Microplastics (MPs) disrupt the endocrine system by interfering with hormone production, signaling, and function, which can lead to hormonal imbalances and developmental disorders. This study systematically examined the effects of polyethylene (PE) MPs on circulatory hormone levels, uncovering the underlying mechanisms involving gut microbiota dysbiosis and metabolic changes. Female mice were exposed to PE MPs for 4 weeks, after which plasma levels of sex and enteropancreatic hormones were measured. Gut microbiota composition was analyzed through 16S rDNA sequencing, and plasma metabolites were profiled using high-throughput targeted metabolomics. The results revealed that PE MPs exposure significantly reduced circulating levels of glucagon-like peptide-1 (GLP-1), peptide YY (PYY), Anti-Müllerian hormone (AMH), and testosterone. Moreover, PE MPs notably altered the gut microbial community and plasma metabolite profile, with significant reductions in Akkermansia abundance and its associated metabolites, such as myristic acid and phenylacetylglycine. In vitro studies with primary colonic cells showed that myristic acid increased GLP-1 secretion through the G-protein coupled receptor 120 (GPR120), while phenylacetylglycine enhanced GLP-1 secretion via the peptide transporter 1 (Pept1). Additionally, Akkermansia abundance and its metabolites were strongly positively correlated with plasma levels of PYY, AMH, and testosterone. In conclusion, exposure to PE MPs disrupted hormonal release, likely mediated by alterations in gut microbiota-particularly Akkermansia-and associated metabolites.

Abstract Background The optimal interpregnancy interval (IPI) before reinitiating frozen-thawed embryo transfer (FET) after pregnancy loss remains uncertain, particularly in women undergoing assisted reproductive technology. Current guidelines recommending a waiting period are largely based on spontaneous conception data and may not apply to FET cycles. This study aimed to evaluate whether the length of IPI following biochemical or clinical pregnancy loss affects subsequent reproductive and neonatal outcomes in an infertile FET population. Methods In this retrospective cohort study, 2,620 infertile women who experienced a biochemical or clinical pregnancy loss after a preceding FET cycle and subsequently underwent a consecutive FET cycle derived from the same oocyte retrieval at a tertiary academic center between January 2011 and December 2022 were included. IPI was defined as the interval from the end of the failed pregnancy to the subsequent embryo transfer and categorized as < 6 months, 6–12 months, or 12–24 months. Live birth was the primary outcome. Secondary outcomes included conception, clinical pregnancy, pregnancy loss, and adverse neonatal outcomes. Multivariable logistic regression models were used to estimate adjusted odds ratios (aORs) with 95% confidence intervals (CIs). Results Using the IPI of 6–12 months as the reference, a shorter IPI (< 6 months) was not associated with a reduced likelihood of clinical pregnancy among women with prior biochemical pregnancy loss (aOR 1.29; 95% CI 0.88–1.89) or clinical pregnancy loss (aOR 0.93; 95% CI 0.71–1.21). Similarly, the odds of live birth were comparable between women who reinitiated FET within 6 months and those who waited 6–12 months, regardless of the type of preceding pregnancy loss (biochemical pregnancy loss: aOR 1.18; 95% CI 0.80–1.74; clinical pregnancy loss: aOR 0.94; 95% CI 0.73–1.23). Extending the IPI to 12–24 months did not confer additional benefits for reproductive outcomes. Rates of adverse neonatal outcomes, including preterm birth, low birth weight, and small for gestational age, were similar across all IPI categories. Conclusions Among infertile women undergoing FET after a biochemical or clinical pregnancy loss, reinitiating FET within 6 months was not associated with compromised reproductive or neonatal outcomes. These findings support the safety of early FET reinitiation and suggest that delaying subsequent treatment in the absence of medical indications may be unnecessary.

