Preimplantation Genetic Screening (PGS) in Patients Undergoing High-Complexity Reproduction Technologies

PICHON RIVIERE, A.; AUGUSTOVSKI, F.; GARCIA MARTI, S.; ALCARAZ, A.; GLUJOVSKY, D.; LOPEZ, A.; REY-ARES, L.; BARDACH, A.; CIAPONI, A

Documento de Evaluación de tecnologías Sanitarias

IECS

Año: 2013 p. 1 - 30

1668-2793

It is estimated that one every six couples will not a live birth after having 12 months of unprotected sex. In Argentina, approximately 10 thousand high-complexity assisted reproduction technologies are performed per year.A high rate of embryos present chromosomal abnormalities (aneuploydies) and this occurs more frequently in embryos whose ovocytes come from women of advanced age. Preimplantation Genetic Screening (PGS) allows tracing these abnormalities. The purpose of this procedure is to transfer an embryo with no chromosomal disorders to the uterus, thus improving the rate of live births due to transfer, reducing the rate of spontaneous abortions, time to pregnancy and rate of newborns with aneuploydies. Several techniques have been used. When PGS was performed in Day 3 embryos using fluorescence in situ hybridization (FISH), heterogeneous results were reported, concluding that there were no evident benefits and that it might also be deleterious. The emergence of PGS with its new techniques assessing all the chromosomes and performing a biopsy in multiple throphoectodermal cells of embryos in blastocyst stage, would allow increasing the method diagnostic certainty and reducing the risk of damaging it.TechnologyPGS through FISH, aCGH (array comparative genomic hybridization), or quantitative PCR (qPCR), is performed by making a biopsy of Day 3 or blastocyst-stage embryos. At present, this may be carried out in a few hours, being it possible to makea fresh embryo transfer or freeze the embryos and transfer them in a following cycle.The combination of the above described variables (technology used, day of biopsy and number of evaluated chromosomes) requires that each alternative should be individually assessed.PurposeTo assess the available evidence on the efficacy, safety and coverage policy related aspects on the use of preimplantation genetic screening in patients undergoing assisted reproduction technologies.MethodsA bibliographic search was carried out on the main databases: DARE, NHS EED, on Internet general search engines, in health technology evaluation agencies and health sponsors. Priority was given to the inclusion of systematic reviews; controlled, randomized clinical trials (RCTs); health technology assessments and economic evaluations; clinical practice guidelines and coverage policies of other health systems.ResultsThis report includes one systematic review, 4 RCTs published at a later date, 3 clinical practice guidelines and one coverage policy.In 2011, one systematic review was published on PGS with FISH assessing some chromosomes mainly at Day 3, in advanced age women. The rate of live births decreased in those using PGS (absolute risk difference: -8%; 95%CI -13% to -3%). The same applied to patients with repeated implantation failures (absolute risk difference: -18%; 95%CI -33% to -3%). No differences between both interventions in patients with good prognosis were found.In 2013, two RCTs assessed FISH in nine chromosomes at Day 3. In the advanced age group, PGS increased the rate of live births per patient (15.5% vs. 32.3%; OR 2.6 95%CI 1.3?5.3). In the repeated failure group, no statistically significant differences (47.9% vs. 27.9%) were found.One RCT published in 2013 randomized 155 patients with good prognosis to real-time quantitative PCR PGS of all the chromosomes in blastocyst stage. The rate of live births was 84.7% in the PGS group versus 67.5% in the control group (RR 1.26; 95%CI, 1.06?1.53).Another 2012 RCT randomized patients of good prognosis to aCGH PGS versus embryo morphology only, making an elective fresh transfer of a single embryo at Day 6. The rate of clinical pregnancy was higher in the PGS group (70.9 % vs. 45.8%, p=0.01).In 2013, one RCT randomized 205 women to quantitative PCR PGS in blastocyst and transfer of a single embryo versus transfer of two blastocysts without PGS. No statistical differences were found in the rage of ongoing pregnancy, while the rate of double pregnancy were higher in the control group (53% vs. 0%, p<0.01).ConclusionsThe available evidence is of good methodological quality, although still heterogeneous and not describing all the relevant outcomes. Also, some study findings (especially with FISH at Day 3) are contradictory.Those studies that made use of the new technologies and assessed all the chromosomes agree that the rates of implantation might increase when using PGS. However, it should be considered that the rate per cycle and the impact on quality of life that a potential reduction in time to pregnancy, rate of live births with chromosomal abnormalities and rates of abortion may have, were not assessed. This technology should be assessed for each method used, whether FISH, aCGH, qPCR or any other, as well as for the time biopsy is performed (Day 3 or blastocyst) and for the number of chromosomes assessed; also consideration should be given to cost-effectiveness and budget impact information. With the information published to date on each of the options, there is still limited information to allow assessing the potential benefit of this technology.