Rescue Intracytoplasmic Sperm Injection Research Articles

Rescue ICSI Improved Cumulative Live Birth Rate for Cycles with Second Polar Body Extrusion Rate

ObjectiveTo determine the indications for early rescue intracytoplasmic sperm injection (ICSI) application. DesignA retrospective cohort study SubjectsThe study included 19,808 patients who underwent conventional in vitro fertilization (IVF) or rescue ICSI for their first cycles between February 2017 and December 2021. ExposureRescue ICSI cycles constituted the study group, where oocytes that had not extruded the second polar body 4-6 hours after insemination were rescued by ICSI. The control group consisted of conventional IVF cycles with no interventions to rescue oocytes without the second polar body. Generalized additive models (GAMs) were constructed to describe the relationship between the second polar body extrusion rate and cumulative live birth rate in conventional IVF and rescue ICSI cycles, respectively. The cutoff value of the second polar body extrusion rate guiding rescue ICSI application was determined from the intersection point of GAMs. Maternal age range applicable to rescue ICSI was further analyzed using the same method. Clinical outcomes were compared between conventional IVF and rescue ICSI cycles across different second polar body extrusion rate and maternal age subgroups. Main outcome measuresThe second polar body extrusion rate and maternal age range for rescue ICSI application, normal fertilization rate, and cumulative live birth rate. ResultsGAMs showed that the cutoff value for the second polar body extrusion rate about rescue ICSI application was 50%. When the rate <50%, normal fertilization rate and cumulative live birth rate (63.7% vs. 46.1%, OR: 1.609, 95% CI: 1.276-2.030) were significantly higher in rescue ICSI cycles than conventional IVF cycles. When the rate ≥50%, rescue ICSI cycles had similar normal fertilization rate and cumulative live birth rate compared to conventional IVF cycles. Further analysis on maternal age in cycles with second polar body extrusion rate <50% released that rescue ICSI cycles showed a higher cumulative live birth rate (67.7% vs. 48.3%, OR: 1.732, 95% CI: 1.361-2.202) than conventional IVF cycles for women aged < 38 years. ConclusionIVF cycles with second polar body extrusion rate <50% in women aged < 38 years was applicable to early rescue ICSI.

P-126 The impact of ICSI versus IVF on the reproductive outcomes of couples with non-male factor infertility and frozen-thawed embryo transfer cycles

Abstract Study question Does Intracytoplasmic Sperm Injection (ICSI) improve reproductive outcomes in patients with non-male factor infertility undergoing Frozen-Thawed Embryo Transfer (FET) treatment? Summary answer ICSI showed slightly improved clinical outcomes compared to IVF, but was associated with higher preterm birth rates and low birthweight when twins were born. What is known already The use of ICSI has seen a significant surge globally, particularly in Europe and the USA, as a solution for fertilization failure resulting from male factor infertility. FET presents a viable option for those considering additional children. Numerous studies have investigated the effectiveness of ICSI in couples with non-male factor infertility undergoing fresh embryo transfer in ovarian stimulation cycles. However, there is a dearth of evidence demonstrating whether ICSI, compared to conventional IVF (cIVF), could influence reproductive outcomes in couples with non-male factor infertility undergoing FET treatment. Study design, size, duration This retrospective cohort study included 10,143 cycles from 6,206 couples who underwent FET at the Third Affiliated Hospital of Zhengzhou University between January 2016 and September 2022. Participants/materials, setting, methods Patients were categorized into two groups based on the insemination methods used for the transferred embryos. Patients were excluded if : 1) Embryos were biopsied and tested; 2) Oocytes had been vitrified; 3) Embryos were derived from donor oocytes, AOA treatment, or rescue ICSI; 4) Embryos that were not transferred; and 5) They had undergone fresh embryo transfer. PSM at a ratio of 1:1 was utilized to ensure comparability of reproductive outcomes. Main results and the role of chance Post-PSM, the general characteristics were comparable across both groups. The clinical pregnancy rates (37.6% vs 40.0%, P = 0.311), miscarriage rates (21.4% vs 23.1%, P = 0.597), and live birth rates (28.2% vs 30.4%, P = 0.329) exhibited no significant disparity post-PSM between the two groups. Notably, a marginally elevated live birth rate was observed in the ICSI group when blastocysts were transferred to the women (39.8% vs 48.3%, P = 0.050). However, the GEE models indicated that ICSI did not enhance the likelihood of clinical pregnancy, miscarriage, and live birth relative to IVF in women with non-male factor infertility. Following adjustments for variables, ICSI yielded consistent OR values [1.14(0.92-1.42), P = 0.241; 1.08(0.72-1.61), P = 0.703; and 1.16(0.92-1.46), P = 0.220, respectively]. The perinatal outcomes were similar between the two grousps. However, a significantly higher incidence of preterm birth was observed in the ICSI group compared to the cIVF group (20.0% vs 12.5%, P = 0.026). While pregnancy complications were comparable between the two groups, neonates born as twins in the ICSI group exhibited significantly reduced live birth-weight [2520.8(572.9) vs 2691.9(423.7), P = 0.043] and birth length [47.5(2.8) vs 48.5(2.3), P = 0.031]. Correspondingly, the rate of low birthweight was significantly higher in the ICSI group (38.9% vs 21.0%, P = 0.025). Limitations, reasons for caution The retrospective design may lead to selection bias among the included patients. The use of ICSI in ART has been strictly regulated in our country, limiting the sample size and potentially reducing the statistical power. Wider implications of the findings The value of ICSI should be thoroughly discussed with patients with non-male factor infertility before ovarian stimulation. Further research is needed to better understand the impact of ICSI on reproductive and neonatal outcomes in this population. Trial registration number 2021YFC2700602

