Are live birth rate and obstetric outcomes different between immediate and delayed embryo transfers following a freeze-all cycle? a retrospective study combined with a meta-analysis

Abstract

Study Question: Do livebirth rate (LBR), obstetric and perinatal outcomes vary between frozen embryo transfers (FET) in the first or subsequent menstrual cycles following a freeze-all approach? Summary Answer: Immediate FET has a higher LBR and similar perinatal outcomes than delayed FET. Quantitative synthesis of available literature shows an increased LBR with immediate transfer. What is Known Already: Whether FET should be done in the first menstrual cycle following oocyte collection (OC) is controversial and the duration of a possible detrimental effect of supraphysiological sex steroid levels on pregnancy outcome is unknown. A multinational survey centers showed that, 61% of clinicians prefer to wait for a washout period before proceeding to FET, even after a failed fresh embryo transfer. Limited number of studies compared FET in the first menstrual cycle with delayed FET in a subsequent cycle with varying results. There is limited data on obstetric outcomes of pregnancies resulting from FET in the first menstrual cycle. Study Design, Size, Duration: 198 women who underwent a freeze-all cycle followed by FET between July 2017 and June 2020 were included. 119 FET in the first menstrual cycle (<30 days from oocyte collection) and 79 FET in subsequent cycles (>30 days from oocyte collection) were retrospectively compared. MEDLINE was searched on 01 January 2021 using relevant keywords. Cohort studies comparing immediate versus delayed transfer following freeze all cycles were included and quantitative summary for LBR was obtained. Participants/Materials, Setting, Methods: Freeze-all was undertaken when (i) the woman is deemed to be at high risk for OHSS, (ii)serum progesterone level is > 1.5 ng/ml on the day of trigger, (iii)preimplantation genetic testing is planned, (iv)the woman will undergo surgery prior to ET, (v)couple preference. Main Results and the Role of Chance: Baseline characteristics were similar between the groups except for antral follicle count (22 vs 18, MD = 5, 95% CI = 0 to 8), and number of metaphase-two oocytes (13 vs 10, MD = 3, 95% CI = 1 to 6) all of which were significantly higher in the immediate transfer group. Clinical pregnancy rate (CPR) per ET was similar in two groups (50.4% vs 44.3%, RR = 1.14, 95% CI = 0.84 to 1.54). Miscarriage rate per pregnancy was significantly lower (12.3 vs 31.1, RR = 0.40, 95% CI = 0.19 to 0.84) and LBR per ET was significantly higher (42.9 vs 26.6, RR = 1.61, 95% CI = 1.06 to 2.46) in the immediate transfer group. Median gestational age at delivery was similar (267.5 (262.5–273) vs 268 (260–271.5) days, MD = 1.00, 95% CI= –4.00 to 5.00). Median birthweight was significantly higher in the delayed transfer group (3520 vs 3195 grams, MD= –300, 95% CI= –660 to –20 grams). Birthweight percentile, height at birth and head circumference were similar between groups. Literature search revealed 1712 studies from which nine were eligible for quantitative summary. Cumulative risk ratio showed a 10% increase in LBR with immediate transfer ompared to delayed transfer (RR = 1.10, 95% CI = 1.01 – 1.20, I2=67%, 17369 embryo transfers). Limitations, Reasons for Caution: Our study is limited by its retrospective design and relatively limited sample size for multivariate analyses. Yet, it is reassuring that the majority of our findings are consistent with previous publications. Wider Implications of the Findings: The hypotheses generated by our retrospective findings, i.e., FET in the immediate menstrual cycle resembling fresh ETs with strong trends towards lower birthweight and lower incidence of preeclampsia is noteworthy for the design of future studies, and these outcomes should be followed and reported.