- 494 women randomized across 7 Danish fertility clinics: Live birth rate was 32.4% for immediate vs. 36.0% for postponed transfer
- While the absolute difference was modest, the trial failed to prove that immediate transfer is non-inferior
- Researchers conclude: “Insufficient evidence to recommend immediate FET as standard care in modified natural cycles”
“Now that egg retrieval is over, can I transfer the embryo during my very next period? Or is it better to let the uterus rest for about a month?”
This is one of the most common questions asked by patients undergoing In Vitro Fertilization (IVF). After undergoing days of ovarian stimulation injections and completing the retrieval, patients with cryopreserved embryos face two main pathways: preparing for a frozen embryo transfer (FET) as soon as the next menstrual period starts, or skipping one cycle before proceeding.
Among fertility patients, a widespread belief holds that “because the body underwent hyperstimulation, resting the uterus and body for a month enhances implantation.” Conversely, many patients eager to shorten the timeline ask whether it is safe to proceed immediately if they feel physically well.
Which approach actually leads to better pregnancy and childbirth outcomes?
A multicenter randomized controlled trial (RCT) presented at the 2026 Annual Meeting of the European Society of Human Reproduction and Embryology (ESHRE) directly addressed this question. The trial could not definitively conclude that “taking a month off is universally superior,” but it also failed to prove that “immediate transfer yields equivalent outcomes.”
Immediate Transfer vs. Postponing by One Cycle
The research team, encompassing seven fertility centers including Copenhagen University Hospital (Rigshospitalet) in Denmark, recruited 494 women between April 2021 and February 2025. Eligible participants were aged 18 to 40 with regular menstrual cycles who had either not conceived following a fresh embryo transfer or had undergone a “freeze-all” cycle and were preparing for their first FET.
The participants were randomized into two distinct arms:
- Immediate FET: Underwent frozen embryo transfer in the first menstrual cycle immediately following oocyte retrieval.
- Postponed FET: Postponed embryo transfer by at least one full menstrual cycle.
The protocol utilized in this trial was a modified natural cycle frozen embryo transfer (mNC-FET). In this protocol, natural follicular development is monitored via ultrasound until the leading follicle measures $\ge 17\text{ mm}$, at which point an ovulation trigger injection (hCG) is administered, followed by blastocyst transfer 6 to 7 days later. This approach differs physiologically from artificial/programmed HRT cycles, where exogenous hormones control endometrial preparation from cycle day 1.
Live Birth Rate: 32.4% vs. 36.0%
The primary clinical endpoint evaluated by the investigators was the live birth rate (LBR)—measuring delivered babies rather than biochemical or clinical pregnancy markers alone.
In the intention-to-treat (ITT) analysis of all 494 randomized women:
- Immediate FET Group: Live birth rate was 32.4%
- Postponed FET Group: Live birth rate was 36.0%
While the postponed group had a 3.6 percentage point numerical advantage, the difference did not reach statistical significance ($P = 0.393$).
Looking solely at the raw numbers (32% vs. 36%), one might assume the difference is negligible and conclude that transferring immediately is completely fine.
However, the statistical architecture of this trial prevents that interpretation.
This study was designed not as a conventional “superiority trial” testing whether waiting is better, but as a non-inferiority trial designed to prove that immediate transfer is not meaningfully worse than waiting. The researchers prespecified a non-inferiority margin of 10%—meaning immediate transfer could only be deemed acceptable if the lower bound of the confidence interval did not fall more than 10% below the postponed group’s birth rate.
The statistical analysis showed that the lower bound crossed this prespecified margin. In other words, the trial could not rule out the possibility that immediate transfer results in an unacceptably lower birth rate.
Consequently, the study failed to statistically confirm that immediate FET is non-inferior to postponed FET.
Per-Protocol Analysis: A Wider Gap in Pregnancy Rates
In the per-protocol (PP) analysis—evaluating the 472 women who completed treatment strictly according to protocol—the gap widened:
- Live Birth Rate: 32.7% (Immediate) vs. 39.2% (Postponed) — a 6.6 percentage point difference (still failing to meet non-inferiority criteria).
- Pregnancy Rate: 44.9% (Immediate) vs. 57.3% (Postponed) — a statistically significant 12.4 percentage point difference ($P = 0.007$).
