ImportanceEndometrial 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.ObjectiveTo compare live birth from single euploid frozen embryo transfer according to endometrial receptivity testing vs standardized timing.Design, Setting, and ParticipantsDouble-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.InterventionsThe 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 MeasuresThe primary outcome was live birth. There were 3 secondary outcomes, including biochemical pregnancy and clinical pregnancy.ResultsAmong 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 RelevanceAmong 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 RegistrationClinicalTrials.gov Identifier: NCT03558399

STUDY QUESTION Do donor oocyte recipients benefit from preimplantation genetic testing for aneuploidy (PGT-A)? SUMMARY ANSWER PGT-A did not improve the likelihood of live birth for recipients of vitrified donor oocytes, but it did avoid embryo transfer in cycles with no euploid embryos. WHAT IS KNOWN ALREADY Relative to slow freeze, oocyte vitrification has led to increased live birth from cryopreserved oocytes and has led to widespread use of this technology in donor egg IVF programs. However, oocyte cryopreservation has the potential to disrupt the meiotic spindle leading to abnormal segregation of chromosome during meiosis II and ultimately increased aneuploidy in resultant embryos. Therefore, PGT-A might have benefits in vitrified donor egg cycles. In contrast, embryos derived from young donor oocytes are expected to be predominantly euploid, and trophectoderm biopsy may have a negative effect relative to transfer without biopsy. STUDY DESIGN, SIZE, DURATION This is a paired cohort study analyzing donor oocyte-recipient cycles with or without PGT-A performed from 2012 to 2018 at 47 US IVF centers. PARTICIPANTS/MATERIALS, SETTING, METHODS Vitrified donor oocyte cycles were analyzed for live birth as the main outcome measure. Outcomes from donors whose oocytes were used by at least two separate recipient couples, one couple using PGT-A (study group) and one using embryos without PGT-A (control group), were compared. Generalized estimating equation models controlled for confounders and nested for individual donors contributing to both PGT-A and non-PGT-A cohorts, enabling a single donor to serve as her own control. MAIN RESULTS AND THE ROLE OF CHANCE In total, 1291 initiated recipient cycles from 223 donors were analyzed, including 262 cycles with and 1029 without PGT-A. The median aneuploidy rate per recipient was 25%. Forty-three percent of PGT-A cycles had only euploid embryos, whereas only 12.7% of cycles had no euploid embryos. On average 1.09 embryos were transferred in the PGT-A group compared to 1.38 in the group without PGT-A (P < 0.01). Live birth occurred in 53.8% of cycles with PGT-A versus 55.8% without PGT-A (P = 0.44). Similar findings persisted in cumulative live birth from per recipient cycle. LIMITATIONS, REASONS FOR CAUTION Pooled clinical data from 47 IVF clinics introduced PGT-A heterogeneity as genetic testing were performed using different embryology laboratories, PGT-A companies and testing platforms. WIDER IMPLICATIONS OF THE FINDINGS PGT-A testing in donor oocyte-recipient cycles does not improve the chance for live birth nor decrease the risk for miscarriage in the first transfer cycle but does increase cost and time for the patient. Further studies are required to test if our findings can be applied to the young infertility patient population using autologous oocytes. STUDY FUNDING/COMPETING INTEREST(S) No external funding was used for this study. There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER N/A.

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ploidy). Reports indicated the % of fragmented sperm DNA (DFI). Patients were divided into 2 groups: (<15% and >15%) and incidence of segmental aneuploidy was compared between the groups in 2 ways: 1) any segmental aneuploidy (among all embryos, including those with an additional whole chromosome aneuploidy) and 2) segmental aneuploidy only (no other whole chromosome aneuploidy).RESULTS: A total of 169 cases were included in the analysis. DFI <15% was found in 123 specimens, while DFI >15% was found in 45 specimens. The median DFI for the entire study population was 11 (interquartile range: 8 to 15). Men in the 15% DFI group were older (40.6 vs. 38.0, p<0.01), but there was no difference in the age of the female partner (37.9 vs. 37.4, p ¼ 0.71). There was no difference in the rate of conversion to blastocyst. The incidence of any segmental aneuploidy and only segmental aneuploidy was no different between the groups. The incidence of whole chromosome aneuploidy was also no different (Table 1).CONCLUSION: Specimens with elevated DNA Fragmentation used for ICSI do not result in an increased incidence of segmental aneuploidy in trophectoderm biopsy samples evaluated by NGS. These results suggest three possible rationales: 1) DNA damage in the male may be at least partially repaired by oocyte-derived mechanisms, 2) small deletions and duplications may be below the diagnostic threshold of current NGS technologies, or 3) SDF testing, which relies on average levels among pooled sperm, may be limited in its ability to prognosticate embryonic segmental aneuploidy.