Environmental estrogens, such as bisphenol A (BisA) and nonylphenol (NP), have been shown to affect the estrogen receptor (ER) expression and induce male reproductive abnormalities. To elucidate molecular mechanisms of action of xenoestrogenic chemicals on the expression of estrogen receptors in the testes of Nile tilapia (Oreochromis niloticus), three full-length cDNAs respectively encoding ntERalpha, ntERbeta1 and ntERbeta2 were cloned from testes. The amino acid sequences of ntERalpha, ntERbeta1 and ntERbeta2 showed a high degree of similarity to the relevant fish species. Tissue-specific expression study showed that three receptors were highly expressed in pituitary, liver, testis, kidney and intestine tissues. The ntERalpha, ntERbeta1 and ntERbeta2 mRNA expressions were significantly higher at the sexual early recrudescing stage than at other recrudesced stages. After being exposed to xenoestrogens from weeks 2 to 4, the ntERalpha mRNA levels were increased significantly in testes after NP treatment at all sampling times or after 4 weeks of exposure to BPA. The ntERbeta1 mRNA levels remained unchanged, while a significant decrease of the ntERbeta2 mRNA level was observed in testes after exposure to NP and BPA. The present study demonstrates that the regulation of all three ntER subtypes in testes may act via different molecular mechanisms of exposure to NP and BPA.

The TD(1) of TLI in patients with rNPC is 107.84 Gy in Lyman NTCP model. The nomogram model can accurately predict the risk of TLI for individual.

e18063 Background: Re-radiotherapy (re-RT) is the main treatment for locally recurrent nasopharyngeal carcinoma (lrNPC) patients, and commonly led to radiation-induced nasopharyngeal (NP) necrosis, which was lethal but rare study has focused on it. The aim of this study was to evaluate the cause and impact of radiation-induced NP necrosis in lrNPC patients who received re-RT. Methods: Totally 252 lrNPC patients who received re-RT between January 2013 and December 2020 were retrospectively collected. The inclusion criteria were as follows: (1) no NP necrosis before re-RT; (2) complete medical records, including treatment, clinical and dosimetric information; (3) conventional fractionated radiotherapy. All patients received intensity-modulated radiotherapy ± chemotherapy. Radiation-induced NP necrosis was diagnosed by magnetic resonance imaging and/or electronic nasopharyngoscopy. Dosimetric factors of the planning target volume of primary tumor (PTVp) were extracted from the dose-volume histogram (DVH), which was rescaled to an equivalent dose of 2 Gy per fraction (EQD 2 Gy) using a linear quadratic model. Logistic regression was used to identify the independent prognostic factors for generating the nomogram. Results: With a median follow-up of 44.63 months (inter-quartile range [IQR], 27.70 – 69.20 months), 47.6% of patients (120/252) occurred radiation-induced NP necrosis, which mostly happened within 1 year post re-RT (median [IQR], 5.83 [3.37 – 11.57] months). The 3-year overall survival was 83.0% vs 39.7% ( P＜0.001) in lrNPC patients with or without radiation-induced NP necrosis. Except for the fractionated dose, other dosimetric factors of PTVp were not significantly different between two groups, including D 98 (dose to 98% of PTVp), D 50 , D 2 and homogeneity index (Table). Furthermore, multivariate analysis showed that continuous variable age (HR [95%CI]: 1.04 [1.02 – 1.07], P = 0.003) and tumor volume (HR [95%CI]: 1.02 [1.01 – 1.03], P＜0.001), and fractionated dose > 2.22 Gy (HR [95%CI]: 2.36 [1.32 – 4.21], P = 0.004) were independent factors in predicting radiation-induced NP necrosis, which yielded a C-index of 0.742 (95% CI, 0.682 - 0.803) for OS in the nomogram. Conclusions: The incidence of radiation-induced NP necrosis was high in lrNPC patients who received re-RT. Patients with older age, larger tumor volume or receiving fractionated dose over 2.22 Gy were more easily to suffer NP necrosis, which need to explore novel treatment strategies to improve patients’ survivals. [Table: see text]

