Is the Transfer of Frozen Embryos Associated With an Increased Risk of High Blood Pressure During Pregnancy?

According to research, in vitro fertilization (IVF) with frozen embryos may be associated with a 74% higher risk of hypertension during pregnancy. In comparison, the study found that pregnancies following fresh embryo transfer—i.e., after transfer of the fertilized egg immediately after in vitro fertilization (IVF) instead of a frozen fertilized egg—and pregnancies following natural conception have a similar risk of developing hypertensive disorders.

Risk of High Blood Pressure During Pregnancy Significantly Higher After Frozen Embryo Transfer

High blood pressure during pregnancy is often a sign of preeclampsia, a pregnancy complication associated with persistent high blood pressure that can endanger the health and life of the mother and fetus. Frozen embryos can be used in IVF: after an egg has been fertilized by sperm in the laboratory, it is frozen using a cryopreservation process before being thawed at a later date and transferred to the uterus.

The procedure is becoming increasingly common as freezing technology and cryopreservation methods have improved significantly since the late 2000s, and more and more patients are opting to freeze embryos. However, it is known that frozen embryo transfer is associated with a higher risk of hypertension during pregnancy than natural conception and fresh embryo transfer. Prior to this study, however, it was not known whether this was due to the freezing process or to a risk factor in the parents. In

Transfer with frozen embryos is becoming increasingly common worldwide, and in recent years some doctors have begun to skip the transfer of fresh embryos and routinely freeze all embryos in their clinical practice, the so-called “freeze-all” approach. Researchers from Norway examined national data from medical birth registries in Denmark, Norway, and Sweden on nearly 2.4 million women aged 20 to 44 who had given birth to a child during the study period, from 1988 to 2015. This data formed the basis for a population-based study that also included a comparison between women with an IVF pregnancy and a naturally conceived pregnancy, known as sibling comparison. This approach was used to determine whether the possible cause of hypertensive disorders was due to parental factors or IVF treatment.

The Results

The study included more than 4.5 million pregnancies, of which 4.4 million were conceived naturally; more than 78,000 pregnancies were transfers with fresh embryos, and more than 18,000 pregnancies were transfers with frozen embryos. Of all pregnancies, more than 33,000 were grouped for sibling comparison—mothers who had become pregnant using more than one of these methods. The study is the largest to date to use sibling comparison.

The likelihood of developing hypertensive disorders in pregnancy after a 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 without complications. However, this analysis found that the risk of high blood pressure during pregnancy was significantly higher after frozen embryo transfer than after fresh embryo transfer or natural conception. Future research should investigate which aspects of frozen embryo transfer may influence the risk of high blood pressure during pregnancy.”

Comprehensive Counseling by Doctors Required

Among other things, the study found that women who gave birth after IVF treatment were on average 34 years old in the case of frozen embryo transfer, 33 years old in the case of fresh embryo transfer, and 29 years old in the case of natural conception. About 7% of babies conceived after a frozen embryo transfer were born prematurely (before 40 weeks of pregnancy), and 8% of babies conceived after a fresh embryo transfer were born prematurely, compared to 5% of babies conceived naturally.

In addition to preeclampsia, the researchers defined hypertensive disorders in pregnancy as a combined outcome, including gestational hypertension, eclampsia (the occurrence of seizures in women with preeclampsia), and chronic hypertension with superimposed preeclampsia. One limitation of the study was the lack of data on the type of frozen embryo cycle, so it was not possible to determine exactly which part of the frozen embryo cycle or the transfer of frozen embryos contributes to the higher risk of hypertensive disorders. Another limitation is that the data from Scandinavian countries may limit the generalizability of the results to people in other countries. Comprehensive counseling by physicians about the benefits and risks of fresh versus frozen embryo transfer is therefore crucial.