Frozen embryo transfers linked to 74% increased risk of dangerous hypertensive disorders in pregnancy

heavily pregnant woman

Conceiving a baby from a frozen embryo can significantly increase the risk of dangerous hypertensive disorders for the mother, according to new research.

Conceiving a baby from a frozen embryo can significantly increase the risk of dangerous hypertensive disorders for the mother, according to a study published in the journal Hypertension.

  • Compared to naturally conceived pregnancies, pregnancies conceived with assisted reproductive technology using frozen embryos may have a 74% higher risk of developing a hypertensive disorder.
  • By comparison, the risk of hypertensive disorders in pregnancies resulting from fresh embryo transfer was similar to naturally conceived pregnancies.
  • High blood pressure during pregnancy can be a sign of preeclampsia, a serious pregnancy complication that can be life-threatening for both mother and fetus.

According to a new study published on September 26 in Hypertensionin vitro fertilization (IVF) using frozen embryos may be associated with a 74% higher risk of hypertensive disorders during pregnancy. Hypertension is a journal of the American Heart Association. In comparison, the study found that pregnancies resulting from fresh embryo transfers – transferring the fertilized egg immediately after in vitro fertilization (IVF) instead of a frozen, fertilized egg – and pregnancy resulting from natural conception shared a similar risk of developing a hypertensive disorder.

High blood pressure during pregnancy often signals preeclampsia, a pregnancy complication that includes persistent high blood pressure that can endanger the health and life of both mother and fetus. According to the American Heart Association, approximately 1 in 25 pregnancies in the United States results in preeclampsia.

Preeclampsia is high blood pressure and signs of kidney or liver damage that occur in women after the 20th week of pregnancy. It occurs in about 3-7% of all pregnancies. Although rare, preeclampsia can also occur in a woman after childbirth, most often within 48 hours. This is called postpartum preeclampsia. Although the exact cause of preeclampsia is unknown, the condition is thought to begin in the placenta.

An available IVF treatment process uses frozen embryos: after an egg has been 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. The procedure is becoming more common due to vastly improved freezing technology or cryopreservation methods that began in the late 2000s and because more and more patients choose to freeze embryos, according to the authors of the study. Yet frozen embryo transfer is known to be associated with a higher risk of hypertensive disorders during pregnancy than natural conception and fresh embryo transfer. However, prior to this study, it was unclear whether this was due to the freezing process or a parental risk factor.

“Frozen embryo transfers are now becoming more common around the world, and in recent years some physicians have begun to skip fresh embryo transfer to routinely freeze all embryos in their clinical practice, l so-called ‘freeze everything’ approach,” said Sindre H. Petersen, MD. He is the lead author of the study and a Ph.D. researcher at the Norwegian University of Science and Technology (NTNU) in Trondheim, Norway.

In vitro fertilization (IVF) is a procedure in which eggs are removed from a woman’s ovary and combined with sperm outside the body to form embryos. After being grown in the lab for several days, the embryos are either placed in a woman’s uterus or cryopreserved (frozen) for future use.

Investigators looked at national data from medical birth registries from Denmark, Norway and Sweden on nearly 2.4 million women aged 20 to 44 who had single births and gave birth during the period of study – 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 isolate whether the potential cause of hypertensive disorders was attributable 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 were fresh embryo transfers; and more than 18,000 pregnancies were frozen embryo transfers. Among all pregnancies, more than 33,000 were grouped for sibling comparison – mothers who conceived via more than one of these methods. The study is the largest to date using sibling comparison. The odds of developing hypertensive disorders in pregnancy after fresh or frozen embryo transfers compared to natural conception were adjusted for variables such as year of birth and maternal age.

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

Specifically, the study found:

  • In the population analysis, women whose pregnancies were the result of frozen embryo transfer were 74% more likely to develop hypertensive disorders during pregnancy compared to those who conceived naturally.
  • Among women who had both natural conception and IVF conception by frozen embryo transfer (the sibling comparison), the risk of hypertensive disorders during pregnancy after frozen embryo transfer was twice as high. higher than pregnancies from natural conception.
  • Pregnancies resulting from fresh embryo transfer did not have a higher risk of developing hypertensive disorders compared to natural conception, either in the population-level analysis or in sibling comparisons.

“Our sibling comparisons indicate that the higher risk is not caused by parental factors, but rather that certain IVF treatment factors may be involved,” Petersen said. “Future research should determine which parts of the frozen embryo transfer process may impact the risk of hypertension in pregnancy.”

Among other findings, the women in the study who gave birth after IVF pregnancy were on average 34 years old for the frozen embryo transfer, 33 years old for the fresh embryo transfer, and 29 years old for those who conceived naturally. About 7% of babies conceived by frozen embryo transfer are born preterm (before 40 weeks gestation) and 8% of babies after fresh embryo transfer are born preterm, compared to 5% of babies after natural conception.

In addition to preeclampsia, scientists have defined hypertensive disorders in pregnancy as a combined outcome, including gestational hypertension, eclampsia (the onset of seizures in people with preeclampsia), and chronic hypertension with superimposed preeclampsia.

One limitation of the study was the lack of data on the type of frozen embryonic cycle, so they were unable to determine which part of the frozen cycle or frozen transfer may contribute to the risk more high in hypertensive disorders. Another limitation is that the data from the Scandinavian countries may limit the generalizability of the results to people from other countries.

“Our results underscore that careful consideration of all potential benefits and risks is necessary before freezing all embryos as a routine in clinical practice. A comprehensive, individualized conversation between physicians and patients about the benefits and risks of “A fresh or frozen embryo transfer is essential,” Petersen said.

Reference: “Risk of Hypertensive Disorders in Pregnancy After Fresh and Frozen Embryo Transfer for Assisted Reproduction: A Population-Based Cohort Study with Within-Sibling Analysis” by Sindre H. Petersen, Kjersti Westvik- Johari, Anne Lærke Spangmose, Anja Pinborg, Liv Bente Romundstad, Christina Bergh, Bjørn Olav Åsvold, Mika Gissler, Aila Tiitinen, Ulla-Britt Wennerholm and Signe Opdahl, September 26, 2022, Hypertension.
DOI: 10.1161/HYPERTENSIONAHA.122.19689

Co-authors are Kjersti Westvik-Johari, MD, Ph.D.; Anne Laerke Spangmose, MD, Ph.D.; Anja Pinborg, MD, Ph.D.; Liv Bente Romundstad, MD, Ph.D.; Christina Bergh, MD, Ph.D.; Bjørn Olav Åsvold, MD, Ph.D.; Mika Gissler, Ph.D.; Aila Tiitinen, MD, Ph.D.; Ulla-Britt Wennerholm, MD, Ph.D.; and Signe Opdahl, MD, Ph.D.

The study was funded by the Norwegian University of Science and Technology, the Nordic Council of Ministers and NordForsk, the regional health authorities of Central Norway, the Nordic Federation of Obstetrics and Gynecology, the European Regional Development Fund Interreg Øresund -Kattegat-Skagerrak and the Norwegian Council Research Centers of Excellence.

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