Efficient Conversion of Inert Nitriles to Multifunctional Poly(5-amino-1,2,3-triazole)s via Regioselective Click Polymerization with Azide Monomers under Ambient Conditions.

Nitrile compounds are abundant, stable, cheap, and readily available natural and chemical industrial sources. However, the efficient conversion of nitrile monomers to functional polymers is mostly limited due to their inert reactivity, and developing efficient polymerizations based on nitrile monomers under very mild conditions is still a big challenge. In this work, a facile and powerful base-catalyzed acetonitrile-azide click polymerization was successfully established under ambient conditions. This polymerization also enjoys the merits of short reaction time (15 min), 100% atom economy, transition-metal-free catalyst system, and regioselectivity. A series of poly(5-amino-1,2,3-triazole)s (PATAs) with high weight-average molecular weights (Mw, up to 204,000) were produced in excellent yields (up to 99%). The PATAs containing tetraphenylethene (TPE) moieties exhibit unique aggregation-induced emission (AIE) characteristics, which could be used to sensitively detect Fe(III) ions with a low limit of detection (1.205 × 10-7 M) and to specifically image lysosomes of living cells. Notably, PATAs could be facilely post-modified due to their containing primary amino groups in the polymer chains even through a one-pot tandem reaction. Thus, this work not only establishes a new powerful click polymerization to convert stable nitriles but also generates a series of PATAs with versatile properties for diverse applications.

First-in-human study of PSMA-targeting agent, [18F]AlF-P16-093: dosimetry and initial evaluation in prostate cancer patients.

PURPOSE: This is a first-in-human study to evaluate the radiation dosimetry of a new prostate-specific membrane antigen (PSMA)-targeted radiopharmaceutical, [18F]AlF-P16-093, and also initial investigation of its ability to detect PSMA-positive tumors using PET scans in a cohort of prostate cancer (PCa) patients. METHODS: The [18F]AlF-P16-093 was automatically synthesized with a GE TRACERlab. A total of 23 patients with histopathologically proven PCa were prospectively enrolled. Dosimetry and biodistribution study investigations were carried out on a subset of six (6) PCa patients, involving multiple time-point scanning. The mean absorbed doses were estimated with PMOD and OLINDA software. RESULTS: [18F]AlF-P16-093 was successfully synthesized, and radiochemical purity was > 95%, and average labeling yield was 36.5 ± 8.3% (decay correction, n = 12). The highest tracer uptake was observed in the kidneys, spleen, and liver, contributing to an effective dose of 16.8 ± 1.3 µSv/MBq, which was ~ 30% lower than that of [68Ga]Ga-P16-093. All subjects tolerated the PET examination well, and no reportable side-effects were observed. The PSMA-positive tumors displayed rapid uptake, and they were all detectable within 10 min, and no additional lesions were observed in the following multi-time points scanning. Each patient had at least one detectable tumor lesion, and a total of 356 tumor lesions were observed, including intraprostatic, lymph node metastases, bone metastases, and other soft tissue metastases. CONCLUSIONS: We report herein a streamlined method for high yield synthesis of [18F]AlF-P16-093. Preliminary study in PCa patients has demonstrated its safety and acceptable radiation dosimetry. The initial diagnostic study indicated that [18F]AlF-P16-093 PET/CT is efficacious and potentially useful for a widespread application in the diagnosis of PCa patients.

Extracellular vesicle-circEHD2 promotes the progression of renal cell carcinoma by activating cancer-associated fibroblasts.

