Rates Of High-quality Blastocysts Research Articles

Micronutrient Antioxidants for Men (Menevit®) Improve Sperm Function by Reducing Oxidative Stress, Resulting in Improved Assisted Reproductive Technology Outcomes

Oxidative stress (OS) affects men’s health and impairs spermatogenesis. Micronutrient antioxidants are available for male infertility as complemental support; however, their efficacy remains debatable. This study aimed to investigate whether antioxidants can help to reduce sperm OS and improve semen analysis and quality. We included 171 male partners of couples planning to undergo assisted reproductive technology (ART). Male partners, aged 29–41 years, of couples intending to conceive were self-selected to take daily antioxidants (n = 84) containing folic acid and zinc, or not to take antioxidants (n = 52) for 6 months. We analyzed the alterations in serum oxidant levels, sperm parameters, OS, and deoxyribonucleic acid fragmentation after 3 and 6 months. Additionally, implantation, clinical pregnancy, and miscarriage rates after vitrified–warmed embryo transfer were compared between those taking antioxidants and those not taking them after 6 months. In men with high static oxidation–reduction potential (sORP), we observed a significant improvement in sperm concentration and sORP. The high-quality blastocyst rate tended to increase, and implantation and clinical pregnancy rates also significantly increased after 6 months of intervention. The micronutrient antioxidants could improve sperm function by reducing OS and improving ART outcomes. Therefore, micronutrient antioxidants may be a viable treatment option for male infertility.

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 < 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. 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 & 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.

Short-interval second ejaculation improves sperm quality, blastocyst formation in oligoasthenozoospermic males in ICSI cycles: a time-lapse sibling oocytes study.

Does short-interval second ejaculation improve sperm quality, embryo development and clinical outcomes for oligoasthenozoospermia males received intracytoplasmic sperm injection (ICSI) treatment? All enrolled male patients underwent short-interval secondary ejaculation on the day of oocyte retrieval, and 786 sibling MII oocytes from 67 cycles were equally divided into two groups based on whether the injected spermatozoons originated from the first or second ejaculation. Semen parameters, embryo development efficiency, morphokinetic parameters and clinical outcomes were compared between the two groups to assess the efficiency and clinical value of short-interval second ejaculation in ICSI cycles. Short-interval second ejaculation significantly improved sperm motility, normal morphological rate, and sperm DNA integrity both before and after sperm swim-up. The high-quality blastocyst rate (24.79% versus 14.67%), available blastocyst rate (57.56% versus 48.44%), and oocyte utilization rate (52.93% versus 45.29%) were significantly higher in the second ejaculation group (P<0.05). The clinical pregnancy rate (59.09% versus 47.37%), implantation rate (42.11% versus 32.35%) and live birth rate (40.91% versus 31.58%) were higher in the second ejaculation group, but the differences were not significant (P>0.05). Time-lapse analysis showed that morphokinetic time points after the 7-cell stage were earlier in the second ejaculation group but without a significant difference (P>0.05), and abnormal embryo cleavage patterns between the two groups were not significantly different (P>0.05). Short-interval second ejaculation significantly improves sperm quality in oligoasthenozoospermic males, and is beneficial for blastocyst formation efficiency in ICSI cycles. This study suggested a non-invasive and simple but effective strategy for improving ICSI treatment outcomes.

P-173 Neuregulin 1 supplementation and sequential stimulation improve post-IVM embryo production

Abstract Study question Can supplementation with neuregulin 1 during a pre-IVM culture step followed by sequential stimulation with FSH and amphiregulin improve IVM outcomes? Summary answer Supplementation with neuregulin 1 during a pre-IVM culture step followed by sequential stimulation with FSH and amphiregulin improves post-IVM bovine embryo production What is known already Evidence that gradual activation of the maturation cascade favours nuclear-cytoplasmic synchrony and cumulus-oocyte communication has motivated the investigation of pre-IVM culture steps. In vivo, the cumulus-oocyte complex (COC) is first exposed to increased FSH levels, after which final maturation is triggered by EGF-like factors secreted by granulosa cells. We have demonstrated that supplementation of the IVM medium with neuregulin 1 (NRG1), a modulatory EGF-like factor, improves oocyte developmental competence. Herein, we utilized the bovine model to assess the impacts of NRG1 supplementation during pre-IVM and sequential exposure to FSH and amphiregulin (AREG) during IVM on post-IVF embryo development Study design, size, duration Bovine COCs were subjected to a pre-IVM culture with (group NS) or without NRG1 (groups D and S). Subsequently, COCs were subjected to direct (group D) or sequential IVM with FSH followed by AREG stimulation (groups S and NS). Post-IVF production of total and high quality (expanded and hatched) blastocysts was compared between groups by ANOVA followed by the Fisher Protected test (n = 3 replicates, each with 20-25 oocytes per treatment-group) Participants/materials, setting, methods Germinal stage vesicle COCs were aspirated from 2-8mm follicles of abattoir bovine ovaries, pooled in groups of 20-25 and subjected to pre-IVM for 9h in the “Follicular System” (FS)-preIVM medium, with or without 1ng/mL NRG1, followed by IVM in the FS-IVM medium for 24h. In sequential IVM, COCs were first subjected to a 6h culture in the FS-IVM medium without AREG and, subsequently, to a 18h culture in the complete FS-IVM medium (AREG 100ng/mL) Main results and the role of chance Supplementation of NRG1 during pre-IVM combined with sequential IVM with FSH followed by AREG stimulation increased post-IVF embryo development as assessed by the percentage of the total oocytes subjected to pre-IVM/IVM generating total and high quality (expanded and hatched) blastocysts. Total blastocyst rates were 34.34 ± 1.66%, 40.26 ± 1.94% and 45.94 ± 3.04% for groups D, S and NS, respectively (P = 0.032). Rates of high quality blastocysts were 30.53 ± 1.47%, 29.71 ± 2.36% and 38.56 ± 1.91%, for groups D, S and NS, respectively (P = 0.036) Limitations, reasons for caution Our study is subjected to the intrinsic limitations of the use of an animal model. Treatment effects may vary with different biological activities associated with different batches and suppliers of EGF-like factors Wider implications of the findings Our findings contribute for a better understanding of the mechanisms regulating oocyte developmental competence and constitute novel parameters for the improvement of IVM efficacy. Therefore, our data may contribute for the development of infertility treatment strategies with reduced hormonal cost and patient discomfort Trial registration number Not applicable

