Timing of frozen-thawed embryo transfer after controlled ovarian stimulation in a non-elective freeze-all policy

Abstract

Background: Non-elective freeze-all policy has been increasingly utilized in assisted reproductive treatment, but the optimal timing of frozen-thawed embryo transfer (FET) after controlled ovarian stimulation (COS) remains to be investigated.Methods: This retrospective cohort study included 2,998 patients who underwent their first FETs after the first COS cycles using the non-elective freeze-all strategy from Jan 2013 to Dec 2016 at a tertiary-care academic medical center. Patients were divided into the "immediate" group in which FET took place within the first menstrual cycle after oocyte retrieval, and the "delayed" group where FET started after one or more menstrual cycles following COS. Results:The mean interval between oocyte retrieval and FET was 33.3±5.8 days in the immediate group (n=280; 9.3%) and 91.3±19.4 days in the delayed group (n=2,718; 90.7%). Cycles with delayed FET had a significantly lower live birth rate than those with immediate FET before [1,246/2,718 (45.8%) vs. 156/280 (55.7%); P=0.002] and after propensity score matching (PSM) [123/280 (43.9%) vs. 156/280 (55.7%); P=0.005]. When controlling for a number of confounding factors by multivariable logistic regression analysis, the risk remained significant with the adjusted odds ratio (aOR) [95% confidence interval (CI)] of 0.69 (0.53-0.90) and 0.60 (0.42-0.85) before and after matching, respectively.Conclusions: Performing FET immediately within the first menstrual cycle following COS was associated with a higher chance to achieve live birth compared with delaying FET to subsequent cycles in a non-elective freeze-all policy. However, further randomized controlled trials are still needed to confirm this conclusion.

Meta‐analysis of the embryo freezing transfer interval

“…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).…”

“…For the study published as an abstract, no data at all were provided concerning cycle management (Table 1). 21 In other cases, regarding the management of the OPU cycle, for downregulation, one study used GnRH agonists in a long protocol, 22 three studies used daily GnRH antagonists, 12,25,26 one study used either GnRH agonists in a short protocol or priming with progestins, 19 four studies used either GnRH agonists in a long protocol or daily GnRH antagonists, 9,20,23,24 and one study GnRH agonists or antagonists, reporting the data separately for these two groups 24 . Further, in one study, three different protocols were used: boost GnRH agonists, GnRH agonists in a long protocol, or GnRH antagonists, 18 while in another, six different protocols were used: ultra‐short, short, long, and modified ultra‐long GnRH agonist protocols, a GnRH antagonist protocol, or a mini‐stimulation protocol 27 …”

“…In two studies, moreover long‐acting FSH was also employed 12,26 . One study only reported the use of “exogenous gonadotropins”, 20 while only recombinant FSH was used in two studies 18,24 and only HMG was employed in another 19 …”

“…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 .…”