Abstract
BackgroundIn assisted reproduction technology embryo competence is routinely evaluated on morphological criteria but efficacy remains relatively low. Additional information could be obtained by evaluating pronuclear (PN) morphology. Up to now controversial results have been reported about the prognostic value of PN score. One of the main limitations of literature data is the use of different PN classification methods. In this regard, in 2011 the ESHRE and Alpha Scientists in Reproductive Medicine defined three PN categories to standardize zygote assessment. In this study we evaluated whether the consensus ESHRE-Alpha system for the pronuclear scoring could be an useful additional criterion to improve prediction of embryo implantation potential.MethodsThis is a retrospective, longitudinal, observational, cohort study. We included 3004 zygotes from 555 women who underwent ICSI treatment at our Center between January 2014 and June 2019. The PN were categorized as score 1: symmetrical, 2: non-symmetrical, 3: abnormal. A subset of 110 zygotes did not cleaved. On day 2–3 1163 embryos were transferred, 232 arrested, and 9 were cryopreserved. Among the 1490 embryos cultured up to day 5–7, 516 became blastocysts: 123 were transferred on day 5 and 393 were cryopreserved.Comparisons of age, cleavage and blastocyst rate, quality of embryos, implantation success among PN score groups were evaluated by chi-square test or Kruskal-Wallis test as appropriate. Potential predictors of embryo implantation were first tested in univariable analysis using generalized estimating equations taking into account correlation between embryos originated from the same patient. Then, variables potentially associated with implantation success (P<0.05) were included in a multivariable analysis for calculating the adjusted odds ratio (OR) and 95% confidence interval (CI).ResultsThere was no significant difference in patients’age, cleavage and blastulation rates, and embryo morphology among the three PNscore groups. The PN score 1-embryos had a greater implantation success respect to score 2-3-ones (OR 1.83; 95% CI 1.34-2.50, P=0.0001). Consistently, the pronuclear score remained predictive of implantation in top quality embryos (OR 1.68; 95%CI 1.17-2.42, P= 0.005).ConclusionsThe consensus pronuclear score may be routinely included among criteria for embryo evaluation to increase patients’ chance of becoming pregnant.
Highlights
Identification of the embryo(s) with the highest implantation potential is a challenge not yet achieved in reproductive medicine, and it is a fundamental step for single embryo transfer approach
Among the embryos originated from the 3004 zygotes enrolled in the study, 1163 embryos were transferred into uterus at their cleavage-stage, 1490 were cultured up to day 5–7, 232 arrested on day 3, 9 were cryopreserved on day 2–3; 110 zygotes did not cleave
We believe that the retrospective nature of this study could hardly have affected the reliability of our findings since at our laboratory all procedures were done by the same embryologists, who did not change throughout the duration of the study and applied the same protocols, including consistent timing of PN assessment. This is the first study of correlation between PN morphology and embryo implantation success, applying the PN score system proposed by European Society of Human Reproduction and Embryology (ESHRE) and a multivariable analysis which evaluated various potential confounding factors
Summary
Identification of the embryo(s) with the highest implantation potential is a challenge not yet achieved in reproductive medicine, and it is a fundamental step for single embryo transfer approach. It has been proposed that additional information on embryo viability potential could be obtained by evaluating pronuclear (PN) morphology based on zygote features 16–18 h after fertilization. The progressive polarization of NPB controls the design of the embryonic axis, a fundamental step for cell determination in the developing embryo [9]. Alterations of these strictly related events may have abnormal consequences, including fertilization failure and uneven cleavage. In this study we evaluated whether the consensus ESHRE-Alpha system for the pronuclear scoring could be an useful additional criterion to improve prediction of embryo implantation potential
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