BACKGROUND: The encapsulation of circular RNAs (circRNAs) into extracellular vesicles (EVs) enables their involvement in intercellular communication and exerts an influence on the malignant advancement of various tumors. However, the regulatory role of EVs-circRNA in renal cell carcinoma (RCC) remains elusive. METHODS: The in vitro and in vivo functional experiments were implemented to measure the effects of circEHD2 on the phenotype of RCC. The functional role of EVs-circEHD2 on the activation of fibroblasts was assessed by collagen contraction assay, western blotting, and enzyme-linked immunosorbent assay (ELISA). The mechanism was investigated by RNA pull-down assay, RNA immunoprecipitation, chromatin isolation by RNA purification, luciferase assay, and co-immunoprecipitation assay. RESULTS: We demonstrated that circEHD2 was upregulated in RCC tissues and serum EVs of RCC patients with metastasis. Silencing circEHD2 inhibited tumor growth in vitro and in vivo. Mechanistic studies indicated that FUS RNA -binding protein (FUS) accelerated the cyclization of circEHD2, then circEHD2 interacts with tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein eta (YWHAH), which acts as a bridge to recruit circEHD2 and Yes1-associated transcriptional regulator (YAP) to the promoter of SRY-box transcription factor 9 (SOX9); this results in the sustained activation of SOX9. Heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2B1) regulates the package of circEHD2 into EVs, then EVs-circEHD2 transmits to fibroblasts, converting fibroblasts to cancer-associated fibroblasts (CAFs). Activated CAFs promote the metastasis of RCC by secreting pro-inflammatory cytokines such as IL-6. Furthermore, antisense oligonucleotides (ASOs) targeting circEHD2 exhibited a strong inhibition of tumor growth in vivo. CONCLUSIONS: The circEHD2/YWHAH/YAP/SOX9 signaling pathway accelerates the growth of RCC. EVs-circEHD2 facilitates the metastasis of RCC by converting fibroblasts to CAFs. Our results suggest that EVs-circEHD2 may be a useful biomarker and therapeutic target for RCC.

Association of computed tomography-based body composition with survival in metastatic renal cancer patient received immunotherapy: a multicenter, retrospective study.

OBJECTIVES: To investigate the association of computed tomography-assessed body composition with survival outcomes of metastatic renal cell carcinoma (mRCC) received immunotherapy. METHODS: In this multicenter, retrospective study, we reviewed 251 mRCC patients who received anti-PD1 from five centers. We analyzed the relationship between BMI, skeletal muscle area (SM), subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and subcutaneous adipose percentage (SAT%) with progression-free survival (PFS) and overall survival (OS). The spatial localization T cells was investigated by multiplex immunofluorescence. RESULTS: Among 224 evaluable patients, 23 (10.3%) patients were underweight, 118 (52.7%) had normal weight, 65 (29%) were overweight, and 18 patients (8%) were obese. The median age was 55 years and most patients were male (71%). No significant improvement in PFS (HR, 0.61; 95% CI, 0.27-1.42) or OS (HR, 1.09; 95% CI, 0.38-3.13) was observed for the obese patients. Besides, SM, VAT, and SAT were not associated with survival outcomes (all p > 0.05). Interestingly, SAT% independently predicted PFS (as continuous variable, HR: 0.02; 95% CI, 0.01-0.11) and OS (HR:0.05; 95% CI, 0.01-0.39), which remained significant in multivariate modeling (as continuous variable, adjusted HR for PFS, 0.01; 95% CI, 0.00-0.04; adjusted HR for OS, 0.08; 95% CI, 0.01-0.72). These associations were consistent in subgroup analysis of different gender, BMI, PD-L1 positive, and sarcopenia group. Tumor of high SAT% patients had a higher intratumoral PD1+ CD8+ T cell density and ratio. CONCLUSION: High SAT% predicts better outcomes in mRCC patients treated with anti-PD1 and T cell location may account for the better response. KEY POINTS: • CT-based subcutaneous adipose percentage independently predicted progression-free survival and overall survival. • Patients with a higher subcutaneous adipose percentage had a higher intratumoral PD1+ CD8+ T cell density and ratio.

Two rare variants reveal the significance of Grainyhead-like 3 Arginine 391 underlying non-syndromic cleft palate only.

OBJECTIVES: Non-syndromic cleft palate only (NSCPO) is one of the most common craniofacial birth defects with largely undetermined genetic etiology. It has been established that Grainyhead-like 3 (GRHL3) plays an essential role in the pathogenesis of NSCPO. This study aimed to identify and verify the first-reported GRHL3 variant underlying NSCPO among the Chinese cohort. METHODS: We performed whole-exome sequencing (WES) on a Chinese NSCPO patient and identified a rare variant of GRHL3 (p.Arg391His). A validated deleterious variant p.Arg391Cys was introduced as a positive control. Zebrafish embryos injection, reporter assays, live-cell imaging, and RNA sequencing were conducted to test the pathogenicity of the variants. RESULTS: Zebrafish embryos microinjection demonstrated that overexpression of the variants could disrupt the normal development of zebrafish embryos. Reporter assays showed that Arg391His disturbed transcriptional activity of GRHL3 and exerted a dominant-negative effect. Interestingly, Arg391His and Arg391Cys displayed distinct nuclear localization patterns from that of wild-type GRHL3 in live-cell imaging. Bulk RNA sequencing suggested that the two variants changed the pattern of gene expression. CONCLUSIONS: In aggregate, this study identified and characterized a rare GRHL3 variant in NSCPO, revealing the critical role of Arginine 391 in GRHL3. Our findings will help facilitate understanding and genetic counseling of NSCPO.