Asthenozoospermia, a prevalent contributor to male infertility, exhibits a multifaceted pathogenesis. This study identified a significant downregulation in sperm dynein heavy chain 3 (DNAH3) protein levels in individuals with asthenozoospermia. To elucidate the role of DNAH3 in asthenozoospermia, we constructed Dnah3-knockout mice, which exhibited asthenozoospermia and sterility. The sperm motility of Dnah3-knockout mice significantly declined compared to wild-type mice. However, spermatozoa from Dnah3-knockout mice displayed normal morphology in hematoxylin and eosin staining and transmission electron microscopy analyses. Sperm metabolomics revealed that DNAH3 deficiency disturbed sperm energy metabolism, resulting in substantial reductions of L-palmitoylcarnitine and glycocholic acid. Notably, offspring were successfully obtained from Dnah3-knockout male mice through intracytoplasmic sperm injection. Collectively, these findings indicate that DNAH3 deficiency induces disturbances in energy metabolism, rather than abnormalities in sperm flagellar morphology, culminating in asthenozoospermia development. Our investigation provides valuable insights into understanding asthenozoospermia and offers guidance for clinical consultation.

Microplastics (MPs) are pervasive environmental contaminants, resulting in unavoidable human exposure. This study identified MPs in follicular fluid and investigated the specific MPs and mechanisms that adversely affect oocytes. MPs in the follicular fluid of 44 infertile women undergoing assisted reproductive technology were measured using Raman microspectroscopy. Differential metabolites in follicular fluid were analyzed via untargeted metabolomics. Female mice were exposed to polyethylene (PE) to validate human findings. MPs, particularly PE, exhibited the highest detection rate (86.4 %) in human follicular fluid and showed a negative correlation with fertilization rates (r = -0.407, P = 0.007). Elevated PE levels altered metabolites primarily involved in metabolic pathways, ferroptosis, and ovarian steroidogenesis. In mice, PE exposure significantly reduced the number of retrieved oocytes (31.5 vs. 36.3, P < 0.05) and fertilization rate (70.8 % vs. 85.2 %, P < 0.001), while increasing the proportion of poor-quality oocytes (28.2 % vs. 16.5 %, P < 0.001) and reactive oxygen species (ROS) production compared to controls. RNA sequencing indicated significant upregulation of inflammation-related genes (Il10ra, Il1a, Il33, Tnfaip8l2, and Tnfrsf1b) in the PE-exposed group. In conclusion, PE exposure impairs oocyte quality possibly by disrupting follicular fluid metabolism, elevating inflammation-related gene expression, and increasing ROS production in oocytes.

Oligoasthenozoospermia, characterized by a low sperm count and impaired progressive motility, significantly contributes to male infertility. This study examines the metabolic disparities between individuals with oligoasthenozoospermia (n = 30) and healthy controls (n = 30) utilizing ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). A total of 1,331 metabolites were identified in positive ion mode and 870 in negative ion mode, with differential analysis indicating 211 significantly different metabolites between the two groups. Pathway analysis identified key metabolic pathways, including the pentose phosphate pathway, TCA cycle, glycerophospholipid metabolism, and fatty acid metabolism. Subsequently, various machine learning models, including Logistic Regression (LR), Random Forest (RF), and Support Vector Machine (SVM) were employed to assess the predictive capability of the identified metabolites, with 1-palmitoyl-2-docosahexaenoyl-sn-glycero-3-phosphocholine and [6]-gingerol demonstrating the highest predictive performance. The diagnostic model, developed using LR, attained high sensitivity (0.93), specificity (1), and accuracy (0.97), with an AUC of 0.998 in the training set and 0.963 in the test set. These findings offer critical insights into the metabolic changes associated with oligoasthenozoospermia and establish a dependable diagnostic framework for differentiating it from controls.

