803–10.
2. Arowojolu AO, Okewole IA, Adekunle AO. Comparative evaluation of the effectiveness and safety of two regimens of levonorgestrel for emergency contraception in Nigerians. Contraception. 2002;66:269–73.
3. Task Force on Postovulatory Methods of Fertility Regulation. Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception. Lancet. 1998;352:428–33.
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17. Wilcox AJ, Weinberg CR, Baird DD. Timing of sexual intercourse in relation to ovulation: effects on the probability of conception, survival of the pregnancy, and sex of the baby. N Engl J Med. 1995;333:1517–21.
18. Trussell J, Raymond EG. Emergency contraception: a last chance to prevent unintended pregnancy. Accessed at http://ec.princeton.edu/questions/ec-review.pdf, June 24, 2010.
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21. Espinos-Gomez JJ, Senosiain R, Mata A, et al. What is the seminal exposition among women requiring emergency contraception? A prospective, observational comparative study. Eur J Obstet Gynecol Reprod Biol. 2007;131:57–60.
22. Massai MR, Forcelledo ML, Brache V, et al. Does meloxicam increase the incidence of anovulation induced by single administration of levonorgestrel in emergency contraception? A pilot study. Hum Reprod. 2007;22:434–9.