Radiation-induced temporal lobe injury (TLI) is one of the most common radiation-induced toxicities in nasopharyngeal carcinoma (NPC) treated by intensity-modulated radiotherapy (IMRT), especially in patients with cavernous sinus invasion whose planning target volume of nasopharynx (PTVnx) and temporal lobe (TL) is often overlapped. We named the overlap area as the sub-volume of PTVnx and TL (PTVsv-TL) and gave it independent prescription dose, and investigated its efficacy and feasibility in this study. From 2015 to 2020, T4 stage NPC patients with cavernous sinus invasion treated by independent prescription dose of PTVsv-TL (60-64Gy) were enrolled in study group, while T4 stage patients with cavernous sinus invasion treated by prescription dose recommended as international guidelines were enrolled in control group. The primary endpoint is the 3-year cumulative incidence of TLI, and secondary endpoints included dose parameters of TL, local recurrence rate and pattern, regional recurrence-free survival (RRFS), distant metastasis-free survival (DMFS) and overall survival (OS). SPSS 25.0 was used for statistical analysis. Totally, 137 and 357 patients were enrolled in the study group and control group, respectively. The median follow-up time was 33.0 months (inter-quartile range, 22.0-44.0 months). 17.6% patients (87/494) were diagnosed as TLI by MRI. The 3-year cumulative incidence of TLI in the study and control group were 15.3% and 28.5% (P=0.006). The dose parameters of TLs in two groups were as follows: D2, D0.5cc, D1cc and D2cc were 62.0 vs 70.5Gy, 66.1 vs 73.2Gy, 64.1 vs 72.1Gy, and 61.8 vs 70.0Gy (all P<0.001). The 3-year cumulative local recurrence rate were 6.2% and 10.4% in the study and control groups (P=0.170), with 2 cases of marginal failure in each group and none out-field failure. The 3-year PFS and OS rates were 87.8% vs 90.4% (P=0.275), 86.3% vs 88.2% (P=0.649), and 97.2% vs 97.3% (P=0.581). Giving independent prescription dose to PTVsv-TL could significantly reduce the irradiated dose of TLs and decrease the incidence of TLI, meanwhile achieved satisfactory local control and long-term survival. Further prospective study is warranted.

Objective:To investigate the clinical characteristics and therapeutic effect of adult primary hemophagocytic syndrome (HPS).Methods:The clinical data of a patient with primary HPS in the Third Affiliated Hospital of Southern Medical University in July 2017 were retrospectively analyzed, and the related literature was reviewed.Results:The patient was a 53-year-old female without history of basic disease, presenting as repeated high fever, with mutation of STXBP2 (FHL5), and was diagnosed as HPS according to hemophagocytic lymphohistiocytosis (HLH)-2004 criteria. The patient was treated with HLH-2004 regimen, and the efficacy was good. The patient was followed up until May 2021, and the overall survival time was 45 months.Conclusions:The atypical primary HPS and delayed primary HPS are rare, with mild clinical symptoms and only manifested by repeated high fever. Therefore, the gene mutations associated with HPS should be detected as soon as possible to confirm the diagnosis and to treat the disease early.

Objective:To analyze the clinical features and survival of acute myeloid leukemia (AML) after chemotherapy and radiotherapy of malignant solid tumors.Method:The clinical characteristics, treatment, and survival of 8 AML patients after chemotherapy and radiotherapy of malignant solid tumors hospitalized in The Sixth Affiliated Hospital of Sun Yat-sen University from August 2016 to February 2021 were analyzed retrospectively.Results:There were 3 males and 5 females in 8 patients, with a median age of 55 (from 48 to 64) years old. According to the French-American-British collaboration group (FAB) type, there were 1 case of M0, 1 case of M2, 1 case of M3, 3 cases of M4, and 2 cases of M5. There were 2 cases of low-risk group, 1 case of medium-risk group, and 5 cases of high-risk group according to the National Comprehensive Cancer Network (NCCN) prognostic stratification. There were 4 cases of colon cancer, 2 cases of breast cancer, 1 case of ovarian cancer, and 1 case of cervical cancer according to the classification of solid tumors, and the main stages were stage Ⅲ-Ⅳ. The median time interval for the diagnosis of two primary malignant tumors was 22 months (from 6 to 132 months). Karyotype analysis showed that 4 cases had complex karyotype abnormalities, 2 cases had normal karyotype, and 2 cases had chromosome karyotype changes with good prognosis. The detection results of AML prognostic mutation gene showed that a total of 11 mutations were detected, including TP53, ASXL1, FLT3-ITD, and other mutations as poor prognostic genes. Of the 8 patients, 4 cases died, 3 cases were still in treatment with partial remission, and 1 case was stable after treatment. The median overall survival of 8 patients was 3 (from 0 to 10) months.Conclusion:Treatment-related AML may occur after radiotherapy and chemotherapy in malignant solid tumors, with poor prognosis and short survival in middle and high risk groups.