BACKGROUND:Oocytes from older females have a diminished ability to repair sperm DNA damage compared with those from younger females. Previous research has indicated that there is no significant correlation between sperm DNA fragmentation index (DFI) and the blastocyst euploidy rate in cycles utilizing oocytes donated by young individuals. However, it is still unclear whether a high DFI impacts the euploidy rate of blastocysts derived from oocytes obtained from women of advanced reproductive age. OBJECTIVE:The aim of this study was to investigate the potential association between sperm DFI and the euploidy rate of viable blastocysts in women of advanced age undergoing preimplantation genetic testing for aneuploidy (PGT-A). MATERIALS AND METHODS:A total of 667 blastocysts from 492 couples, all with maternal ages of 38 years or older, who underwent intracytoplasmic sperm injection (ICSI) combined with PGT-A were included in this study. The sperm DFI values were measured using the Sperm Chromatin Structure Assay (SCSA), and the couples were divided into three groups based on sperm DFI values: low DFI (DFI < 15%), moderate DFI (15% ≤ DFI ≤ 30%), and high DFI (DFI > 30%). RESULTS:No statistically significant differences were found in the rates of normal fertilization among the low, moderate, and high DFI groups (73.3%, 75.8%, and 75.4%, respectively; p > 0.05). Similarly, the rates of high-quality embryos were comparable among the groups (47.2%, 45.5%, and 45.7%, respectively; p > 0.05). The blastocyst formation rates also exhibited no significant differences among the groups (49.9%, 48.0%, and 49.3%, respectively; p > 0.05). Additionally, the aneuploidy rates of viable blastocysts were comparable across the groups (55.1%, 59.1%, and 60.6%, respectively; p > 0.05). Both the categorical analysis based on clinical DFI thresholds (<15%, 15%-30%, >30%) and the multiple linear regression treating DFI as a continuous variable (adjusted for female age, female body mass index [BMI], duration of infertility, number of miscarriages, and male age) revealed no statistically significant association between DFI and blastocyst euploidy rates (p = 0.733 for the categorical analysis; B = -0.003, standard error [SE] = 0.002; p = 0.136 for the continuous model). Furthermore, clinical pregnancy outcomes and neonatal results following the transfer of euploid blastocysts were comparable among the groups. DISCUSSION AND CONCLUSION:This study's findings suggest that elevated sperm DFI, as measured by the SCSA, does not significantly influence the euploidy rate of viable blastocysts in couples with advanced maternal age, whereas maternal age remains the predominant factor influencing embryo euploidy.

Background We aimed to test the hypothesis that transferring blastocysts derived from extended culture of cleavage-stage embryos for single embryo transfer in the first transfer cycle would result in better clinical outcomes than transferring frozen-thawed blastocysts, without affecting neonatal outcomes. Methods We conducted a retrospective propensity score-matched cohort study at a single reproductive medicine center. After excluding transfer cycles that did not meet the inclusion criteria, we classified the subjects into two groups based on the blastocyst transfer strategies. The group receiving blastocysts derived from the extended culture of the frozen-thawed cleavage-stage embryos was labeled the F3T5 group, while the group receiving frozen-thawed blastocysts was labeled the F5T5 group. The primary outcomes of this study were the implantation rate and the ongoing pregnancy rate. Secondary outcomes included the biochemical pregnancy rate, miscarriage rate, clinical pregnancy rate, and neonatal outcomes. Results After propensity score matching, a total of 811 blastocyst transfer cycles were included in the analysis. 307 cycles in the F3T5 group and 504 cycles in the F5T5 group. The results revealed that the F3T5 group had significantly higher rates of biochemical pregnancy (78.83% vs 66.07%, P < 0.001), clinical pregnancy (70.36% vs 59.72%, P = 0.029), implantation (70.36% vs 59.72%, P = 0.036), and ongoing pregnancy (64.17% vs 50.99%, P < 0.001) compared to the F5T5 group. There were no statistically significant differences between the two groups in terms of multiple pregnancy rate, ectopic pregnancy rate, miscarriage rate, and neonatal outcomes such as gestational weeks, single birth weight, and pregnancy complications ( P > 0.05). Conclusion Our findings suggested that transferring the single blastocyst derived from the extended culture of the frozen-thawed cleavage embryos in the first transfer cycle might offer a beneficial approach for optimizing assisted reproduction technology success rates in women under 36 years of age without affecting the neonatal outcomes.