O-186 A novel micro-insemination method, assisted sperm fusion insemination, increases the embryo utilization rate compared to conventional intracytoplasmic sperm injection

Abstract Study question Does a novel micro-insemination method, assisted sperm fusion insemination (ASFI), improve fertilization and embryonic development compared to conventional intracytoplasmic sperm injection (C-ICSI)? Summary answer ASFI showed comparable fertilization and blastocyst formation rates to C-ICSI, while achieving significantly higher embryo utilization rates. Furthermore, there were no degenerated oocytes after ASFI. What is known already We have reported that ASFI yielded fertilization and blastocyst rates similar to those obtained with rescue ICSI performed at 6 hours after in vitro fertilization (IVF). In ASFI, fertilization is achieved by pressing a zona pellucida (ZP)-bound sperm onto the oocyte membrane without breaking the oocyte membrane. However, there was a risk of artificial polyspermy because the sperm were pressed against the unfertilized oocytes after IVF. Moreover, it is uncertain whether fertilization occurred with sperm that penetrated into the oocyte via IVF or that were pressed against the oocyte membrane. Clarifying this requires performing ASFI of the oocyte without IVF. Study design, size, duration We prospectively evaluated the effectiveness of ASFI in a sibling oocyte study including 14 subjects from which at least two metaphase II (MII) oocytes and one immature or degenerated oocyte were retrieved. Between December 2022 and October 2023, 119 MII oocytes were obtained in 22 oocyte retrieval cycles and used in the study. Sibling MII oocytes were randomly assigned to a C-ICSI or ASFI group. The present study was approved by the local ethics committee. Participants/materials, setting, methods In the ASFI group, 10,000 motile sperm were incubated with at least one immature or degenerated oocyte for 3 hours in 100 μL of medium per patient. After incubation, the motile sperm bound to the ZP were aspirated directly using an injection pipette. The heads of these ZP-bound sperm were pressed onto the membrane of MII oocytes for 10 seconds using the injection pipette. C-ICSI was conducted using the conventional method. Main results and the role of chance The mean and standard deviation of age of the women and number of MII oocytes per cycle were 39.9 ± 2.2 years and 5.5 ± 1.8, respectively. All sperm collected from the ZP adhered to the MII oocyte membrane after ASFI. Furthermore, time-lapse imaging revealed that all sperm adhering to the MII oocyte membrane were subsequently incorporated into the oocyte. Comparison of the ASFI and C-ICSI groups did not reveal any significant differences in 2 pronuclear embryo rate (ASFI group: 85.4% vs. C-ICSI group: 71.8%), degeneration rate (0% vs. 5.6%), good-quality embryo rate at day 3 (63.4% vs. 52.9%), blastocyst formation rate (67.6% vs. 51.9%), or good-quality blastocyst (Grade 3BB and above by the Gardner criteria) formation rate (29.4% vs. 15.4%). On the contrary, the embryo utilization rate (defined as the total number of embryos transferred and cryopreserved divided by the number of MII oocytes) was significantly higher in the ASFI group compared to the C-ICSI group (47.9% vs. 25.4%, P &amp;lt; 0.05). Limitations, reasons for caution This study was limited by using the ZP for sperm selection. To expand its applicability, a method to identify sperm capable of fusing with an oocyte without using the ZP must be established. Additionally, since our sample size was small, larger studies are required to confirm our findings. Wider implications of the findings ASFI is expected to enhance the survival rate of oocytes and to increase the number of embryos available for implantation, not only compared to rescue ICSI but also C-ICSI. ASFI could aid in understanding fertilization mechanisms by enabling direct observation of oocyte-sperm fusion during the process. Trial registration number UMIN000050184

Obstetrical and neonatal outcomesafter vitrified-warmed blastocyst transfer in day 1 rescue intracytoplasmic sperm injection cycles: a retrospective cohort study.

Fertilization failure often occurs in conventional IVF cycles, and day 1 rescue ICSI is frequently recommended. In this study, the effect of rescue ICSI on obstetrical and neonatal outcomes after a single blastocyst transfer in vitrified-warmed cyclesis evaluated. This cohort study was a retrospective analysis of 703 vitrified-warmed single blastocyst transfers and 219 singletons in the r-ICSI group compared with 11,611 vitrified-warmed single blastocyst transfers in the IVF/ICSI and 4472 singletons in the IVF/ICSI group, respectively, and patients just undergoing their first IVF treatments were included in this study. Pregnancy rate (PR), live birth rate (LBR), and singleton birthweight were the primary outcome measures. Multiple linear regression analysis and logistic regression analysis were performed to evaluate the possible relationship between obstetrical and neonatal outcomes and fertilization method (including IVF, ICSI, and r-ICSI) after adjusting for other potential confounding factors. PR and the LBR were lower in the r-ICSI group compared with the IVF/ ICSI group. Singletons from the r-ICSI group had a higher Z-score and the proportion of large for gestational age (LGA) newborns was greater compared with singletons from the IVF/ICSI group. The results of the study indicated that a 31% LBR after r-ICSI is acceptable for vitrified-warmed blastocyst transfer, but the safety of transfer is a concern because of the lower PR and LBR compared with IVF/ICSI. The safety of r-ICSI newborns is also a concern because of the significantly higher birthweight and the proportion of LGA in r-ICSI group newborns compared with the IVF/ICSI group.

