Mikolajczyk, R. T., & Stanford, J. B. (2007). Levonorgestrel emergency contraception: a joint analysis of effectiveness and mechanism of action. Fertility and Sterility, 88(3), 565-571. https://doi.org/10.1016/j.fertnstert.2006.11.178
Mikolajczyk RT, Stanford JB. Levonorgestrel emergency contraception: a joint analysis of effectiveness and mechanism of action. Fertil Steril. 2007;88(3):565-571. doi:10.1016/j.fertnstert.2006.11.178
Mikolajczyk, Rafael T., and Joseph B. Stanford. "Levonorgestrel emergency contraception: a joint analysis of effectiveness and mechanism of action." Fertility and Sterility, vol. 88, no. 3, 2007, pp. 565-571.
For EndNote, Zotero or Mendeley:
Open access
Free to read
No reuse license
Free to read at the publisher (reported by Unpaywall and OpenAlex, not verified by RRM Academy)
Levonorgestrel EC trial results exceed ovulation-only model estimates
Disruption of ovulation alone could prevent about 5 out of 10 pregnancies at most, a simulation of levonorgestrel emergency contraception (EC) finds, when taken with no delay. With a 72-hour delay the modeled effect falls to fewer than 1 out of 10. The model used ultrasound data from 107 women. Trial estimates the authors cite run higher.
Key Findings
When disruption of ovulation was the only mechanism, modeled effectiveness fell from 49% with no delay to 8% with a 72-hour delay.
Under the same assumption, modeled effectiveness was 2% at a 96-hour delay and 0% at a 120-hour delay.
If levonorgestrel EC completely prevented fertilization whenever given before the day of ovulation, modeled effectiveness with a 72-hour delay was 16%.
The authors cite a trial of 976 women estimating 85% effectiveness within 72 hours, and a study of 1021 women estimating 64% overall with no trend by delay.
Recent analyses suggest trial estimates were overestimated by approximately 10% (absolute difference), which the authors say could not account for the gap.
Interpretation
This modeling study used ultrasound data from 107 women to see how much of levonorgestrel EC's effect comes from stopping ovulation. Stopping ovulation explained less of the drug's effect than trials have shown. The authors think two things explain the gap. Trial results may run too high. The drug may also work after fertilization. The authors note they could not calculate confidence limits for the model. The findings support further studies with precise timing to clarify how levonorgestrel EC works.
RRM Context
Restorative reproductive medicine puts the ovulatory cycle first. The odds of pregnancy from one act of sex depend on how far it falls from ovulation. Fertility awareness charting tracks body signs to time ovulation. The follicle data came from women with experience in natural family planning methods. Ultrasound of the follicle shows whether ovulation has happened.
Our editorial summary of this paper, not the article's abstract.
Abstract
Objective
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.
Design
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.
Setting
Combined data from multiple clinical studies.
Patients
Simulation models.
Interventions
Disruption of ovulation.
Main Outcome Measures
Effectiveness in the form of proportion of pregnancies prevented.
Results
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).
Conclusions
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.
