Aneuploidy in Morphologically Normal Human Embryos

Author(s): Souter, I. (1), Hill DL (2), Surrey MW (2) (1) University of California Los Angeles, California, USA. Department of Obstetrics / Gynecology, Division of Reproductive Endocrinology and Infertility (2) Southern California Reproductive Center, Beverly Hills, California, USA

Introduction: During in vitro fertilization - embryo transfer cycles (IVF-ET) many morphologically normal embryos fail to implant. One explanation for implantation failure is the existence of chromosomal aneuploidy, or single gene defects. The purpose of the present study was to assess the incidence of aneuploidy in morphologically normal embryos.

Materials and Methods: Design: Retrospective analysis of twenty-four IVF-ET cycles in which preimplantation genetic diagnosis (PGD) was performed on Day 3 post-insemination, with ET on Day 5-6.

Setting: Large private IVF canter in California.

Methods: Embryos were biopsied on Day3 post-insemination. One to two blastomeres were removed by gentle suction from embryos of good morphology (Grade A to B) at the 6-10 cell stage. Twenty one cases were analyzed by fluorescence in situ hybridization (FISH) with chromosome specific probe panels, either 13,18,21,X,Y or 13,16,18,21,22. In three cases, polar body biopsy was used in conjunction with polymerase chain reaction (PCR) and embryo biopsy for the detection of single gene defects.

Main Outcome Measure: Embryo morphology, FISH/PCR analysis of blastomeres or polar bodies, clinical pregnancies and implantation rate.

Results: Twenty-two patients (average age 37.8 years) underwent 24 IVF/PGD cycles. Intracytoplasmicsperm injection (ICSI) was performed in seven (29.2%) of the cycles. A total of 355 oocytes were retrieved, 245 (69%) fertilized normally (2PN) and of them, 156(63.7%) became Day 3 embryos considered morphologically suitable for biopsy.

No results were obtained from 8 blastomeres because the nucleus could not be found. Results obtained from the other 148 blastomeres indicated euploidy at the chromosomes tested for. Embryo transfer with at least one normal embryo was performed in twenty-two cycles, with a total of fifty-four embryos being replaced among them.

Eleven clinical and four biochemical pregnancies resulted for a clinical pregnancy rate of 50% per transfer. The rate of clinical pregnancy loss was 18.2% (9.1% if one pregnancy of a trisomy at chromosome 2, detected at 11 weeks gestation, is excluded).

Conclusions: During IVF, many morphologically high-quality day three embryos are aneuploid. In older women, women with a history of aneuploid pregnancies or multiple IVF failures with morphologically sound embryos, transfer of PGD-evaluated embryos may increase implantation rates per embryo transferred, and significantly reduce the rate of chromosomally unbalanced offspring or pregnancy loss. Expanding the indications for transferring PGD-evaluated embryos might reduce the need for repeat IVF-ET cycles, and improve pregnancy rates for patients undergoing IVF-ET. Presented at ESHRE, Summer 2002