Dataset Information

Effect of Timing by Endometrial Receptivity Testing vs Standard Timing of Frozen Embryo Transfer on Live Birth in Patients Undergoing In Vitro Fertilization: A Randomized Clinical Trial.

ABSTRACT:

Importance

Endometrial receptivity testing is purported to improve live birth following frozen embryo transfer by identifying the optimal embryo transfer time for an individual patient; however, data are conflicting.

Objective

To compare live birth from single euploid frozen embryo transfer according to endometrial receptivity testing vs standardized timing.

Design, setting, and participants

Double-blind, randomized clinical trial at 30 sites within a multicenter private fertility practice in the Eastern US. Enrollment was from May 2018 to September 2020; follow-up concluded in August 2021. Participants underwent in vitro fertilization, preimplantation genetic testing for aneuploidy, endometrial receptivity testing, and frozen embryo transfer. Those with euploid blastocyst(s) and an informative receptivity result were randomized. Exclusion criteria included recurrent pregnancy loss, recurrent implantation failure, surgically aspirated sperm, donor egg(s), and unmitigated anatomic uterine cavity defects.

Interventions

The intervention group (n = 381) underwent receptivity-timed frozen embryo transfer, with adjusted duration of progesterone exposure prior to transfer, if indicated by receptivity testing. The control group (n = 386) underwent transfer at standard timing, regardless of receptivity test results.

Main outcomes and measures

The primary outcome was live birth. There were 3 secondary outcomes, including biochemical pregnancy and clinical pregnancy.

Results

Among 767 participants who were randomized (mean age, 35 years), 755 (98%) completed the trial. All randomized participants were analyzed. The primary outcome of live birth occurred in 58.5% of transfers (223 of 381) in the intervention group vs 61.9% of transfers (239 of 386) in the control group (difference, -3.4% [95% CI, -10.3% to 3.5%]; rate ratio [RR], 0.95 [95% CI, 0.79 to 1.13]; P = .38). There were no significant differences in the intervention vs the control group for the prespecified secondary outcomes, including biochemical pregnancy rate (77.2% vs 79.5%, respectively; difference, -2.3% [95% CI, -8.2% to 3.5%]; RR, 0.97 [95% CI, 0.83 to 1.14]; P = .48) and clinical pregnancy rate (68.8% vs 72.8%, respectively; difference, -4.0% [95% CI, -10.4% to 2.4%]; RR, 0.94 [95% CI, 0.80 to 1.12]; P = .25). There were no reported adverse events.

Conclusions and relevance

Among patients for whom in vitro fertilization yielded a euploid blastocyst, the use of receptivity testing to guide the timing of frozen embryo transfer, compared with standard timing for transfer, did not significantly improve the rate of live birth. The findings do not support routine use of receptivity testing to guide the timing of embryo transfer during in vitro fertilization.

Trial registration

ClinicalTrials.gov Identifier: NCT03558399.

SUBMITTER: Doyle N

PROVIDER: S-EPMC9856480 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Effect of Timing by Endometrial Receptivity Testing vs Standard Timing of Frozen Embryo Transfer on Live Birth in Patients Undergoing In Vitro Fertilization: A Randomized Clinical Trial.

Doyle Nicole N Jahandideh Samad S Hill Micah J MJ Widra Eric A EA Levy Michael M Devine Kate K

JAMA 20221201 21

<h4>Importance</h4>Endometrial receptivity testing is purported to improve live birth following frozen embryo transfer by identifying the optimal embryo transfer time for an individual patient; however, data are conflicting.<h4>Objective</h4>To compare live birth from single euploid frozen embryo transfer according to endometrial receptivity testing vs standardized timing.<h4>Design, setting, and participants</h4>Double-blind, randomized clinical trial at 30 sites within a multicenter private fe ...[more]

PMID: 36472596

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Project description:BackgroundA successful pregnancy using in vitro fertilization and embryo transfer (IVF-ET) requires a receptive endometrium, good-quality embryos, and a synchronized embryo-endometrial dialogue. Although embryo quality and endometrial receptivity (ER) have been fully assessed to exclude substandard conditions, the probability of successful ET is relatively low. Currently, embryo-endometrial synchrony is considered to be a possible explanation, because delayed, advanced, or narrowed window of implantation (WOI) may lead to ET failure.ObjectiveThis study aims to establish a nomogram incorporating a series of ultrasonic ER markers on the day before implantation to assess the embryo-endometrial synchrony, which may contribute to the improvement of clinical pregnancy outcomes.MethodsTotally 583 women with 1135 complete IVF cycles were retrospectively analyzed. Among them, 357 women with 698 cycles and 226 women with 437 cycles were assigned to the training and validation cohorts, respectively. Ultrasonic ER markers obtained on the day before implantation were collected for analyses. In the training cohort, the screened correlates of clinical pregnancy failure were utilized to develop a nomogram for determining whether an infertile woman is suitable for the ET next day. This model was validated both in the training and validation cohorts.ResultsSpiral artery (SA) resistance index (RI), vascularisation index (VI), and flow index (FI) were independently associated with the ET failure (all P < 0.05). They were served as the components of the developed nomogram to visualize the likelihood of implantation failure in IVF-ET. This model was validated to present good discrimination and calibration, and obtained clinical net benefits both in the training and validation cohorts.ConclusionWe developed a nomogram that included SA-RI, VI, and FI on the day before implantation. It may assist physicians to identify patients with displaced WOI, thus avoiding meaningless ET prior to implantation.