BACKGROUND Monomorphic epitheliotropic intestinal T cell lymphoma (MEITL) is a rare extra-nodal T-cell lymphoma that has uniformly aggressive features with a poor prognosis. No standardized treatment protocols have been established. Previous experience has demonstrated favorable outcomes with combination chemotherapy followed by autologous hematopoietic stem cell transplant. However, many patients are unable to tolerate the toxicities. Chidamide is a new histone deacetylase inhibitor that has shown preferential efficacy in mature T-cell lymphoma. CASE SUMMARY We herein present two cases of MEITL who were both intermediate risk according to enteropathy-associated T cell lymphoma prognostic index. Case one was a 61-year-old man. He complained of upper abdominal pain and intermittent black stool for 2 mo. Imaging examination revealed that the intestinal wall was thickened. He received a partial excision of the small intestine. A chidamide-based combination regimen was given postoperatively. Eleven months later, he presented with recurrence in the bilateral lungs. He passed away 15 mo after his diagnosis. Case two was a 35-year-old woman who complained of abdominal distention for 1 mo. Positron emission tomography/computed tomography demonstrated wall thickening of the small intestine and upper sigmoid colon. Colon perforation and septic shock occurred on the fourth day of her admission. She was treated by sigmoid colostomy. Chidamide-based combination therapy was then provided. She was recurrence-free for 6 mo until lesions were found in the bilateral brain and lived for 17 mo since her diagnosis. Compared to historical data, chidamide seems to improve the prognosis of MEITL slightly. CONCLUSION MEITL is a type of aggressive lymphoma. Chidamide is a new promising approach for the treatment of MEITL.

Aristolochic acid (AA) is a compound extracted from the Aristolochia species of herbs. AA exposure is associated with kidney injury known as aristolochic acid nephropathy (AAN). Proximal tubular epithelial cell (PTEC) is the primary target of AA and rich in mitochondria. Recently, increasing evidence suggests that mitochondrial dysfunction plays a critical role in the pathogenesis of kidney disease. However, the status of mitochondrial function in PTEC after exposure to AA remains largely unknown. The aim of this study was to explore the effect of aristolochic acid I (AAI) on cell apoptosis and mitochondrial function in PTEC. Normal rat kidney-52E (NRK-52E) cells were exposed to different concentrations of AAI for different time periods. Cell viability was detected by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide, cell apoptosis was analyzed by flow cytometry, and the expression of cleaved caspase-3 by Western blotting. Mitochondrial function was evaluated by reactive oxygen species (ROS), mitochondrial membrane potential (MMP), mitochondrial DNA (mtDNA) copy number, and adenosine triphosphate (ATP). It was found that AAI reduced cell viability and increased cell apoptosis in a dose- and time-dependent manner. In parallel to increased apoptosis, NRK-52E cell manifested signs of mitochondrial dysfunction in response to AAI treatment. The data indicated that AAI could increase ROS level, lower MMP, decrease mtDNA copy number, and reduce ATP production. In addition, Szeto-Schiller 31, a mitochondria-targeted antioxidant peptide, attenuated AAI-induced mitochondrial dysfunction and apoptosis. Our study depicted significant aberrant of mitochondrial function in AAI-treated NRK-52E cell, which suggested that mitochondrial dysfunction may be involved in AAI-induced apoptosis in PTEC.