O-178 Conventional IVF results in better embryo development when compared with ICSI in patients without severe male factor

Abstract Study question Which fertilisation technique offers better embryo development results in patients without severe male factor? Summary answer Conventional IVF offers better results regarding embryo development than ICSI in patients without male factor when applying both techniques in the same cohort of oocytes. What is known already ICSI was originally indicated for severe male factor. Nevertheless, it is currently used for many other indications so that it has become the most used technique. One of the reasons for the use of ICSI is the fear of a fertilisation failure when using conventional IVF (cIVF). We have to consider that ICSI is more expensive and invasive. For this reason, it is important to know whether there is a justification to use it in these cases. Study design, size, duration It is a randomized prospective study where 68 IVF/ICSI cycles were analysed. The study comprised 812 oocytes and 469 embryos and was conducted from January to December 2022 in the Assisted Reproduction Unit of a tertiary hospital. In each cycle, we performed a mixed technique using cIVF and ICSI in the same cohort of oocytes. MII rate, fertilisation rate and embryo development were analysed. Participants/materials, setting, methods All consecutive cycles with at least 6 fresh oocytes and semen parameters suitable for cIVF were offered to participate. In each cycle, oocytes were divided into two groups in order of collection and the fertilisation technique (cIVF or ICSI) was randomly assigned for each group. All the embryos were cultured to blastocyst stage. Data of maturity, fertilisation and embryo development were individually registered for every oocyte. Data were statistically analysed by applying multilevel regression models. Main results and the role of chance The patients average age was 36.3±3.0 (28 to 40) and the number of oocytes per cycle was 11.9±5.1 (6 to 26). 396 oocytes (48.8%) were allocated to cIVF group and 416 (51.2%) to ICSI group. The percentage of mature oocytes was significantly higher in cIVF group than in ICSI group (88.9% vs 81.5%, p = 0.017), which is consistent with the later assessment of maturity in cIVF. There were no statistically significant differences between cIVF and ICSI groups in terms of fertilisation rate (59.6% vs 56.0%) and high-quality blastocyst rate (A+B) (9.3% vs 8.7%) when analysed per oocyte. We observed clinical but not statistical differences in blastocyst rate per oocyte (30.6% cIVF vs 23.6% ICSI, p = 0.09). However, blastocyst rate per fertilised oocyte showed statistically significant differences (51.3% cIVF vs 41.6% ICSI, p = 0.047). Additionally, we found statistically significant differences between cIVF and ICSI in the rate of usable blastocysts (transferred or cryopreserved) per oocyte (26.3% vs 18.3%, p &amp;lt; 0.01) and per fertilised oocyte (44.1% vs 32.2%, p &amp;lt; 0.01). In 57.8% of the cycles, the best blastocyst was obtained by cIVF and in 42.2% by ICSI. Fertilisation failure was observed in 3 patients with cIVF and 1 patient with ICSI. All of them had ≤4 mature eggs. Limitations, reasons for caution This study includes the 68 patients who met the recruitment requirements until this moment. It is a part of a wider work, which will analyse a higher number of oocytes and pregnancy and perinatal outcomes. For this reason, the sample size is a limitation to the interpretation of the results. Wider implications of the findings Our findings encourage the use of cIVF when there is no severe male factor. Considering that cIVF is cheaper and less invasive than ICSI, the exclusive use of ICSI in these patients does not seem to be justified according to our results. Trial registration number not applicable

Physiological intracytoplasmic sperm injection does not improve the quality of embryos: A cross-sectional investigation on sibling oocytes.

