Fresh versus freeze-all strategy in assisted reproductive technology – a cochrane review

Abstract

In vitro fertilisation (IVF) treatments imply a fresh embryo transfer, possibly followed by one or more frozen-thawed embryo transfers in subsequent cycles. Alternatively, one can opt to freeze all suitable embryos and transfer frozen-thawed embryos in subsequent cycles only, which is also known as the freeze-all strategy. We compared the effectiveness and safety of these treatment strategies. We searched the Cochrane Gynaecology and Fertility Group Trials Register, the Cochrane Central Register of Studies (CRSO), MEDLINE, Embase, PsycINFO, CINAHL, and two registers of ongoing trials in February 2019 for relevant studies, and checked references and contacted study authors in the field to obtain additional data. We used standard methodological procedures as recommended by Cochrane for our search, data extraction, and analyses. The primary outcome was cumulative live birth rate (cLBR). Secondary outcomes included ovarian hyper stimulation syndrome (OHSS), pregnancy complications, and time to pregnancy. We included six RCTs in our meta-analyses, that together reported on 4324 women. The studies compared the freeze-all strategy to IVF with fresh transfer in women with a high risk of OHSS, in ‘good prognosis' women based on the number of follicles, in women with PCOS, and in young women without PCOS. The evidence was of moderate to low quality due to serious risk of bias, serious imprecision for four studies, and serious unexplained heterogeneity for one study. For cLBR we found an OR of 1.10 (95% CI 0.97 to 1.24; 6 RCTs; 4324 women; I2 = 0%, moderate quality of evidence) for the freeze-all strategy versus IVF with fresh transfer of embryos. These data suggest that for a cLBR of 63% following IVF with fresh transfer of embryos, the cLBR following the freeze-all strategy would be between 62% and 67%. Women developed less OHSS after the freeze-all strategy compared to IVF with fresh transfer of embryos (OR 0.29, 95% CI 0.19 to 0.44; 4 RCTs; 4065 women; I2 = 5%, low quality evidence). These data suggest that for an OHSS rate of 4% following the conventional strategy, the rate following the freeze-all strategy would be between 1% and 2%. The risk of maternal hypertensive disorders and having a large for gestational age baby was increased following the freeze-all strategy (OR 2.15, 95% CI 1.42 to 3.25; 3 trials; 3940 women; I2 = 29% and OR 1.87, 95% CI 1.43 to 2.44; 3 trials; 3119 women; I2 = 0%, respectively, both low-quality evidence). The risk of having a small for gestational age baby was lowered following the freeze-all strategy (OR 0.68, 95% CI 0.53 to 0.89; 3 trials; 3119 women; I2 = 56%, low-quality evidence). One trial reported on time to conception and one trial reported on time to live birth which were both longer in the freeze all strategy. We did not find a clear difference in cLBR between the two strategies. The freeze-all strategy lowered the risk of OHSS, increased the risk of maternal hypertensive disorders of pregnancy, increased the risk of a large for gestational age baby, and lowered the risk of a small for gestational age baby. The time to pregnancy was longer in the freeze-all strategy.