After egg collection, can we predict the chance of embryos for day 5 transfer or freezing?

Lay summary Even partway through an IVF cycle, at the point when a woman’s eggs have been collected, it is hard to provide reliable answers to the common question of ‘Am I likely to have a good embryo to transfer?’ Sometimes, it only takes one good egg to be successful. However, doctors and patients are acutely aware that low egg numbers, older age and having conditions such as endometriosis can stack the odds against success. We have developed a model to try and answer this question for those patients who wish for more information to help guide their expectations after egg collection. A new tool is presented to predict whether a woman having IVF treatment will have a good enough embryo either to transfer on day 5 or freeze. It was built using information from all 2015 to 2016 UK cycles and predicts using age, number of eggs collected and cause of subfertility.

Estimating the causal effect of embryo transfer day on clinical in vitro fertilization outcomes using propensity score matching

Background For women undergoing in vitro fertilization (IVF), the clinical benefit of embryo transfer at the blastocyst stage (Day 5) versus cleavage stage (Day 3) remains controversial. The purpose of this study is to compare the implantation rate, clinical pregnancy rate and odds of live birth of Day 3 and Day 5 embryo transfer, and more importantly, to address the issue that patients were chosen to receive either transfer protocol due to their underlying clinical characteristics, i.e., confounding by indication. Methods We conducted a retrospective cohort study of 9,090 IVF cycles collected by Lee Women’s Hospital in Taichung, Taiwan from 1998 to 2014. We utilized the method of propensity score matching to mimic a randomized controlled trial (RCT) where each patient with Day 5 transfer was matched by another patient with Day 3 transfer with respect to other clinical characteristics. Implantation rate, clinical pregnancy rate, and odds of live birth were compared for women underwent Day 5 transfer and Day 3 transfer to estimate the causal effects. We further investigated the causal effects in subgroups by stratifying age and anti-Mullerian hormone (AMH). Results Our analyses uncovered an evidence of a significant difference in implantation rate (p=0.04) favoring Day 5 transfer, and showed that Day 3 and Day 5 transfers made no difference in both odds of live birth (p=0.27) and clinical pregnancy rate (p=0.11). With the increase of gestational age, the trend toward non-significance of embryo transfer day in our result appeared to be consistent for subgroups stratified by age and AMH, while all analyses stratified by age and AMH were not statistically significant. Conclusions We conclude that for women without strong indications for Day 3 or Day 5 transfer, there is a small significant difference in implantation rate in favor of Day 5 transfer. However, the two protocols have indistinguishable outcomes on odds of live birth and clinical pregnancy rate.

P–755 Perinatal outcomes following Day–4 embryo transfer compared to Day–2, Day–3 and Day–5 embryo transfer: an analysis of 56,346 singleton live births

