What are the risks of developing hypertensive disorders in pregnancies after assisted reproduction?

In Western countries, 7% of babies are born by assisted reproductive technology (ART). Traditionally, ART is associated with intracytoplasmic sperm injection (ICSI) and in the laboratory Fertilization (IVF), which involves fresh-ET embryo transfer. Sometimes, in the case of surplus embryos, they are frozen and can be thawed later and used in later cycles. The number of pregnancies using frozen (frozen) embryo transfer has increased dramatically in the past few decades due to advanced cryopreservation methods.

Study: Risk of hypertensive disorders in pregnancy after fresh and frozen embryo transfer in assisted reproduction: a population cohort study with intra-sibling analysis.  Image Credit: fizkes / Shutterstock
Stady: Risks of hypertensive disorders in pregnancy after fresh and frozen embryo transfer in assisted reproduction: a population-based cohort study with intra-fraternal analysis.. Image Credit: fizkes / Shutterstock


Compared with Fresh-ET, frozen ET showed better obstetric and perinatal outcomes according to preliminary reports. Overall results showed that the use of ET frozen prevented ovarian hyperstimulation, which resulted in higher birth rates compared to new cycles.

Although the use of frozen ET has many advantages, several observational studies have highlighted some of the safety concerns associated with this technique. For example, a higher risk of developing hypertensive disorders of pregnancy (HDP) was observed after ET freeze, compared to a normal pregnancy or a normal pregnancy. This finding was supported by a recent meta-analysis of three randomized trials that compared pregnancies using selective freezing and neotransportation.

Recent sibling analyzes revealed that singletons carried by neonates were smaller for gestational age than their normal siblings. However, individual pregnancies after ET freezing were greater for gestational age compared to siblings who were naturally pregnancies. The risk of preterm birth was found to be higher after both ART treatments.

newly Hypertension The study evaluated whether the risk of HDP after fresh ET and frozen ET was higher than in normal pregnancies. Use a sibling design to control for confounders associated with unknown or unmeasured parental factors, such as socioeconomic status, genetics, pre-pregnancy lifestyle, and health.

about studying

The Nordic Art and Safety Committee (CoNARTaS) kit was used for this study. It consists of data on all births registered under the medical birth records of four Nordic countries, i.e. Norway, Denmark, Finland and Sweden. Data from Finland were not used because details of antiretroviral therapy were not available.

The study period was between 1988 and 2014 for Denmark and 1988 to 2015 for Norway and Sweden. The cohort contained all individual births to mothers over the age of 20. After excluding participants who did not meet the criteria for this study, 4,523,028 births from 2,379,130 ​​mothers were included in the final analysis, which included 78,300 new births from ET and 18,037 frozen births from ET. A total of 33,209 single siblings conceived from two to three methods of conception were analyzed in this study.


Nationally data from three Nordic countries were analyzed over three decades. It was observed that the risk of HDP after ET freeze was significantly higher compared to normal pregnancy. However, post-neonatal pregnancies were found to be at lower or lower risk similar to that of a normal pregnancy.

Compared to a normal pregnancy, older women were more likely to use ART. For example, women who were ~34 years old gave birth after freezing ET, and those who were ~33 years old gave birth after recent ET. A lower proportion of mothers who used ART during pregnancy smoked. The average maternal BMI was similar across all pregnancy groups.

All pregnancy methods showed a low prevalence of chronic hypertension. 6.6% of pregnancies after ET freezing, 8.1% after neonates, and 5.0% after normal pregnancies were associated with preterm delivery. Interestingly, compared to normal pregnancies, pregnancies after freezing ET and ET-ET tended toward caesarean section. Unadjusted risk for HDP was found in 7.4% of women after freezing ET, 5.9% after new ET, and 4.3% after normal pregnancy.

For women who had two consecutive single pregnancies, the risk of HDP decreased significantly from the first pregnancy to the second pregnancy in all modes of pregnancy. Importantly, compared to women without HDP, women with HDP in their first pregnancy were less likely to have a second pregnancy. This result remained true for all pregnancy methods.

Points of strength and weakness

The main strength of this study was the sibling design, which took into account confounding factors shared by siblings. Another important feature of this study was the nationwide study cohort containing data from three countries for a period of three decades.

Some limitations of this study were associated with incomplete details in the study group. For example, due to the lack of data on the number of embryos obtained from the stimulation cycle, the authors failed to determine whether couples with new pregnancies with ET had freezing-surplus embryos. In addition, it is not possible to assess whether ET frozen pregnancies are due to the failure of fresh ET or the elective freezing approach. In the future, more research needs to be done to identify treatment factors associated with HDP-inducing frozen ET.

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