Oocyte aneuploidy mechanisms are different in two situations of increased chromosomal risk: older patients and patients with recurrent implantation failure after in vitro fertilization

Objective

To clarify the mechanisms underlying oocyte abnormalities in meiosis: meiotic nondisjunction of a whole chromosome or premature separation of sister chromatids in two situations of increased chromosomal risk.

Design

Preconception diagnosis by first polar-body analysis in two situations of increased chromosomal risk.

Setting

Departments of reproductive biology, cytogenetics, gynecology, and obstetrics.

Patient(s)

First polar body analysis was proposed to 76 patients (91 cycles) for advanced age (AMA; n = 30, 36 cycles), recurrent implantation failure (RIF; >10 embryos transferred without implantation; n = 32, 36 cycles), or both (AMA + RIF; n = 14, 19 cycles), before their intracytoplasmic sperm injection procedure.

Intervention(s)

First polar-body analysis using fluorescence in situ hybridization.

Main Outcome Measure(s)

Mechanisms and frequency of aneuploidy.

Result(s)

Three hundred eighty-four oocytes were analyzed by fluorescence in situ hybridization, 130 from women >38 years of age, 171 from women with RIF, and 83 from women with both indications. The oocyte abnormality rate was similar in the three groups, respectively, 38.5%, 40.4%, and 45.8%. The aneuploidy mechanisms were different for women >38 years of age who had no previous implantation failure (AMA) compared with women of whatever age who had implantation failure (P<.05 vs. RIF; P<.001 vs. AMA+RIF), with, respectively, for the AMA, RIF, and AMA+RIF groups, 72.2%, 56.6%, and 49.2% premature separation of sister chromatids and 27.8%, 43.4%, and 50.8% meiotic nondisjunction. In the two implantation-failure groups, we distinguished a subgroup (22% in the RIF group and 33% in AMA+RIF group) of patients with >2/3 abnormal oocytes, suggesting a meiosis alteration.

Conclusion(s)

The mechanisms accounting for oocyte aneuploidy differed in the two clinical situations of advanced maternal age and RIF. Advanced maternal-age aneuploidy was linked to a loss of sister chromatid cohesion that led to one single chromatid abnormality, whereas implantation failure is a much more heterogeneous situation.

Key Words: First polar-body biopsy, age, recurrent implantation failure, premature separation of sister chromatids, meiotic nondisjunction