Embryo quality ranks one of the most important predictors in determining the success of implantation, and, clinically, some patients experience repeated IVF failure because of refractory poor embryo quality due to poor oocyte quality. Researches over the past decades leave no doubt that mitochondria are a hallmark of quality and developmental potential of human oocytes, therefore, mitochondrial transfer (MIT), i.e, injecting mitochondria into oocyte, was proposed to improve oocyte quality. Recent studies showed that mitochondrial transfer of mesenchymal stem cells (MSC) effectively protects epithelial cells from mitochondrial damage, suggesting mitochondria in MSC is healthy enough to be good sources for MIT treatment. Therefore, the aim of this study is to investigate the effect of MIT from autologous MSC in improving oocyte quality and clinical outcome in an IVF/ICSI program. Patients with repeated IVF/ICSI failure due to refractory poor embryo quality (no good-quality embryos obtained in at least two previous IVF cycles) were recruited in this retrospective study. 52 patients were recruited in this study. Prior to ovarian stimulation, 20 ml of bone marrow were aspirated from each patient's iliac crest under local anesthesia and BMSCs were isolated, cultured and frozen in vitro, and then thawed two days before oocyte retrieval for mitochondria preparation through differential centrifuge. Fluorescent real-time PCR was applied to quantify the absolute copy number of mtDNA. All mitochondria were suspended in fertilization medium for injection and 2 pl of solution (approximately 4000-5000 copy number of mtDNA) were injected into each mature oocyte together with one sperm during ICSI procedure. The average age and number of previous failed IVF cycles of this group of patients were 37.69±5.96 y and 4.75± 2.10 respectively. The mean number of oocytes obtained, mature oocytes, 2PNs, transferrable embryos and good-quality embryos were 8.04±5.41, 6.06±4.23, 4.54±3.46, 2.21±2.19 and 1.48±1.84, respectively. One in three D3 embryos was graded as good-quality after MIT, the rate of good-quality embryo was significantly higher than that in previous cycles (33.17% vs. 0%, P<0.05). Fresh embryo transfer was performed in 19 patients, and the pregnancy rate was 31.58% (6/19). In 18 patients, fresh embryo transfer was cancelled and the mean number of embryos frozen was 1.61±1.20. In summary, transferring mitochondria from autologous BMSCs into oocytes offer a new potential treatment to rescue compromised oocytes and normalizes embryo development without disturbing patients' mtDNA fingerprint.

AIM:We aim to investigate the incidence and associated factors of vitamin D deficiency, a seldom reported factor, in patients with stages 1 and 2 chronic kidney disease (CKD) in southern China. METHODS:We conducted a single-center observational study. Hospitalized patients over 14 years old, who were diagnosed with stages 1 and 2 CKD and had their serum 25-hydroxyvitamin D [25 (OH) D] measured, were included. Patients were divided into vitamin D deficient and non-deficient groups depending on the cutoff serum 25 (OH) D value of 37 nmol/L. Clinical and biochemical parameters were evaluated for associated factors of vitamin D deficiency by logistic regression. RESULTS:A total of 118 patients were included, of which 62 (52.5%) were vitamin D insufficient and 47 (39.8%) were vitamin D deficient. Using multivariate binary logistic regression analysis, high serum level of gamma-glutamyl transpeptidase (GGT) (OR = 5.163; 95%CI, 1.105-24.130; P = 0.037), dyslipidemia (OR = 3.083; 95%CI, 1.029-9.243; P = 0.044), 24-hour urinary protein excretion (UPE) ≥3.5 g/24 hrs (OR = 5.010; 95%CI, 1.316-19.074; P = 0.018), and treatment with glucocorticoids (OR = 2.973; 95%CI, 1.093-8.084; P = 0.033) were independently associated with vitamin D deficiency. In addition, among different types of nephropathy, minimal change disease (MCD) had the highest incidence (85.7%) of vitamin D deficiency. CONCLUSION:Poor vitamin D status is common in patients with stages 1 and 2 CKD in southern China. The incidence of vitamin D deficiency is 39.8%. High serum GGT level, dyslipidemia, 24-hour UPE ≥3.5 g/24 hrs, and treatment with glucocorticoids are independent associated factors of vitamin D deficiency.

