O-024 Exploring the optimal transfer day of day 6 (D6) vitrified blastocysts in Hormone Replacement Therapy Frozen Embryo Transfer (HRT-FET) cycles - a cohort study
Authors: Boel Povlsen B , Alsbjerg B , Humaidan P 
Published: June 2023

Abstract

Study question
Should blastocysts cryopreserved D6 be transferred on the 5th or 6th day of progesterone administration in HRT-FET cycles?

Summary answer
No significant differences in outcome parameters were found when D6 vitrified blastocysts were transferred on either day 5 or day 6 of progesterone in HRT-FET.

What is known already
Several studies have shown that D6 blastocyst transfer should be avoided in fresh transfer IVF cycles; consequently, these more slowly developing embryos are transferred in a HRT-FET cycle on the 6th day of progesterone administration in line with day 5 (D5) blastocysts. For successful implantation, a receptive endometrium and optimal synchronization between the endometrium and embryo are important. However, no definitive evidence exists regarding the optimal timing of transferring D6 blastocysts. Interestingly, a few studies have reported better reproductive outcomes if D6 blastocysts are transferred on the 5th day of progesterone administration instead of the 6th day of progesterone administration.

Study design, size, duration
This cohort study included a total of 718 vitrified D6 single blastocyst HRT-FET cycles performed between 2013 and 2022. 576 blastocysts were transferred on the 6th day of progesterone administration (2013-2021), and 142 blastocysts transferred on the 5th day of progesterone administration (2021-2022). Main outcomes were biochemical pregnancy rate (PR), implantation rate (IR), clinical pregnancy rate (CPR), and early pregnancy loss rate (EPLR).

Participants/materials, setting, methods
Patients undergoing HRT-FET in a public Fertility Clinic. Endometrial preparation included oral oestradiol (6mg/24hours), followed by vaginal micronized progesterone. As mentioned above, single blastocyst transfer was performed on either the 5th or 6th day of progesterone administration. Serum β-hCG level was measured 9-11 days after embryo transfer and biochemical pregnancy was defined as an hCG level &gt;10 IU/L. Clinical pregnancy was defined as visualization of a gestational sac and fetal heartbeat in gestational week 7.

Main results and the role of chance
In this cohort of a total of 718 HRT-FET cycles transferred on either the 5th or 6th day of progesterone administration the mean age of the patients at embryo transfer was 34.5±4.5 years vs. 33.0±4.9 years, respectively, p = 0.30. There was no significant difference between numbers of top-quality blastocyst transfers within the two groups 63% (89/142) vs. 64% (369/576), p = 0.76.
The overall, biochemical pregnancy rate (PR), implantation rate (IR), clinical pregnancy rate (CPR) and early pregnancy loss (EPLR) in the group of patients transferred on the 5th day of progesterone administration were 38% (54/142), 29% (41/142), 25% (36/142) and 33% (18/54). In the group of patients transferred on the 6th day of progesterone administration 41% (235/576), 33% (191/576), 30% (170/576) and 28% (65/235).
There were no significant differences between PR, IR, CPR and EPLR when transferring D6 vitrified blastocysts on either the 5th or the 6th day of progesterone administration (38% vs. 41%, p = 0.53, 29% vs. 33%, p = 0.33, 25% vs. 30%, p = 0.33 and 33% vs. 28%, p = 0.41).

Limitations, reasons for caution
Limitations of the study are the retrospective design and the limited number of D6 vitrified blastocysts transferred on the 5th day of progesterone administration. Furthermore, the two groups represented two different time periods.

Wider implications of the findings
Growing evidence shows that D5 vitrified blastocysts have better reproductive outcomes than slower developing embryos which are vitrified on day 6. Whether this is caused by intrinsic embryonic factors or poor timing of transfer in a subsequent FET cycle still needs to be unraveled.

Trial registration number
not applicable