Optimal number of high-quality cleavage-stage embryos for extended culture to blastocyst-stage for transfer in women 38 years and older.

PURPOSE: We aimed to evaluate the pregnancy outcomes of cleavage-stage embryo transfers (ETs) for the first time and explore optimal number of high-quality cleavage-stage embryos for extended culture to blastocyst-stage in women of advanced maternal age (AMA). METHODS: We retrospectively identified 1646 AMA women ≥ age 38 years for the first fresh ETs between January 2014 and December 2020 at our hospital. Double ETs were divided into three groups as follows: DET-HH (two high-quality embryos), DET-HL (one high-quality and one low-quality embryo), and DET-LL (two low-quality embryos) groups. We mainly analyzed the pregnancy outcomes of double cleavage-stage ETs with different embryo grades and blastocyst-stage ETs with different number of high-quality cleavage-stage embryos on day 3. RESULTS: Our data indicated that the DET-HH group had significantly higher clinical pregnancy, ongoing pregnancy, and live birth rates than DET-HL and DET-LL groups (p < .05). For extended culture to blastocyst-stage with 2 (D3-2H), 3 (D3-3H), and 4 (D3-≥4H) high-quality cleavage-stage embryos, the D3-≥ 4H group had significantly higher ongoing pregnancy and live birth rates than D3-2H and D3-3H groups (p < .05). We observed that the number of high-quality embryos on day 3 was independently associated with live birth rate for blastocyst transfers (OR: 1.133, 95% CI 1.023-1.256, p = .017). There were no significant differences in the clinical pregnancy, ongoing pregnancy and live birth rates among DET-HH, D3-2H and D3-3H groups (p > .05). CONCLUSIONS: Extended culture to blastocyst-stage for transfer was safe and recommended for AMA women with ≥ 4 high-quality embryos on day 3.

Effect of ultra-low O2 (2%) tension on human in-vitro embryo development.

The study was aimed to investigate the effect of culturing human in-vitro embryos in ultra-low O2 (2%) tension. A total of 2298 oocytes from 152 patients between June 2017 and December 2017 treated with conventional in vitro fertilization (IVF) were harvested in this study. Oocytes were randomly assigned to the low (5%) or ultra-low (2%) O2 tension groups on the retrieval day. We observed that the day 3 good quality embryos (43.32 versus 42.01%; p=.635) and available embryos (82.02 versus 83.47%; p=.490) rates were similar between 2% and 5% condition. No differences were observed in the D5 blastulation rate (62.79 versus 61.85%; p=.735) and the proportion of good quality blastocysts on Day 5 (44.51 versus 45.61%; p=.700), nor in the total blastulation rate (71.26 versus 70.29%; p=.710) between 2% and 5% condition. In the first transfer, the blastocysts had similar clinical pregnancy (68.12 versus 71.08%; p= .692) and ongoing pregnancy (59.42 versus 62.65%; p=.684) rates from 2% and 5% condition. The employ of ultra-low O2 tension did not benefit for human in-vitro embryo development.

GTSE1 promotes prostate cancer cell proliferation via the SP1/FOXM1 signaling pathway.

G2 and S phase-expressed-1 (GTSE1) has been implicated in the pathogenesis of several malignant tumors. However, its specific role in prostate cancer (PCa) remains unclear. In this study, RNA-Seq data from patients with PCa and controls were downloaded from the FIREBROWSE database, and it was found that the GTSE1 mRNA level was significantly upregulated in PCa. Moreover, patients with higher GTSE1 mRNA levels had higher Gleason scores (P < 0.001), a more advanced pT stage (P = 0.011), and a more advanced pN stage (P = 0.006) as well as a shorter time to biochemical recurrence (P = 0.005). In addition, overexpression of GTSE1 could promote proliferation in LNCaP cells, whereas silencing GTSE1 could inhibit the growth of C4-2 cells in vitro and in vivo. Mechanistically, GTSE1 enhanced the expression of FOXM1 by upregulating the SP1 protein level, a transcription factor of FOXM1, which ultimately promoted PCa cell proliferation. In summary, GTSE1 is a new candidate oncogene in the development and progression of PCa, and it can promote PCa cell proliferation via the SP1/FOXM1 signaling pathway.

