UPA and LNG in emergency contraception: the information by EMA and the scientific evidences indicate a prevalent anti-implantation effect

Abstract

Rationale and objectives: Emergency contraceptives pills (ECPs) are described as drugs that work by either inhibiting or delaying ovulation without affecting implantation. In our opinion, as we aim at demonstrating, both EMA documents and the experimental papers indicate that they prevalently inhibit embryo-implantation.

LNG-ECPs: literature: LNG-ECPs never prevent ovulation when are taken in the most fertile days (EMA-EPAR on ellaOne^® p. 9, first table). Conversely, they prevent the formation of an adequate corpus luteum. When they are taken pre-ovulatory ovulations occur regularly, but pregnancies do not appear. Taken after ovulation, they seem ineffective in preventing pregnancies.

UPA-ECPs: literature: EllaOne^® prevents ovulation only when is taken in the first fertile day. Thereafter, its anti-ovulatory effect drops sharply and becomes insignificant (8%) 36 h before ovulation, in the most fertile days (Brache); its decreasing anti-ovulatory effect cannot explain a consistently high effectiveness in preventing pregnancies (≥80%) that does not decrease depending on which of the 5 d it is taken after unprotected intercourse. Besides, ovulation occurs regularly in 91.7% of women taking ellaOne^® weekly, for eight consecutive weeks (EMA-CHMP-Assessment Report ‘EMA/73099/2015’: study HRA2914-554, p. 7). Lastly, Lira-Albarrán administered ellaOne^® to women in the most fertile pre-ovulatory days: they had normal ovulation, but their endometrium, evaluated through samples obtained in the implantation window, became inhospitable: the expression of 1183 genes was exactly the opposite of that observed in the receptive pro-gestational endometrium. This agrees with information by EMA-CHMP-Assessment Report ‘EMEA/261787/2009’ (p. 8): after UPA administration ‘the proteins necessary to begin and maintain pregnancy are not synthesized’.

Conclusions: Emergency Contraceptives work prevalently by preventing embryo-implantation. People shall receive correct information.

摘要

原理和目的：紧急避孕药（ECPs）是一种既能抑制排卵又能推迟排卵而又不影响着床的药物。在我们看来, 正如我们要证明的, EMA文献和试验论文都表明紧急避孕药对胚胎着床有明显的抑制作用。

LNG-ECPs:文献：LNG-ECPs在最易受孕的时间使用, 永远不会阻止排卵(在ellaOne®中EMA-EPAR p.9,第一个表)。相反, 它们阻止了足够的黄体形成。当她们在排卵前服用, 排卵会规律发生, 但不会怀孕。排卵后服用, 似乎对避孕无效。

UPA-ECPs:文献：EllaOne®只有易受孕期的第一天服用才能预防排卵。此后, 其抗排卵作用急剧下降, 在最易受孕期(Brache)的排卵前36小时无明显抗排卵效果（8%）。其抗排卵效果的下降不能解释持续高效的避孕作用（≥80%）, 它不会因为在无保护性交后服用的5天中任何一天而下降。此外, 连续8周, 每周服用ellaOne®的女性 91.7%的人有规律的排卵(EMA-CHMP-评估报告“EMA/73099/2015”:研究hra2914-554, p.7)。最后Lira-Albarrán在最易受孕时间给女性服用ellaOne®：女性有正常的排卵, 但是通过植入窗获得的样本评估, 她们的子宫内膜变得不适宜着床：1183个基因表达与受孕前容受性的子宫内膜的表达完全相反。这与EMA-CHMP-评估报告‘EMEA/261787/2009’(p. 8)中的信息一致:予以UPA后, “开始和维持怀孕所必须的蛋白质没有合成”。

结论：紧急避孕药能够有效预防胚胎植入, 人们应得到正确的信息。

Keywords:

• EllaOne
• UPA
• LNG
• emergency contraception
• mechanism of action
• ovulation
• endometrium
• embryo-implantation

Disclosure statement

The authors report no conflicts of interest.