New Injection Reduces Chromosomal Errors in Older Women’s Eggs by 50%

Issues with human eggs, such as aneuploidy (having too many or too few chromosomes), can lead to miscarriages, unsuccessful IVF treatments, or genetic conditions like Down syndrome. Recent research has unveiled a potential solution: a single injection into the egg can significantly mitigate these issues, promising to enhance IVF success rates for women of advanced age.

“This discovery could revolutionize the field,” says Marcos Iuri Ruth Kullman Niro Franz, Ph.D., from Reproductive Medicine in Porto Alegre, Brazil, who was not involved in the study. “This could be the first instance of demonstrating the feasibility of correcting the primary issues behind IVF failures.”

During meiosis, egg and sperm cells typically lose exactly half of their genetic material. This ensures that, upon fertilization, a complete genome is formed. However, irregularities may occur, resulting in sperm or egg cells having an incorrect amount of genetic material, known as aneuploidy.

Aneuploidy affects approximately 10-25% of eggs and its prevalence increases with age, starting from the early 30s. “By the late 30s, over 65% of eggs are aneuploid,” mentions Agata Zielinska from the German biotech company Ovo Labs, during her presentation at the European Society of Human Reproduction and Embryology conference in London on July 6th.

Clinicians may screen IVF embryos for aneuploidy in couples at high risk of miscarriage or IVF failure. However, for many couples, genetic conditions—such as those leading to Down syndrome—can only be identified through blood tests and ultrasounds in the first trimester. Until now, there were limited methods to prevent aneuploidy.

Recent findings by Zielinska and her team indicate that levels of a protein called Shugosin-1 are significantly diminished in older mice and humans compared to their younger counterparts. Shugoshin-1 plays a crucial role during meiosis, ensuring that chromosome pairs line up correctly in immature egg cells, maintaining the molecular integrity that holds each chromosome pair together.

Upon fertilization, these paired chromosomes separate, with one half forming a mature egg cell while the other is discarded. In older eggs, the integrity of this glue deteriorates, resulting in improper chromosome separation before fertilization and leading to aneuploidy.

To investigate the potential for Shugoshin-1 supplementation to preserve chromosome integrity and reduce aneuploidy, researchers collected 111 spare immature eggs from over 30 women aged 22 to 43 undergoing IVF or egg storage.

The study involved injecting mRNA coding for Shugoshin-1 into selected eggs, while others from the same donor remained untreated. Results showed that 53% of untreated eggs exhibited premature chromosome separation, compared to only 29% of those treated. For women over 35, the untreated egg aneuploidy rate averaged 65%, while the treated eggs averaged only 44%. Though the reduction wasn’t statistically significant due to sample size, researchers remain optimistic.

Further experiments showed that this treatment avoided aneuploidy in mouse eggs, allowing them to fertilize and produce healthy offspring without side effects in either mouse or human studies. “We achieved live births in mice, indicating that this approach does not disrupt any phase of embryonic development nor compromise the health of the pups,” Zielinska informed the conference attendees.

Current research focuses on testing the effects of Shugoshin-1 in humans, necessitating adjustments to traditional IVF methods to utilize immature instead of mature eggs—a change that is expected to be smoothly implemented, according to Zielinska.

She envisions that the treatment, dubbed “EmbryoProtect,” will provide a cost-effective option to enhance IVF success rates for older women. “The goal is to make this treatment affordable compared to a full IVF cycle,” Zielinska states. “By significantly boosting IVF success rates, we aim to reduce the number of attempts needed to conceive, especially for women over 35, who typically have lower success rates.”