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Human oocyte calcium analysis predicts the response to assisted oocyte activation in patients experiencing fertilization failure after ICSI

Minerva Ferrer Buitrago (UGent) , Lien Dhaenens (UGent) , Yuechao Lu (UGent) , Davina Bonte (UGent) , Frauke Vanden Meerschaut (UGent) , Petra De Sutter (UGent) , Luc Leybaert (UGent) and Björn Heindryckx (UGent)
(2018) HUMAN REPRODUCTION. 33(3). p.216-225
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Abstract
STUDY QUESTION: Can human oocyte calcium analysis predict fertilization success after assisted oocyte activation (AOA) in patients experiencing fertilization failure after ICSI? SUMMARY ANSWER: ICSI-AOA restores the fertilization rate only in patients displaying abnormal Ca2+ oscillations during human oocyte activation. WHAT IS KNOWN ALREADY: Patients capable of activating mouse oocytes and who showed abnormal Ca2+ profiles after mouse oocyte Ca2+ analysis (M-OCA), have variable responses to ICSI-AOA. It remains unsettled whether human oocyte Ca2+ analysis (H-OCA) would yield an improved accuracy to predict fertilization success after ICSI-AOA. STUDY DESIGN, SIZE, DURATION: Sperm activation potential was first evaluated by MOAT. Subsequently, Ca2+ oscillatory patterns were determined with sperm from patients showing moderate to normal activation potential based on the capacity of human sperm to generate Ca2+ responses upon microinjection in mouse and human oocytes. Altogether, this study includes a total of 255 mouse and 122 human oocytes. M-OCA was performed with 16 different sperm samples before undergoing ICSI-AOA treatment. H-OCA was performed for 11 patients who finally underwent ICSI-AOA treatment. The diagnostic accuracy to predict fertilization success was calculated based on the response to ICSI-AOA. PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients experiencing low or total failed fertilization after conventional ICSI were included in the study. All participants showed moderate to high rates of activation after MOAT. Metaphase II (MII) oocytes from B6D2F1 mice were used for M-OCA. Control fertile sperm samples were used to obtain a reference Ca2+ oscillation profile elicited in human oocytes. Donated human oocytes, non-suitable for IVF treatments, were collected and vitrified at MII stage for further analysis by H-OCA. MAIN RESULTS AND THE ROLE OF CHANCE: M-OCA and H-OCA predicted the response to ICSI-AOA in 8 out of 11 (73%) patients. Compared to M-OCA, H-OCA detected the presence of sperm activation deficiencies with greater sensitivity (75 vs 100%, respectively). ICSI-AOA never showed benefit to overcome fertilization failure in patients showing normal capacity to generate Ca2+ oscillations in H-OCA and was likely to be beneficial in cases displaying abnormal H-OCA Ca2+ oscillations patterns. LIMITATIONS, REASONS FOR CAUTION: The scarce availability of human oocytes donated for research purposes is a limiting factor to perform H-OCA. Ca2+ imaging requires specific equipment to monitor fluorescence changes over time. WIDER IMPLICATIONS OF THE FINDINGS: H-OCA is a sensitive test to diagnose gamete-linked fertilization failure. H-OCA allows treatment counseling for couples experiencing ICSI failures to either undergo ICSI-AOA or to participate in gamete donation programs. The present data provide an important template of the Ca2+ signature observed during human fertilization in cases with normal, low and failed fertilization after conventional ICSI. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the Flemish fund for scientific research (FWO-Vlaanderen, G060615N). The authors have no conflict of interest to declare.
Keywords
fertilization failure, ICSI, calcium oscillations, assisted oocyte activation, mouse oocyte activation test, PHOSPHOLIPASE-C-ZETA, INTRACYTOPLASMIC SPERM INJECTION, INDUCED CA2+ OSCILLATIONS, EGG ACTIVATION, PLC-ZETA, EMBRYO DEVELOPMENT, HUMAN SPERMATOZOA, GENE-EXPRESSION, MOUSE, CRYOPRESERVATION