Indications affect neonatal outcomes following early rescue ICSI: a retrospective study.

To investigate the impact of heterogeneity in patient indications or insemination protocols on neonatal outcomes of singletons following early rescue ICSI (rICSI) treatments. A retrospective study was conducted. Propensity score matching and multivariable logistic regression were used to adjust for confounders and biases. 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. 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.

Fertilization, pregnancy, and neonatal outcomes after IVF, rescue ICSI, and ICSI in unexplained infertility: A retrospective study

AbstractConventional intracytoplasmic sperm injection (ICSI) is not recommended for nonmale infertile patients to avoid fertilization failure (FF) in view of controversies regarding safety issues. Among the strategies that may help to promote the use of in vitro fertilization (IVF) for women with a high risk of FF, rescue ICSI (R‐ICSI) has attracted attention. This study aimed to evaluate the efficacy of short‐term insemination combined with early R‐ICSI in the treatment of unexplained infertility. A total of 952 controlled ovarian stimulation (COS) cycles for unexplained infertility were divided into short‐term IVF (short‐term insemination without R‐ICSI, n = 500), R‐ICSI (short‐term insemination with R‐ICSI, n = 141), and ICSI (conventional ICSI, n = 311) groups. Patients underwent consecutive transfer cycles until live birth, or until all embryos from the first COS cycle were used. Laboratory data and clinical outcomes from short‐term IVF, R‐ICSI, and ICSI groups were compared. Short‐term IVF and ICSI groups were superior to R‐ICSI group in polyspermy rate, available embryo rate, and top‐quality embryos rate. Short‐term IVF, R‐ICSI, and ICSI groups underwent 705 (500 fresh and 205 frozen‐thawed cycles), 190 (141 fresh and 49 frozen‐thawed cycles), and 445 (311 fresh and 134 frozen‐thawed cycles) transfer cycles, resulting in 294, 76, and 190 live birth cycles, respectively. Comparison of pregnancy outcomes among these three groups demonstrated similar clinical pregnancy rates and live birth rates in fresh and frozen‐thawed embryo transfer cycles. There was no significant difference in the cumulative live birth rate among these three groups. R‐ICSI group showed similar neonatal outcomes compared with short‐term IVF and ICSI groups, including the rates of low birth weight, fetal macrosomia, small for gestational age and large for gestational age. Short‐term insemination combined with early R‐ICSI achieved satisfactory pregnancy and neonatal outcomes, albeit with a high polyspermy rate, which was an effective alternative to avoid excessive use of ICSI in unexplained infertility.

Role of sperm morphological parameters in the selection of fertilization methods.

To investigate the role of in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) in cases with isolated teratozoospermia, and to provide reference for infertile patients to choose a reasonable insemination program. From January 2018 to December 2022, 433 couples received assisted reproductive assistance in the Department of Reproductive Medicine of our hospital. Among them, 81 patients presented isolated teratozoospermia (other sperm parameters were normal). These underwent IVF/ICSI, and differences in embryological data were compared between groups. 60 patients with moderate teratozoospermia went IVF, 11 needed rescue ICSI (R-ICSI, 18.33%), and 49 developed up to the blastocyst stage. 14 patients with severe teratozoospermia went IVF, 2 needed R-ICSI (14.29%), and 12 developed up to the blastocyst stage. There were no statistically significant differences in the proportion of R-ICSI between the two groups. Embryological outcomes were not significantly different between groups. The present results suggest that patients with moderate and severe teratozoospermia can be effectively treated with IVF, being R-ICSI performed when necessary.

#245 : The Clinical Outcome of Different Embryo Transfer Strategies After Late Rescue ICSI Procedure

Background and Aims: To evaluate the safety profile and effectiveness of freeze-all blastocyst transfer when applied in the late rescue intracytoplasmic sperm injection (r-ICSI). All participants reproductive Centre of Peking University Third Hospital received treatment from 2009 to 2019 were included. A total of 2,270 patients met the inclusion criteria who encountered an unexpected total fertilization failure (TFF) during 149,054 cycles of in vitro fertilization (IVF) and adopted a late r-ICSI procedure. Methods: Patients were grouped according to the transfer strategies (926 women in Group 1 performing fresh embryo transfer (ET), 365 women in Group 2 performing freeze-all ET, 716 women in Group 3 experiencing a blastulation failure, and another 263 women without available D3 embryos). Different embryo transfer strategies after r-ICSI procedure. Main outcome measure(s) The live birth rate (LBR), cumulative live birth rate (cLBR), and conservative cLBR. Results: The TFF occurred in 7.4% of all IVF cycles. Group 1 tended to be older at oocyte retrieval [33.00 (30.00-37.00) vs. 31.00 (29.00-35.00), P&lt;0.001], with longer infertile years [5.00 (3.00-8.00) vs. 3.00 (2.00-6.00), P&lt;0.001], higher FSH levels [7.10 (5.71- 8.69) vs. 6.61 (5.25-7.95) mIU/mL, P&lt;0.001], more gonadotropin consumption [2850.00 (1950.00-4125.00) vs. 2325.00 (1800.00-3150.00) IU, P&lt;0.001], and oocytes retrieved were also fewer [10.00 (6.00-15.00) vs. 13.00 (9.00-19.00), P&lt;0.001]. Group 2 has achieved considerably better clinical outcomes both in LBR of the first ET cycle (37.53 vs. 4.64%) and cLBR (52.60 vs. 8.21%). After adjustment for covariates using binary logistic regression analyses, Group 2 was still linked to better obstetric performances in calculations for LBR [OR: 11.77, 95% CI (8.42-16.45)], cLBR [OR: 11.29, 95% CI (7.84-16.27)] and conservative cLBR [OR: 2.55, 95% CI (1.83-3.55)]. Two groups had a similar miscarriage rate, and no newborns with malformations or congenital diseases were reported. Conclusions: Our study highlighted r-ICSI as a safe and effective alternative when frustrated couples came up against unexpected TFF. Freeze-all blastocyst stage ET serves as the optimal strategy for late rescue ICSI. However, regarding women with limited oocytes available for r-ICSI use, weighing the benefits against the cost might be prudent before implementing in vitro blastulation.

