Retrospective cohort study on preparation regimens for frozen embryo transfer.

The objective of this study was to examine the pregnancy outcomes from frozen embryo transfer (FET) cycles using different endometrial preparation regimens, compared to ovulation induction with letrozole (letrozole OI). A retrospective cohort study was conducted at a fertility centre in Sydney, Australia, on 6060 FET cycles. The cycles were stratified into one of four ways to achieve endometrial preparation. These were either a natural, letrozole OI, OI with follicle-stimulating hormone (FSH OI) or a programmed cycle. The primary outcome was live birth rate (LBR) per embryo transfer. Secondary outcomes included clinical pregnancy and biochemical pregnancy rates, adverse events including miscarriage, ectopic pregnancy, stillbirth, neonatal death and multiple births. Ovarian stimulation parameters were also analysed including the time taken to reach the luteal phase and the number of blood or urine tests required for monitoring the cycle. The results of the study showed that the LBR following letrozole OI cycles was higher when compared to natural cycles (odds ratio (OR): 1.27 (1.07-1.49)) and programmed cycles (OR: 2.36 (1.67-3.34)). There was no significant difference between letrozole OI and FSH OI LBR (OR: 0.99 (0.76-1.28)). An improved LBR with letrozole OI compared to natural cycles was maintained when only women with a normal length cycle were considered (OR: 1.44 (1.10-1.89)). There was a significant reduction in miscarriage rates when letrozole OI was compared to programmed cycles (OR: 0.46 (0.26-0.83)). It was therefore concluded that the use of letrozole OI for endometrial preparation in an FET cycle may be associated with higher LBR and lower miscarriage rate, compared to using a programmed cycle.

Lay summary: Couples suffering from infertility frequently try to conceive following the transfer of an embryo which has been frozen during an in vitro fertilisation cycle. Embryos will only lead to a pregnancy if the woman's womb lining has particular characteristics that allow it to accept the embryo. Despite the thousands of frozen embryo transfer cycles carried out across the world, it is not known how best to prepare a woman's lining so it has these particular characteristics. This study looked at the pregnancy outcomes of 6060 cycles to compare four different ways to prepare a woman's womb lining. These included relying on a woman's natural menstrual cycle, or using an oral medication called letrozole, or injectable medicine called follicle-stimulating hormone, or oestrogen and progesterone hormonal medications. The comparison found that using letrozole before transfer of a frozen embryo may be associated with higher rates of a live birth for some women.