The characteristics and risk factors of healthcare-seeking men with lower urinary tract symptoms in China: Initial report from the POInT group.

AIMS: To investigate the clinical characteristics of health care-seeking men presenting with lower urinary tract symptoms (LUTS) in China and to reveal risk factors for symptom severity. METHODS: This multicenter, hospital-based, cross-sectional study recruited 1477 eligible male subjects, who were at least 45 years, seeking health care at 9 participating hospitals across the mainland China. The general medical information and subjective symptoms were recorded, followed by the measurement of prostate volume, urodynamic indices, and laboratory tests for kidney function, plus glucose/lipid metabolism. Univariate and multivariate linear regression were employed for the detection of risk factors for symptom severity. RESULTS: The proportion of mild, moderate, and severe LUTS was 14.6%, 32.6%, and 52.8%, respectively, with 62.2% reporting the triple combination of storage, voiding, and postmicturition symptoms. Median prostate volume was 44.6 ml, and 71.1% were experiencing comorbidities. Thirteen independent risk factors for LUTS severity were identified, namely, nocturnal voiding episodes and the presence of straining and weak steam; the triple combination of symptom subtypes; general and nocturia quality of life; Qmax and bladder outlet obstruction index; and numbers of comorbidities, hypertension, estimated glomerular filtration rate, and cholesterol and glycosylated hemoglobin. CONCLUSIONS: The majority of health care-seeking LUTS men present with moderate-to-severe and overlapping symptoms, with a high prevalence of both lower urinary tract dysfunction and systemic comorbidities. The evidence from both urological and nonurological independent risk factors demonstrate the multifactorial nature of LUTS, for which a multidisciplinary management is essential.

Day 3 time lapse selection is beneficial for the patients with no good-quality embryos.

We aimed to evaluate whether or not time lapse selection was beneficial for the cleavage-stage embryo transfers. The study included 838 infertile women with good ovarian reserve (obtaining more than 8 oocytes) from January 2018 to August 2019. Based on the transferred embryos with different grades (grade I, II and III), the patients were divided into day 3 selection with conventional morphology (CM) and day 3 selection with time lapse (TL) groups. For the grade I and II embryos, we observed that CM and TL had similar implantation, clinical pregnancy and ongoing pregnancy (p > .05) rates. For the grade III embryos, we observed that CM group showed slightly lower implantation (36.74 versus 41.03%, p = .261) and clinical pregnancy (56.82 versus 64.10%, p = .182) rates than TL group. CM group showed significantly lower ongoing pregnancy (47.35 versus 59.83%, p = .025) rate than TL group. And we observed that CM group had significantly higher blastulation (38.93 versus 26.61%, p = .019) rate than TL group. We concluded that TL selection was beneficial to the patients with no good-quality embryos in the first cleavage-stage embryo transfers.

Effects of three pro-nuclei (3PN) incidence on laboratory and clinical outcomes after early rescue intracytoplasmic sperm injection (rescue-ICSI): an analysis of a 5-year period.

OBJECTIVES: We aimed to explore the effect of three pro-nuclei (3PN) incidence on laboratory and clinical outcomes after early rescue intracytoplasmic sperm injection (rescue-ICSI). METHODS: This study included 509 early rescue-ICSI cycles from February 2014 to February 2019. The patients were divided into 3PN = 0% (394 cycles) and 3PN > 0% (115 cycles) group. Main outcomes compared were good quality embryo, available embryo, implantation (IR), clinical pregnancy (CPR), abortion (AR) and live birth rates (LBR). RESULTS: There were no significant differences in the basal characteristics between two groups (p > .05). We observed that 3PN = 0% and 3PN > 0% groups had similar good quality embryo (47.02 versus 46.80%; p = .917) and available embryo (83.28 versus 81.37%; p = .247) rates. Our results showed that the IR (47.26 versus 51.05%; p = .357), CPR (61.17 versus 66.08%; p = .338) and LBR (52.80 versus 50.43%; p = .656) were comparable between 3PN = 0% and 3PN > 0% groups. The 3PN = 0% group showed significantly lower AR than that in the 3PN > 0% group (11.20 versus 21.05%; p = .029; OR 2.114; 95% CI 1.069-4.178). CONCLUSIONS: 3PN incidence made negative effects on the clinical outcomes after early rescue-ICSI.

