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Abstract In this multicenter, non-inferiority, randomized trial, we randomly assigned 992 women undergoing in-vitro fertilization (IVF) with a good prognosis (aged 20-40, ≥3 transferrable cleavage-stage embryos) to strategies of blastocyst-stage (n = 497) or cleavage-stage (n = 495) single embryo transfer. Primary outcome was cumulative live-birth rate after up to three transfers. Secondary outcomes were cumulative live-births after all embryo transfers within 1 year of randomization, pregnancy outcomes, obstetric-perinatal complications, and livebirths outcomes. Live-birth rates were 74.8% in blastocyst-stage group versus 66.3% in cleavage-stage group (relative risk 1.13, 95%CI:1.04-1.22; Pnon-inferiority 3 days. Among good prognosis women, a strategy of single blastocyst transfer increases cumulative live-birth rates over single cleavage-stage transfer. Blastocyst transfer resulted in higher preterm birth rates. This information should be used to counsel patients on their choice between cleavage-stage and blastocyst-stage transfer (NCT03152643, https://clinicaltrials.gov/study/NCT03152643 ).

Abstract Background Insulin resistance (IR) is related with adverse outcomes of in vitro fertilization (IVF) in women with obesity, but little is known about the relationship between IR and unexpected poor ovarian response (uPOR) in non-obese subjects with sufficient ovarian parameters (classified as POSEIDON group 1). This research aims to explore the association between the homeostasis model assessment of insulin resistance (HOMA-IR) and uPOR in non-obese women with normal biomarkers of ovarian reserve. Methods The retrospective cohort study was conducted at a fertility center. The main inclusion criteria were age

Abstract Background With the increasing incidence of obesity and the childbearing-age delay among women, a debate over obesity’s impacts on pregnancy and neonatal outcomes becomes hot. The potential negative effects of obesity and aging on fertility lead to an idea, whether an obese female pursuing IVF treatment can benefit from an ideal BMI achieved over a long-time weight loss process at the cost of aging? We aimed to assess the association between body mass index (BMI) and clinical or neonatal outcomes in patients undergoing in vitro fertilization (IVF) treatment, for answering whether it is necessary to lose weight first for obese patients, particularly those at advanced age. Methods A retrospective cohort study was performed using multicentered data from China. The women were stratified into 5 groups in terms of pre-gravid BMI (kg/m2) with the WHO obesity standard (group 1: BMI

Abstract Background PCOS patients with unexpectedly low oocyte yield following conventional ovarian stimulation are referred to as suboptimal responders. However, identifying suboptimal responders presents a significant challenge within reproductive medicine and limited research exists on the occurrence of suboptimal response. This analysis aimed to develop a predictive model of suboptimal response during in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatments in PCOS patients. Methods This retrospective study involved a cohort of 313 PCOS patients undergoing their first IVF/ICSI cycle from 2019 to 2022. Univariate logistic regression analyses, least absolute shrinkage, selection operator regression analysis, and recursive feature elimination were employed to identify relevant characteristics and construct predictive models. Moreover, a nomogram was constructed based on the best model. Receiver operating characteristic curves, decision curve analysis (DCA), and calibration curves were used to evaluate the model. Results The predictors included in the model were age, Anti-Mullerian hormone, antral follicle count, and basal follicle-stimulating hormone. The area under the receiver operating characteristic curve (AUC) was 0.7702 (95% confidence interval 0.7157–0.8191). The AUC, along with the DCA curve and calibration curve, demonstrated a satisfactory level of congruence and discrimination ability. Conclusion The nomogram effectively predicted the probability of suboptimal response in PCOS patients undergoing gonadotropin-releasing hormone antagonist protocol during IVF/ICSI treatment.