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MLA
Ferrer Buitrago, Minerva, et al. “Human Oocyte Calcium Analysis Predicts the Response to Assisted Oocyte Activation in Patients Experiencing Fertilization Failure after ICSI.” HUMAN REPRODUCTION, vol. 33, no. 3, 2018, pp. 216–25.
APA
Ferrer Buitrago, M., Dhaenens, L., Lu, Y., Bonte, D., Vanden Meerschaut, F., De Sutter, P., … Heindryckx, B. (2018). Human oocyte calcium analysis predicts the response to assisted oocyte activation in patients experiencing fertilization failure after ICSI. HUMAN REPRODUCTION, 33(3), 216–225.
Chicago author-date
Ferrer Buitrago, Minerva, Lien Dhaenens, Yuechao Lu, Davina Bonte, Frauke Vanden Meerschaut, Petra De Sutter, Luc Leybaert, and Björn Heindryckx. 2018. “Human Oocyte Calcium Analysis Predicts the Response to Assisted Oocyte Activation in Patients Experiencing Fertilization Failure after ICSI.” HUMAN REPRODUCTION 33 (3): 216–25.
Chicago author-date (all authors)
Ferrer Buitrago, Minerva, Lien Dhaenens, Yuechao Lu, Davina Bonte, Frauke Vanden Meerschaut, Petra De Sutter, Luc Leybaert, and Björn Heindryckx. 2018. “Human Oocyte Calcium Analysis Predicts the Response to Assisted Oocyte Activation in Patients Experiencing Fertilization Failure after ICSI.” HUMAN REPRODUCTION 33 (3): 216–225.
Vancouver
1.
Ferrer Buitrago M, Dhaenens L, Lu Y, Bonte D, Vanden Meerschaut F, De Sutter P, et al. Human oocyte calcium analysis predicts the response to assisted oocyte activation in patients experiencing fertilization failure after ICSI. HUMAN REPRODUCTION. 2018;33(3):216–25.
IEEE
[1]
M. Ferrer Buitrago et al., “Human oocyte calcium analysis predicts the response to assisted oocyte activation in patients experiencing fertilization failure after ICSI,” HUMAN REPRODUCTION, vol. 33, no. 3, pp. 216–225, 2018.
@article{8554093,
  abstract     = {STUDY QUESTION: Can human oocyte calcium analysis predict fertilization success after assisted oocyte activation (AOA) in patients experiencing fertilization failure after ICSI?
SUMMARY ANSWER: ICSI-AOA restores the fertilization rate only in patients displaying abnormal Ca2+ oscillations during human oocyte activation.
WHAT IS KNOWN ALREADY: Patients capable of activating mouse oocytes and who showed abnormal Ca2+ profiles after mouse oocyte Ca2+ analysis (M-OCA), have variable responses to ICSI-AOA. It remains unsettled whether human oocyte Ca2+ analysis (H-OCA) would yield an improved accuracy to predict fertilization success after ICSI-AOA.
STUDY DESIGN, SIZE, DURATION: Sperm activation potential was first evaluated by MOAT. Subsequently, Ca2+ oscillatory patterns were determined with sperm from patients showing moderate to normal activation potential based on the capacity of human sperm to generate Ca2+ responses upon microinjection in mouse and human oocytes. Altogether, this study includes a total of 255 mouse and 122 human oocytes. M-OCA was performed with 16 different sperm samples before undergoing ICSI-AOA treatment. H-OCA was performed for 11 patients who finally underwent ICSI-AOA treatment. The diagnostic accuracy to predict fertilization success was calculated based on the response to ICSI-AOA.
PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients experiencing low or total failed fertilization after conventional ICSI were included in the study. All participants showed moderate to high rates of activation after MOAT. Metaphase II (MII) oocytes from B6D2F1 mice were used for M-OCA. Control fertile sperm samples were used to obtain a reference Ca2+ oscillation profile elicited in human oocytes. Donated human oocytes, non-suitable for IVF treatments, were collected and vitrified at MII stage for further analysis by H-OCA.
MAIN RESULTS AND THE ROLE OF CHANCE: M-OCA and H-OCA predicted the response to ICSI-AOA in 8 out of 11 (73%) patients. Compared to M-OCA, H-OCA detected the presence of sperm activation deficiencies with greater sensitivity (75 vs 100%, respectively). ICSI-AOA never showed benefit to overcome fertilization failure in patients showing normal capacity to generate Ca2+ oscillations in H-OCA and was likely to be beneficial in cases displaying abnormal H-OCA Ca2+ oscillations patterns.
LIMITATIONS, REASONS FOR CAUTION: The scarce availability of human oocytes donated for research purposes is a limiting factor to perform H-OCA. Ca2+ imaging requires specific equipment to monitor fluorescence changes over time.
WIDER IMPLICATIONS OF THE FINDINGS: H-OCA is a sensitive test to diagnose gamete-linked fertilization failure. H-OCA allows treatment counseling for couples experiencing ICSI failures to either undergo ICSI-AOA or to participate in gamete donation programs. The present data provide an important template of the Ca2+ signature observed during human fertilization in cases with normal, low and failed fertilization after conventional ICSI.
STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the Flemish fund for scientific research (FWO-Vlaanderen, G060615N). The authors have no conflict of interest to declare.},
  author       = {Ferrer Buitrago, Minerva and Dhaenens, Lien and Lu, Yuechao and Bonte, Davina and Vanden Meerschaut, Frauke and De Sutter, Petra and Leybaert, Luc and Heindryckx, Björn},
  issn         = {0268-1161},
  journal      = {HUMAN REPRODUCTION},
  keywords     = {fertilization failure,ICSI,calcium oscillations,assisted oocyte activation,mouse oocyte activation test,PHOSPHOLIPASE-C-ZETA,INTRACYTOPLASMIC SPERM INJECTION,INDUCED CA2+ OSCILLATIONS,EGG ACTIVATION,PLC-ZETA,EMBRYO DEVELOPMENT,HUMAN SPERMATOZOA,GENE-EXPRESSION,MOUSE,CRYOPRESERVATION},
  language     = {eng},
  number       = {3},
  pages        = {216--225},
  title        = {Human oocyte calcium analysis predicts the response to assisted oocyte activation in patients experiencing fertilization failure after ICSI},
  url          = {http://dx.doi.org/10.1093/humrep/dex376},
  volume       = {33},
  year         = {2018},
}

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