A new NLRP5 mutation causes female infertility and total fertilization failure.

OBJECTIVE: The genetic reasons of total fertilization failure (TFF), especially regarding suspected oocyte-related factors, are largely unknown. Only PLCZ1, TLE6 and WEE2 mutations have been shown to result in human fertilization failure. The aim of this study is to report a new NLRP5 mutation which causes female infertility and total fertilization failure. METHODS: A patient presenting TFF after two failed cycles was included. In the first cycle, 13 oocytes were obtained, all of which were inseminated by IVF, but there was no sign of fertilization. In the second cycle, 11 oocytes were obtained, 8 of which were matured; however, none were fertilized upon ICSI and ICSI-AOA. Peripheral blood samples were taken from the patient and her family members. The whole-exome sequencing was performed on them. RESULTS: We identified two heterozygous missense variants NLRP5 (NM_153447.4: c.1598G > C and 1919 T > G; p.Arg533Pro and Leu640Arg) which could cause the incidence of TFF. The first mutation of c.1598G > C (p.Arg533Pro) was inherited from her father and the second mutation of c.1919T > G (Leu640Arg) was inherited from her mother. The sister with normal fertility did not carry these variants. CONCLUSIONS: A new NLRP5 mutation causes female infertility and the incidence of TFF.

Heteroaromatic Hyperbranched Polyelectrolytes: Multicomponent Polyannulation and Photodynamic Biopatterning.

We reported an efficient multicomponent polyannulation for in situ generation of heteroaromatic hyperbranched polyelectrolytes by using readily accessible internal diynes and low-cost, commercially available arylnitriles, NaSbF6 , and H2 O/AcOH. The polymers were obtained in excellent yields (up to 99 %) with extraordinary high molecular weights (Mw up to 1.011×106 ) and low polydispersity indices. The resulting polymers showed good processibility and high quantum yields with tunable emission in the solid state, making them ideal materials for highly ordered fluorescent photopatterning. These hyperbranched polyelectrolytes also possessed strong ability to generate reactive oxygen species, which allowed their applications in efficient bacterial killing and customizable photodynamic patterning of living organisms in a simple and cost-effective way.

High three pro-nuclei (3PN) zygotes proportion associated with normal embryo multinucleation at the two-cell stage: two cases report.

Objective: Blastomere multinucleation at the two-cell stage (MN2) is a common nuclear abnormality observed in early human embryos and known to decrease the implantation rate. The aim of this study is to explore whether or not there is a link between high 3PN zygotes proportion and MN2 incidence.Methods: For embryo culture in the conventional incubator, the evaluation of nuclear status of two-cell stage is usually not performed. Therefore, the MN2 phenomenon is easily ignored. The time-lapse monitoring system (TLS) offers a promising new method to evaluate embryo development. We reported two cases who had single 2PN zygote and more than four 3PN zygotes in the conventional in-vitro fertilization (c-IVF) cycle.Results: We observed the MN2 incidence in the single normal embryo by TLS which suggested that it might be resulted from high 3PN zygotes proportion incidence. No available embryo was obtained in the first c-IVF cycle and the intracytoplasmic sperm injection (ICSI) treatment was performed in the second cycle. In subsequent ICSI cycles, we observed no 3PN zygotes incidence and transferred two day 3 embryos for the patients. Finally, the two couples successfully obtained healthy babies.Conclusions: High 3PN zygotes proportion might be associated with the MN2 incidence.

KCNQ1OT1 aggravates cell proliferation and migration in bladder cancer through modulating miR-145-5p/PCBP2 axis.