Project description:BackgroundReceptivity of the uterus is essential for embryo implantation and progression of mammalian pregnancy. Acquisition of receptivity involves major molecular and cellular changes in the endometrial lining of the uterus from a non-receptive state at ovulation, to a receptive state several days later. The precise molecular mechanisms underlying this transition and their upstream regulators remain to be fully characterized. Here, we aimed to generate a comprehensive profile of the endometrial transcriptome in the peri-ovulatory and peri-implantation states, to define the genes and gene pathways that are different between these states, and to identify new candidate upstream regulators of this transition, in the mouse.ResultsHigh throughput RNA-sequencing was utilized to identify genes and pathways expressed in the endometrium of female C57Bl/6 mice at estrus and on day 3.5 post-coitum (pc) after mating with BALB/c males (n = 3-4 biological replicates). Compared to the endometrium at estrus, 388 genes were considered differentially expressed in the endometrium on day 3.5 post-coitum. The transcriptional changes indicated substantial modulation of uterine immune and vascular systems during the pre-implantation phase, with the functional terms Angiogenesis, Chemotaxis, and Lymphangiogenesis predominating. Ingenuity Pathway Analysis software predicted the activation of several upstream regulators previously shown to be involved in the transition to receptivity including various cytokines, ovarian steroid hormones, prostaglandin E2, and vascular endothelial growth factor A. Our analysis also revealed four candidate upstream regulators that have not previously been implicated in the acquisition of uterine receptivity, with growth differentiation factor 2, lysine acetyltransferase 6 A, and N-6 adenine-specific DNA methyltransferase 1 predicted to be activated, and peptidylprolyl isomerase F predicted to be inhibited.ConclusionsThis study confirms that the transcriptome of a receptive uterus is vastly different to the non-receptive uterus and identifies several genes, regulatory pathways, and upstream drivers not previously associated with implantation. The findings will inform further research to investigate the molecular mechanisms of uterine receptivity.

Project description:BackgroundRepeated implantation failure (RIF) is currently believed by some scholars to be mainly related to the poor endometrial receptivity. Three-dimensional (3D) ultrasound, as a noninvasive examination, has attracted the most attention. This paper further discusses whether 3D ultrasound of the endometrial receptivity index has guidance value in the evaluation of pregnancy outcomes in patients with RIF following frozen-thawed embryo transfer.MethodsA total of 79 patients with RIF were retrospectively analyzed. These 79 patients which were confirmed by the transvaginal ultrasonography detection comprised 36 cases of intrauterine pregnancy, which were included in the pregnancy group, and 43 cases with biochemical pregnancy (the HCG in blood or urine is only transient and can be detected by clinical biochemical methods. The pregnancy sac cannot be seen under ultrasound) or negative results of human chorionic gonadotropin (HCG) examination, which were included in the non-pregnancy group. The endometrial thickness, uterine volume, sub-endometrial blood flow type, pulsatility index (PI) and resistance index (RI) of the spiral artery; the RI and PI of the uterine artery; and the peak systolic velocity/end diastolic velocity (S/D) of the two groups were measured and analyzed.Results(I) There were no significant differences in the age, infertility years, body mass index (BMI), anti-Müllerian hormone (AMH), endometrial thickness on the hCG injection day, estradiol (E2), and progesterone (P) between the pregnant and non-pregnant groups (P>0.05). (II) There were no significant differences in the endometrial thickness, uterine volume, and RI and PI of the uterine artery on the day before the implantation between the two groups (P>0.05). (III) There was statistical difference in the sum of the S/D of the two uterine arteries between the two groups (P<0.05) with a cutoff value of 14.47 (P<0.05). (IV) The RI and PI of the spiral artery in the non-pregnancy group were lower than those in the pregnancy group, and the difference was statistically significant (P<0.05). (V) The differences in the endometrial classification and subendometrial blood flow classification between the two groups were statistically significant (P<0.05).ConclusionsUltrasonographic endometrial blood flow classification, spiral artery blood flow parameters, and uterine artery blood flow parameters can be effective indexes for evaluating endometrial receptivity, and they have a certain clinical significance in evaluating the pregnancy outcome of RIF patients after retransplantation.

Dataset Information

Effect of Timing by Endometrial Receptivity Testing vs Standard Timing of Frozen Embryo Transfer on Live Birth in Patients Undergoing In Vitro Fertilization: A Randomized Clinical Trial.

Importance

Objective

Design, setting, and participants

Interventions

Main outcomes and measures

Results

Conclusions and relevance

Trial registration

Publications

Effect of Timing by Endometrial Receptivity Testing vs Standard Timing of Frozen Embryo Transfer on Live Birth in Patients Undergoing In Vitro Fertilization: A Randomized Clinical Trial.

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