Angelica Cheng
Active Member
No outcome benefit of PGT-A in ART patients of advanced maternal age
www.focusonreproduction.eu
No outcome benefit of PGT-A in ART patients of advanced maternal age
The first comprehensive meta-analysis of PGT-A for its effect in older ART patients confirms a decline in LBR but finds that the decline occurs independently of the embryo’s ploidy status.
PGT-A has never been short of controversy, described in one recent opinion paper as ‘a conflict capable of boiling the ocean’.(1) This time, a new study challenges PGT-A’s ‘benefits’ in women of advanced maternal age, an effect given some traction by the indisputable finding that the prevalence of chromosomal abnormalities in embryos increases as women get older.
However, the value of PGT-A as an indication in IVF patients of advanced maternal age has now been questioned by results from what is described as first comprehensive meta-analysis and systematic review of its kind.(2) The findings suggest that an age-related decline in the chance of having a baby with fertility treatment occurs independent of embryo ploidy - thus, similarly seen not only in patients aged 35 and under (the limit commonly used for a good prognosis) but also in older women.
Based on more than 11,000 ART euploid embryo transfers, the review shows that an increase in maternal age is, as expected, associated with both lower ongoing pregnancy rate and LBR, even after transfer of euploid blastocysts, a finding which persisted following sensitivity analysis to explore any inconsistency among studies. In a strongly worded conclusion, the authors write that the message from their analysis is ‘likely to be critical’ for PGT-A in clinical practice. However, they add that the effect of maternal age, even with euploid embryo transfer, ‘cannot be ignored’ and thus represents a need for appropriate counselling before PGT-A so that pre-existing risks are made clear to patients.
The aim of the meta-analysis was to investigate the effect of the two maternal age ranges on ART success rates following euploid embryo transfers. The primary outcome was ongoing pregnancy/LBR after euploid embryo transfer comparing women aged under and over 35. Secondary outcomes included implantation and miscarriage rates.
The analysis represented 11,335 ART euploid embryo transfers in total, most single frozen-thawed blastocysts with PGT-A generally performed at day 5 or 6; most of the studies were RCTs. Euploid was defined as ‘normal’ with comprehensive chromosomal screening technology.
Findings showed a significantly higher OPR/LBR (OR 1.29) in women aged under 35 than in those aged 35 and above. Similarly, implantation rate was found higher in the younger age group (OR 1.22). A statistically significant higher OPR/LBR was also found when comparing women aged under 35 with older participants stratified into shorter age ranges (35-37; 38-40; and 41-42); the lowest results were found in those older than 42.
If LBR is not affected by chromosomal errors - as this study suggests - what age-related factors might be responsible for the lower reproductive potential in women of advanced maternal age? The authors suggest three possible explanations: endometrial ageing; the effect of embryonic factors (other than aneuploidy) on embryo competence (eg, the effect of paternal age); and ‘uterine pathologies’ interfering with embryo implantation (eg, adenomyosis/fibroids).
The proposition suggested by this meta-analysis, that age affects embryo implantation independent of ploidy, may, say the authors, represent an ‘unprecedented incentive’ to investigate additional embryonic and uterine factors in determining outcome. Yet they acknowledge that aneuploidy is the most significant determinant of ART cycle outcomes, and note that PGT-A at the blastocyst stage will ‘probably’ continue, despite its ‘possible negative implications’.
1. Curchoe CL. For whom the artificial intelligence bell tolls: preimplantation genetic testing for aneuploidy, does it toll for thee? Fert and Steril January 2022; vol 117(3); doi.org/10.1016/j.fertnstert.2022.01.005
2. Vitagliano A, Paffoni A, Viganò P. Does maternal age affect Assisted Reproduction Technology success rates after euploid embryo transfer? A systematic review and meta-analysis; Fertil Sterility 2023;
doi.org/10.1016/j.fertnstert.2023.02.036