This study aimed to compare the efficacy of physiological intracytoplasmic sperm injection (PICSI) and intracytoplasmic sperm injection (ICSI) in terms of the fertilization rate and embryo quality using sibling oocyte cycles. This prospective, cross-sectional study collected data from 76 couples who underwent their first cycle at the Hue Center for Reproductive Endocrinology and Infertility, Vietnam, between May 2019 and November 2021. The inclusion criteria were cycles with at least eight oocytes and a sperm concentration of 5×106/mL. Sperm parameters, sperm DNA fragmentation (SDF), fertilization, and the quality of cleavage-stage embryos on day 2 and blastocysts on day 5 were examined. From 76 ICSI cycles, 1,196 metaphase II (MII) oocytes were retrieved, half of which were randomly allocated to either the PICSI (n=592) or ICSI (n=604) treatment group. The results showed no significant difference between the two groups in terms of fertilization (72.80% vs. 75.33%, p=0.32), day 2 cleavage rate (95.13% vs. 96.04%, p=0.51), blastulation rate (52.68% vs. 57.89%), and high-quality blastocyst rate (26.10% vs. 31.13%, p=0.13). However, in cases where SDF was low, 59 cycles consisting of 913 MII oocytes produced a considerably higher blastulation rate with PICSI than with ICSI (50.49% vs. 35.65%, p=0.00). There were no significant differences between the pregnancy outcomes of the PICSI and ICSI embryo groups following embryo transfer. Using variable sperm quality provided no benefit for PICSI versus ICSI in terms of embryo outcomes. When SDF is low, PICSI appears to be able to produce more blastocysts.

Vacuolization in embryos on days 3 and 4 of in vitro development: Association with stimulation protocols, embryo development, chromosomal status, pregnancy and neonatal outcomes.

Is vacuolization in embryos on Days 3 and 4 associated with parent-related factors, stimulation protocols, embryo development, embryo ploidy, pregnancy and neonatal outcomes? This is a retrospective cohort study that comprised 5,703 embryos from 611 patients who underwent preimplantation genetic testing and time-lapse monitoring of their embryos from August 2017 to September 2021. Embryo vacuolization on Days 3 and 4 is associated with the LH level on the day of the hCG trigger and the number of retrieved oocytes. Compared to vacuole-negative embryos, the rates of blastocyst formation and good-blastocyst formation was significantly lower in vacuole-positive embryos. We observed no significant difference in the rates of euploidy, implantation, ongoing pregnancy, and live birth between vacuole-positive and vacuole-negative embryos. In vacuole-positive embryos, the embryos of which the vacuole-positive blastomeres were involved in embryo compaction exhibited significantly higher mosaicism rate compared with those of which the vacuole-positive blastomeres were not involved in embryo compaction. Vacuolization in embryos on Days 3 and 4 is associated with reduced blastocyst formation rate and high-quality blastocyst rate. Blastocysts had a low mosaicism rate if the vacuole-containing cells were rejected in compaction process, which supports the hypothesis that exclusion of abnormal blastomeres from compaction is a self-correction mechanism.

Developmental potential of different embryos on day 3: a retrospective study

To investigate how different quality of day 3 (D3) embryos affect blastocyst formation and clinical outcomes. This retrospective study analysed 699 patients undergoing assisted reproductive technology (ART) between January 2017 and February 2021. A total of 2517 D3 embryos were transferred to blastocyst medium for extended culture. D3 embryos were divided into five groups. Grade A, 6–10 cells, symmetrical blastomeres and <20% fragmentation; grade B, 6–10 cells, uneven blastomeres and ≥20% fragmentation; grade C, >10 cells, symmetrical blastomeres and <20% fragmentation; grade D, >10 cells, uneven blastomeres and ≥20% fragmentation; grade E, <6 cells. Status of day 5 (D5) and day 6 (D6) blastocysts and the clinical outcomes (blastocyst transfer) of each D3 embryo were recorded. The grade C group showed a higher D5 blastocyst formation rate and a high-quality blastocyst rate than other groups (p<.05). However, the clinical pregnancy rates in the grade A group were higher than other groups (p<.05). Embryos with low speed of development (grade E group) showed considerable clinical outcomes that were still worth investigating. D3 embryos with less fragmentation and ≥6 symmetrical blastomeres revealed a higher developmental potential, while embryos with 6–10 blastomeres showed the ideal clinical outcomes. Impact Statement What is already known on this subject? Accurate embryo evaluation can effectively reflect the developmental potential of different embryos. The number of blastomeres, proportion of fragmentation, and blastomere symmetry are three important and popular morphologic parameters used for evaluating day 3 (D3) embryos. However, in existing reports, combining these three parameters for embryo evaluation often results in different results. This is because different researchers have chosen different criteria for these three parameters. What do the results of this study add? In this retrospective study, we summarised the medical records of our reproductive centre in the past three years, redefined the evaluation method of the D3 embryos, and analysed the corresponding developmental potential and clinical outcomes. We conclude that although the embryonic development potential of grade C embryos (>10 cells, symmetrical blastomeres and/or <20% fragmentation) is relatively good, the results of grade A embryos (6–10 cells, symmetrical blastomeres and/or <20% fragmentation) are better in terms of clinical outcomes. What are the implications of these findings for clinical practice and/or further research? We believe this is meaningful for embryologists to choose embryos for transfer and predict the clinical outcome of IVF cycles.