BACKGROUND:Perfluoroalkyl and polyfluoroalkyl substances (PFAS) have been shown to disrupt normal follicular development and ovulation. However, it is unknown which specific PFAS in follicular fluid negatively impact oocyte development and embryo quality or whether any of the metabolites present in the follicular fluid contribute to these adverse effects. OBJECTIVES:We conducted a cross-sectional and cohort study to identify specific PFAS with significant adverse effects on embryo quality and their associated modes of action. METHODS:We enrolled 378 women undergoing assisted reproductive technology (ART) and collected follicular fluid samples during oocyte retrieval. We performed PFAS detection and untargeted metabolomics on the follicular fluid. The associations of individual PFAS with high-quality embryo rates and clinical pregnancy outcomes were assessed using beta regression and logistic regression, respectively, and the potential joint effect of mixtures of PFAS was assessed using Bayesian kernel machine regression (BKMR) and quantile g-computation models. A causal mediation effect model was performed to estimate the average indirect impact of PFAS, mediated by high-quality embryo rates, on clinical pregnancy outcomes, as well as its direct impact representing all other causal effects. Spearman's rank correlation coefficient was used to identify the associations between the differentially expressed metabolites and the high-quality embryo rates. RESULTS:The detection frequencies of 15 PFAS exceeded 85%, and perfluorooctanoic acid (PFOA) had the highest median concentration (6.54 ng/mL). The PFAS mixture was negatively associated with the high-quality embryo rate, and PFOA was the major contributor (conditional posterior inclusion probability=0.97295). PFAS was also negatively associated with clinical pregnancy outcome, and the causal mediation analysis revealed that the embryo quality potentially mediated the relationship between the clinical pregnancy outcome with PFOA [proportion mediated: 0.181; 95% confidence interval (CI): 0.024, 0.755], perfluoro-n-nonanoic acid (PFNA) (proportion mediated: 0.148; 95% CI: 0.022, 0.656), or perfluoro-n-tridecanoic acid (PFTrDA) (proportion mediated: 0.130; 95% CI: 0.005, 0.693). The decreased organonitrogens (Pro-Trp and lauryldimethylamine oxide) and sphingolipids metabolites (phytosphingosine, N-myristoylsphinganine, and N-lauroyl-d-erythro-sphinganine) in the follicular fluid were associated with PFOA-related poor embryo quality. CONCLUSIONS:High exposure to follicular fluid PFAS was negatively correlated with embryo quality during ART, with PFOA likely to be the major contributor. PFOA-related poor embryo quality was associated with the reduction of organonitrogens and sphingolipids metabolites that are crucial for the maintenance of normal cell growth and metabolism. https://doi.org/10.1289/EHP15422.

Research questionDoes the presence of smooth endoplasmic reticulum aggregates (SERa) in oocytes adversely impact the euploidy rate of subsequent blastocysts?DesignWe performed a retrospective cohort study with 671 young patients (< 38 years) undergoing their first preimplantation genetic testing for aneuploidy (PGT-A) between January 2019 and October 2022 at a reproductive medical center of university affiliated teaching hospitals in China. Cycles were categorized as either SERa(+) cycles (containing at least one SERa(+) oocyte) or SERa(-) cycles (all oocytes without SERa). In SERa(+) cycles, oocytes were further subdivided into the SERa(+) oocyte group and the sibling SERa(-) oocyte group, comprising oocytes with normal morphology.ResultsNo significant differences were observed in the normal fertilization rate (72.9% vs. 75.4% vs. 72.6%, P=0.343), and cleavage rate (96.8% vs. 97.1% vs. 96.4%, P=0.839) among the SERa(-) cycle group, the SERa(-) oocyte group, and the SERa(+) oocyte group. Additionally, there were no statistically significant differences in the rates of good quality embryos (44.7% vs. 48.8% vs. 46.2%, P=0.177) or blastocyst formation (60.1% vs. 60.9% vs. 60.5%, P=0.893) among the groups. However, the euploidy rate of blastocysts derived from SERa(+) oocytes was significantly lower compared to those from SERa(-) oocytes in SERa(+) cycles and normal oocytes in SERa(-) cycles (39.3% vs. 51.2% vs. 54.5%, P=0.005). Despite this, there were no significant differences in pregnancy and neonatal outcomes after euploid embryo transfer among the three groups.ConclusionsBlastocysts derived from SERa(+) oocytes have a lower euploidy rate than those derived from SERa(-) oocytes. Nevertheless, comparable reproductive outcomes were achieved following euploid embryo transfer from both SERa(+) and SERa(-) oocytes.