BACKGROUND: The large involvement of long non-coding RNAs (LncRNAs) in the biological progression of numerous cancers has been reported. The function of lncRNA KCNQ1OT1 in bladder cancer (BC) remains largely unknown. This study aimed to explore the critical role of KCNQ1OT1 in BC. MATERIALS AND METHODS: The qRT-PCR was applied to test the expression of RNAs. Cell proliferation was detected by CCK-8 and colony formation assays. Cell apoptosis was measured by TUNEL and flow cytometry experiments. Wound healing and transwell assays were employed to evaluate cell migration and invasion ability respectively. Western blot assay was used to measure relevant protein expression. Immunofluorescence (IF) staining was used to observe EMT process in BC. RESULTS: KCNQ1OT1 was significantly overexpressed in BC tissue and cell lines. KCNQ1OT1 depletion repressed cell proliferation, migration and invasion, whereas encouraged cell apoptosis. KCNQ1OT1 was a negatively/positively correlated with miR-145-5p/PCBP2 in respect with expression. Mechanically, KCNQ1OT1 was sponge of miR-145-5p and up-regulated the expression of PCBP2. MiR-145-5p inhibition and PCBP2 up-regulation could countervail the tumor-inhibitor role of KCNQ1OT1 knockdown in BC. CONCLUSION: KCNQ1OT1 serves as competing endogenous RNA (ceRNA) to up-regulate PCBP2 via sponging miR-145-5p in BC progression.

Do day-3 embryo grade predict day-5 blastocyst transfer outcomes in patients with good prognosis?

The main aim was to investigate whether or not day-3 embryo grade could predict day-5 blastocyst transfer outcomes in patients with good prognosis. This study included 233 elective single blastocyst transfers (eSBT) by D5 selection with conventional morphology (CM) and 121 elective single blastocyst transfers (eSBT) by D5 selection with time-lapse monitoring system (TL) from October 2016 to October 2017. All the patients were submitted to controlled ovarian stimulation (COS) with long-term protocol and transferred for the first time. The main outcome measures were clinical pregnancy rates (CPR) and ongoing pregnancy (OPR). Our results suggested that CPR (58.04 versus 57.89 versus 55.56%; p = .957) and OPR (66.07 versus 65.79 versus 64.44%; p = .981) were comparable among day 3 grades I, grades II, and grades III groups. We also observed that the TL group showed a slightly better CPR and OPR than CM group (p > .05). Our findings suggested that good or poor embryos at day-3 were not predictive of the outcomes of good-quality blastocysts in a good-prognosis population. It needed to be emphasized that time-lapse monitoring might be useful for elective single blastocyst transfer.

Low oxygen environment facilitates embryo availability for older ovarian responders (PORs).

We aimed to investigate the different effects of low oxygen (5% O2) and atmospheric oxygen (20% O2) on in vitro fertilization for older poor ovarian responders (PORs). We selected 1080 older PORs who met two criteria: (i) advanced maternal age (≥40) and (ii) an abnormal ovarian reserve test. All the patients used the ultra-short term protocols with GnRH agonist and recombinant FSH for controlled ovarian hyperstimulation (COH). About 506 cycles were performed in the incubators with 5% O2 and 574 cycles were performed in the incubators with 20% O2. No significant differences were observed in normal fertilization rates (59.68 versus 60.25%; p = .691) and cancelation rates (18.97 versus 19.34%; p = .879) between two groups. The number of available embryos (1.77 ± 0.57 versus 1.52 ± 0.50; p = .041) and mean number of cells on Day 3 (7.49 ± 1.82 versus 7.16 ± 1.70; p = .032) were significantly higher in 5% O2 group compared to that in 20% O2 group. It showed no significant differences in the implantation rates (27.43 versus 24.11%; p = .803) and clinical pregnancy rates (36.34 versus 30.05%; p = .307) between two groups. The employ of low oxygen culture did not improve clinical pregnancy rate for older PORs. However, it benefited early embryonic development for older PORs.

Clinical analysis of the patients with single fair cleavage-stage embryo on day 3.