Effect Analysis of Degranulated Cell in Early Fertilization on FET Outcome and Offspring Safety with Data Mining.

In vitro fertilization and embryo transfer is one type of assisted reproductive technology, although the technology is now more mature. Many factors, however, will have an impact on oocyte fertilization, embryo growth, pregnancy outcome, and child safety due to the journey from clinical to the laboratory. The influence of degranulated cells early in fertilization on frozen embryo transfer (FET) results is investigated in this study. This article analyzes 255 patients who underwent in vitro fertilization (IVF) and FET transplantation at the author's central unit from January 1, 2015, to June 30, 2021. Among them, IVF-assisted conception is the early degranulation of homologous oocyte fertilization. Correlation analysis is performed by observing the embryonic outcome of the early degranulation group and the overnight fertilization group and the clinical outcome after FET. Through data mining analysis, the results show that the polyfertilization rate and 0PN rate for the early degranulation group are significantly higher than the overnight fertilization group (9.87% vs. 8.24% and 3.14% vs. 1.69%). In terms of normal fertilization rate, there is no significant difference between D3 high-quality embryo rate and D5 high-quality blastocyst rate (64.07% vs. 65.15%, 27.5% vs. 26.5%, and 15.97% vs. 17.35%). There is no significant difference in the complete recovery rate of embryos after thawing (93.24% vs. 93.46%), and the implantation rate, clinical pregnancy rate, abortion rate, and live birth rate are not significantly different between the two groups after FET. The offspring outcomes of singletons do not differ significantly between the two groups; however, twins born early degranulate have much greater rates of ultralow birth weight and ultrapreterm children than twins born overnight fertilization (14.29% vs. 0). Therefore, it can be concluded that degranulation of cells early in fertilization is a desirable method to prevent fertilization disorders. However, under the premise of ensuring that no fertilization disorder occurs, it is not appropriate to degranulate all the oocytes of the patient at the early stage of fertilization.

O-099 The use of cumulus cells (CCs) to select spermatozoa for intracytoplasmic sperm injection improves blastocyst development and quality

Abstract Study question Is there a role for sperm selection based on the capacity to pass through cumulus oophorous column in improving the laboratory outcomes in ICSI cycles? Summary answer A higher rate of blastocyst formation and quality are obtained with the use of CCs to select spermatozoa for ICSI compared to conventional density gradients. What is known already The sperm selection for ICSI is an operator-dependent procedure based on sperm morphology and motility. ICSI bypasses all natural barriers of sperm selection, which may impact embryo development. During natural fertilization, only the spermatozoa that pass-through cumulus cells will have the chance to fertilize the egg. Spermatozoa capable of traverse COCs have better morphology, higher chromatin integrity and greater acrosomal reaction. Hyaluronic acid is an important component of these cells and plays a key role in the selection of spermatozoa with intact DNA. However, there is scarce data regarding this selection method for ICSI on the development of the embryo. Study design, size, duration This is a prospective randomized sibling oocyte pilot study (February-December 2021). A total of 996 metaphase II (MII) oocytes were randomized into two groups. In the control group (Group 0, n = 489 MII), ICSI was performed with sperm selected by conventional density gradients. In the study group (Group 1, n = 507 MII) the oocytes were microinjected with sperm selected through CCs. The main outcome was blastocyst formation rate and quality. Reproductive results were analyzed as secondary outcomes. Participants/materials, setting, methods Ninety-eight couples undergoing ICSI (private center) with ≥6 fresh own MII obtained after ovarian stimulation, embryo culture until blastocyst stage and ejaculated sperm samples were included in the study. All seminal samples were processed using density gradients and those in the study group were additionally passed through CCs (the patient's own CCs were used in all cases). Fertilization and day 5 blastocyst formation rates were assessed. Embryo quality was scored according to Gardner's criteria. Main results and the role of chance Data was similar with regards to cause of infertility, maternal age (36.47 vs 36.63 y.o.), sperm count (60.53 vs 58.25 mill/ml) and progressive motility (57.45 vs 57.50%) between group 0 vs 1, respectively. Fertilization rate was similar between groups (74.0% vs 78.7%; p = 0.419. Group 0 vs 1, respectively). However, the blastocyst formation rate was significantly higher in the study group compared to control (70.9% vs 60.1%; p = 0.002). In addition, high-quality blastocyst rate was significantly higher in the CCs compared to the control group (49.6% vs 38.5%; p = 0.003). After the analysis of 145 treatments (131 frozen vs 14 fresh transfers) the cumulative clinical pregnancy rate in the study group was 47.2%, higher than in the control group (32.1%), but without reaching statistical difference (p = 0.07). Limitations, reasons for caution This is an exploratory study, aimed to evaluate the effectiveness of CCs as a more “physiologic” selection of spermatozoa for ICSI treatments in terms of laboratory outcomes (blastocyst formation rate and quality). Albeit not reaching statistical significance, the higher cumulative pregnancy rate in the study group seems clinically relevant. Wider implications of the findings Our results suggest that CCs can select more competent sperm for ICSI. This “physiologic-resembling”, operator-independent selection method has the potential of increasing pregnancy outcomes in ICSI cycles, pending of confirmation in larger studies including cumulative embryo-transfer cycles. Trial registration number NA

