Embryo Development Delayed in Pregnancies Ending in Miscarriage

Embryonic morphological development is delayed in live pregnancies ending in miscarriage, according to a prospective cohort study from the Netherlands.

Among over 600 singleton pregnancies, those ending in a miscarriage were associated with a lower Carnegie stage -- which categorizes embryonic maturity based on physical features -- compared with an ongoing pregnancy (β -0.824, 95% CI -1.190 to -0.458, P<0.001), reported Melek Rousian, PhD, of Erasmus University Medical Center in Rotterdam, and colleagues.

In addition, a live embryo of a pregnancy ending in a miscarriage will reach the final Carnegie stage with a delay of 4 days versus an ongoing pregnancy, they noted in Human Reproduction.

A delay in Carnegie stage increased the odds of a miscarriage by 1.5% per delayed Carnegie stage (OR 1.015, 95% CI 1.002-1.028, P=0.028).

"In the first trimester, so much happens and growth differences can already originate, which will have an impact not only on the fetus, but also on the neonate, on the child, and on the infant," Rousian told MedPage Today. "We really need to let embryonic health into our lives as clinicians and to focus on this very important period in life where a lot happens within the embryo."

According to the Mayo Clinic, most miscarriages occur because the fetus is not developing as it should, including being smaller than average.

In this study, crown-rump length and embryonic volume were both shown to be smaller in pregnancies ending in miscarriage:

• Crown-rump length: β -0.120 (95% CI -0.240 to -0.001, P=0.049)
• Embryonic volume: β -0.060 (95% CI -0.112 to -0.007, P=0.027)

Rousian and team performed three-dimensional transvaginal ultrasound scans on pregnant women and used virtual reality to visualize embryonic development, which was assessed using the Carnegie stages. The 23 stages begin with fertilization and go through 56 days of development, as explained by the Multi-Dimensional Human Embryo collaboration between the University of Michigan and the National Institute of Child Health and Human Development.

In an interview with MedPage Today, co-author Carsten Pietersma, a PhD student at Erasmus University, noted that 3D ultrasounds offer a more detailed look at growing embryos.

"A 3D ultrasound probe is just a probe that can move from left to right, and while moving, it's collecting thousands of images, and it puts together all the thousands of splices," he explained.

Rousian said that the added value of using 3D ultrasound combined with virtual reality is that you can see the details of development, including "how the arms are curved, how the positions of the legs are, and how the brain is curving and developing."

"I think the ideal situation would be to make these kinds of advanced ultrasounds and then have the clinicians and parents get a good look at their developing fetus or embryo," says Rousian. That way, clinicians can warn parents if they see delays in development and counsel them on what that could mean.

"On the other hand, and what we hope to see, is that we can provide parents reassurance that the development is going according to plan," she added.

For this study, Rousian and colleagues included 644 women with singleton pregnancies in the periconception period from 2010 to 2018, with follow-up until 1 year after delivery. In total, 33 pregnancies ended in miscarriage and 611 continued to full term.

Median maternal age was 32.5 among the women with ongoing pregnancies, and 34.7 among those who had a miscarriage.

The researchers adjusted for potential confounders or covariates, including age, parity, and smoking status.

Rousian and team noted that their sample size was small and there were relatively few miscarriages, so larger studies with more participants are needed.

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