Endometrial Receptivity Testing Before Embryo Transfer Did Not Improve Live Births

Use of endometrial receptivity testing to determine optimal timing for a frozen embryo transfer during in vitro fertilization (IVF) did not improve live birth rates, a randomized trial showed.

Among over 700 participants, 58.5% of those who underwent endometrial receptivity testing before a frozen embryo transfer had a live birth compared with 61.9% of those who underwent transfer at standard timing (rate ratio [RR] 0.95, 95% CI 0.79-1.13, P=0.38), reported Nicole Doyle, MD, PhD, of Shady Grove Fertility Center in Fairfax, Virginia, and colleagues.

There were also no significant differences between the two groups for secondary outcomes, including biochemical pregnancy rate (77.2% vs 79.5%, respectively; RR 0.97, 95% CI 0.83-1.14, P=0.48) and clinical pregnancy rate (68.8% vs 72.8%, respectively; RR 0.94, 95% CI 0.80-1.12, P=0.25), they noted in JAMA.

"The findings do not support routine use of receptivity testing to guide the timing of embryo transfer during in vitro fertilization," Doyle and colleagues wrote.

The endometrium only allows for embryo implantation during the receptive phase, which typically occurs 6 to 12 days after ovulation, the authors explained. Physicians follow hormone replacement protocols to prepare the endometrium for implantation, mimicking the duration of progesterone exposure before a natural implantation. However, the optimal duration of progesterone exposure remains unknown, and no biomarkers have shown the ability to reliably predict endometrial receptivity.

Endometrial receptivity testing is a uterine biopsy used to identify gene expression across different phases of the menstrual cycle, helping clinicians detect the receptive phase. Ultimately, the test aims to identify the peak 6-hour window to perform a frozen embryo transfer relative to progesterone exposure.

While more than 150,000 endometrial receptivity tests have been performed, retrospective data on outcomes have been mixed, Doyle and colleagues noted.

For this double-blind study, they enrolled 767 participants from 30 sites within a private fertility practice in the Eastern U.S. from May 2018 to September 2020. Participants who were planning IVF, preimplantation genetic testing for aneuploidy, and a frozen embryo transfer were included. All were between the ages of 30 and 40 at the time of egg retrieval, and were likely to produce at least one euploid blastocyst.

Patients in the control group underwent frozen embryo transfer about 5 days after they started taking progesterone, while those in the intervention group underwent a transfer as recommended by endometrial receptivity testing.

Of the 767 participants randomized, about half underwent endometrial receptivity testing. Mean age was 35, and mean body mass index was 27. Approximately 17% of the participants in both groups had a previous live birth.

Receptivity rates were similar between groups, with non-receptive rates of 55% and 54% in the intervention and control groups, respectively. Most of the non-receptive rates were classified as pre-receptive.

No adverse events were reported in this trial.

In an exploratory post-hoc analysis that looked at patients who were recommended to change the timing of an embryo transfer by at least 24 hours after endometrial receptivity testing, biochemical loss was significantly higher in the intervention versus the control group (15.2% vs 4.0%; RR 3.77, 95% CI 1.24-11.44, P=0.02), and clinical pregnancy rate was significantly lower (61.8% vs 78.3%, respectively; RR 0.79, 95% CI 0.58-1.07, P=0.01). Although there was no difference in live birth rates, Doyle and team noted that a potential negative effect of this testing should be considered "hypothesis generating."

The authors acknowledged that patients with recurrent implantation failure and pregnancy loss were excluded from this trial, and therefore the findings may not be applicable to the subgroup of infertile patients. They also noted that 16% of planned participants were withdrawn because they did not have a suitable embryo to transfer, compared with 5% anticipated before the analysis, which may impact the generalizability of these findings. Finally, this study was not powered for analyses limited to non-receptive patients.

Comment