Embryo morphokinetics analysis and reproductive outcomes with assisted oocyte activation by a calcium ionophore after prior fertilization failure. A multicentric retrospective study

2020 ◽  
Vol 7 (3) ◽  
pp. 89-97
Author(s):  
Jesus Aguilar ◽  
Elkin Munoz ◽  
Lucia Alegre ◽  
Zaloa Larreategui ◽  
Jose Remohi ◽  
...  
2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
G Lópe. Ruiz ◽  
C Olmed. Illueca ◽  
M Bare. Gómez ◽  
S Roy. Bolea ◽  
L Aba. d. Velasco ◽  
...  

Abstract Study question Does Calcymicin improve reproductive outcomes of ICSI cycles in cases of fertilization failure and/or embryo blockage indications? Summary answer The application of the Calcymicin after ICSI improves reproductive outcomes, especially in cases with clinical indication of fertilization failure. What is known already According to the bibliography, deficiencies in the oocyte activation process frequently lead to failed ICSI cycles, and these can be corrected by increasing initial levels of calcium (Ca2+) in the oocyte using assisted oocyte activation techniques (AOA), such as the use of Ca2+ ionophores. Ca2+ Ionophores have been shown to trigger an initial Ca2+ spike in the ooplasm that activates Ca2+/Calmodulin dependent protein kinase II, which initiates the cascade of cellular events leading to oocyte activation. Previous results suggest that Ca2+ ionophore treatment can give live offspring after failed ICSI cycles. Study design, size, duration 270 oocytes collected from 17 patients who presented cycles with low fertilization rates and/or embryo blockage or poor quality embryos (according to ASEBIR’s embryo classification criteria) were retrospectively analyzed. Oocytes were divided into two groups, a control group that underwent conventional IVF/ICSI and another group that underwent an ICSI cycle with AOA. Study groups were defined according to clinical indications and subgroups according to AOA or control. All data were collected from 2017 until 2020. Participants/materials, setting, methods Among the 270 oocytes of the study sample, 142 belonged to the control group and 128 belonged to the AOA group. The AOA group oocytes were activated for 15 minutes immediately after ICSI using a prepared solution containing the Ca2+ ionophore A23187, CultActive© (Gynemed, Germany). Fertilization rate and type, blastocyst formation rate, blastocyst quality, embryo kinetics, and pregnancy rates were analyzed, all of them were compared to FIV/ICSI cycles without oocyte activation (control group). Main results and the role of chance In the analyses of the whole sample of oocytes, the AOA treatment gave a fertilization rate of 72.5%, which was significantly higher compared to 53.8% of the control cycles (p = 0.002). Good quality blastocysts and pregnancy rates were also significantly higher than the control (p = 0.01). In the group with an indication of fertilization failure, a significantly higher fertilization rate was recorded compared to the control (65% and 33%, respectively). A higher rate of abnormal embryos with three pronuclei was also found compared to the control (p < 0.001). There were no significant differences in blastocyst formation rates, quality, or embryo kinetics (p > 0.05). In the group with an indication of embryo blockage/poor embryo quality, a significantly higher rate of good quality blastocysts and lower blastulation time were recorded compared to the control (p < 0.05). Limitations, reasons for caution The safety of the AOA technique with Ca2+ ionophore has not been fully demonstrated. In our study, none of the newborns had malformations, and gestational weeks and birth weights were normal. However, further studies on the safety of this technique are needed to implement it routinely in human reproduction clinics. Wider implications of the findings: According to these findings, an increase in the initial levels of calcium in the oocyte through the application of the Ca2+ ionophore A23187 after ICSI improves the results of failed assisted reproduction cycles, especially in the case of those diagnosed with fertility failure, which is a clear indication for AOA. Trial registration number Not applicable


2015 ◽  
Vol 104 (3) ◽  
pp. e302
Author(s):  
A. Sdrigotti ◽  
G.J. Rey Valzacchi ◽  
F.A. Leocata Nieto ◽  
V.E. Canada

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
J Dai ◽  
T Zhang ◽  
J Guo ◽  
Q Zhou ◽  
Y Gu ◽  
...  

Abstract Study question What are the other male factors that cause total fertilization failure (TFF) excepting for variants in PLCZ1? Summary answer Homozygous variants in ACTL9 (actin like 9) cause abnormal localization of PLCζ in a loosened perinuclear theca (PT) structure and leads to TFF. What is known already In previous studies, investigators have reported that the female factors in TFF after intracytoplasmic sperm injection (ICSI) include pathogenic variants in WEE2, TLE6, and TUBB8, whereas for male factors, pathogenic variants in PLCZ1 were reported to be the primary cause of TFF, which account for approximately 30% of couples with male factors in TFF excluding globozoospermia. Most recently, it was reported that pathogenic variants in ACTL7A led to reduced expression and abnormal localization of PLCζ, thereby identifying this genetic variant as a potential cause of TFF. Study design, size, duration Fifty-four infertile couples with TFF or poor fertilization (fertilization rate of < 20%) at the Reproductive and Genetic Hospital of CITIC-Xiangya during January 2014 to June 2020 were recruited into this study. Participants/materials, setting, methods Male factors were identified in (MOAT). WES analysis was used to analyze the genetic factors of individuals with male factors. Sperm morphological study was conducted by H&E staining and TEM. Immunostaining of PLCζ was used to analyze the status of sperm-borne activation factor. A knock-in mouse model was generated by CRISPER-Cas9 technology. Sperm from homozygous Actl9 variant mice were analyzed by TEM and ICSI. ICSI with AOA was performed in couples with ACTL9 variants. Main results and the role of chance A total of 54 couples with TFF or poor fertilization were screened, with 21 couples determined to have a male infertility factor by MOAT. Whole-exome sequencing of these 21 male individuals identified three homozygous pathogenic variants in ACTL9 in three individuals. ACTL9 variations led to abnormal ultrastructure of the PT, with PLCζ absent in the head and present in the neck of the mutant sperm, which contributed to failed normal calcium oscillations in oocytes and subsequent TFF. The key roles of ACTL9 in the PT structure and TFF after ICSI were further confirmed in Actl9-mutated mouse model. Furthermore, assisted oocyte activation by calcium ionophore exposure successfully overcame TFF and achieved live births in a couple with an ACTL9 variant. Limitations, reasons for caution The mechanism of how ACTL9 regulate PLCζ remains unknown. Wider implications of the findings: It provided a genetic marker and a therapeutic option for individuals who have undergone ICSI without successful fertilization. Trial registration number not applioable


2014 ◽  
Vol 28 (5) ◽  
pp. 560-571 ◽  
Author(s):  
Frauke Vanden Meerschaut ◽  
Dimitra Nikiforaki ◽  
Björn Heindryckx ◽  
Petra De Sutter

2013 ◽  
Vol 28 (4) ◽  
pp. 1054-1061 ◽  
Author(s):  
P. Kuentz ◽  
F. Vanden Meerschaut ◽  
E. ElInati ◽  
M. H. Nasr-Esfahani ◽  
T. Gurgan ◽  
...  

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