Artificial oocyte activation with calcium ionophore does not cause a widespread increase in chromosome segregation errors in the second meiotic division of the oocyte

Abstract

Objective: To study the effect of artificial oocyte activation (AOA) on chromosome segregation errors in the meiotic divisions.

Design: Prospective cohort study with historical control.

Setting: Private/academic IVF centers.

Patient(s): Fifty-six metaphase II oocytes were donated from 12 patients who had undergone IVF between June 2008 and May 2009.

Intervention(s): Oocytes were activated by 40 minutes' exposure to 100 μM calcium-ionophore. The activated oocyte was tubed and analyzed by array comparative genomic hybridization and/or single-nucleotide polymorphism genotyping and maternal haplotyping (meiomapping). A control sample of embryos derived from normally fertilized oocytes was included for comparison.

Main outcome measure(s): Incidence of chromosome segregation errors in artificially activated and normally fertilized oocytes in relation to pronuclear evaluation.

Result(s): Of 49 oocytes that survived the warming procedure, thirty-nine (79.6%) activated. Most activated normally, resulting in extrusion of the second polar body and formation of a single or no pronucleus (2PB1PN: 30 of 39, 76.9%; or 2PB0PN: 5 of 39, 12.8%). Twenty-seven of these were analyzed, and 16 (59.3%) were euploid, showing no effect of AOA on meiotic segregation. Single-nucleotide polymorphism analysis of normally activated oocytes confirmed normal segregation of maternal chromosomes. No difference in the proportion of meiosis II type errors was observed between artificially activated oocytes (28.6%; 95% confidence interval 3.7%-71.0%) compared with embryos obtained from normally fertilized oocytes (44.4%; 95% confidence interval 13.7%-78.8%). The abnormally activated oocytes, with ≥2PN (4 of 39, 10.3%) were diploid, indicating a failure to coordinate telophase of meiosis II with polar body extrusion.

Conclusion(s): From this preliminary dataset, there is no evidence that AOA causes a widespread increase in chromosome segregation errors in meiosis II. However, we recommend that it be applied selectively to patients with specific indications.

Keywords: Calcium ionophore; chromosome segregation; fertilization failure; meiosis; oocyte activation.