Effects of low doses of mifepristone on human embryo implantation process in a three-dimensional human endometrial in vitro co-culture system

Author: Boggavarapu, N.R.; Berger, C.; von Grothusen, C.; Menezes, J.; Gemzell-Danielsson, K.; Lalitkumar, P.G.L.

Description: OBJECTIVES: We wanted to explore the effects of two different low doses (0.5muM and 0.05muM) of mifepristone, exposed during the receptive period, on the human embryo implantation process, using a well-established three-dimensional in vitro cell culture model, specifically developed to study this process.

METHODS: An in vitro three-dimensional cell culture model was constructed using human endometrial cells isolated from the endometrium of proven fertile women, collected on cycle day LH+4. After 5 days of culture, supernumerary human embryos were added and cultured for another 5 days with mifepristone 0.5muM (n=8) or 0.05muM (n=10) or vehicle as control (n=10). The cultures were checked for embryo attachment and terminated. We studied the expression of 16 reported endometrial receptivity markers in the endometrial constructs using real-time polymerase chain reaction.

RESULTS: None of the embryos in 0.5muM of mifepristone attached to the endometrial constructs (p=.004), whereas 4 out of 10 in 0.05muM (p=.3698) and 7 out of 10 embryos in the control group attached to the cultures. We found that most of the studied receptivity markers were significantly altered with mifepristone exposure in a similar direction in both treatment groups. Only IL6 was significantly differentially expressed between the treatment groups (p=.017).

CONCLUSION: We report for the first time that exposure to a low concentration (0.5muM) of mifepristone during the receptive period successfully inhibits human embryo implantation process in vitro. Further, we observed a dose-dependent effect of mifepristone on endometrial receptivity at the functional level.

IMPLICATION: This study contributes new knowledge that low dose of mifepristone during the short period of receptive phase can inhibit endometrial receptivity, which further promotes mifepristone as a contraceptive agent. This could give women a treatment choice to avoid unwanted pregnancy with high efficacy and minimal side effects.

Subject headings: Contraception; Embryo implantation; Emergency contraception; Endometrial receptivity; Mifepristone; Progesterone receptor modulator

Publication year: 2016

Journal or book title: Contraception

Volume: 94

Issue: 2

Pages: 143-151

Find the full text : https://www.sciencedirect.com/science/article/pii/S0010782415302134

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Type: Journal Article

Serial number: 1600