Preimplantation genetic screening (PGS) for aneuploidy in embryos after in vitro fertilization (IVF) does not improve reproductive outcome in women over 35: a prospective controlled randomized study

Abstract

In view of insufficient evidence to routinely use PGS in order to improve success rates after IVF, we tested the hypothesis that patients with advanced maternal age (AMA) have a higher pregnancy rate (PR) and implantation rate (IR) after embryo transfer (ET) of chromosomally normal embryos following PGS compared to patients who had an ET without PGS. Prospective randomized controlled study (RCT) in an academic tertiary setting. Female patients with a medical indication for IVF who were at least 35 years old, recruited for this study after informed consent, were randomized to a PGS group or a control group without PGS at the time of hCG injection. In the PGS group, 2 blastomeres were removed in all ≥6c stage embryos on day 3 using laser technology (Fertilase, MTG, Germany) and analysed by fluorescent in situ hybridization (FISH) using specific probes for chromosomes 13, 16, 18, 21, 22, X and Y. In the control group, no embryo biopsy was performed. The ET was performed on day 5/6 in both groups. Outcome variables were clinical (fetal sac on ultrasound at 6–8 weeks of pregnancy) and ongoing (at 12 weeks of pregnancy) PR per ET and IR per embryo transferred. Statistical analysis for significant differences was performed using Fisher's exact Chi square test. A P-value <0.05 was considered to be statistically significant. A total of 104 cycles were randomized to either PGS group (n = 52) or control group (n = 52). Reproductive outcome data were available for 37 cycles in the PGS group and for 24 cycles in the control group for the following reasons: no oocytes at retrieval (Control, n = 1), no fertilization (PGS, n = 2; Control, n = 2); N of fertilized oocytes available ≤2 (PGS, n = 5; Control, n = 10); N of ≥6c stage embryos available on day 3 ≤2 (PGS, n = 4; Control, n = 10); no embryo available for biopsy (PGS, n = 1), no technical support available for FISH during weekend (PGS, n = 3) or request of the patient to drop out of the study (control, n = 5). More embryos were transferred in the PGS group (2 ± 0.6) than in the control group (1.6 ± 0.6, P=0.02). The FISH result, obtained in 96% (240/249) of the successfully biopsied embryos, was normal in 30% (73/240) of the embryos. The PGS group and control group were comparable for clinical PR (18% and 25%), ongoing PR (12% and 25%), clinical IR (15% and 15%) and ongoing IR (9%, 15%). In this RCT, PGS did not improve reproductive outcome in AMA patients.