Clinical outcomes after the first 100 cycles of preimplantation genetic diagnosis at the fertility center of New England

Abstract

Objective: Preimplantation genetic diagnosis (PGD) is increasingly utilized to enable couples to build healthy families. Since 1998, we have utilized PGD for single gene defects, balanced translocations and aneuploidy screening in patients with both recurrent pregnancy loss and advanced maternal age. We present our experiences after the first 100 cycles in a private practice setting.Design: Retrospective quantitative analysis of 100 PGD cycles from February 1998 to March 2003 in a private IVF center.Materials and Methods: 100 IVF cycles were scheduled for PGD. Genetic counseling was provided for all patients. Indications for PGD included single gene defects, recurrent pregnancy loss and advanced maternal age (>40) with at least 2 prior failed IVF cycles. Day 3 single blastomere biopsies were fixed and shipped to either Reprogenetics, West Orange, NJ (9-panel aneuploidy screening or balanced translocations) or Wayne State University Molecular Medicine and Genetics, Detroit, MI (single gene defects). Genetic results were analyzed from 891 embryos and correlated with clinical IVF data including pregnancy rates. Rate differences were analyzed utilizing Chi-square analysis.Results: 98 cycles resulted in embryos for biopsy, 27 of these for recurrent pregnancy loss, 25 for balanced translocations, 11 for advanced maternal age, 5 for X-linked sex selection, and 30 for single gene defects (including 14 for cystic fibrosis, 4 for Huntington’s, 3 for myotonic dystrophy, 3 for aplastic anemia, 2 for hemophilia, and 1 each for metachromatic leukodystrophy, ectodermal dysplasia, familial polyposis, and chronic granulomatous disease). There did not appear to be a learning curve with regards to blastomere biopsy as 73% of the total pregnancies occurred in the first 50 cycles. In 12 of the 98 cycles, no genetically normal embryos were available for transfer. Pregnancy rates per cycle (not per ET) are depicted below. Tabled 1Conclusion: Although time and labor intensive, PGD has shown to be a feasible technique to reduce the transfer of genetically defective embryos. Positive hCG rates are consistent with previously reported ESHRE PGD consortium rates (24.0%; 281/1171 PGD cycles). However, on-going pregnancy rates are reduced when compared to reported SART rates (25%) from non-PGD cycles. Further clinical trials will continue to define which group of patients may most benefit from PGD technology. Objective: Preimplantation genetic diagnosis (PGD) is increasingly utilized to enable couples to build healthy families. Since 1998, we have utilized PGD for single gene defects, balanced translocations and aneuploidy screening in patients with both recurrent pregnancy loss and advanced maternal age. We present our experiences after the first 100 cycles in a private practice setting. Design: Retrospective quantitative analysis of 100 PGD cycles from February 1998 to March 2003 in a private IVF center. Materials and Methods: 100 IVF cycles were scheduled for PGD. Genetic counseling was provided for all patients. Indications for PGD included single gene defects, recurrent pregnancy loss and advanced maternal age (>40) with at least 2 prior failed IVF cycles. Day 3 single blastomere biopsies were fixed and shipped to either Reprogenetics, West Orange, NJ (9-panel aneuploidy screening or balanced translocations) or Wayne State University Molecular Medicine and Genetics, Detroit, MI (single gene defects). Genetic results were analyzed from 891 embryos and correlated with clinical IVF data including pregnancy rates. Rate differences were analyzed utilizing Chi-square analysis. Results: 98 cycles resulted in embryos for biopsy, 27 of these for recurrent pregnancy loss, 25 for balanced translocations, 11 for advanced maternal age, 5 for X-linked sex selection, and 30 for single gene defects (including 14 for cystic fibrosis, 4 for Huntington’s, 3 for myotonic dystrophy, 3 for aplastic anemia, 2 for hemophilia, and 1 each for metachromatic leukodystrophy, ectodermal dysplasia, familial polyposis, and chronic granulomatous disease). There did not appear to be a learning curve with regards to blastomere biopsy as 73% of the total pregnancies occurred in the first 50 cycles. In 12 of the 98 cycles, no genetically normal embryos were available for transfer. Pregnancy rates per cycle (not per ET) are depicted below. Tabled 1 Conclusion: Although time and labor intensive, PGD has shown to be a feasible technique to reduce the transfer of genetically defective embryos. Positive hCG rates are consistent with previously reported ESHRE PGD consortium rates (24.0%; 281/1171 PGD cycles). However, on-going pregnancy rates are reduced when compared to reported SART rates (25%) from non-PGD cycles. Further clinical trials will continue to define which group of patients may most benefit from PGD technology.