In vitro fertilization (IVF) using frozen embryos may be associated with a 74% higher risk of hypertension during pregnancy, according to new research published today. blood pressurethe Journal of the American Heart Association compared the study to show that pregnancies from fresh embryos – the immediate transfer of a fertilized egg through in vitro fertilization (IVF) rather than from a frozen, fertilized egg – and pregnancies from natural conception were at similar risk for high blood pressure.

High blood pressure during pregnancy can indicate preeclampsia, including persistent high blood pressure that threatens the health and life of the mother and fetus. About 1 in 25 pregnancies in the United States results in preeclampsia, according to the American Heart Association.

One IVF treatment process uses frozen embryos: After the egg is fertilized with sperm in the laboratory, it is thawed and frozen in a cryopreservation process before being transferred to the uterus. In the year With the introduction of greatly improved freezing technology, or cryopreservation, in the late 2000s, and more patients opting to freeze embryos, the procedure is becoming more common, the study authors said. However, frozen embryo transfer is known to be associated with a higher risk of hypertensive disorders than natural conception and fresh embryo transfer. However, before this study, it was not known whether this was due to the cooling process or the parents’ concern.

Frozen embryo transfer is now becoming more common around the world, and in the last few years some doctors have begun skipping a new embryo transfer to routinely freeze all embryos in their clinical practice, the so-called ‘freeze-all’ approach.

Cindre H. Peterson, MD, the study’s lead author and Ph.D. Fellow, Norwegian University of Science and Technology in Trondheim, Norway

Researchers examined national data from medical birth registries in Denmark, Norway and Sweden on nearly 2.4 million singleton women aged 20 to 44 who gave birth during the study period – from 1988 to 2015. A population-based study also includes a comparison of women who had both an IVF pregnancy and a naturally conceived pregnancy, called a sibling comparison. This approach has been used to determine whether the cause of hypertensive disorders is due to parental factors or IVF treatment.

The study included more than 4.5 million pregnancies, of which 4.4 million were conceived naturally; More than 78,000 pregnancies with new embryo transfers; And more than 18,000 pregnancies were arrested embryo transfers. More than 33,000 of all pregnancies were assigned to sibling comparisons—mothers with more than one of these methods. The study is the largest to date using sibling comparisons. The odds of hypertensive complications during pregnancy after fresh and frozen embryo transfer compared with natural conception were adjusted for variables such as year of birth and maternal age.

“In conclusion, though, most IVF pregnancies are healthy and uncomplicated,” Peterson said. “This analysis shows that hypertension during pregnancy is higher compared to frozen embryo transfer or natural conception pregnancies.”

Specifically, the study found the following.

  • In a population analysis, women whose pregnancies were the result of frozen embryo transfer were 74% more likely to develop hypertension during pregnancy compared to those who conceived naturally.
  • In women with natural conception and frozen embryo transfer IVF conception (sibling comparison), the risk of hypertension during pregnancy after frozen embryo transfer is twice as high as compared to naturally conceived pregnancies.
  • Pregnancies from new embryo transfer compared with natural conception did not have an increased risk of hypertensive disorders, either in population-level analyzes or in sibling comparisons.

“Our sibling comparison suggests that the increased risk is not due to factors related to the parents, but some IVF treatment factors may be involved,” said Petersen. “Future research should examine which aspects of the frozen embryo transfer process may increase the risk of hypertension during pregnancy.”

Among other findings, women in the study who gave birth after IVF pregnancies averaged 34 years for frozen embryo transfer, 33 years for fresh embryo transfer and 29 years for natural conception. About 7% of babies conceived from frozen embryo transfer are born prematurely (before 40 weeks’ gestation), and 8% of babies born after fresh embryo transfer are born prematurely, compared to 5% of babies born naturally.

In addition to early preeclampsia, the researchers described hypertensive disorders in pregnancy as a combined outcome, including gestational hypertension, eclampsia (seizure onset in those with early preeclampsia), and chronic hypertension with severe preeclampsia.

One limitation of the study was the lack of data on the type of frozen fetal cycle, so it could not distinguish whether frozen cycle or frozen transfers contributed to the risk of hypertensive disorders. Another limitation is that data from Scandinavian countries may limit the generalizability of the findings to populations in other countries.

“Our results show that all benefits and potential risks need to be carefully considered before freezing all embryos as a routine practice in clinical practice. A comprehensive, individualized discussion between physicians and patients about the benefits and risks of fresh and frozen embryo transfer is key,” said Peterson.


Journal Reference:

Peterson, S. inter alia. (2022) Risk of Hypertensive Disorders in Pregnancy After Fresh and Frozen Embryo Transfer: A Population-Based Cohort Study in Sibship. blood pressure.

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