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The impact of ovarian stimulation on implantation and fetal development in mice
1Department of Obstetrics and Gynecology, The National Hospital, University of Oslo, 0027 Oslo, Norway. gudvor.ertzeid@rikshopitalet.no
Abstract:
The objective of this study was to evaluate, using an embryo donation model, whether impaired oocyte/embryo developmental competence and/or changes in uterine milieu are responsible for the previously observed adverse effects of superovulation with gonadotrophins on implantation and fetal development in mice. Embryos from superovulated and non-stimulated females were transferred to separate uterine horns within the same superovulated or non-stimulated pseudopregnant recipient mice. Embryo development was impaired as a significantly higher proportion of normal embryos from control donors (61%) were blastocysts on transfer day compared with superovulated donors (41%; P = 0.001). The implantation rate in control recipients was significantly reduced after transfer of embryos from superovulated donors (12%) compared with control donors (25%; P = 0.001). Uterine receptivity was impaired in superovulated recipients. The implantation rate of control embryos was significantly higher in control (25%) than in superovulated recipients (7%; P = 0.001). Transfer of embryos recovered from superovulated donors resulted in significantly higher post-implantation fetal mortality in superovulated recipients (69%) than in control recipients (36%; P = 0.01), and the mean weight of live fetuses was significantly lower for fetuses obtained from superovulated recipients (0.51 g) compared with that of fetuses obtained from control recipients (0.72 g; P = 0.006). Hence, ovarian stimulation appears to impair oocyte/embryo quality as well as uterine milieu.
Insights
Superovulation with gonadotropins impairs both embryo quality and uterine receptivity in mice, negatively impacting implantation and fetal development. This suggests ovarian stimulation affects oocyte/embryo competence and the uterine environment.
Area of Science:
- Reproductive Biology
- Developmental Biology
- Animal Models
Background:
- Superovulation using gonadotropins is a common practice in assisted reproduction.
- Previous studies indicated adverse effects of superovulation on implantation and fetal development.
Purpose of the Study:
- To investigate whether impaired oocyte/embryo developmental competence or altered uterine milieu causes adverse effects of superovulation.
- To utilize an embryo donation model in mice to dissect these effects.
Main Methods:
- Embryos from superovulated and control mice were transferred to pseudopregnant recipients (superovulated or control).
- Evaluated embryo development to blastocyst stage, implantation rates, and fetal outcomes (mortality, weight).
Main Results:
- Superovulated donors produced fewer blastocysts (41%) compared to controls (61%).
- Implantation rates were significantly reduced when embryos from superovulated donors were transferred to any recipient (12% vs 25%).
- Uterine receptivity was impaired in superovulated recipients, with lower implantation rates for control embryos (7% vs 25%).
- Superovulated recipients experienced higher fetal mortality (69% vs 36%) and lower fetal weight (0.51g vs 0.72g).
Conclusions:
- Ovarian stimulation with gonadotropins impairs oocyte/embryo quality.
- Superovulation also negatively affects the uterine environment, reducing receptivity.
- Both factors contribute to the observed adverse effects on implantation and fetal development.