Impact of inclusion of a poor-quality embryo with a good-quality embryo on pregnancy outcomes in vitrified-warmed blastocyst transfers.

RESEARCH QUESTION: Does the co-transfer of a good-quality embryo and a poor-quality embryo influence pregnancy outcomes in comparison to the transfer of a single good-quality embryo in vitrified-warmed blastocyst transfer cycles? DESIGN: This retrospective cohort study involved a total of 11,738 women who underwent IVF/intracytoplasmic sperm injection cycles and vitrified-warmed blastocyst transfer at a tertiary-care academic medical from January 2015 to June 2022. The study population was categorized into two groups: single-blastocyst transfer (SBT; participants who underwent single good-quality embryo transfer, n = 9338) versus double-blastocyst transfer (DBT; participants who underwent transfers with a poor and a good-quality embryo, n = 2400). RESULTS: The live birth rate (LBR) was significantly higher in the DBT group in comparison with the SBT group (65.6% versus 56.3%, P < 0.001). Multivariable logistic regression analysis showed that DBT was an independent predictor for LBR with a strong potential impact (adjusted odds ratio 1.55, 95% confidence interval 1.41-1.71; P < 0.001). However, the multiple birth rate was significantly higher in the good-quality embryo and poor-quality embryo group compared with patients undergoing a single good-quality embryo transfer (41.4% versus 1.8%; P < 0.001). CONCLUSIONS: In vitrified-warmed blastocyst transfer cycles, LBR was higher following DBT with one good-quality and one poor-quality embryo compared with SBT. However, this was at the expense of a marked increase in the likelihood of multiple gestations. Physicians should still balance the benefits and risks of double-embryo transfer.

Spontaneously hatching human blastocyst is associated with high development potential and live birth rate in vitrified-warmed single blastocyst transfer: A retrospective cohort study.

OBJECTIVE: To investigate the effect of hatching status on predicting pregnancy outcomes in single vitrified-warmed blastocyst transfer (SVBT) by objectively subdividing pre-implantation blastocysts according to hatching status. METHODS: This retrospective study included 817 SVBT cycles performed between January 2016 and December 2017. Transferred embryos were categorized according to their hatching status as follows: group I (n = 147), non-hatching blastocysts; group II (n = 484), hatching blastocysts; and group III (n = 186), completely hatched blastocysts. Hatching blastocysts (group II) were then classified based on the ratio of the blastocystic diameter outside and inside the zona pellucida into early (n = 185), mid- (n = 103), and late (n = 196) hatching stages. Implantation rate (IR), clinical pregnancy rate (CPR), live birth rate (LBR), multiple pregnancy rate (MPR), miscarriage rate, and neonatal outcomes were evaluated. RESULTS: For groups I, II, and III, respectively, the results were as follows: IR (28.6%, 43.6%, and 53.8%; P < 0.001), CPR (27.9%, 42.8%, and 53.2%; P < 0.001), and LBR (23.1%, 32.0%, and 42.5%; P < 0.001). Group III had better IR, CPR, and LBR. Among hatching blastocysts, late-hatching blastocysts had the highest IR (33.5%, 46.6%, and 51.5% for early, mid-, and late hatching, respectively; P = 0.002) and CPR (33.0%, 45.6%, and 50.5%; P = 0.002), with a tendency for a higher rate of LBR. Neonatal outcomes were not influenced by the hatching status. CONCLUSION: Advanced hatching status is positively associated with a higher rate of clinical pregnancy and live birth with no negative effects on neonatal outcomes. Additionally, the quantitative classification of hatching status was found to be predictive of pregnancy outcomes.

Correlation between an annotation-free embryo scoring system based on deep learning and live birth/neonatal outcomes after single vitrified-warmed blastocyst transfer: a single-centre, large-cohort retrospective study.

PROPOSE: Does an annotation-free embryo scoring system based on deep learning and time-lapse sequence images correlate with live birth (LB) and neonatal outcomes? METHODS: Patients who underwent SVBT cycles (3010 cycles, mean age: 39.3 ± 4.0). Scores were calculated using the iDAScore software module in the Vitrolife Technology Hub (Vitrolife, Gothenburg, Sweden). The correlation between iDAScore, LB rates, and total miscarriage (TM), including 1st- and 2nd-trimester miscarriage, was analysed using a trend test and multivariable logistic regression analysis. Furthermore, the correlation between the iDAScore and neonatal outcomes was analysed. RESULTS: LB rates decreased as iDAScore decreased (P < 0.05), and a similar inverse trend was observed for the TM rates. Additionally, multivariate logistic regression analysis showed that iDAScore significantly correlated with increased LB (adjusted odds ratio: 1.811, 95% CI: 1.666-1.976, P < 0.05) and decreased TM (adjusted odds ratio: 0.799, 95% CI: 0.706-0.905, P < 0.05). There was no significant correlation between iDAScore and neonatal outcomes, including congenital malformations, sex, gestational age, and birth weight. Multivariate logistic regression analysis, which included maternal and paternal age, maternal body mass index, parity, smoking, and presence or absence of caesarean section as confounding factors, revealed no significant difference in any neonatal characteristics. CONCLUSION: Automatic embryo scoring using iDAScore correlates with decreased miscarriage and increased LB and has no correlation with neonatal outcomes.