ObjectiveTo investigate whether progesterone levels on the human chorionic gonadotropin (hCG) trigger day are associated with clinical outcomes in fresh cycles and the first frozen–thawed cycles (the freeze-all strategy) following the transfer of a high-quality single blastocyst.MethodsThis single-center retrospective analysis was conducted on patients undergoing in vitro fertilization with the gonadotropin-releasing hormone (GnRH) antagonist protocol from January 2017 to December 2023. The study included the first and second oocyte retrieval cycles with progesterone levels ≤2 ng/ml on hCG trigger day. Clinical pregnancy rates and early miscarriage rates were compared among groups using curve fitting, threshold effect analysis, and multivariable regression.ResultsWhen progesterone levels were between 1 and 2 ng/ml, the pregnancy rate in fresh cycles was only 51% of that in cycles with progesterone levels ≤1 ng/ml (95% CI: 0.33, 0.79, p = 0.0028). And the pregnancy rate decreased by 25% (95% CI: 0.51, 1.09) for frozen cycles, although there was no statistically significant (p = 0.1273). When cycle types were used as a binary variable in multivariate regression analysis, it was found that the clinical pregnancy rate in frozen cycles was 1.84 times higher than in fresh cycles (OR = 1.84, 95% CI: 1.38–2.47). For progesterone levels between 1 and 2 ng/ml, the clinical pregnancy rate in frozen cycles was 2.90 times that of fresh cycles (OR = 2.90, 95% CI: 1.59, 5.29, p = 0.0015). Progesterone levels on hCG day had no impact on the clinical pregnancy rate in thaw cycles, nor did they affect miscarriage rates in fresh or thaw cycles (p > 0.05).ConclusionWhen progesterone levels on hCG trigger day were between 1 and 2 ng/ml, the clinical pregnancy rate for frozen–thawed cycles of high-quality single blastocyst transfer using an GnRH antagonist protocol significantly surpasses that of fresh cycles, thus elective frozen embryo transfer after the freeze-all strategy is recommended.

ObjectiveTo investigate the effects of combining gonadotropin-releasing hormone agonist (GnRHa) downregulation with hormone replacement therapy (HRT, GnRHa-HRT) on the clinical outcomes of patients undergoing frozen–thawed embryo transfer (FET).MethodsIn this retrospective study, we included patients who had FET between January 2018 and December 2022. They were categorized into HRT and GnRHa-HRT groups based on the endometrial preparation protocol. The study compared the clinical outcomes of patients in two groups. Possible factors affecting clinical outcomes were analyzed using univariate analysis. To analyze the impact of two endometrial preparation methods on clinical outcomes, multifactorial logistic regression was performed.ResultsThe rates of clinical pregnancy (47.31% vs. 59.60%), embryo implantation (37.58% vs. 49.65%), biochemical pregnancy (52.36% vs. 64.31%), and early abortion (7.07% vs. 10.77%) were statistically different between the two groups (p

Cancer stem cells (CSCs), accounting for only a minor cell proportion (< 1%) within tumors, have profound implications in tumor initiation, metastasis, recurrence, and treatment resistance due to their inherent ability of self-renewal, multi-lineage differentiation, and tumor-initiating potential. In recent years, accumulating studies indicate that CSCs and tumor immune microenvironment act reciprocally in driving tumor progression and diminishing the efficacy of cancer therapies. Extracellular vesicles (EVs), pivotal mediators of intercellular communications, build indispensable biological connections between CSCs and immune cells. By transferring bioactive molecules, including proteins, nucleic acids, and lipids, EVs can exert mutual influence on both CSCs and immune cells. This interaction plays a significant role in reshaping the tumor immune microenvironment, creating conditions favorable for the sustenance and propagation of CSCs. Deciphering the intricate interplay between CSCs and immune cells would provide valuable insights into the mechanisms of CSCs being more susceptible to immune escape. This review will highlight the EV-mediated communications between CSCs and each immune cell lineage in the tumor microenvironment and explore potential therapeutic opportunities.