To analyze spontaneous abortion rate and explore associated risk factors in patients with polycystic ovarian syndrome (PCOS) after in vitro fertilization/ intracytoplasmic sperm injection intracytoplasmic sperm injection- embryo transfers (IVF/ICSI-ET). A retrospective cohort study. We enrolled patients undergoing IVF/ICSI treatment in reproductive medicine center of the sixth affiliated hospital of sun yat-sen university between January 2013 and August 2017. A total of 2231 patients with PCOS were included. For comparison, we enrolled 2231 patients with tubular factors as control group. We compared spontaneous abortion rate and chromosomal abnormality rate between two groups in order to investigate the status of embryo -aneuploidy abnormality in etiologies of spontaneous abortion after IVF/ICSI-ET in PCOS patients. Furthermore, we compared clinical data between patients of spontaneous abortion and those of ongoing- pregnancy using univariate and multivariate analysis for risk factors of spontaneous abortion in PCOS patients after IVF/ICSI-ET. Patients in PCOS group had higher spontaneous abortion rate(24.15% vs.12.75%,P<0.001) and difference reached statistical significance. Chromosomal abnormality rate was significantly lower in PCOS group (36.05% vs. 55.56%,P=0.009). In patients with PCOS, those of spontaneous abortion had older age, higher body mass index (BMI) and HOMA-IR than those of ongoing pregnancy. All difference reached statistical significance. The further logistics regress analysis confirmed that the age, BMI and HOMA-IR were risk factors of spontaneous abortion in PCOS patients. There was no significant difference in the type of cycles, the quality of embryo transferred, the number of embryo transferred, fasting blood glucose, fasting insulin ect. Compared with non-PCOS patients, PCOS patients had higher rate of miscarriage, but chromosomal abnormalities were not a major factor for the high rate of miscarriage in PCOS patients. Age, BMI, and HOMA-IR were risk factors for spontaneous abortions after IVF/ICSI-ET in PCOS patients.

经常看到市面上有养生馆打着"淋巴结按摩排毒"的广告标语,那么,按摩淋巴结真的能达到排毒的作用吗? 淋巴属于免疫系统组成部分,网状似地分布于全身,由淋巴管和淋巴结组成.全身淋巴结有很多,淋巴管相交的地方都会形成淋巴结,体表可见的淋巴结主要分布于颈部、腋窝、腹股沟、盆腔等处;内脏深部的淋巴结一般不可见.人体局部的各种感染如细菌感染,会影响到引流的局部淋巴结,导致淋巴结肿大,也就是我们常说的发炎.

Objective: To study the effect of Bmi1 gene overexpression on hematopoietic differentiation colony-forming assay of human embryonic stem cells. Method: Human embryonic stem cell H1 was co-cultured with mouse bone marrow mesenchymal stem cells OP9 to simulate hematopoietic differentiation in vitro. On the eighth day of co-culture, CD34(+) hematopoietic progenitor cells were selected for colony- forming assay to induce hematopoietic colonies. The expression of Bmi1 gene and BMI1 protein in the process of H1 in vitro hematopoietic differentiation to CD34(+) precursor cells was respectively detected by real-time PCR and Western Blot. The human embryonic stem cell H1 which overexpress Bmi1 gene was subjected to hematopoietic differentiation in the same way. Compare the colonies generated by hematopoietic differentiation of the two types of H1 cells. Results: The expression of Bmi1 gene was first increased and then decreased in the process of in vitro hematopoietic differentiation to CD34(+) hematopoietic progenitor cells of human embryonic stem cells. Colony-forming assay showed H1 cells which overexpress Bmi1 gene produced significantly more erythroid colony forming units and mixed colony forming units than normal H1 cells. Conclusion: Overexpression of Bmi1 gene promote the production of erythroid and mixed colony forming units during hematopoietic differentiation of human embryonic stem cell H1.

