OBJECTIVE: To investigate the impact of heterogeneity in patient indications or insemination protocols on neonatal outcomes of singletons following early rescue ICSI (rICSI) treatments.
METHODS: A retrospective study was conducted. Propensity score matching and multivariable logistic regression were used to adjust for confounders and biases.
RESULTS: A total of 9095 IVF patients, 2063 ICSI patients, and 642 early rICSI patients were included in the study. No differences were detected in neonatal outcomes except small for gestational age (SGA) which increased in early rICSI patients compared with both unmatched and matched IVF groups with the risk ratio (RR) of 1.31 (95% CI: 1.05, 1.64) and 1.49 (95% CI: 1.05, 2.12). Further analysis showed that SGA increased significantly in partial fertilization failure (PFF) cycles with RRs of 1.56 (95% CI: 1.08, 2.27) and 1.78 (95% CI: 1.22, 2.59) compared with both unmatched and matched IVF patients but not in TFF patients. A positive association between fertilization rate via IVF and birth weight z-score was revealed in the PFF patients.
CONCLUSIONS: Early rICSI in patients with total fertilization failure (TFF) appeared to be safe in terms of neonatal outcomes. However, when expanding the indications of rICSI to PFF patients, the SGA in the offspring increased, suggesting a potential effect on long-term health. Since other treatment options, such as using only the IVF-origin embryos still exist for these patients, further studies were needed to confirm the optimal decision for these patients.

OBJECTIVE: Is early rescue ICSI (E-RICSI) an effective and safe technique compared to conventional ICSI?
CONCLUSIONS: Despite the higher multi-pronucleus (PN) rate compared to conventional ICSI, E-RICSI did not add extra risks to clinical and neonatal outcomes.
BACKGROUND: Based on the finding that the second polar body was released in 80% of fertilized oocytes by 4 h after exposure to spermatozoa and in ∼90% of fertilized oocytes by 6 h, E-RICSI brings forward the timing of rescue ICSI to 6 h after initial insemination, and effectively prevents oocyte aging and embryo-uterus asynchrony. However, some researchers still voice concerns about the efficacy and safety of E-RICSI, and comparative studies are limited.
UNASSIGNED: A retrospective cohort study was conducted on patients who underwent conventional ICSI or E-RICSI treatment between January 2015 and December 2020 at a university-affiliated hospital. Using 1:1 propensity score matching, 1496 cases entered each group.
METHODS: In total, 1496 couples undergoing conventional ICSI oocyte retrieval cycles and 1496 undergoing E-RICSI oocyte retrieval cycles were enrolled in this study, and basic clinical characteristics, embryologic data, clinical outcomes and neonatal data were compared between groups. The embryos in the E-RICSI group were divided into two subgroups: those fertilized by iIVF (IVF subgroup) and those fertilized by E-RICSI (E-RICSI subgroup); the embryologic data, clinical outcomes, and neonatal data for these subgroups were also compared with the conventional ICSI group. Logistic regression was used for statistical analysis with potential confounder adjustment.
RESULTS: The 2PN rate, blastocyst formation rate, and viable blastocyst formation rate of the E-RICSI group were significantly lower compared to the conventional ICSI group (2PN rate: P < 0.001; blastocyst formation rate: P < 0.001; viable blastocyst formation rate: P = 0.004), and the multi-PN rate in the E-RICSI group was significantly higher than the conventional ICSI group (P < 0.001). However, the number of 2PN embryos, normal cleavage embryo rate, Day 3 high-quality cleavage embryo rate, and high-quality blastocyst rate were similar between groups. When considering the IVF embryos and E-RCSI embryos in the E-RICSI group independently, the 2PN rate of the conventional ICSI group was significantly lower than E-RICSI subgroup but higher than the IVF subgroup, whereas the blastocyst formation rate and viable blastocyst formation rate were higher than E-RICSI embryos but comparable to IVF embryos. As for the clinical and neonatal outcomes, the implantation rate of the E-RICSI subgroup was significantly lower than the IVF subgroup but comparable to the conventional ICSI group, while the low birthweight (LBW) rate was significantly lower compared with the conventional ICSI group but similar with the IVF subgroup. No other differences were observed among the three groups for cumulative clinical pregnancy rate, cumulative live birth rate, and the pregnancy outcomes per transfer including clinical pregnancy, ectopic pregnancy, miscarriage, and live birth, either in fresh or frozen embryo transfer cycles. Furthermore, neonatal outcomes, including cesarean section, sex ratio, LBW, preterm birth, and macrosomia, were similar among groups.
CONCLUSIONS: This study is limited by the retrospective design, limited sample size, and short follow-up period. However, our study underlies the need for large-scale, multi-center randomized controlled trials with long-term follow-up.
CONCLUSIONS: Short-term insemination (3 h) combined with E-RICSI may be a safe and effective method to prevent the occurrence of total fertilization failure, and patients with normal or borderline sperm could be encouraged to try IVF first.
BACKGROUND: This study was supported by grants from the National Key & Development Program of China (No. 2021YFC2700603) and the National Natural Science Foundation of China (No. 81801443). The authors declare no conflicts of interest.
BACKGROUND: N/A.