Cumulative live birth rate and neonatal outcomes after early rescue ICSI: a propensity score matching analysis

Abstract STUDY QUESTION Is early rescue ICSI (E-RICSI) an effective and safe technique compared to conventional ICSI? SUMMARY ANSWER Despite the higher multi-pronucleus (PN) rate compared to conventional ICSI, E-RICSI did not add extra risks to clinical and neonatal outcomes. WHAT IS KNOWN ALREADY 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. STUDY DESIGN, SIZE, DURATION 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. PARTICIPANTS/MATERIALS, SETTING, 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. MAIN RESULTS AND THE ROLE OF CHANCE 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 &amp;lt; 0.001; blastocyst formation rate: P &amp;lt; 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 &amp;lt; 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. LIMITATIONS, REASONS FOR CAUTION 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. WIDER IMPLICATIONS OF THE FINDINGS 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. STUDY FUNDING/COMPETING INTEREST(S) This study was supported by grants from the National Key &amp; Development Program of China (No. 2021YFC2700603) and the National Natural Science Foundation of China (No. 81801443). The authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER N/A.

Comparing the pregnancy outcomes of Re‑ICSI and ICSI embryos in fresh ET and FET cycles.

Early rescue intracytoplasmic sperm injection (Re-ICSI) can prevent total fertilization failure (TFF) during conventional in vitro fertilization (IVF). However, the implantation rate of Re-ICSI embryos is lower than that of direct ICSI during fresh embryo transfer (ET). The aim of the present study was to investigate the effect of frozen ET (FET) after Re-ICSI. In the present retrospective study, primary infertility patients that underwent the first Re-ICSI and ICSI treatment, were studied. The clinical pregnancy rate, implantation rate, ectopic pregnancy, abortion rate and live birth rate were analyzed between the Re-ICSI and ICSI groups in fresh ET and FET cycles. The average age of patients between Re-ICSI and ICSI groups in fresh ET and FET cycles was (29.0±3.2 vs. 29.1±3.1, and 29.1±3.3 vs. 28.9±3.0), respectively (P>0.05). Compared with ICSI embryos, the clinical pregnancy, implantation and live birth rates of Re-ICSI embryos were lower in fresh ET cycles. By contrast, there were no significant differences in the pregnancy, implantation and live birth rates between the Re-ICSI and ICSI embryos during the FET cycles. Re-ICSI coupled with FET may overcome the impaired outcomes in fresh ET.

Clinical outcome of different embryo transfer strategies after late rescue ICSI procedure: a 10-year total fertilisation failure cohort study

BackgroundLate rescue intracytoplasmic sperm injection (r-ICSI) has not been widely accepted as an alternative solution for unexpected total fertilisation failure (TFF) after in vitro fertilisation (IVF), due to the time-dependent in vitro deterioration of oocyte quality and endometrial growth not being synchronised with embryo development. This study aimed to evaluate the safety profile and effectiveness of freeze-all blastocyst transfer in combination with late r-ICSI.MethodsThis was a retrospective cohort study carried out at the Reproductive Centre of Peking University Third Hospital, Beijing, China. All participants received treatment between 2009 and 2019. 2,270 patients in the aggregate encountered unexpected TFF during 149,054 cycles of IVF and adopted a late r-ICSI procedure. Among these patients, 263 women did not have cleavage-stage embryos available for evaluation. The remaining patients were grouped according to different embryo transfer (ET) strategies (926 women in Group 1 underwent fresh ET, 365 women in Group 2 underwent freeze-all ET, 716 women in Group 3 experienced blastulation failure). Patients received different ET strategies after r-ICSI, with the main outcome measures included live birth rate (LBR), cumulative live birth rate (cLBR), and conservative cLBR.ResultsTFF occurred in 7.4% of all IVF cycles. Group 1 tended to be older at oocyte retrieval, with more infertile years, higher follicle-stimulating hormone (FSH) levels, higher gonadotropin consumption, and fewer oocytes retrieved. Group 2 exhibited considerably better LBRs following the first ET cycle (37.53% vs. 4.64%) and cLBRs (52.60% vs. 8.21%). After adjustment for covariates using binary logistic regression analyses, Group 2 still showed better obstetric performance in LBRs [OR:11.77, 95% CI (8.42–16.45)], cLBRs (OR:11.29, 95% CI (7.84–16.27)], and conservative cLBRs (OR:2.55, 95% CI (1.83–3.55)]. Additionally, the two groups showed similar miscarriage rates, whilst no new-borns with malformations or congenital diseases were reported.ConclusionsFreeze-all blastocyst stage ET serves as an optimal strategy to support late r-ICSI. However, for women with limited oocytes available for r-ICSI use, weighing the benefits against the costs of the procedure might be prudent before implementing in vitro blastulation.