The effect of vitrified-warmed blastocyst transfer on postnatal growth: a 1-year follow-up questionnaire study.

RESEARCH QUESTION: Is postnatal growth of singletons aged 12 months born after vitrified-warmed blastocyst transfer (frozen embryo transfer [FET]) different from children born after fresh blastocyst transfer? DESIGN: A retrospective cohort study conducted at a single university-affiliated obstetrics and fertility centre between 2014 and 2016. Women who underwent fresh transfer or FET at blastocyst stage and obtained a singleton live birth were included. Propensity score inverse probability weighting was used to balance baseline maternal characteristics between fresh and FET cycles. RESULTS: Of the 382 women with singleton live births, 124 underwent a fresh blastocyst transfer and 258 underwent a FET. Significantly higher birth weight and length z-scores were observed after FET (P = 0.01 and P = 0.002, respectively) compared with the fresh transfer group. At 12 months of age, the fresh and FET groups showed no significant effect on the weight z-score, but the FET was associated with a higher height z-score (P = 0.001) compared with fresh blastocyst transfer. The comparison between males and females from the same study group showed higher birth weight z-score for males in the FET group (P < 0.001). During the first 12 months, however, males in the FET group showed a slower growth trajectory in terms of weight (P = 0.007). CONCLUSIONS: At 12 months of postnatal life, an increased height and sex-dependent differences in growth trajectories were observed in singletons born after FET compared with those born after fresh embryo transfer.

Efficiency and safety of laser-assisted hatching on vitrified-warmed blastocyst transfer cycles: a prospective control trial.

To clarify the efficiency and safety of laser-assisted hatching (LAH) application on vitrified-warmed blastocyst transfer (VBT) cycles, we designed the non-randomized concurrent control trial included 4039 VBT cycles in the Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, during the even days from November 2014 to December 2015. The VBT cycles were divided into LAH group (n = 1932) and non-LAH group (n = 2107) according to the date of blastocyst thawing. Laser-partial zona pellucida dissection was performed on all blastocysts thawed on that day every 4 days, and those blastocysts were assigned to the LAH group. There were a higher biochemical pregnancy rate (66.87% vs 63.69%; P = 0.034; rate ratio for LAH vs non-LAH group [RR], 1.050; 95% confidence interval [CI], 1.004-1.098) and an increased live birth rate (48.81% vs 45.51%; P = 0.036; RR, 1.072; 95% CI, 1.005-1.145) with comparable ectopic pregnancy, twin or multiple pregnancies, spontaneous abortion and birth defect rates of the LAH group than those of the non-LAH group. Subgroup analysis showed that live birth rate, birth defect rate, and other pregnancy outcomes were comparable for patients younger than 35 years when blastocyst transfer, patients with endometrium thickness less than 0.9 cm during ovulation or the initiation of progesterone treatment, ICSI blastocysts, AC or BC blastocysts according to Gardner morphological criteria and day 5 blastocysts of the LAH group than it of non-LAH group. LAH could be performed selectively on vitrified-warmed blastocysts before transfer for better pregnancy outcomes. Trial registration number: ChiCTR2000032975. Date of registration: May 17, 2020. Retrospectively registered.

Pregnancy prediction performance of an annotation-free embryo scoring system on the basis of deep learning after single vitrified-warmed blastocyst transfer: a single-center large cohort retrospective study.

