How the Yuzpe method acts as an abortifacient

The mechanism(s) of action of the Yuzpe method of pre-implantation birth regulation have been the subject of research since the mid-1980s. A review of published papers indicates a consistent reference to a direct inhibitory effect on the proper development of the endometrium. As a consequence, implantation of the 5-6 day old human embryo is frequently blocked.

Illustrating this point was work by Kubba and co-workers (1986), who observed that the correct levels of natural, ovarian produced estrogen and progesterone are indispensable to the proper development of the endometrium to a stage that is compatible with blastocyst implantation. They further noted that the endometrium must be at the secretory phase of development for proper implantation, and theorised that a high dose of a progestin may disrupt this necessary development. Importantly, they named levonorgestrel as responsible for the retardation in endometrial growth.(1)

Supportive research was also reported by Rowlands and co-workers (1986), who found that the Yuzpe method works "at the endometrial level and operates before implantation." (2) More precisely, Rabone (1990) determined that 'Yuzpe' caused a 'desynchronisation' in the development of the endometrium, rendering implantation improbable. (3) Grou (1994), Harper (1995), the American Food and Drug Administration (1997), Trussell (1999), and Wellbery (2000) have all reported similarly. (4) (5) (6) (7) (8)

The American Food and Drug Administration's (FDA) product information for Preven™, a branded version of the Yuzpe method, lists three ways this product could work: delayed or prevented ovulation, changes to the viscosity of cervical mucus or it "may produce changes in the lining of the womb (uterus)." (9)

A research paper by Raymond et al (2000)(10) reported that the Yuzpe method had a statistically significant impact on 5 key characteristics of implantation, including a reduced endometrial thickness and an increase in estrogen receptors (the level should be decreasing for implantation), but no change in the levels of other uterine receptivity markers such as integrins or glycodelin when a control and treatment cycle in the same women was compared.

Raymond also reported an increase in oestrogen levels, which could have an anti-implantation action, because a decrease oestrogen level has been shown to improve uterine receptivity.

The authors also noted that "our results leave a puzzling gap in our understanding of the mechanism of action of this therapy ... in order for the Yuzpe regimen to be able to prevent 75% of expected pregnancies ... perhaps the (Yuzpe) regimen affects endometrial function in ways undetectable by the tests we chose to perform ..." (11)

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(1) Kubba AA, White JO, Guillebaud J, Elder M. The biochemistry of human endometrium after two regimens of postcoital contraception: a dl-norgestrel/ethinylestradiol combination or danazol. Fert Steril 1986; 45:512-516

(2) Rowlands S, Kubba AA, Guillebaud J, Bounds W. A possible mechanism of danazol and ethinyl estradiol/norgestrel combination used as postcoital contraceptive agents. Contraception. 1986; 33; 539-545

(3) Rabone D. Postcoital contraception - coping with the morning after. Current Therapeutics 1990 January pp 45-49

(4) Grou F, Rodrigues I. The morning-after pill - how long after? Amer J Obstet Gynecol 1994; 171:1529-1534 "... the modification of the endometrium is probably the main mechanism of action of the morning-after pill. Most of the researchers attempting to understand how the morning-after pill works supports this view."

(5) Harper C, Ellerston C. Knowledge and perceptions of emergency contraceptive pills among a college-age population: a qualitative approach. Fam Plan Perspectives 1995; 27:149-154. "Emergency contraceptive pills, also known as morning-after pills, are a postcoital hormonal treatment that appears to inhibit implantation of the fertilized ovum."

(6) Kessler DA. Commissioner of Food and Drugs. pp.8609-8612 "Emergency contraceptive pills are not effective if the woman is pregnant; they act by delaying or inhibiting ovulation, and/or altering tubal transport of sperm and/or ova (thereby inhibiting fertilization), and/or altering the endometrium (thereby inhibiting implantation)."

(7) Trussell J, Raymond E. Statistical effectiveness about the mechanism of action of the Yuzpe regimen of emergency contraception. Obstet Gynecol 1999; 93:872-876 "...the best information currently available indicates that the Yuzpe regimen could not be as effective as it appears to be if it only worked by preventing or delaying ovulation."

(8) Wellbery C. Emergency Contraception. Arch Fam Med 2000; 9:642-64: "Thus, numerous factors, including prevention of implantation, may play a role (in the Yuzpe method)."

(9) Do search for Preven. See p.19

(10) Raymond EG, Lovely LP, Chen-Mok M et al. Effect of the Yuzpe regimen of emergency contraception on markers of endometrial receptivity. Hum Reprod. 2000;15(11):2351-2355

(11) Ibid, p. 2354