Frozen embryo transfer at the cleavage stage can be performed within the first menstrual cycle following the freeze-all strategy without adversely affecting the live birth rate

Abstract

Thus far, all clinical trials evaluating the efficacy of embryo transfer strategies have selectively delayed the first frozen embryo transfer (FET) by at least 1 menstrual cycle. Nevertheless, this approach, which is based solely on clinical experience, may create unnecessary psychological stress on infertile patients who are anxious to conceive as soon as possible. This study aimed to investigate whether the time interval between oocyte retrieval and subsequent FET affects reproductive outcomes.We implemented a large retrospective cohort study in a single assisted reproductive technology (ART) unit at a university-based hospital, including 1540 autologous FET cycles performed in freeze-all cycles. The beginning of the FET was classified as either ‘cycle 1’ (performing FET within the first menstrual cycle) or ‘cycle ≥2’ (performing FET after one or more menstrual cycles). Live birth rate (LBR) was the primary outcome of our study.The mean interval for ‘cycle 1’ and ‘cycle ≥2’ FETs was 25.72 ± 5.10 days and 75.33 ± 24.85 days, respectively (P < .001). The type of controlled ovarian hyperstimulation (COH) and endometrial preparation protocols differed significantly between groups (P = .008 and P = .004, respectively). However, FET groups were similar in many ways. Univariate analysis showed that there was no significant difference in LBR between the different cycles (33.1% after ‘cycle 1’ FET vs 34.2% after ‘cycle ≥2’ FET, P = .68). To evaluate whether LBR remained unchanged after adjustment for potential confounders, we performed multivariate logistic regression. FET timing had no significant impact on LBR in the first FET (odds ratio [OR]: 1.06, 95% confidence interval [CI]: 0.80–1.39).In accordance with the present study, it might not be necessary for clinicians to wait more than 1 menstrual cycle before performing FET. This allows us to reduce otiose deferment in FET, without adversely affecting reproductive outcomes.

Meta‐analysis of the embryo freezing transfer interval

“…As we can see in Table 1, the 12 studies included a total of 18 127 FET cycles (5457 immediate and 12 570 delayed) carried out in women from centers in 6 different countries (Belgium, Spain, Australia, China, Israel, USA, and Turkey). Ten of the publications reported single‐center studies, 9,19‐27 while one was based on a multisite IVF clinic 18 and one 12 included two centers.…”

“…Six studies reported an upper limit of age in the inclusion criteria: >38 years, 22 >40 years, 23,24 >42 years, 25 and >45 years 9,27 . Four reported a lower limit: <18 years 9,23 and <20 years 22,24 …”

“…Eight studies excluded preimplantation genetic diagnosis/preimplantation genetic screening cycles, 9,12,19,22,24‐27 and five excluded donor oocyte cycles 9,12,19,24,26 . The other inclusion/exclusion criteria are listed in Table 1.…”

“…In six studies, FET was considered immediate when performed within the first menstrual cycle after OPU, and delayed when performed after at least 2 menses 12,19,20,22,23,27 . Another author applied the same criteria but with the limit that in delayed ET, the transferred embryos were cryopreserved for less than 6 months 24 (Table S3).…”

“…In retrospective studies, some authors have found higher PRs when ET is performed in the immediately following menstrual cycle 18‐21 . On the other hand, there have also been reports of better results when ET is delayed ≥ 1 menstrual cycle 22 or better clinical results in delayed FET, though the difference did not reach significance, 23 while others have reported no differences 9,12,24‐27 . Further, the differences in some of the reports that were reported in favor of immediate FET disappeared when controlling for associated variables 20 …”