Scientists have reported a method designed to enhance the quality of human eggs, which they suggest could impact In Vitro Fertilization (IVF) success rates, particularly for older women.
Research Findings
The research indicates that an age-related defect leading to genetic errors in embryos might be mitigated by supplementing eggs with a specific protein. Eggs donated by fertility patients received microinjections of this protein, resulting in a reduction by nearly half in the incidence of the defect compared to untreated eggs.
Prof. Melina Schuh, a director at the Max Planck Institute for Multidisciplinary Sciences in Göttingen and a co-founder of Ovo Labs, stated that the approach nearly halved the number of eggs with abnormal chromosomes. Schuh, whose laboratory has studied egg biology for two decades, noted that while women in their early 40s typically have eggs, nearly all of these eggs frequently exhibit incorrect chromosome numbers. This observation served as a motivation for addressing the issue.
The findings are scheduled for presentation at the British Fertility Conference in Edinburgh and have been published as a preprint on the Biorxiv website.
IVF Success Rates and Age
Declining egg quality is identified as a primary factor for the decrease in IVF success rates with increasing female age, and it also contributes to the increased risk of chromosome disorders like Down’s syndrome with maternal age. Recent UK data shows that for patients under 35, the average birthrate per embryo transferred in IVF was 35%. This figure decreased to 5% for women aged 43-44. The average age for individuals starting IVF treatment in the UK for the first time is currently over 35.
Dr. Agata Zielinska, co-founder and co-CEO of Ovo Labs, observed that current solutions for female factor infertility often involve multiple IVF cycles to increase the cumulative likelihood of success. She expressed a vision for this approach to enable more women to conceive within a single IVF cycle.
Mechanism of Action
The reported method addresses a specific vulnerability in eggs related to meiosis, the process by which sex cells reduce their genetic material to prepare for embryo formation. During meiosis in eggs, 23 pairs of X-shaped chromosomes are intended to align along a single axis. Upon fertilization, the cell divides, ideally resulting in each chromosome pair separating symmetrically to yield a cell with 23 single chromosomes from the mother. The remaining chromosomes are supplied by the sperm.
In older eggs, chromosome pairs tend to loosen at their midpoint, potentially separating prematurely before fertilization. This can prevent the X-shaped structures from aligning correctly, causing them to move irregularly within the cell. Consequently, when the cell divides, the chromosomes may not separate symmetrically, leading to an embryo with an atypical number of chromosomes.
Schuh and colleagues previously identified that a protein, Shugoshin 1, which functions in maintaining chromosome pair cohesion, decreases with age. In their recent experiments involving mouse and human eggs, microinjections of Shugoshin 1 appeared to reverse the premature separation of chromosome pairs.
Experimental Results
Using eggs donated by patients at the Bourn Hall fertility clinic in Cambridge, researchers observed that the percentage of eggs exhibiting the defect decreased from 53% in control eggs to 29% in treated eggs. For eggs from women over 35 years of age, a similar trend was noted, with the defect present in 65% of control eggs and 44% of treated eggs. The scientists attributed the lack of statistical significance in the over-35 age group to the limited sample size of nine treated eggs.
Schuh commented on the identification of a single protein that declines with age, stating that restoring it to levels observed in younger cells demonstrated an observable effect.
Future Prospects and Limitations
The approach is not expected to extend fertility beyond menopause, when the ovarian reserve is depleted.
While current treatments rarely involve microinjections directly into eggs, the team anticipates no significant safety issues and is engaging in discussions with regulatory bodies regarding a clinical trial. A key aspect for future investigation will be to determine whether the observed improvements in egg quality translate to embryos with fewer genetic errors.
Dr. Güneş Taylor, from the University of Edinburgh, who was not involved in the research, described the findings as "promising" and highlighted the importance of developing approaches for older eggs, as this demographic represents a significant portion of women seeking fertility treatments. She suggested that a single injection substantially increasing the number of eggs with properly organized chromosomes would provide a more favorable starting point for IVF.