Comparative Clinical Study of Percutaneous Epididymal Sperm Aspiration and Testicular Biopsy in the Outcome of ICSI-Assisted Fertility Treatment in Patients with Obstructive Azoospermia.

ObjectiveTo compare and contrast the effects of percutaneous epididymal sperm aspiration (PESA) and testicular sperm aspiration (TESA) on the outcome of intracytoplasmic sperm injection (ICSI)-assisted fertility treatment in patients with obstructive azoospermia.MethodsPatients with obstructive azoospermia with an age distribution of 20–36 years admitted to the male department of the Reproductive Center of the Second Affiliated Hospital of South China University (Hengyang Nanhua Xing Hui Reproductive Health Hospital) from December 2018 to December 2020 were used in this study. One group was set up as the PESA group to perform PESA, and the other group was set up as the TESA group to perform percutaneous testicular biopsy for sperm extraction. Patients who were unsuccessful in PESA continued to undergo TESA, and if sperm were retrieved, they were classified as the TESA group. General information on male patients and their partners was collected and compared in patients from different sperm source groups. Embryo development (normal fertilization rate, high-quality embryo rate, and high-quality blastocyst rate) and pregnancy outcome (clinical pregnancy rate, miscarriage rate, and ectopic pregnancy rate) were compared between the two groups.ResultsFinally, there were 26 patients in the PESA group and 31 patients in the TESA group. There were no significant differences in terms of age, years of infertility, testosterone level, (FSH) follicle-stimulating hormone level, and testicular volume between the male patients in the PESA and TESA groups of two different sperm sources, and no significant differences were found in the general conditions of the female patients in terms of age, number of eggs obtained, number of sinus follicles, basal FSH value, and basal E2 value (p > 0.05). The rate of high-quality blastocysts in the TESA group was significantly higher than that in the PESA group (p < 0.05); the differences in clinical normal fertilization rate, high-quality embryo rate, clinical pregnancy rate, miscarriage rate, and ectopic pregnancy rate between the two groups were not statistically significant (p > 0.05).ConclusionICSI with different sources of sperm in patients with male factor infertility alone, which had no significant effect on embryo development, embryo implantation rate, clinical pregnancy rate, and miscarriage rate, resulting in better clinical outcomes.

Investigate the effect of COVID-19 inactivated vaccine on sperm parameters and embryo quality in in vitro fertilization.

Since the reproductive toxicity of COVID‐19 vaccines have not been assessed in previous clinical trials, and studies have shown that SARS‐CoV‐2 is associated with a decrease in sperm parameters. Although it has been reported that the mRNA SARS‐CoV‐2 vaccines do not adversely affect semen parameters, whether this conclusion applies to inactivated vaccines remains unclear. Here, we conducted a study among patients who accepted in vitro fertilization (IVF) at the reproductive centre between June and August of 2021. In the enrolled cases, men who have completed two doses of COVID‐19 inactivated vaccine were included in “vaccine group” (N = 105), and those who were not vaccinated were included in “control group” (N = 155). In this study, we compare the sperm parameters and embryo quality between these two groups. Our data showed that the sperm parameters were similar in terms of volume, sperm concentration, sperm count, progressive motility, total motility and total motile sperm count between these two groups. Similarly, no significant differences were observed in IVF outcomes. The mean number of 2PN, cleavage‐stage embryos, blastocysts, and good‐quality blastocysts was 8.59 ± 4.47, 5.06 ± 3.17 and 2.08 ± 1.79 in vaccine group, 7.75 ± 4.14, 4.34 ± 3.06 and 1.74 ± 1.54 in control group, respectively. The high‐quality blastocyst rate was 41.05% (218 of 531) in vaccine group and 40.03% (269 of 672) in control group (p > 0.05). In addition, no differences were observed in biochemical and clinical pregnancy rates between the two groups. In summary, our results revealed that COVID‐19 inactivated vaccine administration exhibited no negative effect on sperm parameters and embryo quality in IVF.

