Analysis of the endometrial transcriptome at the time of implantation in women receiving a single post-ovulatory dose of levonorgestrel or mifepristone

Abstract Background: Levonorgestrel (LNG) is a progesterone receptor agonist used in both regular and emergency hormonal contraception; however, its effects on the endometrium as a contraceptive remain widely unknown and under public debate. Objective: To analyze the effects of LNG or mifepristone (MFP), a progesterone receptor antagonist and also known as RU-486, administered at the time of follicle rupture (FR) on endometrial transcriptome during the receptive period of the menstrual cycle. Methods: Ten volunteers ovulatory women were studied during two menstrual cycles, a control cycle and a consecutively treated cycle; in this last case, women were randomly allocated to two groups of 5 women each, receiving one dose of LNG (1.5 mg) or MFP (50 mg) the day of the FR by ultrasound. Endometrial biopsies were taken 6 days after drug administration and prepared for microarray analysis. Results: Genomic functional analysis in the LNG-treated group showed as activated the bio-functions embryo implantation and decidualization, while these bio-functions in the T-MFP group were predicted as inhibited. Conclusions: The administration of LNG as a hormonal emergency contraceptive resulted in an endometrial gene expression profile associated with receptivity. These results agree on the concept that LNG does not affect endometrial receptivity and/or embryo implantation when used as an emergency contraceptive.

Les contraceptifs oraux

Les contraceptifs (alias anticonceptionnels) sont des moyens qui empechent la fecondation; ou plus generalement la grossesse. Les raisons de recourir a une contraception sont variees; et les contraceptifs estroprogestatifs oraux font partie des moyens de contraception les plus efficaces pour les femmes (1 a 3). Quelles associations estroprogestatives retenir en priorite ?

Mecanismo de acción del levonorgestrel como anticoncepción de emergencia con principal énfasis en su acción sobre los espermatozoides / Mechanism of action of levonorgestrel as emergency contraception with principal emphasis in its spermatozoa action

A pesar de lo extendido del uso de la anticoncepción de emergencia (AE) con levonorgestrel (LNG) en el mundo, el mecanismo de acción continúa siendo discutido, lo que ha sido aprovechado para que grupos confesionales aaquen su uso, argumentando que la misma es abortiva. Actualmente, dos comprimido de LNG de 0,75 mg hasta 5 días posteriores al coito no protegido, ha sido recomendada y mostrada como eficaz para AE. El mecanismo de acción probablemente depende del momento de la toma en relación al día del ciclo menstrual. Cuando el LNG para AE es administrado antes del período ovulatorio, el mismo inhibe la ovulación en algunas mujeres y afecta el endometrio. Sin embargo la administración de LNG antes de la ruptura folicular no mostró tener influencia sobre la expresión de glicodelina-A en biopsias de endometrio tomadas 24 o 48 horas después de la toma de las píldoras de LNG. Los resultados de los estudios no apoyan la idea de que el LNG como AE causaría un efecto anti-implantatorio. Fue especulado que el LNG podría actuar sobre los espermatozoides. En estudios muy antiguos de la Argentina fue observado que la administración de 0,4 mg de LNG dado 3-10 horas post coito reducía el número de espermatozoides recuperados de la cavidad uterina, causaba alcalinización del fluido intrauterino, inmovilizaba los espermatozoides y aumentaba la viscosidad del moco cervical. Esto llevó a sugerir que la migración espermática a los lugares de fertilización podría esar comprometida después de la ingesta de LNG como AE. Sin embargo, nosotros hemos trabajado sobre esta hipótesis, pero no observamos efectos sobre reacción acrosomal después de la exposición in vitro al LNG de espermatozoides capacitados...

Although emergency contraception (EC) with levonorgestrel (LNG) is widely extended worldwide, the mechanism of action is still under discussion, which may be used by religious groups to argue that it is an abortifacient drug. Actually, two pills of LNG with 0.75 mg every 12 hours or the administration of a single doses of 1.5 mg up to 5 days after unprotected coitus, has been recommended and with a good efficacy to EC. The mechanism of action probably depends of the time of ingestion in relationship to the day of the menstrual cycle. When the LNG as EC is taken before of the ovulatory period, it's inhibited ovulation in some women and affects the endometrium. However, the intake of LNG before the follicular rupture did not show any influence upon the expression of glycodelin-A in endometrial biopsies taken 24 or 48 hours after the intake of the pills of LNG. The results of the studies did not support the idea that LNG as EC caused an anti-implantation effect. It was speculated that LNG could acted upon the spermatozoa. In older studies conducted in Argentina it was observed that the administration of 0.4 mg of LNG taken 3-10 hours post coitus reduced the number of spermatozoa recovery from the uterine cavity, cause alkalinization of uterine fluid, immobilized spermatozoa and increase the viscosity of cervical mucus. This suggests that sperm migration to the fertilization local could be impaired after taken a LNG as EC. Nevertheless, we have been working in this hypothesis but we did not observed effects upon acrosomal reaction (AR) after exposition in vitro to LNG of capacitated spermatozoa. In the aggregate, the in vivo exposition of spermatozoa to LNG as EC showed that the intake of 1.5 mg of LNG as EC alter different times post coitus and the recovery of spermatozoa from the uterine cavity alter different times of the pill intake (12, 24 or 36 hours), did not affect the quality of cervical mucus, or the sperm penetration, neither the fertilizing capacity showed through the AR rate, which was similar to observed after the intake of placebo