A groundbreaking pilot study has demonstrated that genetic testing of IVF embryos may help women over 35 achieve pregnancy faster and with higher success rates. The randomized controlled trial, conducted by researchers from King's College London, King's College Hospital, and King's Fertility, represents the first study worldwide to focus exclusively on women aged 35-42 undergoing preimplantation genetic testing for aneuploidy (PGT-A).
Published in the Journal of Clinical Medicine, the study addressed a critical evidence gap in fertility treatment for older women, who face increased risks of producing embryos with chromosomal abnormalities that can lead to implantation failure and miscarriage.
Study Design and Methodology
The unblinded trial enrolled 100 women undergoing fertility treatment at King's Fertility between June 2021 and June 2023. Participants were equally randomized into two groups: 50 women received PGT-A screening before embryo transfer, while 50 followed traditional morphological embryo selection without genetic testing.
The study broke new ground by including mosaic embryos—those containing both normal and abnormal cells—which are frequently encountered in IVF practice but rarely included in research. All clinical treatment and embryology procedures were centralized at King's Fertility, ensuring standardized handling across all patients.
Promising Results Despite Small Sample Size
The PGT-A group demonstrated a cumulative live birth rate of 72% after up to three embryo transfers, compared to 52% in the control group. Additionally, women in the PGT-A cohort achieved pregnancies in fewer transfers, effectively reducing time to conception—a crucial factor for women of advanced reproductive age.
"The number of women starting their family above the age of 35 is increasing and women in this age group are more likely to create embryos with the wrong number of chromosomes. This increases the risk of unsuccessful implantation and miscarriages," explained Dr. Yusuf Beebeejaun, first author of the paper. "Our findings suggest that targeted use of PGT-A in this age group could help more women have a baby sooner, while also reducing the emotional toll of repeated unsuccessful cycles."
Addressing Current Guidelines and Practice Gaps
Current NICE guidance does not recommend routine use of PGT-A, based primarily on previous studies with younger average participant ages where aneuploidy rates are lower. This has driven many women to pursue genetic testing privately or forgo it altogether.
Lead author Dr. Sesh Sunkara from King's College London emphasized the study's unique contribution: "By focusing exclusively on women aged 35-42 and including mosaic embryos, we have addressed questions that previous studies have not adequately explored. While larger multi-centre trials are needed to confirm these findings, improving treatment efficiency with a shorter time to achieving pregnancy and live birth could reduce the physical and emotional burden of IVF for women of advanced reproductive age."
Technical Innovation and Clinical Implications
PGT-A involves biopsy of trophectoderm cells from blastocyst-stage embryos, followed by molecular assays to detect chromosomal copy number variations. This genetic approach contrasts with traditional morphological assessment, which relies on visual grading of embryo appearance.
The inclusion of mosaic embryos in the analysis provided deeper insights into their viability, potentially expanding the scope of embryos considered suitable for transfer. This approach aligns with emerging evidence that some mosaic embryos can result in healthy live births.
Future Research Directions
While the pilot study's results did not achieve statistical significance due to the small sample size, the observed trends strongly suggest potential benefits warranting further investigation. Dr. Ippokratis Sarris, Director of King's Fertility and co-author, noted: "This research is a testament to the dedication and expertise of the team at King's Fertility. We are proud to have led this pioneering trial, which addresses one of the most important questions in IVF treatment for women over 35, and we look forward to building on these findings in larger, multi-centre studies."
The researchers emphasized that larger, multi-center randomized controlled trials will be essential to validate these preliminary findings and potentially influence clinical guidelines. Such studies would need to evaluate long-term outcomes, including obstetric and neonatal health, while conducting cost-effectiveness analyses to balance the upfront expenses of PGT-A against potential savings from reduced cycle repetition.