When evaluating only the cycles where an embryo transfer actually took place, the pregnancy rate remained significantly higher in the postponed arm (60.8% vs. 50.7%).
Conversely, other secondary reproductive outcomes, including miscarriage rates, showed no significant disparities. Cycle cancellation rates were 10.1% in the immediate group and 6.2% in the postponed group, which did not reach statistical significance.
Why Did the Idea of ‘Taking a Month Off’ Arise?
Why has delaying FET by one cycle become common practice?
During controlled ovarian hyperstimulation, high doses of gonadotropins stimulate multiple follicles simultaneously, creating a supraphysiological hormonal environment unlike that of a natural cycle. Clinicians have long hypothesized that residual endocrine effects could persist into the immediately following cycle, potentially impairing endometrial receptivity or disrupting normal follicular recruitment.
Additionally, multiple resolving corpora lutea frequently persist in the ovaries immediately post-retrieval, making it difficult to distinguish an emerging dominant follicle on ultrasound. For these physiological and diagnostic reasons, many fertility clinics routinely postpone FET.
However, waiting has its own downsides. Deferring transfer extends the overall time to pregnancy (TTP), and for couples who have already navigated prolonged infertility, waiting another month introduces emotional strain.
Notably, in a prior sub-study affiliated with this trial, women in the immediate transfer arm reported more physical discomfort, whereas those in the postponed arm experienced greater psychological stress from treatment delay.
Contradicting Previous Trials: Protocol Selection Matters
Intriguingly, earlier randomized trials have reported the exact opposite outcome.
A large-scale randomized trial of 724 women published in 2021 found that women who underwent immediate FET achieved a higher live birth rate (47.2%) than those who postponed (37.7%).
The crucial distinction lies in the endometrial preparation protocol:
- The 2021 study evaluated artificial/programmed cycles (HRT-FET), where suppression and exogenous estrogen/progesterone dictate endometrial priming.
- The 2026 Danish trial evaluated modified natural cycles (mNC-FET), which rely on endogenous follicular growth and ovulation.
This demonstrates that a single blanket rule—”transfer immediately” or “always wait a month”—cannot be applied across all FET protocols. The optimal timing appears to interact directly with whether the endometrium is prepared via natural ovulation or exogenous hormone replacement.
Neither “Waiting Is Always Best” Nor “Immediate Is Identical”
Interpreting these findings as definitive proof that “waiting a month always increases birth rates” would be inaccurate.
The difference in live birth rates between the two groups did not achieve clear statistical superiority. The primary finding of this trial is that immediate transfer failed to demonstrate non-inferiority.
The investigators highlighted that a single trial of roughly 500 women cannot establish definitive clinical policy and that larger prospective studies are warranted. Furthermore, because these findings are specific to modified natural cycles, they cannot be directly extrapolated to programmed HRT cycles or true unmedicated natural cycles.
For now, evidence remains insufficient to assert that every patient must wait a month after retrieval, but neither is it justified to claim that immediate transfer offers identical success rates in natural cycle transfers.
The study authors concluded that in modified natural cycles, routinely offering immediate FET in the first cycle post-retrieval as standard care cannot yet be recommended.
Ultimately, the takeaway for patients is not simply whether to wait or proceed. Transfer timing should be decided collaboratively with the clinical team, taking into account ovarian recovery, cycle regularity, endometrial readiness, and the specific protocol selected for embryo transfer.
※ This article was written based on the multicenter randomized controlled trial “Immediate versus postponed frozen embryo transfer in a modified natural cycle – A multicentre randomised controlled trial” conducted by researchers from Copenhagen University Hospital (Rigshospitalet) and six other fertility centers, published in Human Reproduction, Volume 41, Supplement 1, on July 8, 2026. The study enrolled 494 women aged 18–40 (Presentation: L26/P-902, Abstract: deag083.1226, DOI: 10.1093/humrep/deag083.1226). It does not provide individualized clinical diagnoses or treatment recommendations, and decisions regarding transfer timing and endometrial preparation should always be made in consultation with an attending fertility specialist.
※ The images associated with this article were generated using generative AI (ChatGPT, OpenAI) as illustrative visual references and do not depict real individuals.
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