Comparison of pregnancy and neonatal outcomes of intracytoplasmic sperm injection performed with frozen versus fresh testicular sperm.

BackgroundIt remains controversial whether there is a difference in the prognosis of intracytoplasmic sperm injection (ICSI) using frozen or fresh testicular sperm in patients with obstructive azoospermia (OA). Moreover, in the available studies, few have tracked neonatal outcomes. This study aimed to compare the pregnancy and neonatal outcomes of ICSI using cryopreserved sperm versus fresh sperm collected by testicular sperm aspiration (TESA).MethodsA total of 317 OA patients treated with ICSI in a university affiliated hospital from January 2016 to December 2020 were included in this study. The participants were divided into two groups according to the type of sperm used for ICSI: frozen sperm group (n=154) and fresh sperm group (n=163). The pregnancy and neonatal outcomes of the two groups were compared.ResultsThe data produced by this study showed no significant statistical difference in the 2 pronuclei (2PN) fertilization rate, 2PN cleavage rate, high-quality blastocyst rate, and the average number of transferred embryos in the frozen and fresh sperm groups. Similarly, no difference was found in implantation rate, clinical pregnancy rate, multiple pregnancy rate, miscarriage rate, premature delivery rate, live birth rate, and gender ratio at birth (P>0.05). The average newborn birth weight was similar in both groups (2,932.61±728.40 vs. 3,100.32±515.64 g, respectively) (P>0.05). A higher incidence of low birthweight (LBW) newborns was found in the frozen sperm group (20.91% vs. 8.49%) (P<0.05). Multiple logistic regression analysis showed that LBW is related to single or twin pregnancies (P<0.01), but not sperm (frozen or fresh) (P>0.05). We further analyzed the twin and single pregnancies in the two groups separately, and found that the incidences of LBW were both similar (P>0.05). There was no difference in the Apgar scores at 1 min and 5 min after birth between the two groups (P>0.05).ConclusionsThe use of frozen testicular sperm by TESA was efficient for men with OA. There were similar pregnancy and neonatal outcomes following TESA-ICSI using frozen or fresh sperm in this retrospective study. Prospective investigations are needed for further validation.

Decreased DNA Repair Ability: A Mechanism for Low Early Embryonic Development Potential of Oocytes From Overweight Patients After Fertilization in IVF Cycles.

BackgroundWhether female BMI impacts the DNA repair ability in the oocytes after fertilization has not been investigated. The aim of this study is to assess the early embryo quality and reproductive outcomes of oocytes from overweight women when fertilized with sperm with varying degrees of DNA fragmentation.MethodsA total number of 1,612 patients undergoing fresh autologous in vitro fertilization (IVF) cycles was included. These patients were divided into two groups according to maternal body mass index (BMI): normal weight group (18.5–24.9 kg/m2; n=1187; 73.64%) and overweight group (≥25 kg/m2; n=425; 26.36%). Each group was then subdivided into two groups by sperm DNA fragmentation index (DFI): low fragmentation group (<20% DFI, LF) and high fragmentation group (≥20% DFI, HF). Laboratory and clinical outcomes were compared between subgroups.ResultsFor the normal-weight group, there was no statistical significance in embryo quality and reproductive outcomes between the LF and HF groups. But in the overweight group, significantly lower fertilization rate (LF: 64%; HF: 59%; p=0.011), blastocyst development rate (LF: 57%; HF: 44%; p=0.001), as well as high-quality blastocyst rate (LF: 32%; HF: 22%; p=0.034) were found in the HF group, despite the similar pregnancy rates (LF: 56%; HF: 60%; p=0.630).ConclusionsDecreased DNA repair activity in oocytes may be a possible mechanism for the low early development potential of embryos from overweight patients in in vitro fertilization cycles.

Outcome of in vitro fertilization cycles with automatic time-lapse instrumentation combined with the early embryo viability assessment score.

To evaluate whether embryo selection using the early embryo viability assessment (EEVA) score increases the ongoing pregnancy rate of in vitro fertilization and intracytoplasmic sperm injection patients. One hundred eighty-one patients whose serum anti mullerian hormone (AMH) level was greater than 0.5ng/μL were enrolled in the study. All patients received oocyte retrieval repeatedly from June 2017 to January 2019. Transferred embryos were selected using the EEVA score and Veeck's criteria. We investigated the blastocyst rate according to the EEVA score and Veeck's criteria and also evaluated the clinical outcome following embryo transfer of the blastocysts. Blastocyst development rate (48.7%) and high-quality blastocyst (42.4%) of Veeck 1 was statistically higher than others. The blastocyst rate (71.4%) and high-quality blastocyst rate (60.0%) for EEVA 1 was the highest, and a correlation between the EEVA score and the blastocyst rate was also identified in cases younger than 40 years. Blastocyst rate of EEVA 1 + 2 (69.8% 208/298) was statistically higher than that of Veeck 1 + 2 (40.1% 317/791) (p < 0.05) and high-quality blastocyst rate of EEVA 1 + 2 (50.0% 104/208) was also higher than that of Veeck 1 + 2 (36.6% 117/320) (p < 0.05). However, there was a significant correlation between EEVA and the pregnancy rate and pregnancy rate of EEVA 1 + 2 showed no statistical difference compared with Veeck 1 + 2. Although it remains to be answered whether a computer can substitute Veeck's classification, the EEVA score could be a viable alternative to predict the blastocyst rate and to select those high-potential embryos that improve the pregnancy rate.