Background Semen quality is negatively correlated with male age and is mainly quantified by a routine semen analysis, which is descriptive and inconclusive. Sperm proteins or semen metabolites are used as the intermediate or end-products, reflecting changes in semen quality, and hold much promise as a new biomarker to predict fertility in advanced-aged males. Objectives In this study, we sought to assess whether the semen metabolome and proteome of aged males can affect semen quality and serve as biomarkers for predicting semen quality. Materials and methods We retrospectively analyzed 12825 males that underwent semen routine analysis to understand the age-dependent changes in sperm quality. To identify the difference between aged and young adults, metabolomics (n=60) analyses of semen and proteomics (n=12) analyses of sperm were conducted. Finally, integrated machine learning of metabolomics was conducted to screen biomarkers to identify aging semen. Results We discovered that male age was positively correlated with sperm concentration as well as DNA fragmentation index(DFI), and negatively with progressive motile sperm count, total sperm count, sperm volume and progressive sperm motility. The differential metabolites were significantly enriched in various metabolic pathways, and four of these differential metabolites (Pipamperone, 2,2-Bis(hydroxymethyl)-2,2’,2’’-nitrilotriethanol, Arg-Pro and Triethyl phosphate) were utilized to establish a biomarker panel to identify aging semen. Proteomic analysis showed that differential proteins were significantly enriched in protein digestion and absorption and some energy-related pathways. An integrated analysis of the metabolome and proteome identified differential energy metabolism and oxidative stress-related proteins, which could explain the decreased motility and the increased DFI of aging sperm Discussion and conclusion We provide compelling evidence that the changes in semen metabolome and sperm proteome are related to the decline of semen quality in aged males. Moreover, a biomarker panel based on four metabolites was established to identify aging semen.

To ascertain if assisted hatching (AH) increases the risk of placenta-associated diseases and perinatal outcomes after frozen–thawed cleavage-stage embryo transfer. We retrospectively evaluated 924 women who conceived with frozen–thawed cleavage-stage embryos transfer with (n = 390) or without (n = 534) laser-AH between 2013 and 2015. Data were obtained from the database on in vitro fertilization (IVF) patients in Shanghai First Maternity and Infant Hospital. We assessed neonatal (preterm birth, low birthweight, fetal macrosomia, stillbirth) and obstetric (miscarriage, ectopic pregnancy, post-term pregnancy, gestational diabetes (GDM), preeclampsia, intrahepatic cholestasis (ICP), placenta previa, placental abruption, premature rupture of membranes) outcomes. In twins, the median birthweight was lower in the AH group than that in the control group, and the prevalence of low birthweight (< 2500 g) was significantly higher in the AH group; after adjusting for maternal age, body mass index, mode of fertilization, and parity, no significant difference was found. In twins, no significant difference was detected in the prevalence of stillbirth or preterm pregnancy. In singleton births, there was no significant difference in the prevalence of low birthweight, macrosomia, preterm pregnancy or post-term pregnancy between the two groups. In singletons and twins, there were no significant differences in the prevalence of miscarriage, ectopic pregnancy, preeclampsia, GDM, ICP, or placenta abruption between the two groups. AH is a relatively safe method and our study provides important information for using this method in carefully selected patients.

Background The application of artificial oocyte activation (AOA) after intracytoplasmic sperm injection (ICSI) is successful in mitigating fertilization failure problems in assisted reproductive technology (ART). Nevertheless, there is no relevant study to investigate whether AOA procedures increase developmental risk by disturbing subsequent gene expression at different embryonic development stages. Methods We used a mouse model to explore the influence of AOA treatment on pre- and post-implantation events. Firstly, the developmental potential of embryos with or without AOA treatment were assessed by the rates of fertilization and blastocyst formation. Secondly, transcriptome high-throughput sequencing was performed among the three groups (ICSI, ICSI-AOA and dICSI-AOA groups). The hierarchical clustering and Principal Component Analysis (PCA) analysis were used. Subsequently, Igf2r/Airn methylation analysis were detected using methylation-specific PCR sequencing following bisulfite treatment. Finally, birth rate and birth weight were examined following mouse embryo transfer. Results The rates of fertilization and blastocyst formation were significantly lower in oocyte activation-deficient sperm injection group (dICSI group) when compared with the ICSI group (30.8 % vs. 84.4 %, 10.0 % vs. 41.5 %). There were 133 differentially expressed genes (DEGs) between the ICSI-AOA group and ICSI group, and 266 DEGs between the dICSI-AOA group and ICSI group. In addition, the imprinted gene, Igf2r is up regulated in AOA treatment group compared to control group. The Igf2r/Airn imprinted expression model demonstrates that AOA treatment stimulates maternal allele-specific mehtylation spreads at differentially methylated region 2, followed by the initiation of paternal imprinted Airn long non-coding (lnc) RNA, resulting in the up regulated expression of Igf2r. Furthermore, the birth weight of newborn mice originating from AOA group was significantly lower compared to that of ICSI group. The pups born following AOA treatment did not show any other abnormalities during early development. All offspring mated successfully with fertile controls. Conclusions AOA treatment affects imprinted gene Igf2r expression and mehtylation states in mouse pre- and post-implantation embryo, which is regulated by the imprinted Airn. Nevertheless, no significant differences were found in post-natal growth of the pups in the present study. It is hoped that this study could provide valuable insights of AOA technology in assisted reproduction biology.

