Does Levonorgestrel Emergency Contraceptive have a Post-Fertilization Effect? A Review of its Mechanism of Action

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 preovulation, it may have a post-fertilization MOA.

Hormonal Contraceptives: What If Exposed During Pregnancy?

“…It can prevent or delay ovulation, increase the thickness of the cervical mucus, and disrupt the corpus luteum formation (12). Recent studies showed that preovulatory levonorgestrel administration can lead to post-fertilization luteal effects and may explain its clinical effects when used before ovulation (13). In a follow-up study, children exposed to levonorgestrel were compared with a control group of children over a period of 2 years.…”

β-Lactoglobulin and Glycodelin: Two Sides of the Same Coin?

“…UPA on the other hand, has a decreasing effect as ovulation approaches but, since it blocks progesterone receptors, prevents implantation ( Mozzanega et al, 2014 ). Mozzanega and Nardelli (2019) consider the mechanisms of LNG and UPA from the viewpoint of informed consent since there is significant ethical concern if the action is directed toward the conceptus ( Kahlenborn et al, 2015 ; Peck et al, 2016 ).…”

Ulipristal Acetate (UPA) in Emergency Contraception: The Mechanism of Action, Toxicity and Perspectives

“…In those days, in which most fertilizations do occur [1][2][3]12 , ECPs transform the endometrium into an inhospitable environment for the embryo. As to Levonorgestrel (LNG;Norlevo ® ,Levonelle ® ,Escapelle ® ), we showed that it does never affect ovulation [16][17][18] . Besides, we highlighted that the FIGO (International Federation of Gynecology & Obstetrics) and ICEC (International Consortium for Emergency Contraception) share a false information in their 2008, 2011 and 2012 joint Statements 15 : in fact, they state as a dogma that LNG-ECPs delay or inhibit ovulation and consequently prevent fertilization, without ever affecting embryoimplantation, while -on the contrary -in the studies quoted in support 15,[19][20][21][22][23] ovulation is never inhibited when LNG is taken in the most fertile days of the cycle.…”