Reproductive Endocrinology Luteal Phase

Does levonorgestrel emergency contraceptive have a post-fertilization effect? A review of its mechanism of action

Peck R, Rella W, Tudela J, Aznar J, Mozzanega B

Published February 2016 The Linacre Quarterly, 83(1), 35-51
DOI 10.1179/2050854915Y.0000000011 PMID 27833181 PMC PMC5102184

RRM Academy Synopsis

Levonorgestrel taken before ovulation may act after fertilization

A 2016 systematic review of 38 studies estimates that levonorgestrel's ovulation inhibition could prevent fewer than 15 out of 100 expected conceptions. The drug had no effect on sperm function at usual doses. The authors say luteal phase changes may point to an effect after fertilization.

Study at a glance, systematic review of 38 studies: Levonorgestrel taken before ovulation may act after fertilization
Study at a glance, systematic review of 38 studies: Levonorgestrel taken before ovulation may act after fertilization. Source: Peck R et al., 2016, PMID 27833181.

Key Findings

  • The searches returned 2,425 titles. After screening, 38 studies were included, and six of them examined overlapping mechanisms of action such as ovulation and luteal effects.
  • At follicle size 18 to 20 mm, ovulation was inhibited in 10 of 122 women (8 percent), matching 3 of 36 placebo-treated controls (8 percent).
  • The model put ovulation inhibitory potential at 92.4 percent (84.5 to 96.5) at follicle size 12 to 14 mm and 10.2 percent (6.1 to 16.6) at 18 to 20 mm.
  • Applied to the phase III study, the estimate was that 12.7 percent of pregnancies are prevented by inhibition or delay of ovulation.
  • One included study reported that emergency contraception given before the LH surge significantly shortened cycle length in 69 women by a mean of 11 days.

Interpretation

This systematic review built a model from pooled ovulation studies and applied it to findings from a phase III trial of levonorgestrel emergency contraception. The authors argue the post-fertilization case from luteal measures such as progesterone and luteal phase length. The authors note that no available study settles the question unequivocally. The findings support further study of levonorgestrel's luteal-phase effects.

RRM Context

Levonorgestrel is a synthetic progestin. The body makes progesterone after ovulation. Restorative reproductive medicine treats ovulation and the luteal phase after it as the events of a healthy cycle. The review's luteal findings come from women who ovulated after taking the drug.

Abstract

Background

Recent studies have identified that levonorgestrel administered orally in emergency contraception (LNG-EC) is only efficacious when taken before ovulation. However, the drug does not consistently prevent follicular rupture or impair sperm function.

Objective

The present systematic review is performed to analyze and more precisely define the extent to which pre-fertilization mechanisms of action may explain the drug's efficacy in pregnancy avoidance. We also examine the available evidence to determine if pre-ovulatory drug administration may be associated with post-fertilization effects.

Conclusion

The mechanism of action of LNG-EC is reviewed. The drug has no ability to alter sperm function at doses used in vivo and has limited ability to suppress ovulation. Our analysis estimates that the drug's ovulatory inhibition potential could prevent less than 15 percent of potential conceptions, thus making a pre-fertilization mechanism of action significantly less likely than previously thought. Luteal effects (such as decreased progesterone, altered glycodelin levels, and shortened luteal phase) present in the literature may suggest a pre-ovulatory induced post-fertilization drug effect.

Lay Summary

Plan B is the most widely used emergency contraceptive available. It is important for patients and physicians to clearly understand the drug's mechanism of action (MOA). The drug was originally thought to work by preventing fertilization. Recent research has cast doubt on this. Our review of the research suggests that it could act in a pre-fertilization capacity, and we estimate that it could prevent ovulation in only 15 percent or less of cases. The drug has no ability to alter sperm function and limited ability to suppress ovulation. Further, data suggest that when administered pre-ovulation, it may have a post-fertilization MOA.

Topics

By this author

Related research

Reproductive Endocrinology › Luteal Phase › Luteal Phase Deficiency · Contraception › Emergency Contraception › Mechanism and Effectiveness · Therapeutics › Hormonal Agents › Progesterone and Progestins
Rebecca Peck, Walter Rella, Julio Tudela, Justo Aznar, Bruno Mozzanega
Becky Peck, R Peck, W Rella, J Tudela, J Aznar, B Mozzanega
PMID 27833181 27833181 DOI 10.1179/2050854915Y.0000000011 10.1179/2050854915Y.0000000011 Peck et al. 2016, Peck 2016