BACKGROUND:The effect of male age on pregnancy outcomes after assisted reproductive technology (ART) treatment shown in the previous literature is controversial. In addition, the influence of male age on neonatal outcomes following ART treatment has less been investigated.OBJECTIVES:The aim of this study was to evaluate the effect of male age on reproductive and neonatal outcomes in couples following ART treatment.MATERIALS AND METHODS:A retrospective cohort study was performed in two centers for assisted reproduction from June 2010 to February 2019. A total of 5512 frozen-thawed embryo transfer (FET) cycles were included according to the criteria. The primary outcome measures were pregnancy and neonatal outcomes. Patients were categorized into five groups according to male age (younger than 30, 31-35, 36-40, 41-45, and older than 45), and the group younger than 30 years old was treated as the reference group.RESULTS:The logistic regression analysis showed that clinical pregnancy and live birth were all no statistic difference among the male age-groups compared with the reference group (p values, 0.743, 0.979, 0.948, 0.28; p values, 0.823, 0.342, 0.817, 0.381, respectively). Furthermore, no significant differences were found in the preterm birth rate, child sex, neonatal malformation, birth weight, and gestational age (p > 0.05). The advanced male age was not associated with a higher risk of adverse neonatal outcomes.DISCUSSION AND CONCLUSION:This study showed that there were no effects of male age on pregnancy or neonatal outcomes in infertile couples following their first FET cycles when females were younger than 36 years old.

BackgroundEarly cumulus cell removal combined with early rescue intracytoplasmic sperm injection (ICSI) has been widely practiced in many in vitro fertilization (IVF) centers in China in order to avoid total fertilization failure. However, uncertainty remains whether the pregnancy and neonatal outcomes are associated with early cumulus cell removal.ObjectivesTo investigate if early cumulus cell removal alone after 4 hours co-incubation of gametes (4 h group), has detrimental effect on the pregnancy and neonatal outcomes in patients undergoing IVF, through a comparison with conventional cumulus cell removal after 20 hours of insemination (20 h group).MethodsThis retrospective cohort study included 1784 patients who underwent their first fresh cleavage stage embryo transfer at the Centre for Assisted Reproduction of Shanghai First Maternity and Infant Hospital from June 2016 to December 2018 (4 h group, n=570; 20 h group, n=1214). A logistic regression analysis was performed to examine the independent association between early cumulus cell removal and pregnancy outcomes after adjustment for potential confounders. The neonatal outcomes between the two groups were compared.ResultsWhen compared with the 20 h group, the 4 h group had similar pregnancy outcomes, including rates for biochemical pregnancy, clinical pregnancy, ongoing pregnancy, miscarriage, ectopic pregnancy, multiple pregnancy, live birth. There were 1073 infants delivered after embryo transfer (4 h group, n=337; 20 h group, n=736). Outcomes in both groups were similar for both singleton and twin gestations, including preterm birth rate and very preterm birth rate, mean birth weight, mean gestational age, sex ratio at birth and rate of congenital birth defects. In addition, findings pertaining to singleton gestations were also similar in the two groups for Z-scores (gestational age- and sex-adjusted birth weight), rates of small for gestational age, very small for gestational age, large for gestational age and very large for gestational age infants.ConclusionsIn this study early cumulus cell removal alone was not associated with adverse pregnancy and neonatal outcomes. From this perspective, early cumulus cell removal to assess for a potential early rescue ICSI is therefore considered to be a safe option in patients undergoing IVF.

目的 探讨不同受精方式治疗非男性因素不孕高龄女性患者的效果.方法 选取2017年1月至2019年12月同济大学附属第一妇婴保健院生殖医学中心606例非男性因素不孕高龄女性患者,根据受精方式分为常规体外受精(IVF)组(421例)和卵胞浆内单精子注射(ICSI)组(185例).比较两组的临床结局及子代出生情况.结果 两组受精率、囊胚形成率比较,差异有统计学意义(P<0.05);两组卵裂率、D3可用胚胎率、D3优质胚胎率、临床妊娠率、种植率比较,差异无统计学意义(P>0.05).两组孕龄、出生体重、出生率、低体重儿出生率、早产率比较,差异无统计学意义(P>0.05).结论 在非男性因素不孕高龄女性患者中,常规IVF治疗比ICSI可以获得更高的受精率和囊胚形成率,且ICSI治疗非男性因素不孕症并不能提高其种植率和出生率.