OBJECTIVE: To determine the utility of short gamete coincubation in in vitro fertilization (IVF-S) combined with early rescue intracytoplasmic sperm injection (R-ICSI) and split IVF-ICSI in preventing low fertilization based on a retrospective cohort study.
METHODS: Couples with a high risk of low IVF fertilization during the first ART cycle underwent IVF-S with R-ICSI or split IVF-ICSI. Fertilization rate, embryo quality, and clinical outcomes were measured.
RESULTS: After propensity score matching, we included 188 couples in the IVF-S with R-ICSI group as Group 1 and 720 in the split IVF-ICSI group as Group 2. Normal fertilization rates were similar; however, Group 1 had a higher multiple pronuclei rate (10.42% vs. 4.50%, p < 0.001) but a higher embryo utilization rate (59.84% vs. 53.60%, p < 0.001). The groups were similar in the rates of high-quality embryos, embryo implantation, clinical pregnancy, and live birth. Low IVF fertilization rate was 4.79% and 9.03% in Group 1 and Group 2, respectively, with similar fertilization rate and embryo development.
CONCLUSIONS: IVF-S with early R-ICSI and split IVF-ICSI were effective strategies in preventing low fertilization rate. IVF-S with early R-ICSI could become the preferred approach because of its advantages-higher embryo utilization rate, fewer ICSI procedures, similar clinical pregnancy rate, and live birth rate.

OBJECTIVE: The objective of this retrospective study was to evaluate clinical outcomes of early cumulus cells removal and early rescue intracytoplasmic sperm injection (ICSI) in high-risk patients of fertilization failure during human in vitro fertilization (IVF).
METHODS: A total of 5,518 patients were enrolled between January 2014 to December 2016. Of which 505 couples performed short insemination with >30% fertilization rate were included in short-term IVF group, 102 patients detected total fertilization failure (TFF) were treated with early rescue ICSI (R-ICSI group), and 4911 couples underwent conventional IVF with overnight co-incubation of gametes (traditional IVF group). The clinical outcomes were analyzed among the three groups.
RESULTS: The embryo implantation rates (40.34%, 39.78% and 42.42% for traditional, short-term IVF and R-ICSI groups, respectively) were comparable in the three groups. The clinical pregnancy rates among traditional IVF group, short-term IVF group and R-ICSI group were 57.95%, 57.03% and 60.78%, respectively, and the difference among three groups didn\'t reach significance.
CONCLUSIONS: The present study indicated that short insemination had no detrimental effects on clinical outcomes in human IVF and could prevent the occurrence of TFF combined with early rescue ICSI for high-risk patients of fertilization failure, which attained acceptable pregnancy outcomes.

OBJECTIVE: To evaluate the safety and efficacy of early rescue intracytoplasmic sperm injection (ICSI).
METHODS: Retrospective cohort study.
METHODS: Teaching hospital.
METHODS: There were 13,232 ovarian stimulation cycles (IVF, n = 9,631; ICSI, n = 2,871; early rescue ICSI, n = 730) that resulted in the delivery of 5,001 babies (IVF, n = 3,670; ICSI, n = 1,095; early rescue ICSI, n = 246) from August 2008 to August 2013.
METHODS: Early rescue ICSI.
METHODS: Clinical pregnancy rates, neonatal outcomes, and congenital birth defects were analyzed.
RESULTS: The early rescue ICSI cycles did not seem to have a negative effect on the clinical pregnancy rate (43.42%) when IVF cycles (45.33%) were compared with ICSI cycles (44.39%). In the early rescue ICSI group, a total of 254 clinical pregnancies were achieved: 197 (33.67%) live births, 38 (6.49%) miscarriages, 2 (0.79%) induced abortions, 3 (1.18%) fetal deaths, and 4 pregnancies (1.57%) without completion at follow-up. Overall, the multiple gestations, the delivery method, mean gestational age, preterm deliveries, mean birth weight, and rate of congenital birth defects of the early rescue ICSI group were similar to those in the conventional IVF and ICSI groups.
CONCLUSIONS: Early rescue ICSI had similar clinical pregnancy rates when compared with conventional IVF and ICSI, in addition to the delivery of healthy children. The clinical evidence from the early rescue ICSI group did not show an elevated rate of malformations. Early rescue ICSI seems to be a safe alternative method for individuals with total fertilization failure or near total fertilization failure when compared with conventional IVF treatment.