To investigate the influence of supra-normal serum estradiol level in the endometrial receptivity of infertile women. To reveal the mechanism of estrogen action mediated through its novel membrane receptor. Single-centre, prospective cohorts study. Two cohorts of endometrial samples of 40 infertile women were used: 30 women underwent controlled ovarian hyperstimulation with GnRH-agonist long protocols, the other 10 women underwent nature cycle. Forty infertile women with regular BMI aged <40 years were recruited for endometrial microbiopsies at day 5 after oocyte retrieval, respectively. Women who were undergoing their first IVF/ICSI cycle were infertile mainly due to tubal or pelvic disease, ovulatory dysfunction, or male infertility. Endometriosis, polycystic ovary syndrome, endometrial polyps, abnormal uterine development and hydrosalpinx etc. were excluded. Women with nature cycle were defined as group A, and serum estradiol concentrations on the day of human chorionic gonadotrophin (hCG) administration of the 30 women were categorized into two groups: group B <3000 pg/ml, group C>3000 pg/ml. The serum progesterone concentration on the hCG day of all the subjects was less than 1.5 ng/ml. Various genes expression were analyzed, including the novel estrogen membrane receptor: G-protein-coupled estrogen receptor (Gper), and several endometrial receptive markers. In addition to the real-time PCR examination, the endometrial samples were also checked by histological results (histopathology and immunocytochemistry/ immunochemistry) and TUNEL assay. Statistical tests were carried out using one-way analysis of variance (ANOVA). Real-time PCR analysis of relative Gper expression revealed increased expression in the group C, which was significantly higher compared to group B (P < 0.05), with no difference between group A and B. Among the several receptive markers, mRNA of ITGα5 and ITGβ3 expression in group C were significantly decreased than in group B (P < 0.05), with no significant changes of other markers. However, the immunoreactive protein abundance of Gper did not parallel mRNA abundance. Its protein expression was significantly decreased in group C (P < 0.05). All protein expression of ITGα5, LIF (P < 0.01) and ITGβ3, EGF (P < 0.05) were decreased in group C than that of group B. The result of TUNEL sowed significantly increased apoptosis signals in group C than in group B, with no difference between group A and B. High serum estradiol concentrations on hCG day down regulated the protein expression of Gper. The increased apoptosis of endometrial cells was probably due to the impairment of estrogen response through Gper resulting from high serum estradiol concentrations, which may adversely affect the receptivity of endometrium. The present data suggestes a potential role for Gper in the hormonal regulation of endometrial receptivity, which should be taken into consideration for future hormonal treatment strategies.

To compare the in vitro fertilisation (IVF) outcomes of poor ovarian responders among women with laparoscopically diagnosed minimal–mild endometriosis (Group A), moderate–severe endometriosis (Group B) and those without endometriosis (Group C). The comparisons were made separately for age groups younger than 35 years and 35 years or older.