The Influence of Chromosomal Polymorphism on Embryo Development and Embryonic Molecular Karyotype in Preimplantation Genetic Testing for Chromosomal Translocation.

Traditionally, chromosomal polymorphisms (CPMs) are normal genetic variants in individuals with no phenotypic variations. However, some studies have shown that CPM is related to reproductive diseases. We explored the influence of CPM on embryonic development and molecular karyotype in chromosomal translocation (CT) patients undergoing preimplantation genetic testing (PGT) between February 2013 and May 2019. Twenty-six cases with CPM and 56 controls with normal chromosomes were included. Furthermore, a 1:4 match pair analysis by female age included 39 cases with CTCPM and 185 controls with CT. There was no statistical difference in fertilization rate (78.48% vs. 78.33%), cleavage rate on Day 3 (90.32% vs. 89.16%), blastocyst rate (60.00% vs. 60.80%), and the high-quality blastocyst rate (36.31% vs. 35.22%) between CPM and normal chromosomes. The high-quality blastocyst rate of CTCPM was significantly lower than that for CT (26.78% vs. 38.89%). Moreover, there was no statistical difference in fertilization rate (70.65% vs. 70.37%), cleavage rate on Day 3 (88.67% vs. 89.53%), and blastocyst rate (48.48% vs. 53.17%) between CTCPM and CT. In addition, one CTCPM spouse had a lower high-quality blastocyst rate, especially of males with CTCPM. Abnormal embryo rates of CTCPM were significantly higher than those for CT (78.64% vs. 68.93%). Abnormal embryo rates were higher in both CTCPM and CPM paternal carriers with CT partners, respectively. For CT, CTCPM may have an impact on the high-quality blastocyst rate and embryonic molecular karyotype, especially in male patients. Patients with CTCPM are relatively rare, but this population would benefit from being explored using a larger sample size.

The relationship between a novel evaluation parameter of premature luteinization and IVF outcomes

Research questionCan premature luteinization of granulosa cells (PLGC) act as a novel parameter of premature luteinization and affect IVF outcomes? Study designIn this retrospective cohort study, infertile patients undergoing fresh IVF cycles between January 2006 and December 2016 at the Reproductive Medicine Center in Tongji Hospital were included. A total of 42,468 cycles were conducted. Propensity score matching was carried out to match the baseline characteristics, and participants were assigned to the PLGC group and control group. The main outcomes were pregnancy rate and live birth rate. ResultsPatient characteristics and clinical outcomes were compared before and after matching. In general, the fate of oocytes in the PLGC group was much worse than those in the control group after matching, including metaphase II rate, two-pronuclei rate, available embryo rate, blastocyst formation rate, high-quality blastocyst rate, pregnancy rate, implantation rate and live birth rate. Among those potential risk factors, gonadotrophin duration, oestradiol and progesterone on HCG day were positively associated with the occurrence of PLGC in the multivariate logistic regression model, with gonadotrophin dosage negatively related. Moreover, cumulus–oocyte complexes with PLGC showed a high correlation with elevated progesterone levels over 1.5 ng/ml. ConclusionsOur findings demonstrated the adverse effect of PLGC on oocyte competency. In evaluating cumulus–oocyte complexes, PLGC provide an available novel parameter for premature luteinization judgement in clinical and individualized precise treatment. Close monitoring of progesterone level as well as critical analysis of progesterone elevation can reduce the occurrence of premature luteinization.

Association between mitochondrial DNA D-loop region polymorphisms and endometriosis in a Chinese population.