P-116 How does the short insemination method affect clinical outcomes and laboratory management?

Abstract Study question Does the short insemination method using a time-lapse monitoring system improve clinical outcomes and laboratory management? Summary answer The method increased the normal fertilization rate of Conventional IVF and also increased the 3PN rate. The working environment of the laboratory staff was improved. What is known already Short insemination using a time-lapse monitoring system has been reported to reduce fertilization confirmation failures due to loss of pronuclei, but many reports indicate that the method was implemented to perform so-called 'rescue ICSI' for unfertilized oocytes on the day of egg retrieval and there are not many reports of clinical outcomes in conventional IVF without rescue ICSI. There are also few reports on the working environment and working hours in the laboratory. Study design, size, duration This was a retrospective study of 3,714 oocytes from 715 cycles in 595 patients who underwent Conventional IVF with egg retrieval in 2016-2022. Long insemination (1,577 oocytes) was performed in cycles up to May 2019 and short insemination (2,137 oocytes) in later cycles. In IVF, 40,000 motile sperm were placed in 1 ml of culture medium per oocyte. Participants/materials, setting, methods Oocytes of the long insemination group (group L) were inseminated 5 hours after egg retrieval and denuded 19 hours later to observe their pronuclei. Oocytes from the short insemination group (group S) were inseminated 2 hours after egg retrieval, denuded 4 hours later, and cultured in EmbryoScope (Vitrolife, Sweden) to observe the pronuclei. Since the working hours set at our clinic are 8:00 a.m.-5:00 p.m., the time schedule for both groups followed this schedule. Main results and the role of chance The 2PN rate was 60.9% in group L and 64.7% in group S. The 3PN rates were 7.5% and 10.2% respectively, both rates being significantly higher in group S (P &amp;lt; 0.05). The non-fertilization rates were significantly higher in group L (25.3% and 21.7% respectively); the 1PN rate was not significantly different (3.6% vs. 3.4%). The rate of missed pronuclei was 2.8% in group L and 0% in group S. Early embryo transfer pregnancy rate (25.4% vs 27.8%), good blastocyst development rate (52.2% vs 63.6%) and blastocyst transfer pregnancy rate (41.1% vs 31.7%) in groups L and S respectively. The good blastocyst incidence was significantly higher in group S. In the case of the Conventional IVF cycle in which egg retrieval was performed at 8:00 a.m., the embryologists in group L were to observe the pronuclei at 8:00 a.m. the next day, but in reality the embryologists had to come to work earlier because of denudation, and even then pronuclear loss occurred. In contrast, the group S did not require an earlier attendance because denudation was not performed the next morning, and the time-lapse images did not fail to confirm the pronuclei at all. Limitations, reasons for caution Since the short insemination method was introduced at our clinic in June 2019, this study compared clinical outcomes before and after that date. Wider implications of the findings It has been reported in the past that early insemination time increases both 2PN and 3PN rates. The short insemination method in this study also used a faster insemination time, which may have led to similar insemination results. Trial registration number not applicable

P-153 Clinical outcome of different embryo transfer strategies after late rescue ICSI procedure: A cohort study based on over 140 thousand ART cycles

Abstract Study question How effective and safe is freeze-all blastocyst transfer in combination with late rescue intracytoplasmic sperm injection (r-ICSI)? Summary answer Freeze-all blastocyst stage embryo transfer (ET) serves as an optimal strategy to support late r-ICSI. What is known already Late r-ICSI has not been widely adopted due to the time-dependent in vitro deterioration of oocyte quality and endometrial growth not being synchronised with embryo development. Study design, size, duration This was a retrospective cohort study. All participants received treatment between 2009 and 2019. 2,270 patients in the aggregate encountered unexpected total fertilisation failure (TFF) during 149,054 cycles of in vitro fertilisation (IVF) and adopted a late r-ICSI procedure, whilst meeting the inclusion criteria for this study. Participants/materials, setting, methods Patients were grouped according to transfer strategies (926 women in Group 1 underwent fresh ET, 365 women in Group 2 underwent freeze-all ET, 716 women in Group 3 experienced blastulation failure, and 263 women did not have available D3 embryos). Patients received different ET strategies after r-ICSI, with the main outcome measures included live birth rate (LBR), cumulative live birth rate (cLBR), and conservative cLBR. Main results and the role of chance TFF occurred in 7.4 % of all IVF cycles. Group 1 tended to be older at oocyte retrieval [33.00 (30.00–37.00) vs. 31.00 (29.00–35.00), P &amp;lt; 0.001], with more infertile years [5.00 (3.00–8.00) vs. 3.00 (2.00–6.00), P &amp;lt; 0.001], higher follicle-stimulating hormone (FSH) levels [7.10 (5.71–8.69) vs. 6.61 (5.25–7.95) mIU/mL, P &amp;lt; 0.001], higher gonadotropin consumption [2850.00 (1950.00–4125.00) vs. 2325.00 (1800.00–3150.00) IU, P &amp;lt; 0.001], and fewer oocytes retrieved [10.00 (6.00–15.00) vs. 13.00 (9.00–19.00), P &amp;lt; 0.001]. Group 2 exhibited considerably better LBRs following the first ET cycle (37.53 % vs. 4.64 %) and cLBR (52.60 % vs. 8.21 %). After adjustment for covariates using binary logistic regression analyses, Group 2 still showed better obstetric performance in LBR (OR:11.77, 95 % CI (8.42–16.45)], cLBR (OR:11.29, 95 % CI (7.84–16.27)], and conservative cLBR (OR:2.55, 95 % CI (1.83–3.55)]. Additionally, the two groups showed similar miscarriage rates, whilst no new-borns with malformations or congenital diseases were reported. Limitations, reasons for caution This study was based on a retrospective cohort, which is inevitably associated with a skewed data distribution and inherent biases. Wider implications of the findings Our study highlights r-ICSI as a safe and effective alternate solution for unexpected TFF to aid frustrated couples. However, for women with limited oocytes available for r-ICSI use, weighing the benefits against the costs of the procedure might be prudent before implementing in vitro blastulation. Trial registration number NA