OBJECTIVE: To analyze the performance of an annotation-free embryo scoring system on the basis of deep learning for pregnancy prediction after single vitrified blastocyst transfer (SVBT) compared with the performance of other blastocyst grading systems dependent on annotation or morphology scores. DESIGN: A single-center large cohort retrospective study from an independent validation test. SETTING: Infertility clinic. PATIENT(S): Patients who underwent SVBT cycles (3,018 cycles, mean ± SD patient age 39.3 ± 4.0 years). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The pregnancy prediction performances of each embryo scoring model were compared using the area under curve (AUC) for predicting the fetal heartbeat status for each maternal age group. RESULT(S): The AUCs of the <35 years age group (n = 389) for pregnancy prediction were 0.72 for iDAScore, 0.66 for KIDScore, and 0.64 for the Gardner criteria. The AUC of iDAScore was significantly greater than those of the other two models. For the 35-37 years age group (n = 514), the AUCs were 0.68, 0.68, and 0.65 for iDAScore, KIDScore, and the Gardner criteria, respectively, and were not significantly different. The AUCs of the 38-40 years age group (n = 796) were 0.67 for iDAScore, 0.65 for KIDScore, and 0.64 for the Gardner criteria, and there were no significant differences. The AUCs of the 41-42 years age group (n = 636) were 0.66, 0.66, and 0.63 for iDAScore, KIDScore, and the Gardner criteria, respectively, and there were no significant differences among the pregnancy prediction models. For the >42 years age group (n = 389), the AUCs were 0.76 for iDAScore, 0.75 for KIDScore, and 0.75 for the Gardner criteria, and there were no significant differences. Thus, iDAScore AUC was either the highest or equal to the highest AUC for all age groups, although a significant difference was observed only in the youngest age group. CONCLUSION(S): Our results showed that objective embryo assessment by a completely automatic and annotation-free model, iDAScore, performed as well as or even better than more traditional embryo assessment or annotation-dependent ranking tools. iDAScore could be an optimal pregnancy prediction model after SVBT, especially in young patients.

Embryo Selection Based on Morphological Parameters in a Single Vitrified-Warmed Blastocyst Transfer Cycle.

The process of selecting a good quality embryo to improve the pregnancy outcomes is very important. The aim of our study was to elaborate the embryo selection process in a single vitrified-warmed blastocyst transfer (VBT) cycle by analyzing pre-vitrified and post-warmed blastocyst morphological factors to improve pregnancy outcomes. In this retrospective cohort study, we performed 329 single VBT cycles. The pre-vitrified and post-warmed morphological factors of all blastocysts were analyzed. Logistic regression analysis was conducted to select the independent morphological factor associated with ongoing pregnancy. The expansion of blastocoel (mid blastocoel; aOR 2.27, 95% CI.0.80-6.42, p = 0.12, expanded blastocoel; aOR 3.15, 95% CI.1.18-8.44, p = 0.02) in a pre-vitrified blastocyst and the grade of inner cell mass (ICM) (grade B; aOR 0.47, 95% CI.0.27-0.83, p = 0.01, grade C; aOR 0.22, 95% CI 0.09-0.56 p < 0.01) in post-warmed blastocysts significantly predicted the ongoing pregnancy. After fertilization, the embryo developed as a blastocyst on day 5 (day 5) showed a higher ongoing pregnancy than that on day 6 (day 6) (aOR 0.50, 95% CI.0.26-0.94, p = 0.03). The results suggest that while selecting a vitrified-warmed blastocyst in a single VBT cycle, the day 5 vitrified blastocyst should be considered, and a higher expansion grade in the pre-vitrified blastocyst should be selected. Our study has shown that post-warmed ICM grade tends to be a predictive indicator for the selection of the best blastocyst and allows for successful pregnancy, with ongoing pregnancy in a single blastocyst transfer.

Does duration of cryostorage affect survival rate, pregnancy, and neonatal outcomes? Large-scale single-center study of slush nitrogen (SN2 ) vitrified-warmed blastocysts.

OBJECTIVE: To evaluate the effects of the duration of cryostorage on clinical outcomes after embryo transfer of vitrified blastocysts stored in an open-device slush-nitrogen (SN2 ) system. METHODS: A retrospective cohort study was carried out on 1632 autologous vitrified-warmed blastocyst transfer cycles between January 2013 and June 2014. Duration of cryostorage was divided into four groups: Group I: 0-6 months (n=937); Group II: 7-12 months (n=299); Group III: 13-24 months (n=165); and Group IV: ≥25 months (n=231). The effects of the duration of cryostorage on the survival rate (SR), clinical pregnancy rate (CPR), live birth rate (LBR), and neonatal outcomes of vitrified blastocysts stored in an open-device SN2 system were evaluated. RESULTS: There were no significant differences between groups in SR, CPR, LBR, and neonatal outcomes after autologous vitrified-warmed blastocyst transfer. Multivariate logistic regression analysis showed no effect on LBR from duration of cryostorage. CONCLUSION: Vitrification using SN2 and long-term cryostorage in an open-device system are safe and effective and do not significantly affect clinical outcomes after embryo transfer.