ObjectiveThe objective of this study is to investigate the factors that influence the live birth rate (LBR) of the first single euploid frozen-thawed blastocyst transfer (FBT) cycles after preimplantation genetic testing for structural rearrangements (PGT-SR) in couples with balanced chromosomal translocations (BCT).DesignSingle center, retrospective and observational study.MethodsA total of 336 PGT-SR and the first single euploid FBT cycles between July 2016 and December 2022 were included in this study. The patients were divided into two groups according to the live birth outcomes. The parameters of the study population, controlled ovarian stimulation cycles, and FBT cycles were analyzed. Multivariable binary logistic regression was performed to find the factors that affected the LBR.ResultsThe percentage of blastocysts at developmental stage Day 5 compared to Day 6 (51.8% vs. 30.8%; P

BackgroundIdentifying poor ovarian response (POR) among patients with good ovarian reserve poses a significant challenge within reproductive medicine. Currently, there is a lack of published data on the potential risk factors that could predict the occurrence of unexpected POR. The objective of this study was to develop a predictive model to assess the individual probability of unexpected POR during in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatments.MethodsThe development of the nomogram involved a cohort of 10,404 patients with normal ovarian reserve [age, ≤40 years; antral follicle count (AFC), ≥5; and anti-Müllerian hormone (AMH), ≥1.2 ng/ml] from January 2019 to December 2022. Univariate regression analyses and least absolute shrinkage and selection operator regression analysis were employed to ascertain the characteristics associated with POR. Subsequently, the selected variables were utilized to construct the nomogram.ResultsThe predictors included in our model were body mass index, basal follicle-stimulating hormone, AMH, AFC, homeostasis model assessment of insulin resistance (HOMA-IR), protocol, and initial dose of gonadotropin. The area under the receiver operating characteristic curve (AUC) was 0.753 [95% confidence interval (CI) = 0.7257–0.7735]. The AUC, along with the Hosmer–Lemeshow test (p = 0.167), demonstrated a satisfactory level of congruence and discrimination ability of the developed model.ConclusionThe nomogram can anticipate the probability of unexpected POR in IVF/ICSI treatment, thereby assisting professionals in making appropriate clinical judgments and in helping patients to effectively manage expectations.

BackgroundsThe present study was designed to establish and validate a prediction model for high ovarian response (HOR) in the GnRH antagonist protocol.MethodsIn this retrospective study, the data of 4160 cycles were analyzed following the in vitro fertilization (IVF) at our reproductive medical center from June 2018 to May 2022. The cycles were divided into a training cohort (n=3121) and a validation cohort (n=1039) using a random sampling method. Univariate and multivariate logistic regression analyses were used to screen out the risk factors for HOR, and the nomogram was established based on the regression coefficient of the relevant variables. The area under the receiver operating characteristic curve (AUC), the calibration curve, and the decision curve analysis were used to evaluate the performance of the prediction model.ResultsMultivariate logistic regression analysis revealed that age, body mass index (BMI), follicle-stimulating hormone (FSH), antral follicle count (AFC), and anti-mullerian hormone (AMH) were independent risk factors for HOR (all P< 0.05). The prediction model for HOR was constructed based on these factors. The AUC of the training cohort was 0.884 (95% CI: 0.869–0.899), and the AUC of the validation cohort was 0.884 (95% CI:0.863–0.905).ConclusionThe prediction model can predict the probability of high ovarian response prior to IVF treatment, enabling clinicians to better predict the risk of HOR and guide treatment strategies.

