Live birth rates and perinatal outcomes when all embryos are frozen compared with conventional fresh and frozen embryo transfer: A cohort study of 337,148 in vitro fertilisation cycles

Abstract

Background: It is not known whether segmentation of an in vitro fertilisation (IVF) cycle, with freezing of all embryos prior to transfer, increases the chance of a live birth after all embryos are transferred. Methods: In a prospective study of UK Human Fertilisation and Embryology Authority data, we investigated the impact of segmentation, compared with initial fresh embryo followed by frozen embryo transfers, on live birth rate and perinatal outcomes. We used generalised linear models to assess the effect of segmentation in the whole cohort, with additional analyses within women who had experienced both segmentation and non-segmentation. We compared rates of live birth, low birthweight (LBW < 2.5 kg), preterm birth (< 37 weeks), macrosomia (> 4 kg), small for gestational age (SGA < 10th centile), and large for gestational age (LGA > 90th centile) for a given ovarian stimulation cycle accounting for all embryo transfers. Results: We assessed 202,968 women undergoing 337,148 ovarian stimulation cycles and 399,896 embryo transfer procedures. Live birth rates were similar in unadjusted analyses for segmented and non-segmented cycles (rate ratio 1.05, 95% CI 1.02-1.08) but lower in segmented cycles when adjusted for age, cycle number, cause of infertility, and ovarian response (rate ratio 0.80, 95% CI 0.78-0.83). Segmented cycles were associated with increased risk of macrosomia (adjusted risk ratio 1.72, 95% CI 1.55-1.92) and LGA (1.51, 1.38-1.66) but lower risk of LBW (0.71, 0.65-0.78) and SGA (0.64, 0.56-0.72). With adjustment for blastocyst/cleavage-stage embryo transfer in those with data on this (329,621 cycles), results were not notably changed. Similar results were observed comparing segmented to non-segmented within 3261 women who had both and when analyses were repeated excluding multiple embryo cycles and multiple pregnancies. When analyses were restricted to women with a single embryo transfer, the transfer of a frozen-thawed embryo in a segmented cycles was no longer associated with a lower risk of LBW (0.97, 0.71-1.33) or SGA (0.84, 0.61-1.15), but the risk of macrosomia (1.74, 1.39-2.20) and LGA (1.49, 1.20-1.86) persisted. When the analyses for perinatal outcomes were further restricted to solely frozen embryo transfers, there was no strong statistical evidence for associations. Conclusions: Widespread application of segmentation and freezing of all embryos to unselected patient populations may be associated with lower cumulative live birth rates and should be restricted to those with a clinical indication.