Establishment of day 7 blastocyst freezing criteria using blastocyst diameter for single vitrified-warmed blastocyst transfer from live birth outcomes: a single-center, large cohort, retrospectively matched study.

PURPOSE: To establish blastocyst freezing criteria for day 7 blastocyst (day 7 BL) for single vitrified-warmed blastocyst transfer (SVBT) by examining the diameter of blastocysts. METHODS: Patients who underwent day 7 BL transfer cycles (1143 cycles, mean age: 38.5 ± 3.5) and randomly selected patients after 1:1 matching who underwent day 6 BL transfer cycles and day 2-single-embryo transfer (SET) cycles were used for analysis. Comparison of the miscarriage (per clinical pregnancy) and live birth rates were made among day 2-SET, day 7 BL, and day 6 BL. These blastocyst groups were stratified into six groups based on blastocyst diameter, namely, 180 µm, 190 µm, 200 µm, 210 µm, over 220 µm, and hatched, for making the freezing criteria. RESULTS: For each diameter, 180 µm, 190 µm, 200 µm, 210 µm, over 220 µm, and hatched, the live birth rates of day 7 BL after SVBT were 9.0%, 11.9%, 11.5%, 15.6%, 20.0%, and 19.9%, respectively. Compared with the 14.6% live birth rate of the day 2-SET group, the live birth rate of 220 µm day 7 BL was significantly higher (P < 0.05) and was around the same in other diameter groups. CONCLUSION: Our study demonstrates that sufficient live birth rates can be obtained after SVBT even from blastocysts on day 7 when blastocysts were vitrified at expanded blastocyst stage of over 180 µm of diameter or at hatched blastocyst stage and were transferred at the optimal time. This is the first study to establish a day 7 blastocyst freezing criteria using blastocyst diameter, which is an objective assessment way.

Cumulative live birth rate after GnRH agonist trigger and elective cryopreservation of all embryos in high responders.

Elective embryo cryopreservation after using gonadotrophin-releasing hormone (GnRH) antagonist protocols and GnRH agonist triggering is becoming an increasingly important part of medically assisted reproduction. We designed a single-centre retrospective study to assess the cumulative probability of achieving a live birth through consecutive transfers of vitrified-warmed blastocysts after elective embryo cryopreservation in high-responding patients. Hence, 123 women identified to be at high risk for developing ovarian hyperstimulation syndrome were included. They were stimulated using GnRH antagonist protocol, and GnRH agonist was used to trigger final oocyte maturation. All embryos were vitrified at the blastocyst stage and transferred in the subsequent menstrual cycles. Using the Kaplan-Meier survival analysis, a total of 65.9% (95% CI 57.5 to 74.3) women achieved a live birth after a maximum of six embryo transfer cycles using the 'conservative' approach. Applying the 'optimistic' approach, presuming that women who still had cryopreserved embryos and did not return for embryo transfer had the same chance of achieving a live birth as those returning for transfer, the cumulative live birth rate estimated in six embryo transfer cycles was 76.6% (95% CI 69.1 to 84.1). No cases of severe ovarian hyperstimulation syndrome were recorded.

Clinical outcomes after IVF or ICSI using human blastocysts derived from oocytes containing aggregates of smooth endoplasmic reticulum.

In this study the clinical and neo-natal outcomes after transfer of blastocysts derived from oocytes containing aggregates of smooth endoplasmic reticulum (SER) were compared between IVF and intracytoplasmic sperm injection (ICSI) cycles. Clinical and neo-natal outcomes of blastocysts in cycles with at least one SER metaphase II oocyte (SER + MII; SER + cycles) did not significantly differ between the two insemination methods. When SER + MII were cultured to day 5/6, fertilization, embryo cleavage and blastocyst rates were not significantly different between IVF and ICSI cycles. In vitrified-warmed blastocyst transfer cycles, the clinical pregnancy rates from SER + MII in IVF and ICSI did not significantly differ. In this study, 52 blastocysts (27 IVF and 25 ICSI) derived from SER + MII were transferred, yielding 15 newborns (5 IVF and 10 ICSI) and no malformations. Moreover, 300 blastocysts (175 IVF and 125 ICSI) derived from SER-MII were transferred, yielding 55 newborns (24 IVF and 31 ICSI cycles). Thus, blastocysts derived from SER + cycles exhibited an acceptable ongoing pregnancy rate after IVF (n = 125) or ICSI (n = 117) cycles. In conclusion, blastocysts from SER + MII in both IVF and ICSI cycles yield adequate ongoing pregnancy rates with neo-natal outcomes that do not differ from SER-MII.