Smith, A. D.A.C., Tilling, K., Lawlor, D. A. and Nelson, S. M. (2019) 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. BMC Medicine, 17(1), 202. (doi: 10.1186/s12916-019-1429-z) (PMID:31718643) (PMCID:PMC6852977)
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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.
| Item Type: | Articles |
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| Additional Information: | This work was supported by Wellbeing of Women (grant RG1907 to all authors), Ferring Pharmaceuticals (grant to SMN), the National Institute for Health Research Biomedical Centre at the University Hospitals Bristol NHS Foundation Trust and the University of Bristol (DAL, KT and SMN), and a National Institute for Health Research Senior Investigator award (NF-SI-0611-10196 to DAL). KT and DAL contribution was supported by their MRC Integrative Epidemiology Unit (IEU) programmes and IEU receives support from the University of Bristol and the UK Medical Research Council ( MC_UU_00011/3 (KT programme) and MC_UU_00011/6 (DAL programme)). |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Nelson, Professor Scott |
| Authors: | Smith, A. D.A.C., Tilling, K., Lawlor, D. A., and Nelson, S. M. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing |
| Journal Name: | BMC Medicine |
| Publisher: | BioMed Central |
| ISSN: | 1741-7015 |
| ISSN (Online): | 1741-7015 |
| Published Online: | 13 November 2019 |
| Copyright Holders: | Copyright © 2019 The Authors |
| First Published: | First published in BMC Medicine 17(1):202 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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