Embryo freezing for IVF linked to blood pressure problems in pregnancy: Study

The risk of pre-eclampsia and other pregnancy-related disorders of pregnancy has been raised in a growing number of studies of freezing in IVF. However, 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 pre-eclampsia. While some studies have observed such risks in frozen embryo transfers, few studies, said Dr Epelboin, have compared these "maternal vascular morbidities with the two hormonal environments that preside over the early stages of embryonic development".

Results showed a higher rate of pre-eclampsia with frozen embryos transferred in the artificial (ie, prepared with hormone therapy) frozen cycle (5.3%) than in an ovulatory cycle (2.3%) or in fresh cycles (2.4%). The rates were found similarly distinct in pregnancy-induced hypertension (4.7% vs 3.4% vs 3.3%). These differences were statistically significant, even after adjusting for maternal characteristics (age, parity, tobacco, obesity, history of diabetes, hypertension, endometriosis, polycystic ovaries, premature ovarian failure) to avoid bias.

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.

The use of frozen embryos has increased in IVF in recent years. Success rates in frozen-thawed embryo transfers are reported to be as or more successful than with fresh embryos and, because frozen transfers appear to reduce the risk of hyperstimulation, it also has safety advantages; the blood pressure risks observed in this study and others do not appear to outweigh these benefits, said Dr Epelboin.

Moreover, because 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.

1. The corpus luteum in pregnancy

   The corpus luteum is a naturally developing cluster of cells which form in the ovary during early pregnancy and pump out a pulse of progesterone, a fertility hormone. Progesterone supports the lining of the uterus (endometrium) during pregnancy and improves blood flow.

2. Embryo freezing and the risk of pre-eclampsia in pregnancy
   • This is the first large-scale study to identify an association between a hormonally prepared uterus (artificial cycle) and a significantly raised risk of pre-eclampsia in pregnancies following the transfer of a frozen-thawed embryo. Several (but not all) randomised trials of freezing embryos generated from an initial egg collection ("freeze-all") have observed such trends as a secondary endpoint. A substantial review of the literature published in 2018 (Maheshewari et al, Hum Reprod Update 2018) concluded that the evidence in favour of embryo freezing was "reassuring" while adding "a need for caution" from the increased risk of hypertension in pregnancy. Generally, embryo freezing allows several transfers from an initial egg collection treatment (and thereby encourages single embryo transfer and the avoidance of multiple pregnancies) and in freeze-all protocols avoids transfer in the same cycle in which the ovaries were stimulated.