Immediate versus postponed frozen embryo transfer after IVF/ICSI: a systematic review and meta-analysis

Abstract

BACKGROUND In Europe, the number of frozen embryo transfer (FET) cycles is steadily increasing, now accounting for more than 190 000 cycles per year. It is standard clinical practice to postpone FET for at least one menstrual cycle following a failed fresh transfer or after a freeze-all cycle. The purpose of this practice is to minimise the possible residual negative effect of ovarian stimulation on the resumption of a normal ovulatory cycle and receptivity of the endometrium. Although elective deferral of FET may unnecessarily delay time to pregnancy, immediate FET may be inefficient in a clinical setting, following an increased risk of irregular ovulatory cycles and the presence of functional cysts, increasing the risk of cycle cancellation. OBJECTIVE AND RATIONALE This review explores the impact of timing of FET in the first cycle (immediate FET) versus the second or subsequent cycle (postponed FET) following a failed fresh transfer or a freeze-all cycle on live birth rate (LBR). Secondary endpoints were implantation, pregnancy and clinical pregnancy rates (CPR) as well as miscarriage rate (MR). SEARCH METHODS We searched PubMed (MEDLINE) and EMBASE databases for MeSH and Emtree terms, as well as text words related to timing of FET, up to March 2020, in English language. There were no limitations regarding year of publication or duration of follow-up. Inclusion criteria were subfertile women aged 18-46 years with any indication for treatment with IVF/ICSI. Studies on oocyte donation were excluded. All original studies were included, except for case reports, study protocols and abstracts only. Covidence, a Cochrane-tool, was used for sorting and screening of literature. Risk of bias was assessed using the Robins-I tool and the quality of evidence using the Grading of Recommendations, Assessment, Development and Evaluation framework. OUTCOMES Out of 4124 search results, 15 studies were included in the review. Studies reporting adjusted odds ratios (aOR) for LBR, CPR and MR were included in meta-analyses. All studies (n = 15) were retrospective cohort studies involving a total of 6,304 immediate FET cycles and 13,851 postponed FET cycles including 8,019 matched controls. Twelve studies of very low to moderate quality reported no difference in LBR with immediate versus postponed FET. Two studies of moderate quality reported a statistically significant increase in LBR with immediate FET and one small study of very low quality reported better LBR with postponed FET. Trends in rates of secondary outcomes followed trends in LBR regarding timing of FET. The meta-analyses showed a significant advantage of immediate FET (n =2,076) compared to postponed FET (n =3,833), with a pooled aOR of 1.20 (95% CI 1.01–1.44) for LBR and a pooled aOR of 1.22 (95% CI 1.07–1.39) for CPR. WIDER IMPLICATIONS The results of this review indicate a slightly higher LBR and CPR in immediate versus postponed FET. Thus, the standard clinical practice of postponing FET for at least one menstrual cycle following a failed fresh transfer or a freeze-all cycle may not be best clinical practice. However, as only retrospective cohort studies were assessed, the presence of selection bias is apparent, and the quality of evidence thus seems low. Randomised controlled trials including data on cancellation rates and reasons for cancellation are highly needed to provide high-grade evidence regarding clinical practice and patient counselling.

Association between Available Blastocyst Formation Rate and Pregnancy Outcome Following Fresh Embryo Transfer

“…The success of ET relies on synchronization between the embryo and endometrium so that the endometrium is optimally receptive for the embryo to implant [9,22]. Previous studies had investigated that women with repeated implantation failure (RIF), personalized timing for transfer resulted in a higher clinical pregnancy rate compared with routine protocol [23][24][25]. Thus, although there is a bene t favoring blastocyst transfer in fresh cycle, it remains unclear whether the day of transfer impacts on pregnancy rate [4].…”

Immediate versus postponed single blastocyst transfer in modified natural cycle frozen embryo transfer (mNC-FET): a study protocol for a multicentre randomised controlled trial

“…The reviews are based on retrospective data including a variety of FET protocols, hence, the presence of selection bias is apparent and the quality of evidence is low. Despite a significant overlap in studies included in the reviews, the results differ slightly, probably due to inclusion of unadjusted 14 versus adjusted 15 results. Huang et al reported no significant association between timing of FET and pregnancy outcomes; clinical pregnancy rate (CPR) (relative risk (RR) 0.94 (95% CI 0.87 to 1.03)) and live birth rate (LBR) (RR 0.94 (95% CI 0.85 to 1.03)) while Bergenheim et al found a slightly higher CPR (adjusted OR (aOR) 1.22 (95% CI 1.07 to 1.39)) and LBR (aOR 1.20 (95% CI 1.01 to 1.44)) in immediate versus postponed FET.…”

Effect of interval between oocyte retrieval and resuscitation embryo transfer on pregnancy outcomes

“…In addition, more and more young cancer patients accept fertility preservation services at present since they receive certain types of cancer surgery which lead to removal of organs needed for a pregnancy, and certain therapy might increase hormone levels or cause damage to a female’s eggs ( 7 ). Previous studies have not come to a definitive conclusion on how immediate or delayed resuscitation will benefit pregnancy rates ( 8 , 9 ). Additionally, many of the retrospective studies on this issue were conducted in years ago, and the results of these studies may be biased against changes in the existing COH protocols ( 1 , 10 , 11 ).…”