Delayed embryo development linked to miscarriage

Pregnancies that end in miscarriage have embryos that take longer to develop in the womb than those that result in live births, Dutch researchers report today.

For the first time, researchers in The Netherlands have examined the way embryos develop while pregnancies are ongoing, using imaging technology, including 3D ultrasound with high resolution transvaginal probes, and virtual reality techniques, to create 3D holograms of the embryo.

This work, which is published in Human Reproduction, enabled them to assess the overall development of the embryo, while 3D ultrasound and virtual reality techniques allowed the team to measure embryonic volume and crown-rump length.

Study leader Dr Melek Rousian, a gynaecologist at Erasmus MC, University Medical Centre, Rotterdam, said: “We found that in the first ten weeks of the pregnancy, embryos in pregnancies that end in a miscarriage took four days longer to develop than babies that did not miscarry. We also found that the longer it takes for an embryo to develop, the more likely it is to miscarry.

“In the future, the ability to assess the shape and development of embryos could be used to estimate the likelihood of a pregnancy continuing to the delivery of a healthy baby. This would enable health professionals to provide counselling to women and their partners about the prospective outcome of the pregnancy and the timely identification of a miscarriage.

“This would be particularly useful for couples who have had previous pregnancies that have ended in miscarriage; we might be able to indicate the risk of another miscarriage or maybe offer some early reassurance.”

The researchers collected data from women taking part in the ongoing Rotterdam Periconception Cohort (PREDICT study). A total of 611 ongoing pregnancies and 33 pregnancies ending in a miscarriage were included from women recruited to the study between 2010 and 2018 when they were between seven and 10 weeks pregnant.

They used virtual reality to create holograms to look at the embryos’ development and compared the morphology against the Carnegie Stages of development, which cover the first 10 weeks of gestation and run from one to 23.

First study author, Dr Carsten Pietersma, an ultrasonographer at Erasmus MC, said: “Without the aid of 3D and virtual reality, it is far more difficult to examine the development of the embryo. For instance, the 3D virtual reality technology makes it much easier to see the development of the arms and legs.

“In the Carnegie staging system, the curvature and position of the arms and legs have an important role. Many historic studies have examined the products of miscarriage, but this is the first time we have been able to look at the developing pregnancy while the pregnancy was still intact.”

Compared to an ongoing pregnancy, a pregnancy ending in a miscarriage was associated with a lower Carnegie stage and the embryo would reach the final Carnegie stage four days later than an embryo from a pregnancy that resulted in a healthy baby.

A delay in Carnegie stage increased the likelihood of a miscarriage by 1.5% per delayed stage.

Because there is no staging system for embryo development after 10 weeks, the researchers used foetal growth and birth weight to assess development and found a pregnancy ending in a miscarriage was linked to a shorter crown-rump length and smaller embryonic volume.

The authors say their study was limited because it involved a small number of pregnancies that ended in miscarriage from a group of women attending tertiary care hospital for preconception and prenatal care and so they may not be representative of the general population.

Pietersma CS, Mulders AGMGJ, Willemsen SP et al. Embryonic morphological development is delayed in pregnancies ending in a spontaneous miscarriage. Human Reproduction 27 March 2023; doi:10.1093/humrep/dead032

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