Day after rescue ICSI: eliminating total fertilization failure after conventional IVF with high live birth rates following cryopreserved blastocyst transfer.

What is the impact of day after rescue ICSI (r-ICSI) on success of fresh and frozen embryo transfers? The use of r-ICSI can virtually allay fears of total fertilization failure (TFF) after conventional IVF (C-IVF) and achieve high live birth rates after frozen blastocyst transfer. More infertility clinics have resorted to the use of ICSI in place of C-IVF in IVF treatment owing to fear of TFF or a low fertilization rate. r-ICSI has been attempted either on the day of IVF or the day after. Day after r-ICSI has proved unsuccessful in the past. A retrospective data analysis was performed of 16 608 qualifying cases between April 2010 and July 2021 conducted at a single private academically affiliated fertility clinic. r-ICSI was performed principally on patients with >4 metaphase II oocytes, showing no signs of fertilization 18 h after C-IVF. C-IVF was performed on patients who had >4 million total motile sperm after preparation. r-ICSI was then performed 18-24 h after insemination, using the sperm sample from the previous day. r-ICSI fertilization rates, cryopreservation of cleavage and blastocysts embryos, and pregnancy rates after fresh or frozen transfer were then assessed. r-ICSI was performed on 377 patients (2.3% of eligible retrieval cycles) who had a mean (±SD) female and male age of 35.9 ± 4.5 and 38.1 ± 9.1 years, respectively. A total of 5459 oocytes were initially retrieved. Of the oocytes undergoing r-ICSI, 2389 (49.5%) fertilized normally, and 205 (54.4%) patients underwent a fresh embryo transfer. The live birth rates were 23/186 (12.3%) for fresh cleavage and 5/19 (26.3%) for fresh blastocyst stage transfers. In 145 cycles a blastocyst was frozen, and 137 transfers were performed with a 64/137 (46.7%) live birth rate. Of the 377 cycles receiving r-ICSI only, 25 of the qualifying cases failed to have any fertilization, reducing TFF to 25/16 608 (0.15%). This was a single-center retrospective study on a specific subset of patients, which may limit its generalizability to other clinics. r-ICSI allows a second opportunity to fertilize oocytes despite poor initial outcomes. Patients who had a frozen blastocyst transfer achieved high live birth rates, indicating that a resynchronization of the embryo with the endometrium can optimize r-ICSI cases. r-ICSI allays fears of TFF when using C-IVF, providing evidence that the overuse of ICSI in patients without male factor may not be warranted. The study was internally funded by Boston IVF. The authors declare that they have no conflict of interest in relation to the data published in the article. N/A.

Safety of early cumulus cell removal combined with early rescue ICSI in the prevention of fertilization failure

Research questionWhat are the clinical outcomes and safety implications of early cumulus cell removal after short-term insemination combined with early rescue intracytoplasmic sperm injection (ICSI) in preventing fertilization failure? DesignIn this retrospective study, a total of 14,360 cycles were divided into four groups based on insemination method and fertilization ability: conventional IVF group (n = 5519); early cumulus cell removal group (n = 4107); conventional ICSI group (n = 4215); and early rescue ICSI group (where failed or low fertilization was predicted, n = 519). Fertilization outcomes, pregnancy outcomes, neonatal outcomes and birth defects were analysed by comparing the early cumulus cell removal group with the conventional IVF group, and the early rescue ICSI group with the conventional ICSI group. ResultsThere were no significant differences in the outcomes of fertilization, pregnancy, neonates or birth defects between the conventional IVF group and the early cumulus cell removal group (P > 0.05). When compared with the conventional ICSI group, the early rescue ICSI group had similar rates of two pronuclei (2PN) at fertilization, clinical pregnancy, miscarriage, ectopic pregnancy, live birth, sex, mean gestational age, very low birthweight, macrosomia and birth defects (P > 0.05) but a higher polyploidy rate, lower high-quality embryo rate (both P < 0.001), lower twin pregnancy rate (P < 0.01), lower rate of low birthweight, and a higher rate of normal birthweight (both P = 0.024). ConclusionsEarly cumulus cell removal combined with early rescue ICSI led to good pregnancy and neonatal outcomes without an increase in birth defects. This approach could therefore be an effective and safe method for patients with fertilization failure in conventional IVF.