目的 探讨35岁以下患者进行受精后第2天(D2)和第3天(D3)胚胎移植的妊娠结局及子代出生情况.方法 回顾性分析2017年1月-2019年12月上海市第一妇婴保健院辅助生殖医学科35岁以下患者行D2和D3胚胎移植的资料,其中在D2移植共158个周期,其中D3移植共3 601个周期.比较两组患者一般情况、妊娠结局及子代出生情况.结果 D2移植组患者基础FSH水平与D3移植组比较,差异有统计学意义(P＜0.05);两组患者其他基本资料比较,差异均无统计学意义(均P＞0.05).两组患者临床妊娠率、着床率、多胎妊娠率、异位妊娠率及流产率比较,差异均无统计学意义(均P＞0.05).两组新生儿孕周、出生体质量、出生率、低体质量儿出生率及早产率比较,差异均无统计学意义(均P＞0.05).结论 对于35岁以下患者,D2胚胎移植相对于D3胚胎移植不影响妊娠结果和子代出生情况,对于患者和生殖中心可以更加灵活地安排移植日期.

Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder in reproductive women where abnormal folliculogenesis is considered as a common characteristic. Our aim is to evaluate the potential of follicular fluid (FF) Raman spectra to predict embryo development and pregnancy outcome, so as to prioritize the best promising embryo for implantation, reducing both physiological and economical burdens of PCOS patients. In addition, the altered metabolic profiles will be identified to explore the aetiology and pathobiology of PCOS. In this study, follicular fluid samples obtained from 150 PCOS and 150 non-PCOS women were measured with Raman spectroscopy. Individual Raman spectrum was analyzed to find biologic components contributing to the occurrence of PCOS. More importantly, the Raman spectra of follicular fluid from the 150 PCOS patients were analyzed via machine-learning algorithms to evaluate their predictive value for oocyte development potential and clinical pregnancy. Mean-centered Raman spectra and principal component analysis (PCA) showed global differences in the footprints of follicular fluid between PCOS and non-PCOS women. Two Raman zones (993–1,165 cm−1 and 1,439–1,678 cm−1) were identified for describing the largest variances between the two groups, with the former higher and the latter lower in PCOS FF. The tentative assignments of corresponding Raman bands included phenylalanine and β -carotene. Moreover, it was found that FF, in which oocytes would develop into high-quality blastocysts and obtain high clinical pregnancy rate, were detected with lower quantification of the integration at 993–1,165 cm−1 and higher quantification of the integration at 1,439–1,678 cm−1 in PCOS. In addition, based on Raman spectra of PCOS FF, the machine-learning algorithms via the fully connected artificial neural network (ANN) achieved the overall accuracies of 90 and 74% in correctly assigning oocyte developmental potential and clinical pregnancy, respectively. The study suggests that the PCOS displays unique metabolic profiles in follicular fluid which could be detected by Raman spectroscopy. Specific bands in Raman spectra have the biomarker potential to predict the embryo development and pregnancy outcome for PCOS patients. Importantly, these data may provide some valuable biochemical information and metabolic signatures that will help us to understand the abnormal follicular development in PCOS.

