Sept. 27, 2022 – Pregnancies that use frozen embryos through in vitro fertilization, or IVF, appear to be linked to a higher risk of complications related to high blood pressure, as compared with non-frozen embryos or natural conception, according to a new study published in Hypertension.
The risk of developing a hypertensive disorder may be 74% higher after the transfer of frozen embryos, as compared with natural conception. The risk after the transfer of fresh embryos appears similar to that of naturally conceived pregnancies.
“Frozen embryo transfers are now increasingly common all over the world, and in the last few years, some doctors have begun skipping fresh embryo transfer to routinely freeze all embryos in their clinical practice, the so-called ‘freeze-all’ approach,” Sindre Petersen, PhD, the lead study author and a fellow at the Norwegian University of Science and Technology, said in a statement.
“Our results highlight that careful consideration of all benefits and potential risks is needed before freezing all embryos as a routine in clinical practice,” he said. “A comprehensive, individualized conversation between physicians and patients about the benefits and risks of a fresh vs. frozen embryo transfer is key.”
High blood pressure during pregnancy may be a sign of preeclampsia, which is a serious pregnancy complication that can be life-threatening to the mother and baby, according to the American Heart Association. About 1 out of 25 pregnancies in the U.S. result in preeclampsia. Most mothers deliver healthy babies and fully recover after preeclampsia, but in some cases, the condition can cause liver or kidney damage and increase the risk for future heart issues.
Petersen and colleagues analyzed data from medical birth registries for more than 4.5 million pregnancies across 3 decades in Denmark, Norway, and Sweden. The registries included about 4.4 million pregnancies with natural conception, 78,300 pregnancies with fresh embryo transfer, and 18,037 pregnancies with frozen embryo transfer.
The researchers compared 33,000 pregnancies among mothers who had both an IVF pregnancy and a naturally conceived pregnancy, called sibling comparison, to find out if this possible reason for the hypertensive disorder is linked to parental factors or to IVF.
The research team found the odds of hypertensive disorders during pregnancies were 7.4% after frozen embryo transfer, 5.9% after fresh embryo transfer, and 4.3% after natural conception.
Preterm pregnancies were also more common with embryo transfer. About 8.1% of the pregnancies were preterm after fresh embryo transfer, followed by 6.6% for frozen embryo transfer, and 5% for natural conception.
The findings are “in agreement with earlier population-level studies” that show a higher risk of hypertensive disorders during pregnancy after frozen embryo transfer, the study authors said.
For instance, in a study done in France last year, the risks for preeclampsia and hypertension were higher in pregnancies with frozen-thawed embryos. In particular, the risk was greater when the uterus was prepared for implantation with hormone replacement therapies.
“There is one thing that is not clear: Is it from the actual procedure of freezing the embryo or is it from the protocol used? Most IVF doctors believe from recent studies and evidence that it’s actually the medication protocol, not the IVF procedure,” Aimee Eyvazzadeh, MD, a reproductive endocrinologist in San Francisco, told CNN.
The uterus can be prepared for transfer in different ways, she explained. One way involves the corpus luteum, which produces the hormone progesterone needed during pregnancy. Another way relies on medications to mimic ovulation. Several studies have found that the lack of corpus luteum could increase the risk for preeclampsia, particularly with frozen transfers, she said.
“Everyone taking care of pregnant people after IVF should pay extremely close attention to this study,” Eyvazzadeh said. “More and more studies are showing what IVF doctors already know, and that is that IVF after frozen embryo transfer can increase risk of preeclampsia.”