Study question Are perinatal outcomes of singleton live births following Day–4 embryo transfer (ET) different to Day–2, Day–3 and Day–5 ET? Summary answer Perinatal outcomes of singleton live births following Day–4 ET are similar with those following Day–2, Day–3 and Day–5 ET. What is known already The morula represents a critical stage in preimplantation embryo development, but the usage of morula transfer on Day–4 has received little attention. Recent work from our group suggested that live birth rates following Day–4 ET appear higher than cleavage-stage ET, but lower than blastocyst ET. Therefore, Day–4 appears an alternative day to perform ET, offering the benefits of extended culture for embryo selection, but with shorter in-vitro culture exposure, as well as improving flexibility and planning in the IVF Clinic. However, there are extremely limited data available on the perinatal outcomes after Day–4 ET compared to cleavage-stage and blastocyst ET. Study design, size, duration Retrospective cohort study using data from the anonymised dataset of the Human Fertilisation and Embryology Authority (HFEA) in the UK between 2000 and 2016. Data from singleton live births of women undergoing their first IVF/ICSI cycle were analysed to compare perinatal outcomes after fresh Day–2,3,4,5 embryo transfers. Participants/materials, setting, methods Births resulting from the first, fresh, autologous, stimulated, non-PGT cycles, with full data, were included. After exclusions, a total 56,346 singleton live births were included in the analysis (17,613 from Day–2 ET, 15,533 from Day–3 ET, 508 from Day–4, 22,692 from Day–5 ET). Binary/multinomial logistic regression analysis was performed to adjust for important cofounders. Adjusted odds ratios (aORs) and 95% confidence intervals (95%CI) were calculated. The level of significance was set at < 0.05. Main results and the role of chance The probabilities of birth at full-term (FT) and normal birthweight (NBW) after Day–4 transfer (FT 90.4%; NBW 84.6%) were similar to Day–2 (FT 89.7%, aOR 0.994, [0.734–1.344]; NBW 81.9%, aOR 0.881, [0.708–1.096]), Day–3 (FT 90.2%, aOR 1.026, [0.760–1.386]; NBW 82.4%, aOR 0.894, [0.719–1.111]) and Day–5 transfer (FT 90.4%, aOR 1.001, [0.743–1.350]; NBW 83.7%, aOR 0.920, [0.741–1.142]). The probabilities of preterm birth (PTB) and very preterm birth (VPTB) after Day–4 transfer (PTB 9.3%; VPTB 0.4%) were similar to Day–2 (PTB 9.5%; aOR=0.952; VPTB 0.8%; aOR=2.172), Day–3 (PTB 9.0%, aOR=0.920; VPTB 0.9%, aOR=2.174), and Day–5 transfer (PTB 8.8%; aOR=0.955; VPTB 0.8%, aOR=1.956). The probabilities of very-low birthweight (VLBW), low birthweight (LBW), high birthweight (HBW) and very-high birthweight (VHBW) after Day–4 transfer (VLBW 0.9%, LBW 7.9%, HBW 6.3%, VHBW 0.3%) were similar to Day–2 (VLBW 1.8%, aOR=1.827; LBW 8.0%, aOR=1.015; HBW 8.1%, aOR=1.174; VHBW 0.2%, aOR=0.590), Day–3 (VLBW 1.8%, aOR=1.788; LBW 7.4%, aOR=0.927; HBW 8.3%, aOR=1.256; VHBW 0.2%, aOR=0.503) and Day–5 transfer (VLBW 1.6%, aOR=1.782; LBW 6.9%, aOR=0.894; HBW 7.5%, aOR=1.215; VHBW 0.2%, aOR=0.796). The probability of having a female baby after Day–4 transfer (51.6%) was similar to Day–2 (49.2%, aOR 0.940), Day–3 (49.3%, aOR 0.931) and Day–5 transfer (48.3%, aOR 0.869). Limitations, reasons for caution The study is limited by its retrospective nature, the inability to adjust for additional confounders and the small number of singleton births after Day–4 ET. It is not known how Day–4 ET was decided. The incidence of congenital abnormalities was not analysed due to incomplete registration in the dataset. Wider implications of the findings: Perinatal outcomes of singleton live births following Day–4 ET are similar with those following Day–2, Day–3 and Day–5 ET, suggesting that morula transfer is equally safe as cleavage-stage and blastocyst transfer. Data on a larger number of live births from well-designed RCTs are required to confirm these findings. Trial registration number Not applicable

Day 5 vitrified blastocyst transfer versus day 6 vitrified blastocyst transfer in oocyte donation program

The superiority of day 5 blastocysts compared to day 6 blastocysts in fresh cycle transfers was previously demonstrated and attributed mainly to endometrial asynchrony. Data from frozen blastocysts transfers showed conflicting results, possibly due to heterogeneous patient population and embryo quality. The aim of this study was to compare clinical pregnancy rate (CPR) and live birth rate (LBR) between transfers of vitrified day 5 blastocysts and day 6 blastocysts in oocyte donation, blastocyst-only cycles. In a retrospective, multi-center study, with a single oocyte donation program, a total of 1840 frozen embryo transfers (FET’s) were analyzed, including 1180 day 5 blastocysts and 660 day 6 blastocysts transfers. Day 5 blastocyst transfers had better embryonic development and significantly higher CPRs (34.24% vs. 20.15%, P < 0.0001), higher LBRs (26.89% vs. 14.77%, P < 0.0001), less cycles to LBR (1.83 ± 0.08 vs. 2.39 ± 0.18, P = 0.003) and shorter time to LBRs (76.32 ± 8.7 vs. 123.24 ± 19.1 days, P = 0.01), compared to day 6 transfers, respectively. A multivariate stepwise logistic regression indicated, that day 5 transfer was an independent factor for CPRs (OR 1.91; 95% CI 1.43–2.54, P < 0.001) and LBRs (OR 2.26; 95% CI 1.19–4.28, P = 0.01), regardless of embryo quality, compared to day 6. In conclusion, day 5 blastocysts in oocyte donation program have significantly higher CPRs and LBRs, and present shorter time to delivery, compared to day 6 blastocysts, regardless of embryo quality.