Cycle Characteristics and Pregnancy Outcomes of Early Rescue Intracytoplasmic Sperm Injection Cycles in Normal and Hyper-Ovarian Response Women: A Six-Year Retrospective Study

This study aims to analyze the cycle characteristics, pregnancy, and neonatal outcomes in early rescue intracytoplasmic sperm injection (r-ICSI) cycles in normal and hyper-ovarian response women in their first IVF/ICSI attempts. Data from short-term in vitro fertilization (IVF, N = 7148), early r-ICSI (N = 618), and ICSI (N = 1744) cycles were retrospectively analyzed from normal and hyper-ovarian women who underwent their first IVF/ICSI cycles at our center from October 2015 to October 2021. The r-ICSI group was subdivided into partial r-ICSI (N = 451) and total r-ICSI (N = 167) based on the number of fertilized oocytes in the IVF part. Cyclic characteristics, pregnancy, delivery and neonatal outcomes in the fresh cycle were compared among the four groups; pregnancy, delivery and neonatal outcomes in frozen-thawed cycles were compared regarding cleavage and blastocyst transfers derived from r-ICSI cycles. Partial r-ICSI cycles showed different cyclic characteristics compared to total r-ICSI cycles, presenting as elevated AMH and estradiol levels on trigger day and an increased number of oocytes retrieved. Early r-ICSI delayed blastocyst development as seen by the increase in the number of day 6 blastocysts. There was no significant difference among the groups in clinical pregnancy, pregnancy loss, and live birth in fresh cleavage-stage embryo transfer cycles. However, early r-ICSI groups showed a reduction in clinical pregnancy and live birth rates in fresh blastocyst transfer cycles but not in the frozen-thawed cycles. For pregnant women, early r-ICSI did not show a negative effect on the risk of preterm birth, Cesarean section, neonatal birth weight, and sex ratio. In conclusion, early r-ICSI had comparable pregnancy, delivery, and neonatal outcomes when compared with short-term IVF and ICSI groups in fresh cleavage-stage embryo transfer cycles, but early r-ICSI did result in reduced pregnancy outcomes in fresh blastocyst embryo cycles, possibly due to delayed blastocyst development and asynchronization with the endometrium.

Should Intra Cytoplasmic Sperm Injection (ICSI) be the primary insemination method in women undergoing IVF cycles with donor sperm?

To compare efficacy of Intra Cytoplasmic Sperm Injection (ICSI) with conventional in vitro fertilization (IVF) on treatment outcome in women undergoing in vitro fertilization with donor sperm. We examined retrospectively the outcome data from 203 patients undergoing fresh cycles of conventional IVF (cIVF) or ICSI and an additional 77 frozen-thawed embryo transfer (FET) cycles during 2003-2014, all using donor sperm. Fertilization, cleavage, pregnancy and live birth rates and number of high-quality embryos were compared between cIVF and ICSI. Altogether 185 women underwent 479 transfer cycles of fresh embryos (237 cIVF vs. 224 ICSI and 18 "rescue ICSI" cycles). In addition, 77 FET cycles were compared (24 cIVF vs. 53 ICSI cycles). No differences were found between cIVF and ICSI in fertilization, cleavage, pregnancy and live birth rates (92.6% vs 92.2%, 73.4% vs 72.4%, 25.3% vs 27.2% and 13.1% vs 14.7%, respectively). Pregnancy and life birth rates remained similar even when FET cycles were included (25.8% vs 26.2% and 13.1% vs 13.7%, respectively). The use of ICSI was associated with lower rates of high-quality embryos (52.7% vs. 63.3%, P < 0.0001). A multivariate logistic regression analysis found that patients' age, number of transferred embryos and smoking were independently associated with the chance to conceive. Patient age correlated inversely with fertilization rate (r =-0.13, P < 0.006).Non-smokers were more likely to become pregnant (OR = 2.23, P < 0.012). Our results show that ICSI does not bypass the age-related decrease in oocyte quality in patients using donor sperm for IVF. Use of ICSI was associated with lower rates of high-quality embryos. The findings imply that ICSI should not be the primary method of insemination in patients undergoing IVF with donor sperm.

Intracytoplasmic Sperm Injection May Not Improve Clinical Outcomes Despite Its Positive Effect on Embryo Results: A Retrospective Analysis of 1130 Half-ICSI Treatments.