To investigate the correlation between endometriosis and mitochondrial DNA (mtDNA) D-loop single nucleotide polymorphisms (SNPs) and haplotype, as well as the predictive power of certain SNPs in reproductive outcomes in a Chinese Han population. A case-control study was conducted in which 125 endometriosis patients and 124 controls were recruited from an academic fertility center. The entire 1124-bp D-loop region of mtDNA of whole blood samples from all subjects was amplified, sequenced, and compared with the revised Cambridge Reference Sequence (rCRS) to identify SNPs and haplotypes. The association between D-loop SNPs and embryo quality and clinical outcome following in vitro fertilization (IVF) was also assessed. A total of 321 polymorphisms were identified by sequencing, allowing comparison of the D-loop between endometriosis patients and controls. The frequency of the AC523-524 del, T16172C, and C16290T variants were significantly higher, while the frequency of polymorphisms T195C, 573XCins, 16036Gins, 16049Gins, T16140C, A16183C, T16189C, and 16193Cins were lower, in the endometriosis group compared with the control group (p < 0.05). Within the endometriosis group, the high-quality blastocyst rate in the 16,290T subgroup was significantly lower than that in the 16290C subgroup (p < 0.05). In the control group, 16519C carriers showed a lower rate of high-quality blastocyst development compared with 16519T (p < 0.05). In endometriosis patients clinical pregnancy rate was significantly lower in the 150T subgroup compared with the 150C subgroup (p < 0.05). Data confirms a correlation between D-loop polymorphisms and endometriosis. The polymorphisms AC523-524 del, T16172C, and C16290T are associated with increased risk of endometriosis, while T195C, 573XCins, 16036Gins, 16049Gins, T16140C, A16183C, T16189C, and 16193Cins are associated with decreased risk of endometriosis. In addition, C16290T and T16519C can be associated with poor quality blastocyst development in population with and without endometriosis, respectively and C150T can be a predictor of poor IVF outcome.

The influence of balanced complex chromosomal rearrangements on preimplantation embryonic development potential and molecular karyotype

BackgroundBalanced complex chromosome rearrangements (BCCR) are balanced chromosomal structural aberrations that involve two or more chromosomes and at least three breakpoints. It is very rare in the population. The objective is to explore the difference of influence of three types of BCCR on early embryonic development and molecular karyotype.ResultsTwelve couples were recruited including four couples of three-way rearrangements carriers (group A), three couples of double two-way translocations carriers (group B) and five couples of exceptional CCR carriers (group C). A total of 243 oocytes were retrievedin the seventeen preimplantation genetic testing (PGT) cycles, and 207 of these were available for fertilization. After intracytoplasmic sperm injection, 181oocytes normally fertilized. The rates of embryos forming on day3 in three groups were 87.88, 97.78 and77.14%, which was significantly different (P = 0.01). Compared with group B, the rate of embryo formation was statistically significantly lower in group C (P = 0.01). Furthermore, the rates of high-quality blastocysts in three group were 14.71, 48.15 and 62.96%, respectively, which was significantly different (P = 0.00). Compared with group B andC, the rate of high-quality blastocysts in group A was statistically significantly lower (P = 0.00;P = 0.00).Comprehensive chromosome analysis was performed on 83 embryos, including 75 trophectodermcellsand 8 blastomeres. Except 7 embryos failed to amplify, 9.01%embryos were diagnosed as euploidy, and 90.91% were diagnosed as abnormal. As for group A, the euploid embryo rate was 10.71%and the abnormal embryo rate was 89.29%. In group B,the euploid embryo rate was 3.85%, the abnormal embryo rate was 96.15%. The euploid embryo rate was 13.04%, the abnormal embryo rate was 86.96% in group C. There were no significant differences among the three groups (P = 0.55).ConclusionsThe lowest rate of high quality blastocysts has been for three-way rearrangements and the lowest rate of euploidy has been for double two-way translocations, although no significant difference. Different types of BCCR maybe have little effect on the embryonic molecular karyotype. The difference of influence of BCCR on early embryonic developmentandmolecular karyotypeshould be further studied.

Artificial oocyte activation to improve reproductive outcomes in couples with various causes of infertility: a retrospective cohort study.

Does calcium ionophore treatment of oocytes improve fertilization rate, embryo development and outcomes in specific groups of infertile couples? This retrospective cohort study involved 796 couples undergoing oocyte activation with calcium ionophore (A23187) after intracytoplasmic sperm injection (ICSI) between 2016 and 2018. All metaphase II oocytes were exposed to 5 μmol/l ionophore for 15 min immediately after ICSI, cultured in vitro to the blastocyst stage, and transferred to the uteri of recipients on day 5 or cryopreserved for transfer in the next cycle. The previous cycles of the same patients formed the control group. Among 1261 ICSI cycles and 796 ICSI-artificial oocyte activation (ICSI-AOA) cycles, implantation, positive beta-HCG, clinical pregnancy and live birth rates were significantly (P < 0.05 to P < 0.001) improved for all groups, compared with previous cycles, except live birth rate in women with primary ovarian insufficiency (POI). Compared with previous cycles, rates of blastulation (all P < 0.001) and high-quality blastocysts (P < 0.05 to P < 0.001) were increased significantly for couples with male factor (oligoasthenoteratozoospermia [OAT]), unexplained infertility and couples with both factors in the ICSI-AOA cycles. High-quality blastocyst rate was increased in couples with polycystic ovary syndrome (PCOS) (P = 0.0453). Miscarriage rates were decreased significantly (P < 0.05 to P < 0.001) in couples with OAT, PCOS and unexplained infertility in the treatment cycles. No significant differences were found for fertilization rate, embryo development or live birth rate in patients with POI between both groups. Artificial oocyte activation was able to 'rescue' the poor reproductive outcomes in certain types of infertile couples with history of failure to achieve pregnancy.