IVF using frozen embryos may increase risk of high blood pressure

In vitro fertilisation (IVF) utilising frozen embryos may be associated with a 74% greater risk of hypertensive problems in pregnancy, according to new research published today in Hypertension, an American Heart Association publication.

According to the study, pregnancies from fresh embryo transfers (transferring the fertilised egg immediately after IVF rather than a frozen, fertilised egg) and natural conception had a similar chance of having a hypertension disease.

Preeclampsia is a pregnancy complication characterised by persistently high blood pressure that might risk the mother’s and fetus’s health and life. Preeclampsia affects around one out of every 25 pregnancies in the United States, according to the American Heart Association.

In one IVF treatment procedure, frozen embryos are used: after an egg is fertilised by sperm in the lab, it is frozen using a cryopreservation process before being thawed and delivered to the uterus at a later date. According to the study’s authors, the process is becoming more prevalent as a result of greatly enhanced freezing technology or cryopreservation methods that began in the late 2000s, as well as more patients opting to preserve embryos.

Frozen embryo transfer, on the other hand, has been associated to a higher risk of hypertensive problems in pregnancy than both normal conception and fresh embryo transfer. Prior to this study, it was uncertain whether this was related to the freezing method or a risk factor from the parents.

“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,” said Sindre H. Petersen, M.D., the study’s lead author and a PhD fellow at the Norwegian University of Science and Technology in Trondheim, Norway.

Researchers evaluated national data from Danish, Norwegian, and Swedish medical birth registries on roughly 2.4 million women aged 20 to 44 who had single births and gave birth between 1988 and 2015. These findings formed the basis of a population-based study that also included a sibling comparison of women who had both IVF and spontaneously conceived pregnancies. This approach was utilised to identify whether parental factors or IVF therapy were the potential causes of the hypertension problems.

Over 4.5 million pregnancies were included in the study, of which 4.4 million were naturally conceived; over 78,000 were fresh embryo transfers, and over 18,000 were frozen embryo transfers.

More than 33,000 pregnancies were grouped for sibling comparison among all pregnancies – mothers who conceived using more than one of these methods. The study is the largest sibling comparison study to date. The odds of developing hypertensive disorders in pregnancy after fresh vs. frozen embryo transfers were adjusted for factors such as birth year and mother’s age.

“In summary,” Petersen said, “most IVF pregnancies are healthy and uncomplicated.” “This study discovered that the risk of high blood pressure during pregnancy was significantly higher after frozen embryo transfer compared to fresh embryo transfer or natural conception.”

* In the population analysis, women whose pregnancy was the result of a frozen embryo transfer were 74% more likely to develop hypertensive disorders in pregnancy than those who conceived naturally.

* Among women who had both a natural conception and a frozen embryo transfer IVF conception (the sibling comparison), the risk of hypertensive disorders in pregnancy after frozen embryo transfer was twice as high as in pregnancies without frozen embryo transfer.

* Pregnancies resulting from fresh embryo transfer were not associated with a higher risk of developing hypertensive disorders when compared to natural conception, neither at the population level nor in sibling comparisons.

“Our sibling comparisons show that the increased risk is not due to factors related to the parents, but rather to some IVF treatment factors,” Petersen said. “Future research should look into which aspects of the frozen embryo transfer process may influence the risk of hypertension during pregnancy.”

IVF and preeclampsia

Among other findings, women in the study who gave birth after IVF pregnancies were 34 years old on average for frozen embryo transfer, 33 years old for fresh embryo transfer, and 29 years old for natural conception. Preterm birth occurred in approximately 7% of babies conceived through frozen embryo transfer and 8% of babies conceived through fresh embryo transfer, compared to 5% of babies conceived naturally.

The researchers classified prenatal hypertension, eclampsia (the onset of convulsions in patients with preeclampsia), and chronic hypertension with superimposed preeclampsia as a composite outcome in addition to preeclampsia.

The study’s ability to determine which stage of the frozen cycle or frozen transfer may contribute to the elevated risk of hypertensive disorders was restricted by a lack of data on the type of frozen embryo cycle. Another issue is that the data from Scandinavian countries may limit the generalizability of the findings to persons in other countries.

“Our findings highlight the importance of carefully weighing all benefits and potential risks before freezing all embryos as a routine in clinical practice.” “A comprehensive, personalised discussion between physicians and patients about the benefits and risks of fresh vs. frozen embryo transfer is critical,” Petersen said.

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