ObjectiveTo explore the clinical application value of half-ICSI treatment for infertility in assisted reproductive technology.MethodA retrospective analysis of 1130 half-ICSI treatments was conducted at the Affiliated Reproductive Hospital of Shandong University from January 2011 to December 2015. Patients with low fertilization rates in previous cycles, primary infertility for >5 years with unexplained reason, or secondary infertility for >5 years without fallopian tube factor were involved in this study. The 2PN rate, high-quality embryo rate, oocyte utilization rate, and clinical outcomes were compared between IVF insemination group (IVF group) and ICSI insemination group (ICSI group). The clinical outcome of half-ICSI insemination treatment, grouped according primary and secondary infertility, was also analyzed.ResultsCompared with IVF, ICSI resulted in a significantly higher 2PN rate (74.8% vs. 62.9%), high-quality embryo rate (54.6% vs. 51.7%), and oocyte utilization rate (35.9% vs. 32.8%; P<0.05). Among the 884 fresh-embryo transfer cycles, there were no notable differences in clinical pregnancy rate, live birth rate, or neonatal abnormality rate between the IVF and ICSI groups. Among the 792 primary infertility cycles, ICSI resulted in a significantly higher 2PN rate, high-quality embryo rate, and oocyte utilization rate compared with IVF (75.3% vs. 62.4%, 54.3% vs. 50.8%, 36.4% vs. 32.6%, P<0.05). For the 338 secondary infertility cycles, ICSI resulted in a significantly higher 2PN rate (73.6% vs. 63.9%, P<0.05) compared with IVF, but there were no notable differences in other laboratory results. Moreover, the biochemical pregnancy rate of the ICSI group was significantly lower than for IVF in secondary infertility cycles (49.3% vs. 65.6%; P<0.05). A total of 89 cycles (7.9%) with complete IVF fertilization failure showed a low second polar body (2PB) rate (33.6%) after a 5-h short-time fertilization period, including 34 cycles (3.0%) with no 2PB oocytes observed in the IVF group.ConclusionICSI insemination improved laboratory results compared with IVF insemination, however, fresh-embryo transfer of ICSI originated embryos did not improve clinical pregnancy and live birth rates. Rescue ICSI has been successfully applied in clinical IVF insemination to avoid fertilization failure. Therefore, as an extra intervention, it is suggested that ICSI be used judiciously.

Fertilization and neonatal outcomes after early rescue intracytoplasmic sperm injection: a retrospective analysis of 16,769 patients

PurposeTo evaluate the efficacy and safety of short-term insemination and early-rescue intracytoplasmic sperm injection (ICSI), an approach that rescued oocytes with unclear second polar body 6 h after initial insemination by ICSI (early R-ICSI) to avoid total or near-total fertilization failure in conventional in vitro fertilization (IVF).MethodsWe performed a retrospective study in 16,769 patients (short-term IVF, n = 12,094; ICSI, n = 3452; early R-ICSI, n = 1223) who received IVF/ICSI treatment in our hospital from January 2009 to October 2018. Fertilization and clinical outcomes were compared among those three groups.ResultsWhen considering the R-ICSI embryos in the early R-ICSI group independently, the rates of fertilization and day-3 cleaved embryos in 2PN oocytes were comparable, the rates of fertilization (2PN) and high-quality embryos were lower, whereas the multi-PN fertilization rate (3.27%) was significantly higher than the ICSI group (1.26%). The difference of clinical pregnancy rate between the part of transferred R-ICSI embryos (40.81%) and the ICSI group (44.73%) remained nonsignificant. Furthermore, the rate of congenital birth defects in the early R-ICSI group (0.99%) was not significantly different from those in the short-term IVF (0.76%) and ICSI groups (1.07%).ConclusionDespite the multi-PN fertilization rate, our study highlights early R-ICSI as a safe and effective alternative in assisted reproduction to decrease complete IVF fertilization failure and reduce ICSI utilization. Additional large amount and long-term follow-up studies are needed to further validate the use of early R-ICSI.

In vitro maturation of human oocytes maintaining good development potential for rescue intracytoplasmic sperm injection with fresh sperm.

BACKGROUNDThe outcomes of the use of commercial in vitro maturation (IVM) medium to culture immature oocytes obtained from conventional ovulation induction, followed by rescue intracytoplasmic sperm injection (RICSI), are not ideal. It is thus difficult to widely adopt this approach in clinical practice. Therefore, it is necessary to explore methods for improving the clinical outcome of IVM.AIMTo study the effect of sperm on the developmental potential of in vitro-matured oocytes in conventional culture.METHODSThis was a retrospective study of patients whose immature oocytes were harvested from conventional oocyte stimulation cycles and underwent ICSI at our hospital between June 2018 and August 2020. RICSI was performed using sperm collected on the day of oocyte harvest (old) and sperm collected on the day of RICSI (fresh) and oocytes matured in vitro after 24 h of culture in conventional medium. The rates of in vitro oocyte maturation, normal fertilization, normal cleavage, day-3 top-quality embryos, and useful blastocyst formation were compared between the two groups.RESULTSIn total, 102 germinal vesicle (GV)-stage immature oocytes were cultured in the old sperm group. In the fresh sperm group, 122 GV-stage immature oocytes were collected and cultured in vitro for 24 h. There were no significant differences in the general conditions of males and females between the two groups (P > 0.05). The oocyte maturation, normal fertilization, and normal cleavage rates of the old and fresh groups were 51.0% vs 55.7%, 61.5% vs 64.7%, and 93.8% vs 93.2%, respectively. None of the rates differed significantly (P > 0.05) between the two groups. However, the day-3 top-quality embryo and useful blastocyst rates of the old and fresh sperm groups were 16.6% vs 63.4%; 6.67% vs 34.6%, respectively. The day-3 top-quality embryos and useful blastocyst rates of the old sperm group were significantly lower than those of the fresh group (P < 0.05). CONCLUSION In vitro maturation with conventional culture medium combined with the use of fresh sperm collected on the day of RICSI is an easy-to-implement strategy for patients whose oocytes are completely or mostly immature.