ObjectiveThis study aimed to assess live birth rate after fresh or frozen thawed embryo transfers in relation to maternal age for an individualized strategy for overall reproductive outcome.DesignA retrospective cochort study.Materials and MethodsAll patients undergoing fresh or frozen embryo transfers from 2010 to 2015 in our unit were enrolled. Individualized controlled ovarian hyper-stimulation protocols included long GnRH agonist, GnRH antagonist and minimal stimulation protocols. 5000-10,000 IU hCG (Ovidrel, Merck Serono) was utilized for follicular maturation and oocyte retrieval performed when appropriate. Intracytoplasmic sperm injection was adopted if the concentration of motile sperm was <1×106/mL, otherwise in vitro fertilization was used. Vitrification was performed for embryo freezing. The primary outcome was Live birth rate (LBR), defined as rate of deliveries that resulted in at least one live born baby per transfer. Chi-square and binary regression analysis were used for data analysis. A P39 years. Firstly, we found frozen cycles had higher LBR than that of fresh cycles (42.62% vs.38.81%, P<0.01). As expected, in blastocyst embryo transfer, LBR was significantly higher in frozen cycles in patients older than 30 years (56.02% vs.53.71%, P=0.106; 52.46%vs.42.93%, P<0.01; 38.11% vs. 29.27%, P<0.01; 19.38%vs.11.21%, P=0.01 for group1-4 respectively). Nevertheless, for cleavage-stage embryo, frozen cycles had lower LBR than that of fresh cycles in all age groups (37.41% vs.49.84%, P<0.05; 35.70% vs.44.58%, P <0.01; 23.75%vs.29.09%, P= 0.01; 8.70% vs.10.38%, P=0.17 for age group1-4 respectively), despite difference didn't reached statistical significance in those over 40 years. Further multivariate analysis confirmed the above results after adjusting covariates (such as age, number of embryo transferred, embryo quality, infertility etiologies etc.). Specifically, frozen blastocyst embryo transfers in cases over 40 years had more than twice chance getting live born baby than that of fresh cycles (adjusted OR 2.18,P=0.04). In term of miscarriage rate, no significant difference was observed between fresh and frozen cycles regardless of maternal age.ConclusionsIn every age-group, frozen cleavage-stage embryo transfers had lower LBR than that of fresh cleavage-stage embryo transfers, while frozen blastocyst transfers resulted in higher LBR than that of fresh cycles, showing blastocyst was the suitable stage for cryopreservation. Frozen blastocyst transfers obtained a comparatively stabile high LBR, especially in cases over 40 years. ObjectiveThis study aimed to assess live birth rate after fresh or frozen thawed embryo transfers in relation to maternal age for an individualized strategy for overall reproductive outcome. This study aimed to assess live birth rate after fresh or frozen thawed embryo transfers in relation to maternal age for an individualized strategy for overall reproductive outcome. DesignA retrospective cochort study. A retrospective cochort study. Materials and MethodsAll patients undergoing fresh or frozen embryo transfers from 2010 to 2015 in our unit were enrolled. Individualized controlled ovarian hyper-stimulation protocols included long GnRH agonist, GnRH antagonist and minimal stimulation protocols. 5000-10,000 IU hCG (Ovidrel, Merck Serono) was utilized for follicular maturation and oocyte retrieval performed when appropriate. Intracytoplasmic sperm injection was adopted if the concentration of motile sperm was <1×106/mL, otherwise in vitro fertilization was used. Vitrification was performed for embryo freezing. The primary outcome was Live birth rate (LBR), defined as rate of deliveries that resulted in at least one live born baby per transfer. Chi-square and binary regression analysis were used for data analysis. A P39 years. Firstly, we found frozen cycles had higher LBR than that of fresh cycles (42.62% vs.38.81%, P<0.01). As expected, in blastocyst embryo transfer, LBR was significantly higher in frozen cycles in patients older than 30 years (56.02% vs.53.71%, P=0.106; 52.46%vs.42.93%, P<0.01; 38.11% vs. 29.27%, P<0.01; 19.38%vs.11.21%, P=0.01 for group1-4 respectively). Nevertheless, for cleavage-stage embryo, frozen cycles had lower LBR than that of fresh cycles in all age groups (37.41% vs.49.84%, P<0.05; 35.70% vs.44.58%, P <0.01; 23.75%vs.29.09%, P= 0.01; 8.70% vs.10.38%, P=0.17 for age group1-4 respectively), despite difference didn't reached statistical significance in those over 40 years. Further multivariate analysis confirmed the above results after adjusting covariates (such as age, number of embryo transferred, embryo quality, infertility etiologies etc.). Specifically, frozen blastocyst embryo transfers in cases over 40 years had more than twice chance getting live born baby than that of fresh cycles (adjusted OR 2.18,P=0.04). In term of miscarriage rate, no significant difference was observed between fresh and frozen cycles regardless of maternal age. A total of 13426 cycles were assessed. We stratified patients into different age groups, i.e. <30 years, 30-34 years, 35-39 years and >39 years. Firstly, we found frozen cycles had higher LBR than that of fresh cycles (42.62% vs.38.81%, P<0.01). As expected, in blastocyst embryo transfer, LBR was significantly higher in frozen cycles in patients older than 30 years (56.02% vs.53.71%, P=0.106; 52.46%vs.42.93%, P<0.01; 38.11% vs. 29.27%, P<0.01; 19.38%vs.11.21%, P=0.01 for group1-4 respectively). Nevertheless, for cleavage-stage embryo, frozen cycles had lower LBR than that of fresh cycles in all age groups (37.41% vs.49.84%, P<0.05; 35.70% vs.44.58%, P <0.01; 23.75%vs.29.09%, P= 0.01; 8.70% vs.10.38%, P=0.17 for age group1-4 respectively), despite difference didn't reached statistical significance in those over 40 years. Further multivariate analysis confirmed the above results after adjusting covariates (such as age, number of embryo transferred, embryo quality, infertility etiologies etc.). Specifically, frozen blastocyst embryo transfers in cases over 40 years had more than twice chance getting live born baby than that of fresh cycles (adjusted OR 2.18,P=0.04). In term of miscarriage rate, no significant difference was observed between fresh and frozen cycles regardless of maternal age. ConclusionsIn every age-group, frozen cleavage-stage embryo transfers had lower LBR than that of fresh cleavage-stage embryo transfers, while frozen blastocyst transfers resulted in higher LBR than that of fresh cycles, showing blastocyst was the suitable stage for cryopreservation. Frozen blastocyst transfers obtained a comparatively stabile high LBR, especially in cases over 40 years. In every age-group, frozen cleavage-stage embryo transfers had lower LBR than that of fresh cleavage-stage embryo transfers, while frozen blastocyst transfers resulted in higher LBR than that of fresh cycles, showing blastocyst was the suitable stage for cryopreservation. Frozen blastocyst transfers obtained a comparatively stabile high LBR, especially in cases over 40 years.