Introduction The time-lapse imaging system (TLS) is a newly developed non-invasive embryo assessment system. Compared with conventional incubators, a TLS provides stable culture conditions and consistent observations of embryo development, thereby potentially improving embryo quality and selection of the best quality embryo. Although TLSs have been routinely used in many in vitro fertilisation (IVF) centres globally, there is insufficient evidence to indicate that TLSs result in higher cumulative live birth rates over conventional incubators. The purpose of this study is to compare the cumulative live birth rates and safety including miscarriage in infertile patients with diminished ovarian reserve (DOR) from both TLSs and conventional incubators.Methods and analysis This study is a double-blind randomised controlled clinical trial (1:1 treatment ratio of TLSs vs conventional incubator). A total of 730 patients with DOR undergoing the first or second cycle of IVF or intracytoplasmic sperm injection (ICSI) will be enrolled and randomised into two parallel groups. Participants will undergo embryo culture in the TLSs (group A) or the conventional incubators (group B), respectively. Embryos are selected for transfer in both groups by the morphological characteristics. The embryo selection algorithm software is not used in the TLSs. The primary outcome is the cumulative live birth rate of the trial IVF/ICSI cycle within 12 months after randomisation. This study is powered to detect an absolute difference of 10% (35% vs 25%) at the significance level of 0.05% and 80% statistical power based on a two-sided test.Ethics and dissemination This trial has been approved by the Institutional Ethical Committee of Shanghai First Maternity and Infant Hospital (KS1958). All participants in the trial will provide written informed consent. The study will be conducted according to the principles outlined in the Declaration of Helsinki and its amendments. Results of this study will be disseminated in peer-reviewed scientific journals.Trial registration number Chinese Clinical Trial Registry (ChiCTR1900027746).

PURPOSE:Tubulin beta eight class VIII (TUBB8) is essential for oogenesis, fertilization, and pre-implantation embryo development in human. Although TUBB8 mutations were recently discovered in meiosis-arrested oocytes of infertile females, there is no effective therapy for this gene mutation caused infertility. Our study aims to further reveal the infertility-causing gene mutations in the patient's family and to explore whether the infertility could be rescued by optimizing the conditions of embryo culture and finally achieve the purpose of making the patient pregnant. METHODS:Whole-exome sequence analysis and Sanger sequencing were performed on patients' family members to screen and identify candidate mutant genes. Construction of plasmids, in vitro transcription, microinjection of disease-causing gene cRNA, and immunofluorescence staining were used to recapitulate the infertility phenotype observed in patients and to understand the pathogenic principles. Simultaneously, overexpression of mutant and wild-type cRNA of the candidate gene in mouse oocytes at either germinal vesicle (GV) or metaphase II (MII) stage was performed in the rescue experiment. RESULTS:We first identified a novel heritable TUBB8 mutation (c.1041C>A: p.N347K) in the coding region which specifically affects the first mitosis and causes the developmental arrest of early embryos in a three-generation family. We further demonstrated that TUBB8 mutation could lead to abnormal spindle assemble. And moreover, additional expression of wild-type TUBB8 cRNA in the mouse oocytes in which the mutant TUBB8 were expressed can successfully rescue the developmental defects of resulting embryo and produce full-term offspring. CONCLUSIONS:Our study not only defines a novel mutation of TUBB8 causing the early cleavage arrest of embryos, but also provides an important basis for treating such female infertility in the future.

Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder in reproductive women and is characterized by polycystic ovaries, hyperandrogenism and chronic anovulation. Abnormal folliculogenesis is considered as a common characteristic of PCOS. Our aim is to identify the altered circRNA expression profile in exosomes isolated from follicular fluid (FF) of PCOS patients to investigate the molecular function of exosomal circRNA, as a vital mediator in follicular microenvironment, in the aetiology and pathobiology of PCOS. In this study, the circRNA expression profile of FF exosomes were compared between PCOS and control patients by RNA sequencing (N=5 vs 5). Sixteen circRNAs showed significantly different expression. GO and KEGG pathway analyses indicated that their parental genes were enriched in PCOS-related pathways, including ovarian steroidogenesis, aldosterone synthesis and secretion, and Jak-STAT signaling. Among sixteen differentially expressed circRNAs, hsa_circ_0006877 (circLDLR) was processed from its parental LDLR (low density lipoprotein receptor) transcript, which participated in ovarian steroidogenesis. Its depletion in PCOS FF exosomes was further verified in an additional cohort (N=25 vs 25) by qRT-PCR. And a circLDLR-miR-1294-CYP19A1 competing endogenous RNA (ceRNA) network was predicted by cytoscape software, and confirmed by luciferase assay and correlative expression in the cumulus cells of PCOS patients. Mechanistically, the intercellular transfer of functional circLDLR assay and its withdrawal experiments in KGN cells showed that depleting circLDLR in exosomes increased miR-1294 expression and inhibited CYP19A1 expression in recipient cells, as well as reduced their estrogen (E2) secretion. Our findings revealed a ceRNA network of circLDLR and provided new information on abnormal follicle development in PCOS.