| BackgroundDuring mammalian fertilization,calcium(Ca2+)oscillations after the fusion of sperm and oocyte plasma membranes are essential for normal fertilization and the onset of embryogenesis.Calcium ionophores are now mainly considered as efficient treatments for fertilization failure.Recently,its application for rescuing poor embryo development was proposed but still non-routine due to inconsistent conclusions among relative studies.This study aimed to explore whether Ca2+ionophore improves embryo development and pregnancy outcomes in patients with poor embryo development in previous intracytoplasmic sperm injection(ICSI)cycles.MethodsThis study included 97 patients undergoing assisted oocyte activation(AOA)with Ca2+ionophore(calcimycin,A23187)treatment due to poor embryo development in at least two ICSI cycles previously in Hospital for Reproductive Medicine Affiliated to Shandong University from March 2020 to December 2021.Poor embryo development was defined as 1)no good-quality embryo on day 3,or 2)having good quality embryos on day 3 but less than 20%good-quality blastocyst formation rate.Preimplantation embryonic development and clinical outcomes for fresh and frozen embryo transfers were compared between ICSI-AOA cycles(AOA group)and the last ICSI cycles within the past half year(non-AOA group).Subgroups stratified by maternal age(<35,35-40,≥40 years,respectively)were analyzed separately.ResultsNo differences in controlled ovarian stimulation protocols,gonadotropin doses,sperm origins and the number of metaphase Ⅱ oocytes between AOA and non-AOA groups were observed.Normal fertilization rate in AOA group is significantly lower than non-AOA group(65.3%±27.9%vs.74.0%± 20.1%,P=0.006).Significantly higher day 3 good-quality embryo rate(median:33.3%vs.25.0%,P=0.034),good-quality blastocyst formation rate(median:25.0%vs.0.0%,mean:29.5%vs.2.0%,P<0.001),and oocyte utilization rate(24.0%±21.1%vs.7.6%± 8.9%,P<0.001)were seen in AOA group.For pregnancy outcomes,there were higher clinical pregnancy rate(37.7%vs.19.6%,P=0.039),ongoing pregnancy rate(29.0%vs.10.9%,P=0.021)and live birth rate(27.5%vs.8.7%,P=0.013)in AOA group compared to non-AOA group.No birth defects were found.In subgroup aged<35 years,there was no difference in normal fertilization rate between AOA and non-AOA group.AOA group had higher day 3 good-quality embryo rate(median:33.3%vs.12.1%,P=0.001),good-quality blastocyst formation rate(median:23.1%vs.0.0%,mean:28.9%vs.2.2%,P<0.001),and oocyte utilization rate(24.1%± 22.5%vs.7.9%±8.8%,P<0.001)than non-AOA group.Biochemical pregnancy rate(52.3%vs.26.9%,P=0.038),clinical pregnancy rate(43.2%vs.19.2%,P=0.041),ongoing pregnancy rate(34.1%vs.11.5%,P=0.037)and live birth rate(34.1%vs.11.5%,P=0.037)in AOA group were significantly higher than that in non-AOA group.In subgroup aged 35-40 years,normal fertilization rate and day 3 good-quality embryo rate were not different between AOA and non-AOA groups.Good-quality blastocyst formation rate(median:33.3%vs.0.0%,mean:27.2%vs.1.7%,P<0.001),and oocyte utilization rate(24.4%± 20.2%vs.7.2%±8.8%,P=0.001)were higher in AOA group compared to non-AOA group.There were no differences in clinical outcomes between AOA and non-AOA groups.In subgroup aged≥40 years,there were significantly lower normal fertilization rate(59.3%± 26.7%vs.79.1%±18.7%,P=0.007)but higher good-quality blastocyst formation rate(median:33.3%vs.0.0%,mean:34.7%vs.1.7%,P=0.005),and oocyte utilization rate(22.9%±19.6%vs.7.5%±9.8%,P=0.006)in AOA group than non-AOA group.No significant difference in day 3 good-quality embryo rate between groups was found.There were no differences in clinical outcomes between AOA and non-AOA groups.ConclusionThe study suggests that AOA with A23187 could improve preimplantation embryo development and pregnancy outcomes in patients with poor embryo development in previous ICSI cycles.Women aged<35 years may be the optimal population for AOA with calcium ionophore treatment.A clinical randomized controlled trial is needed for further validation. |
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