IVF with frozen embryos may be associated with a higher risk of hypertension in pregnancy

IVF with frozen embryos may be associated with a higher risk of hypertension in pregnancy

In vitro fertilization (IVF) using frozen embryos may be associated with a 74% higher risk of hypertension disorders in pregnancy, according to a new study published today in Hypertension, a journal of the American Heart Association. In comparison, the study found that pregnancies through fresh embryo transfer - in which the fertilized egg is transferred immediately after in vitro fertilization (IVF) instead of a frozen, fertilized egg - and pregnancies after natural conception have a similar risk of developing hypertensive disease.

High blood pressure during pregnancy often indicates preeclampsia, a pregnancy complication that includes persistent high blood pressure, which can endanger the health and life of the mother and fetus. According to the American Heart Association, about one in 25 pregnancies in the United States results in preeclampsia.

One available IVF treatment method uses frozen embryos: After an egg is fertilized by sperm in the laboratory, it is frozen using a cryopreservation process before being thawed and transferred to the uterus at a later date. According to the study authors, the procedure is becoming more widely used because of significantly improved freezing technology, or cryopreservation methods, introduced in the late 2000s and because more patients are choosing to freeze embryos. Nevertheless, it is known that frozen embryo transfer is associated with a higher risk of hypertension disorders in pregnancy than both natural conception and fresh embryo transfer. However, prior to this study, it was not known whether this was due to the freezing process or a parental risk factor.

“Frozen embryo transfer is now becoming increasingly common around the world, and in recent years some physicians have begun to forgo fresh embryo transfer and routinely freeze all embryos in their clinical practice, the so-called “freeze everything” approach.”

Sindre H. Petersen, MD, lead author of the study and Ph.D. Fellow, Norwegian University of Science and Technology in Trondheim, Norway

The researchers examined national data from medical birth registries from Denmark, Norway and Sweden on nearly 2.4 million women aged 20 to 44 who had a single delivery and gave birth to a child during the study period - from 1988 to 2015. These data formed the basis of a population-based study that also included a comparison of women who had both an IVF pregnancy and a naturally conceived pregnancy, called a sibling comparison. This approach was used to find out whether the possible reason for the hypertensive disorders was due to parental factors or to the IVF treatment.

The study included more than 4.5 million pregnancies, of which 4.4 million were conceived naturally; more than 78,000 pregnancies were fresh embryo transfers; and more than 18,000 pregnancies were frozen embryo transfers. Among all pregnancies, more than 33,000 were pooled for sibling comparison - mothers who became pregnant using more than one of these methods. The study is the largest to date using a sibling comparison. The probability of developing hypertensive disease in pregnancy after fresh or frozen embryo transfer compared to natural conception was adjusted for variables such as year of birth and maternal age.

“In summary, most IVF pregnancies are healthy and uncomplicated,” said Petersen. “This analysis found that the risk of hypertension in pregnancies following frozen embryo transfer was significantly higher than in pregnancies following fresh embryo transfer or natural conception.”

Specifically, the study found:

• In der Bevölkerungsanalyse hatten Frauen, deren Schwangerschaft das Ergebnis eines gefrorenen Embryotransfers war, ein um 74 % höheres Risiko, während der Schwangerschaft Bluthochdruckstörungen zu entwickeln, als Frauen, die auf natürlichem Weg schwanger wurden.
• Bei Frauen, die sowohl eine natürliche Empfängnis als auch eine IVF-Konzeption mit gefrorenem Embryotransfer hatten (Geschwistervergleich), war das Risiko für Bluthochdruckstörungen in der Schwangerschaft nach dem Transfer gefrorener Embryonen doppelt so hoch wie bei Schwangerschaften nach natürlicher Empfängnis.
• Schwangerschaften nach dem Transfer frischer Embryonen hatten im Vergleich zur natürlichen Empfängnis kein höheres Risiko für die Entwicklung von Bluthochdruckstörungen, weder in der Populationsanalyse noch im Geschwistervergleich.

“Our sibling comparisons suggest that the higher risk is not caused by parental factors, but that some factors may play a role in IVF treatment,” Petersen said. “Future research should examine which parts of the frozen embryo transfer process may influence the risk of hypertension during pregnancy.”

Among other things, the average age of women in the study who gave birth after an IVF pregnancy was 34 years for frozen embryo transfer, 33 years for fresh embryo transfer, and 29 years for women who conceived naturally. About 7% of babies conceived through frozen embryo transfer were born prematurely (before 40 weeks of gestation) and 8% of babies conceived after fresh embryo transfer were born prematurely, compared to 5% of babies conceived through natural conception.

In addition to preeclampsia, researchers defined hypertensive disorders of pregnancy as a composite outcome, including gestational hypertension, eclampsia (the occurrence of seizures in individuals with preeclampsia), and chronic hypertension with superimposed preeclampsia.

A limitation of the study was the lack of data on the type of frozen embryo cycle, so they could not determine exactly which part of the frozen embryo cycle or frozen embryo transfer might contribute to a higher risk of hypertensive diseases. Another limitation is that data from Scandinavian countries may limit the generalizability of the results to people in other countries.

"Our results show that careful consideration of all benefits and potential risks is required before routine freezing of all embryos in clinical practice. A comprehensive, individual discussion between physicians and patients about the benefits and risks of fresh versus frozen embryo transfer is critical." said Petersen.

Source:

American Heart Association

Reference:

Petersen, SH, et al. (2022) Risk of Hypertensive Disorders in Pregnancy After Fresh and Frozen Embryo Transfer in Assisted Reproduction: A Population-Based Cohort Study with Within-Sibship Analysis. Hypertension. doi.org/10.1161/HYPERTENSIONAHA.122.19689.