A stepwise approach to move from a cleavage-stage to a blastocyst-stage transfer policy for all patients in the IVF clinic

STUDY QUESTION Is a stepwise change management approach an efficacious method to move from a Day 3 transfer policy to a Day 5 transfer policy for all patients in an IVF program? SUMMARY ANSWER A stepwise change from a Day 3 to a Day 5 transfer policy maintained the live birth rates per oocyte collection cycle (OCC) of the IVF program, with increased single embryo transfer (SET) and reduction of twin pregnancies. WHAT IS KNOWN ALREADY Evidence has shown that the probability of a live birth following IVF with a fresh embryo transfer (ET) is significantly higher after blastocyst-stage transfer than after cleavage-stage transfer. Blastocyst culture and transfer are usually performed in cases of good prognosis patients but many centers keep transferring cleavage-stage embryos for most of their patients because of the higher transfer cancelation rate in a blastocyst transfer policy. STUDY DESIGN, SIZE, DURATION In January 2012, a Day 5 embryo culture and blastocyst transfer policy including vitrification of supernumerary Day 5 blastocysts were implemented in a stepwise approach. The retrospective descriptive single-center analysis involving a preintervention phase consisted of Day 3 ETs and Day 3 slow freezing from 2010 until 2012. The postintervention phase involved a 6-year period from 2012 until 2017 in which three consecutive changes in the transfer policy were made, each over a 2-year period, based on the number of zygotes on Day 1. The primary outcome was live birth delivery rate per OCC during the stepwise change. PARTICIPANTS/MATERIALS, SETTING, METHODS All patients with at least one zygote available on Day 1 were scheduled for a fresh transfer, either on Day 3 or 5. Cycles with preimplantation genetic testing, freeze-all and oocyte donation cycles and cycles with a Day 2 transfer in the preintervention period were excluded. In the preintervention group, all cycles were scheduled for Day 3 transfer (n = 671 OCC) and slow freezing of the remaining Day 3 embryos. In the postintervention period, three periods were analyzed: period 1 (n = 1510 OCC; 1–9 zygotes: Day 3 transfer and &gt;9 zygotes: Day 5 transfer); period 2 (n = 1456 OCC; 1–4 zygotes: Day 3 transfer and &gt;4 zygotes: Day 5 transfer) and period 3 (n = 1764 OCC; Day 5 transfer). All remaining embryos underwent extend culture and were vitrified on Day 5, if developed to at least an early blastocyst. Data were analyzed using a mixed regression model with patient as a random factor. MAIN RESULTS AND THE ROLE OF CHANCE In the preintervention group, all OCC were scheduled for a Day 3 transfer. In period 1, period 2 and period 3, 20.9%, 61.5% and 100% of the OCCs were scheduled for a Day 5 transfer, respectively. More transfers per OCC were canceled in the postintervention period 2 and period 3 compared to the preintervention period (5.3% and 18.7% versus 3.4%, respectively; P &lt; 0.0001). The mean number of embryos used per transfer decreased gradually after the introduction of the Day 5 transfer policy, from 1.62 ± 0.65 in the preintervention group to 1.12 ± 0.61 in period 3 (P &lt; 0.0001). The percentage of SET cycles increased from 48.4% in the preintervention group to 54.6%, 73.8% and 87.8% in period 1, period 2 and period 3, respectively (P &lt; 0.0001). The mean number of cryopreserved surplus embryos was significantly lower in period 3 compared to the preintervention group (1.29 ± 1.97 versus 1.78 ± 2.80; P &lt; 0.0001). Pregnancy and live birth delivery rate per fresh transfer, respectively, were significantly lower in the preintervention group (26.7% and 19.1%) as compared to period 3 (39.3% and 24.2%) (P &lt; 0.0001). Twin pregnancy rate decreased gradually from 11.0% to 8.2%, 5.7% and 2.5% in the preintervention group, period 1, period 2 and period 3, respectively (P &lt; 0.0001). Live birth rate and cumulative live birth delivery rates per OCC were significantly higher in group 2 compared to the preintervention period (25.6% and 35.8% versus 18.5% and 25.9%, respectively). Similar live birth and cumulative live birth delivery rates per OCC were achieved between the preintervention period and period 3 (18.5% and 25.6% versus 19.7% and 24.9%; respectively). LIMITATIONS, REASONS FOR CAUTION The primary limitation is the retrospective design of the study. The allocation of the cycles was done by the number of zygotes available without taking into account both embryological and clinical prognostic factors. Furthermore, the analysis was restricted to cycles where the standard transfer policy was followed. Embryos which were in the morula or compaction stage were not vitrified or cultured to Day 6, which could have contributed to the slight, not statistically significant, drop in live birth rate per OCC in group 3. WIDER IMPLICATIONS OF THE FINDINGS Live birth and cumulative live birth delivery rate per OCC in an unselected patient population is maintained in a Day 5 transfer policy compared to a Day 3 transfer policy. Additionally, a significantly reduction in twin pregnancy rate and a significant increase in SET were observed in a Day 5 transfer policy. For centers wanting to make the step from Day 3 to Day 5, this study provides a practical stepwise change management approach. STUDY FUNDING/COMPETING INTEREST(S) None. TRIAL REGISTRATION NUMBER None.