False risk attribution results in misleading assessment of the relationship between suppression of ovulation and the effectiveness of the Yuzpe regimen for emergency contraception
PMID 12684157 12684157 DOI 10.1016/s0010-7824(02)00479-1 10.1016/s0010-7824(02)00479-1 Mikolajczyk et al. 2003, Mikolajczyk 2003
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Mikolajczyk, R. T., & Stanford, J. B. (2003). False risk attribution results in misleading assessment of the relationship between suppression of ovulation and the effectiveness of the Yuzpe regimen for emergency contraception. Contraception, 67(4), 333-5; author reply 335-7. https://doi.org/10.1016/s0010-7824(02)00479-1
Mikolajczyk RT, Stanford JB. False risk attribution results in misleading assessment of the relationship between suppression of ovulation and the effectiveness of the Yuzpe regimen for emergency contraception. Contraception. 2003;67(4):333-5; author reply 335-7. doi:10.1016/s0010-7824(02)00479-1
Mikolajczyk, R. T., and J. B. Stanford. "False risk attribution results in misleading assessment of the relationship between suppression of ovulation and the effectiveness of the Yuzpe regimen for emergency contraception." Contraception, vol. 67, no. 4, 2003, pp. 333-5; author reply 335-7.
To assess the possibility of a postfertilization effect in regard to the most common types of hormonal emergency contraception (EC) used in the US and to explore the ethical impact of this possibility. DATA A MEDLINE search (1966-November 2001) was done to identify all pertinent English-language journal articles. A review of reference sections of the major review articles was performed to identify additional articles. Search terms included emergency contraception, postcoital contraception, postfertilization effect, Yuzpe regimen, levonorgestrel, mechanism of action, Plan B. The 2 most common types of hormonal EC used in the US are the Yuzpe regimen (high-dose ethinyl estradiol with high-dose levonorgestrel) and Plan B (high-dose levonorgestrel alone). Although both methods sometimes stop ovulation, they may also act by reducing the probability of implantation, due to their adverse effect on the endometrium (a postfertilization effect). The available evidence for a postfertilization effect is moderately strong, whether hormonal EC is used in the preovulatory, ovulatory, or postovulatory phase of the menstrual cycle. Based on the present theoretical and empirical evidence, both the Yuzpe regimen and Plan B likely act at times by causing a postfertilization effect, regardless of when in the menstrual cycle they are used. These findings have potential implications in such areas as informed consent, emergency department protocols, and conscience clauses.
To model the effectiveness that can be obtained if levonorgestrel-only emergency contraception (EC) acts only through disrupting ovulation, in relation to other effects that may occur before or after fertilization and accounting for delays in administration. We modeled follicular growth as a function of follicular size, using known day-specific probabilities of conception and known disruption of ovulation by levonorgestrel-only EC, to estimate the expected effectiveness of EC. Combined data from multiple clinical studies. PATIENT(S): Simulation models. INTERVENTION(S): Disruption of ovulation. MAIN OUTCOME MEASURE(S): Effectiveness in the form of proportion of pregnancies prevented. RESULT(S): With disruption of ovulation alone, the potential effectiveness of levonorgestrel EC ranged from 49% (no delay) to 8% (72-hour delay). With complete inhibition of fertilization before the day of ovulation, the potential effectiveness of levonorgestrel EC ranged from 90% (no delay) to 16% (72-hour delay). CONCLUSION(S): The gap between effectiveness of levonorgestrel EC estimated from clinical studies and what can be attributed to disruption of ovulation may be explained by overestimation of actual effectiveness and supplementary mechanisms of action, including postfertilization effects. Additional data with follicular ultrasound and precise measures of delay between intercourse and EC administration would yield greater insight into effectiveness and mechanisms of action.