Study Discovers Why IVF Embryos Fail to Develop

Key Takeaways

  • A new study sheds light on why many IVF embryos fail to develop.
  • Columbia University researchers say it’s due to DNA replication errors in the earliest stages of cell division.
  • Long term, the findings might lead to better IVF success rates.

In vitro fertilization (IVF) rates are fairly good—a study of approximately 156,000 women found that the average live-birth rate for the first cycle was 29.5%, which is comparable to the success rates for a natural cycle in couples with no fertility issues.

A number of reasons could cause IVF to not be successful, but sometimes it’s not possible to pinpoint one. A new study from the Columbia University Vagelos College of Physicians and Surgeons, published in Cell, found a possible explanation for why IVF embryos fail.

The researchers discovered that chromosomal abnormalities stop the embryo from developing in the early stages of cell division. This is contrary to previous assumptions it occurs in the later stages of the process.

After an egg is fertilized with sperm, cell division starts within about 24 hours. The cell divides into two new “daughter cells”. Before this, the fertilized egg creates two sets of the complete human genome, which consists of 46 chromosomes. So each daughter cell gets one full set of 46 chromosomes.

Why IVF Embryos Don’t Develop

The problem with IVF is that sometimes the chromosomes are distributed incorrectly. Before the new study, scientists thought the malfunctioning of an organelle known as the microtubule spindle (which has the important task of dividing the cell) was to blame for this. The Columbia University researchers found that the problem is caused at a much earlier stage. It’s the duplication part of the process that’s faulty, causing the spindle to malfunction.

According to the study’s lead author Dieter Egli, Assistant Professor of Developmental Cell Biology (in Pediatrics), this has largely been overlooked in previous studies.

What’s not yet known is why the duplication process doesn’t go without a hitch. One explanation is there’s a fundamental issue with the DNA itself. The same group of Columbia researchers is planning additional studies into this issue.

In the meantime, science is one step closer to understanding why IVF isn’t successful, which may be helpful to people who choose to go down that route.

Meaghan Bowling, MD, FACOG

This study is helping us better understand how eggs develop damage to the chromosomes.

— Meaghan Bowling, MD, FACOG

What many people don’t realize is that embryo development in humans is incredibly inefficient, which is ultimately due to egg quality factors, says Meaghan Bowling, MD, FACOG, who is board-certified in both obstetrics and gynecology and reproductive endocrinology and infertility.

“When your fertility doctor refers to your egg quality, they are referring to how many eggs left in a woman’s ovaries are still chromosomally normal,” Dr. Bowling explains. “These are considered the ‘viable’ eggs. Since women are born with all the eggs they will ever have and do not make new eggs in their lifetime, these single cells must survive for decades before they may have a chance at making an embryo.”

For women under 35, about 70% of eggs are chromosomally normal. For women at age 37, about 40% of eggs are chromosomally normal. For women at age 40, about 25% of eggs are chromosomally normal, and at 45 about 5% of eggs are chromosomally normal.

“As time passes, chromosomes in the egg can start to break down, or even stick together,” says Dr. Bowling. These eggs can still be fertilized, but the embryo will have too many or too few chromosomes. Embryos with abnormal chromosome numbers typically either result in no pregnancy since many will not implant. They could also end in miscarriage if the embryo successfully implants but then inevitably cannot grow much beyond 8 weeks of pregnancy.

“This study is helping us better understand how eggs develop damage to the chromosomes,” Dr. Bowling adds.

What This Means for People Undergoing IVF

“IVF can be incredibly stressful for many reasons,” says Carly Snyder, MD, a reproductive and perinatal psychiatrist, and Verywell Family & Mind review board member. “There is physical discomfort, shots, and lots of expensive medications, plus very frequent early morning appointments for labs and ultrasounds to see follicles, etc.”

The average couple needs more than one course of IVF to conceive, and each failed month causes more sadness and stress, Dr. Snyder adds. “Plus, of course, IVF can be very anxiety-inducing when only a few embryos survive past day 5—this number becomes the focus and fear that if none work, are you up to starting anew?”

“IVF is an emotional rollercoaster, and ultimately the stress is due to lack of control,” says Dr. Bowling. “We can’t control which eggs grow in an IVF cycle in a woman’s ovaries. There are viable and nonviable eggs for each woman, and there is no way for us to encourage the ‘good’ eggs to grow and prevent the ‘bad’ eggs from being harvested.”

Each IVF cycle has a statistical chance of success based on a woman’s age, ovarian reserve, and infertility diagnosis. “For some women, they will become pregnant on the first try. For others, they will have to try multiple cycles before they achieve success,” Dr. Bowling says. “This lack of control and lack of knowing what the future will bring leads to the incredible stress we see women go through in fertility treatment.”

Dr. Bowling adds that it’s important to note the ability to treat chromosome problems in eggs is still a long way off from being something that is routine in clinical practice. “Unfortunately, we haven’t developed technology or treatments that can overcome the effect of aging on egg quality,” she says.

What This Means For You

This new study out of Columbia University gives hopeful parents-to-be a potential scientific reason why an IVF embryo may fail to develop. It’s providing researchers with insight into the biology behind reproduction and could lead to improvements in IVF success rates. The decision to undergo IVF is a deeply personal one. While IVF success rates have risen, it is important to fully understand all scenarios. IVF can be challenging both mentally and physically, so it’s important to take steps to protect your mental health.

Read the full article here

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