N R Boggavarapu1, C Berger1, C von Grothusen1, J Menezes2, K Gemzell-Danielsson3, P G L Lalitkumar4. 1. Department of Women's and Children's Health, Division of Obstetrics and Gynecology, Karolinska Institutet/Karolinska University Hospital, S-171 76, Stockholm, Sweden. 2. Fertilitetscentrum, Stockholm, Sweden. 3. Department of Women's and Children's Health, Division of Obstetrics and Gynecology, Karolinska Institutet/Karolinska University Hospital, S-171 76, Stockholm, Sweden. Electronic address: kristina.gemzell@ki.se. 4. Department of Women's and Children's Health, Division of Obstetrics and Gynecology, Karolinska Institutet/Karolinska University Hospital, S-171 76, Stockholm, Sweden. Electronic address: lalit.kumar@ki.se.
Abstract
OBJECTIVES: We wanted to explore the effects of two different low doses (0.5μM and 0.05μM) 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 0.5μM (n=8) or 0.05μM (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 0.5μM of mifepristone attached to the endometrial constructs (p=.004), whereas 4 out of 10 in 0.05μM (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 (0.5μM) 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.
OBJECTIVES: We wanted to explore the effects of two different low doses (0.5μM and 0.05μM) 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 0.5μM (n=8) or 0.05μM (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 0.5μM of mifepristone attached to the endometrial constructs (p=.004), whereas 4 out of 10 in 0.05μM (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 (0.5μM) 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.
Authors: Peter T Ruane; Chelsea J Buck; Phoebe A Babbington; Wedad Aboussahoud; Stéphane C Berneau; Melissa Westwood; Susan J Kimber; John D Aplin; Daniel R Brison Journal: Hum Reprod Open Date: 2020-02-28
Authors: Peter T Ruane; Terence Garner; Lydia Parsons; Phoebe A Babbington; Ivan Wangsaputra; Susan J Kimber; Adam Stevens; Melissa Westwood; Daniel R Brison; John D Aplin Journal: Hum Reprod Date: 2022-04-01 Impact factor: 6.353