Clinical Indications for Preimplantation Genetic Diagnosis (PGD)—A Lab Perspective and Comparison of the Type of Abnormalities Based on the Clinical Indication

Abstract

To review the indications used in clinical practice to request PGD and to compare the rate of abnormalities observed by varying clinical indication. Retrospective analysis. Test requisition forms accompanying the PGD samples were reviewed for 303 cases received in the laboratory for 5 probe or 10 probe analysis. Blastomere samples of 2585 embryos from these 303 cases were analyzed for aneuploidy screen using either a 5-probe or a 10 probe fluorescence in situ hybridization (FISH) panel. The 5-probe panel screens for aneuploidy of chromosomes 13, 18, 21, X, and Y using probes RB1 at 13q14, D18Z1 at 18cen, D21S259/D21S341/D21S342 at 21q22.13-q22.2, DXZ1 at Xcen, and DYZ3 at Ycen (Vysis MultiVysion− PGT). The 10-probe set additionally screens for aneuploidy of chromosomes 8, 9, 15, 16, and 22 using probes D8Z2 at 8p11.1-q11.1, CEP9 at 9p11-q11, D15Z4 at 15p11.1-q11.1, D16Z3 at 16q11.2, and BCR at 22q11.2 (Vysis MultiVysion− Custom 5A). The most common referral indication for PGD was advanced maternal age (AMA-group). 62.2 % of cases received in our laboratory for analysis were for patients over 35 years of age. Recurrent miscarriages (SAB group) accounted for only 2.6 % of cases. Other indications (Other group), including male factor infertility, poor oocyte quality, repeated IVF failure, and family history of chromosome abnormalities was a referral indication in 1.6 % cases. Gender identification (Gender group) was specifically requested in about 5.9 % of cases, some of which included family history of X-linked disorders. 27.4 % of cases, our second biggest group were cases referred for aneuploidy screen (AS group) without another specific indication. Most of these cases were patients less than 35 years as based on the date of birth provided on the test requisition. The rate of abnormalities observed varied by the indication. Comparing the AMA group to AS group, the rate of abnormalities for complex and monosomic abnormalities were very similar at 63.2% and 61.7% respectively. The rate of abnormalities for complex and monosomic abnormalities were also very similar (statistically no significant difference was noted, p ≤ 1) in these two groups; but a statistically significant difference was noted for the trisomic and sex chromosome abnormalities. The rate of trisomic and sex chromosome abnormalities was 14.9 % and 8 % respectively in the AMA group as compared to 10.8 % and 6 % in the AS group (p ≤ 0.05). The rate of abnormality observed in the recurrent SAB group of 61.5 % was also similar to the AMA group (p ≤ 1). The rate of abnormality in the Other group was higher at 72% higher, but this was not found to be statistically significant (p ≤ 0.10). In contrast, the rate of abnormalities seen in the gender identification category was only 54 %. PGD has been increasingly used in infertility practices to improve the overall outcome and success rate. As expected, AMA cases are associated with increased incidence of aneuploidy. Therefore, offering PGD to this group of patients is most appropriate. Patients undergoing IVF for other indications may also benefit from aneuploidy screening.