Fresh versus elective frozen embryo transfer in IVF/ICSI cycles: a systematic review and meta-analysis of reproductive outcomes

• Published in: Human reproduction update 2019-01, Vol.25 (1), p.2-14
• Main Authors: Roque, Matheus, Haahr, Thor, Geber, Selmo, Esteves, Sandro C, Humaidan, Peter
• Format: Article
• Language: English
• Subjects: Abortion, Spontaneous - epidemiology; Birth Rate; Embryo Transfer - methods; Embryo Transfer - statistics & numerical data; Female; Fertilization in Vitro - methods; Fertilization in Vitro - statistics & numerical data; Humans; Infant, Newborn; Infertility - epidemiology; Infertility - therapy; Ovarian Hyperstimulation Syndrome - epidemiology; Pregnancy; Pregnancy Outcome - epidemiology; Pregnancy Rate; Sperm Injections, Intracytoplasmic - statistics & numerical data; Treatment Outcome
• ISSN: 1355-4786; 1460-2369
• DOI: 10.1093/humupd/dmy033

ABSTRACT BACKGROUND Elective freezing of all good quality embryos and transfer in subsequent cycles, i.e. elective frozen embryo transfer (eFET), has recently increased significantly with the introduction of the GnRH agonist trigger protocol and improvements in cryo-techniques. The ongoing discussion focuses on whether eFET should be offered to the overall IVF population or only to specific subsets of patients. Until recently, the clinical usage of eFET was supported by only a few randomized controlled trials (RCT) and meta-analyses, suggesting that the eFET not only reduced ovarian hyperstimulation syndrome (OHSS), but also improved reproductive outcomes. However, the evidence is not unequivocal, and recent RCTs challenge the use of eFET for the general IVF population. OBJECTIVE AND RATIONALE This systematic review and meta-analysis aimed at evaluating whether eFET is advantageous for reproductive, obstetric and perinatal outcomes compared with fresh embryo transfer in IVF/ICSI cycles. Additionally, we evaluated the effectiveness of eFET in comparison to fresh embryo transfer in different subgroups of patients undergoing IVF/ICSI cycles. SEARCH METHODS We conducted a systematic review, using PubMed/Medline and EMBASE to identify all relevant RCTs published until March 2018. The participants included infertile couples undergoing IVF/ICSI with or without preimplantation genetic testing for aneuploidy (PGT-A). The primary outcome was the live birth rate (LBR), whereas secondary outcomes were cumulative LBR, implantation rate, miscarriage, OHSS, ectopic pregnancy, preterm birth, pregnancy-induced hypertension, pre-eclampsia, mean birthweight and congenital anomalies. Subgroup analyses included normal and hyper-responder patients, embryo developmental stage on the day of embryo transfer, freezing method and the route of progesterone administration for luteal phase support in eFET cycles. OUTCOMES Eleven studies, including 5379 patients, fulfilling the inclusion criteria were subjected to qualitative and quantitative analysis. A significant increase in LBR was noted with eFET compared with fresh embryo transfer in the overall IVF/ICSI population [risk ratio (RR) = 1.12; 95% CI: 1.01–1.24]. Subgroup analyses indicated higher LBRs by eFET than by fresh embryo transfer in hyper-responders (RR = 1.16; 95% CI: 1.05–1.28) and in PGT-A cycles (RR = 1.55; 95% CI: 1.14–2.10). However, no differences were observed for LBR in normo-responders (RR = 1.03; 95% CI: 0.91–1.17