Researchers in a 2021 study found that women who had a frozen embryo transfer the month immediately after their IVF cycle had improved pregnancy outcomes compared to women who delayed their FET for 2 or more months.
Frozen embryo transfers (FET) are extremely popular these days. One question that comes up is when to perform the FET. Should it be done immediately after the stimulated IVF cycle (in the next menstrual cycle), or should it be delayed a month (or longer) before starting? Most would like to transfer as soon as possible, so does it matter?
A 2020 meta-analysis by Huang et al. compared 12 retrospective studies and overall found no significant differences between pregnancy rates, live birth rates, or miscarriage rates. The data was scattered: some studies showed a benefit to immediate FETs, while others found that this was detrimental. Furthermore, these were retrospective studies with a high amount of inconsistencies (heterogeneity), so the overall quality of the data is low.
🔗 Original studies are referenced in this post or within the linked Remembryo posts.
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Li et al. (2021) recently completed an RCT on this subject with 724 women in two fertility centers in China between 2017 and 2018. There were two groups:
- The immediate FET group consisted of women who either had a freeze-all cycle, or had a failed fresh embryo transfer. They began their FET the month immediately following their stimulated IVF cycle.
- The delayed FET group began their FET 2 months (or more) after their stimulated IVF cycle.
Endometrial preparation for FET was done by hormone replacement treatment. On cycle day 3, oestradiol valerate was given at 4 mg/day for 10 days until the endometrium was 8 mm thick. Vaginal progesterone gel (Crinone) was then given at 90 mg/day until transfer (either Day 3 or Day 5 embryos, up to 2 embryos per transfer).
Let’s get to the data! I’ll present the intention-to-treat analysis:
- The ongoing pregnancy rate (beyond 12 weeks) was higher in the immediate group compared to the delayed group (47.2% vs 39.2%, p= 0.030, odds ratio 0.72 (0.54-0.97)). So the odds of an ongoing pregnancy decreased by 28% (1-0.72 = 0.28) in the delayed group compared to the immediate group.
- The live birth rate was higher in the immediate group compared to the delayed group (45.0% vs 35.6%, p= 0.010, odds ratio 0.68 (0.50-0.91)).
- The miscarriage rate was lower in the immediate group compared to the delayed group (13.2% vs 24.2%, p= 0.006, odds ratio 2.10 (1.23-3.58)).
- There were no significant differences in multiple pregnancy or ectopic pregnancy rates between the groups.
So basically, women who did an FET in the month immediately following their stimulated IVF cycle had about a 10% increase in live birth and a 10% reduction in miscarriage.
The big question – why? Unfortunately, they’re not really sure! One explanation is that there could be a difference in the state of the endometrium following a stimulated IVF cycle. Another explanation is that women who delay their FET may be more stressed compared to those who dive right in. But they didn’t evaluate this in this study, and the evidence for stress and IVF outcomes is controversial. Still, it’s interesting that there is an increase right after a stimulated IVF cycle, and is a reassuring study for those who want to do an FET as soon as possible.
A few issues with the study!
Women in the immediate group were slightly younger compared to those in the delayed group (30.0 (27.7-33.5 years) vs 31.0 (28.5-34.2 years)), despite randomization. This doesn’t seem like much, but it’s possible that this difference in age had an impact on the results. There was no difference in the number of women <35 however.
They were allowed to transfer up to two Day 3 embryos or Day 5 embryos (blasts). A better RCT would have used a single embryo transfer strategy (and probably blastocysts only). Still, there were no differences in the average number of embryos transferred between groups, or the stage of the embryos transferred.
Reference
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About Embryoman
Embryoman (Sean Lauber) is a former embryologist and the founder of Remembryo, an IVF research and fertility education website. After working in an IVF lab in the US, he returned to Canada and now focuses on making fertility research more accessible. He holds a Master’s in Immunology and launched Remembryo in 2018 to help patients and professionals make sense of IVF research. Sean shares weekly study updates on Facebook, Instagram, and Reddit regularly. He also answers questions on Reddit or in his private Facebook group.
Related posts:
Vaginal or intramuscular progesterone? Results of a 2021 clinical trial
2 embryos or 1? The risks of a double embryo transfer for women under 35
Prolonged frozen embryo storage may result in lower success
Comparing pregnancy outcomes for letrozole, natural and medicated FETs
Pregnancy outcomes and complications with medicated, natural and mild stimulated FETs
Survey examines the use and attitude of natural cycle FETs in US clinics
Study finds no difference in live birth rates for embryos frozen up to 10 years
Study finds more flexible triggering timing for modified natural cycle FETs