BackgroundIntrauterine adhesions (IUA), arising from diverse etiological factors, pose a significant threat to female fertility, particularly during in vitro fertilization (IVF) treatment.ObjectiveTo assess the effectiveness of hysteroscopic adhesiolysis (HA) combined with periodic balloon dilation in treating IUA and its impact on reproductive outcomes in women undergoing IVF treatment.MethodsA total of 234 patients diagnosed with IUA were included in this study. The IUA women were categorized into three subgroups based on the severity of adhesion. All IUA patients underwent HA separation followed by periodic balloon dilation along with hormone replacement therapy (HRT). Frozen embryo transfer was performed post-treatment, and a comparative analysis of the general characteristics and clinical outcomes among the subgroups was conducted. The control group consisted of patients who underwent their first embryo transfer of HRT cycle without any uterine abnormalities, as assessed by the propensity score matching (PSM). The clinical outcomes of IUA group and control group were compared. Multivariate logistic regression analyses were employed to investigate the risk factors associated with live birth.Results① The endometrial thickness was significantly increased post-operation compared to pre-operation in all three IUA subgroups (all P 0.05). Multivariate logistic regression analyses revealed that age (aOR 0.878, 95% CI 0.817~0.944, P=0.001) and endometrial thickness after treatment (aOR 1.292, 95% CI 1.046~1.597, P=0.018) were the two significant risk factors for live birth rate. ③ Following the process of matching, a total of 114 patients were successfully enrolled in the control group. The baselines and the clinical outcomes were all comparable between the IUA group and control group (all P>0.05).ConclusionThe combination of HA and periodic balloon dilation is beneficial for improving endometrial receptivity and has a significant clinical impact on patients with IUA undergoing IVF.

Introduction Hormone replacement treatment (HRT) is the most commonly used endometrial preparation protocol for frozen embryo transfer (FET) in patients with polycystic ovary syndrome (PCOS). However, studies have found that HRT may increase the risk of hypertensive disorders of pregnancy and some obstetric complications. Letrozole is a new first-line ovulation induction drug for PCOS and can effectively induce spontaneous ovulation by reducing oestrogen levels. However, letrozole is still rarely used in FET and has only been reported in a few studies in Asian populations. High-quality, well-powered randomised controlled trials (RCTs) comparing HRT and letrozole-stimulated protocols are lacking. The aim of this study is to compare the efficacy and safety of two protocols in patients with PCOS.Methods and analysis This is a multicentre, open-label RCT in four reproductive medical centres in China. In total, 1078 women with PCOS will be randomised (1:1) to the letrozole-stimulated or HRT group in their first FET cycle and their pregnancy and perinatal outcomes during this cycle will be followed up and analysed. The primary outcome is live birth. Secondary outcomes are cycle cancellation rate, biochemical pregnancy, clinical pregnancy, miscarriage, ectopic pregnancy, obstetric and perinatal complications, neonatal complications and birth weight.Ethics and dissemination Ethical approval was obtained from the Institutional Review Board of Reproductive and Genetic Hospital of CITIC-XIANGYA (LL-SC-2022-001). Written informed consent will be obtained from each participant. The findings will be disseminated through conference presentations and publication in peer-reviewed journals.Trial registration number NCT05227391.

Abstract Biallelic variants in Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) are the main pathogenic factor of congenital absence of the vas deferens (CAVD), including congenital bilateral absence of the vas deferens (CBAVD) and congenital unilateral absence of the vas deferens (CUAVD). However, there are few reports about the correlation between CFTR variant and outcomes of assisted reproductive technology (ART) in CAVD patients of China. In this study, 104 patients with CAVD were recruited in Central China, and provided gene detection by the whole-exome sequencing, among them 69% (72/104) carried at least one variant in CFTR and one carried adhesion G protein-coupled receptor G2 (ADGRG2) variant. A total of 81 CAVD patients were treated with ART, of which 21 and 60 carried none or at least one variant in CFTR, respectively. The fertilization rate, cleavage rate, effective embryo rate, implantation rate, clinical pregnancy rate and live birth rate per fresh embryo transfer were compared between patients with and without CFTR variants. It was found that the ART outcomes had no significant difference whether the patients carried the CFTR variant or not. In addition, all of the offspring were healthy after follow-up. In conclusion, rare CFTR variants may play a major role in patients with CAVD in Central China, which were greatly different from other descent. There was no significant difference in ART outcomes in CAVD patients with or without CFTR variants. The limitations of this study were that there was no statistical analysis of the sperm quality through TESA and conclusions were relatively limited due to the small sample size of the study.

