This document reflects emerging clinical and scientific advances as of the date issued and is subject to change. The information should not be construed as dictating an exclusive course of treatment or procedure to be followed.
ABSTRACT: Preimplantation genetic screening differs from preimplantation genetic diagnosis for single gene disorders and was introduced for the detection of chromosomal aneuploidy. Current data does not support a recommendation for preimplantation genetic screening for aneuploidy using fluorescence in situ hybridization solely because of maternal age. Also, preimplantation genetic screening for aneuploidy does not improve in vitro fertilization success rates and may be detrimental. At this time there are no data to support preimplantation genetic screening for recurrent unexplained miscarriage and recurrent implantation failures; its use for these indications should be restricted to research studies with appropriate informed consent.
Preimplantation genetic screening differs from preimplantation genetic diagnosis (PGD) for single gene disorders. In order to perform genetic testing for single gene disorders, PGD was introduced in 1990 as a component of in vitro fertilization programs. Such testing allows the identification and transfer of embryos unaffected by the disorder in question and may avoid the need for pregnancy termination (1). Assessment of polar bodies as well as single blastomeres from cleavage stage embryos has been reported, although the latter is the approach most widely practiced. Preimplantation genetic diagnosis has become a standard method of testing for single gene disorders, and there have been no reports to suggest adverse postnatal effects of the technology. Preimplantation genetic diagnosis has been used for diagnosis of translocations and single-gene disorders, such as cystic fibrosis, X-linked recessive conditions, and inherited mutations, which increase one's risk of developing cancer.
In contrast, in the latter half of the 1990s, preimplantation genetic screening was introduced for the detection of chromosomal aneuploidy (2–4). Aneuploidy leads to increased pregnancy loss with increasing maternal age and also was thought to be a major cause of recurrent pregnancy loss in patients using assisted reproductive technologies. However, when compared with the molecular diagnostics available for PGD of single gene disorders, the current technologies available for preimplantation genetic screening for aneuploidy are more limited. Preimplantation genetic screening using fluorescence in situ hybridization is constrained by the technical limitations of assessing the numerical status of each chromosome. Typically assessed are the chromosome abnormalities associated with common aneuploidies found in spontaneous abortion material, and because of this, and other limitations noted in this Committee Opinion, a significant false-negative rate exists. Therefore, this form of testing should be considered a screening test, and not a diagnostic test, as is the case for PGD for single gene disorders. Because preimplantation chromosome assessment tests a single cell, there are certain limitations: Testing a single cell prohibits confirmation of results. There is a limit to the number of tests that can be done with a single cell. Embryo mosaicism of normal and aneuploid cell lines may not be clinically significant.
Guidelines for counseling on limitations of this screening have been developed by the American Society for Reproductive Medicine (5).
Nonrandomized studies of preimplantation genetic screening in women with advanced maternal age suggested improved implantation rates and decreased spontaneous abortion rates but did not document an improvement in live birth rates (3–6). A study of women with recurrent miscarriages found no evidence of benefit of preimplantation genetic screening in women of any age (7). There have now been two randomized trials for women older than 35 years comparing in vitro fertilization with and without preimplantation genetic screening for aneuploidy (8–9). Neither study provides support for preimplantation genetic screening in women older than 35 years, and one study suggests lowered live birth rates, possibly due to the impact of the biopsy on the embryo's ability to implant (8).
Current data does not support a recommendation for preimplantation genetic screening for aneuploidy using fluorescence in situ hybridization solely because of maternal age. Preimplantation genetic screening for aneuploidy does not improve in vitro fertilization success rates and may be detrimental. At this time there are no data to support preimplantation genetic screening for recurrent unexplained miscarriage and recurrent implantation failures; its use for these indications should be restricted to research studies with appropriate informed consent.
- Handyside AH, Kontogianni EH, Hardy K, Winston RM. Pregnancies from biopsied human preimplantation embryos sexed by Y-specific DNA amplification. Nature 1990;344:768–70.
- Gianaroli L, Magli MC, Ferraretti AP, Fiorentino A, Garrisi J, Munne S. Preimplantation genetic diagnosis increases the implantation rate in human in vitro fertilization by avoiding the transfer of chromosomally abnormal embryos. Fertil Steril 1997;68:1128–31.
- Munne S, Magli C, Cohen J, Morton P, Sadowy S, Gianaroli L, et al. Positive outcome after preimplantation diagnosis of aneuploidy in human embryos. Hum Reprod 1999;14: 2191–9.
- Gianaroli L, Magli MC, Ferraretti AP, Munne S. Preimplantation diagnosis for aneuploidies in patients undergoing in vitro fertilization with a poor prognosis: identification of the categories for which it should be proposed. Fertil Steril 1999;72:837–44.
- Preimplantation genetic testing: a Practice Committee opinion. Practice Committee of the Society for Assisted Reproductive Technology; Practice Committee of the American Society for Reproductive Medicine. Fertil Steril 2007;88:1497–504.
- Munne S, Chen S, Fischer J, Colls P, Zheng X, Stevens J, et al. Preimplantation genetic diagnosis reduces pregnancy loss in women aged 35 years and older with a history of recurrent miscarriages. Fertil Steril 2005;84:331–5.
- Munne S, Fischer J, Warner A, Chen S, Zouves C, Cohen J. Preimplantation genetic diagnosis significantly reduces pregnancy loss in infertile couples: a multicenter study. Referring Centers PGD Group. Fertil Steril 2006;85:326–32.
- Platteau P, Staessen C, Michiels A, Van Steirteghem A, Liebaers I, Devroey P. Preimplantation genetic diagnosis for aneuploidy screening in patients with unexplained recurrent miscarriages. Fertil Steril 2005;83:393,7; quiz 525–6.
- Staessen C, Platteau P, Van Assche E, Michiels A, Tournaye H, Camus M, et al. Comparison of blastocyst transfer with or without preimplantation genetic diagnosis for aneuploidy screening in couples with advanced maternal age: a prospective randomized controlled trial. Hum Reprod 2004;19:2849–58.
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Preimplantation Genetic Screening for Aneuploidy. ACOG Committee Opinion No.430. American College of Obstetricians and Gynecologists. Obstet Gynecol 2009;113:766–7.