OBJECTIVE: This study aimed to explore an appropriate selection for the patients with single fair cleavage-stage embryo on day 3. METHODS: This study included 469 fresh transfers and 220 frozen-thawed transfers from January 2014 to June 2016. Furthermore, in 72 patients who have only 4-6 fair embryos (4-5 blastomeres) on day 3, the blastocysts were cultured to day 5 for transfer. RESULTS: In the fresh transfers, the clinical pregnancy rate of 4-5 blastomeres group was significantly lower than 6-7 and 8-10 blastomeres group (5.88 vs. 30.13%, p<.001and 5.88 vs. 26.09%, p < .001). In the frozen-thawed transfers, the clinical pregnancy rate of 4-5 blastomeres group was also significantly lower than 6-7 and 8-10 blastomeres group (10.00 vs. 28.57%, p = .040 and 10.00 vs. 33.33%, p = .005). For the blastocyst transfers derived from fair embryos with 4-5 blastomeres, the clinical pregnancy rate was significantly higher than single and double fair embryo transfers of similar quality (44.44 vs. 7.04%, p < .001 and 44.44 vs. 28.09%, p = .013). CONCLUSIONS: For the patients with single fair embryo (6-7 blastomeres or 8-10 blastomeres), transfer at the cleavage stage is feasible. For the patients with single fair embryo (4-5 blastomeres), transfer of single fair embryo at the blastocyst stage or accumulating two fair embryos might be worthy of consideration.

Effect of normal sperm morphology rate (NSMR) on clinical outcomes for rescue-ICSI(R-ICSI) patients.

PURPOSE: To investigate whether the normal sperm morphology rate (NSMR) can affect the clinical outcomes of rescue-ICSI(R-ICSI) patients. METHODS: Based on different NSMR, the patients were divided into two groups as follows: NSMR < 4% and NSMR ≥ 4% group. Main outcomes compared were fertilization, cleavage, normal fertilization, high-quality embryo, transferrable embryo, no transferrable embryo cycles, implantation, clinical pregnancy and abortion rate. Some men's and women's basic parameters were compared between pregnancy and non-pregnancy group. RESULTS: The basic parameter such as female age, endometrial thickness, infertility duration, Gn administration, Gn days, basal serum FSH and basal serum E2 found no significant difference between NSMR < 4% and NSMR ≥ 4% group (p > 0.05). There was no significant difference in aspects of the number of retrieved oocytes, the number of transferred embryos, fertilization, cleavage, normal fertilization, high-quality embryo, transferrable embryo, no transferred embryo cycle, implantation, clinical pregnancy and abortion rate between two groups (p > 0.05). Between pregnancy and non-pregnancy group, we observed no significant difference in the female age, the number of retrieved oocytes, the number of high-quality embryo, the number of transferrable embryos, Gn administration, Gn does, endometrial thickness, infertility duration, basal serum FSH, basal serum E2, sperm concentration and progressively motile sperm (p > 0.05). CONCLUSIONS: Teratospermia made no effect on clinical outcomes of rescue-ICSI(R-ICSI) patients.

Effects of high three pro-nuclei (3PN) proportion incidence on clinical outcomes in the fresh cleavage-stage and blastocyst-stage embryo transfer (ET) cycles.

OBJECTIVES: The aim of this study was to explore the effect of three pro-nuclei (3PN) incidence on clinical outcomes in the fresh cleavage-stage embryo transfer (CSET) and blastocyst-stage embryo transfer (BSET) cycles. METHODS: This retrospective cohort study included 1427 CSET cycles, 632 BSET cycles, and 313 elective single BSET cycles from January 2013 to June 2015. The patients were divided into two groups as follows: Group 1 included patients with no 3PN zygotes and Group 2 included patients with >20% 3PN zygotes. RESULTS: We observed that the fertilization rate was significantly lower in 3PN = 0% than 3PN > 20% group (p < 0.05), but the day-3 grade I + II embryo and day-3 grade I + II + III embryo rates were not significantly different between 3PN = 0% and 3PN > 20% group (p > 0.05). Interestingly, in the CSET, the implantation (42.87% and 41.76%, p = 0.585) and clinical pregnancy (59.94% and 58.25%, p = 0.538) rates were not significantly different between two groups. In the BSET, the implantation (61.93% and 49.62%, p < 0.001) and clinical pregnancy rates (69.45% and 61.02%, p = 0.043) were significantly higher in 3PN = 0% than 3PN > 20% group. In the elective single BSET, the implantation (68.91% and 61.33%, p = 0.223) and clinical pregnancy rates (68.48% and 61.33%, p = 0.251) were higher in 3PN = 0% than 3PN > 20% group, but there was no significant difference. CONCLUSIONS: We concluded that a high 3PN incidence may predict poor outcomes in BSET but not CSET cleavage-stage.