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Higher risk of preeclampsia and pregnancy-induced hypertension as a result of embryo freezing for IVF

Researchers have established a strong association between the risk of developing hypertension and preeclampsia and the artificial cycle for frozen-thawed embryo transfer.
Nearly 5% increased risk of both hypertension and pre-eclampsia when choosing embryonic cryopreservation
In vitro fertilization (IVF) is a common practice to overcome fertility problems and consists of removing an egg from the woman’s ovaries that is then fertilized in vitro to become an embryo, which is then returned to the woman’s womb to develop.
During this process, embryos can be frozen during embryonic cryopreservation, allowing individuals to store multiple embryos for transplantation at a later date. Embryo freezing is an increasingly common practice in recent years due to the higher success rates observed in frozen-thawed embryo transfers and because frozen transfers appear to reduce the risk of hyperstimulation.
However, a new study encompassing data from almost 70,000 pregnancies has shown that the embryo cryopreservation process is associated with a higher risk of maternal blood pressure issues.
The study categorized pregnancies from IVF and ICSI in the French national database into three groups: those derived from frozen embryo transfer in a natural “ovulatory” cycle (n = 9,500); those from frozen embryo transfer with hormone replacement therapy (n = 10,373); and conventional fresh transfers (n = 48,152).
After controlling for potentially confounding behavioral biases, the analysis demonstrated that women experienced a higher rate of pre-eclampsia with frozen embryos transferred in the artificial (i.e., prepared with hormone therapy) frozen cycle (5.3%) than in an ovulatory cycle (2.3%) or in fresh cycles (2.4%).
Moreover, the rates were also similar across groups when considering pregnancy-induced hypertension (4.7% vs 3.4% vs 3.3%).
Hormone replacement therapy ahead of embryo transfer puts patients at risk
The results were presented today by Dr. Sylvie Epelboin from the Hôpital Bichat-Claude Bernard, Paris, at the annual meeting of ESHRE and were performed on behalf of the Mother & child health after ART network, of the French Biomedicine Agency.
Dr. Sylvie Epelboin describes that findings highlight two key considerations in IVF: the potentially harmful effects on vascular pathologies of high and prolonged doses of hormone replacement therapies used to prepare the uterus for the implantation of frozen-thawed embryos; and the protective effect of a corpus luteum.
Hormone replacement therapy is given to prepare the uterus for embryo transfer, explained Dr. Epelboin, and is used to suppress ovulation and therefore the formation of the corpus luteum. The corpus luteum is a naturally developing cell cluster formed in the ovary during early pregnancy, which produces progesterone supporting the lining of the uterus (endometrium) during pregnancy and improves blood flow.
Therefore, the hormone replacement treatment could be interfering with progesterone function and leading to a higher risk of pregnancy-related disorders.
Amounting evidence has been raised in previous studies but the overall risks of maternal morbidity are known to be generally lower in pregnancies resulting from frozen embryo transfer than in those from fresh transfers – except in relation to the risk of vascular disorders such as preeclampsia.
Dr. Epelboin and colleagues concluded that the study demonstrates that preparation of the uterus with hormones in an artificial cycle is significantly associated with a higher risk of vascular disorders than from cycles with preserved ovulation and fresh embryo transfers.
Additional research investigating the exact hormonal mechanisms at play may provide further insights into potential treatments.
For instance, as the results obtained in an ovulatory cycle appear not to affect the chance of pregnancy, preservation of the ovulatory cycle could be advocated as first-line preparation in frozen embryo transfers whenever the choice is possible. Developing suitable alternatives may therefore be the key to reducing the risk of pregnancy-related disorders.


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