ObjectiveThe objective of the study was to explore the effect of body mass index (BMI) and insulin resistance (IR) levels on first-time assisted conception results and perinatal outcomes in young polycystic ovary syndrome (PCOS) patients.DesignThis was a single-center, retrospective, observational cohort study.PatientsYoung women with PCOS undergoing their first embryo transfer were included in the study.Main outcome measureEarly pregnancy loss rate was the main outcome measure.ResultsThe early pregnancy loss rate in the overweight + insulin resistance group (OW+IR group) was significantly higher than that in the non-overweight + non-insulin resistance group (NOW+NIR group) (18.16% vs. 9.02%, Bonferroni correction, P = 0.012). The early pregnancy loss rate in the non-overweight + insulin resistance group (NOW+IR group) and overweight + non-insulin resistance group (OW+NIR group) (18.18% and 17.14%, respectively) were also higher than that in the NOW+NIR group (6.07%), but the difference was not statistically significant (Bonferroni correction, all P > 0.05). No significant difference was found in clinical pregnancy rate, live birth rate, and macrosomia rate (all P > 0.05). After adjusting for confounding factors, BMI and IR levels were identified as independent risk factors for early pregnancy loss rate.ConclusionBMI and IR levels are independent risk factors for early pregnancy loss in young PCOS patients during the first embryo transfer cycle. Multiple indicators should be considered when assessing pregnancy outcomes, which will promote individualized pregnancy guidance and treatment procedures for PCOS patients.

ObjectiveTo investigate the impact of the progesterone concentration on the human chorionic gonadotropin (hCG) trigger day on clinical outcomes with an antagonist protocol.MethodsThe retrospective cohort study included a total of 1,550 fresh autologous ART cycles with one top-quality embryo transfer. Multivariate regression analysis, curve fitting, and threshold effect analysis were performed.ResultsA significant association was found between the progesterone concentration and clinical pregnancy rate (adjusted OR, 0.77; 95% CI, 0.62–0.97; P = 0.0234), especially in blastocyst transfer (adjusted OR, 0.56; 95% CI, 0.39–0.78; P = 0.0008). The association between the progesterone concentration and the ongoing pregnancy rate was insignificant. The clinical pregnancy rate showed a linear relationship with an increased progesterone concentration in cleavage-stage embryo transfer. In blastocyst transfer, as the progesterone concentration increased, the clinical and ongoing pregnancy rates showed a parabolic reverse-U curve; the curve initially increased before declining at high progesterone concentrations. The clinical pregnancy rate increased with a progesterone concentration up to 0.80 ng/mL rather than tended to be stable. The clinical pregnancy rate significantly decreased when the progesterone concentration was ≥0.80 ng/mL.ConclusionThe progesterone concentration on the hCG trigger day exhibits a curvilinear relationship with pregnancy outcomes in blastocyst transfer cycles, and the optimal threshold of the progesterone concentration is 0.80 ng/mL.

ObjectivesAssisted reproductive technology (ART) is an important part of reproductive medicine, whose possible effects on offspring’s health have drawn widespread attention in recent years. However, relevant studies are limited to postnatal short-term follow-up and lack of diverse sample sources analysis other than blood.MethodsIn this study, a mouse model was used to explore the effects of ART on fetal development and gene expression in the organs of offspring in the adulthood using next-generation sequencing. The sequencing results were then analyzed.ResultsThe results showed that it caused abnormal expression in 1060 genes and 179 genes in the heart and spleen, respectively. Differentially expressed genes (DEGs) in the heart are mainly enriched in RNA synthesis and processing, and the cardiovascular system development also shows enrichment. STRING analysis identified Ccl2, Ptgs2, Rock1, Mapk14, Agt, and Wnt5a as the core interacting factors. DEGs in the spleen are significantly enriched in anti-infection and immune responses, which include the core factors Fos, Jun and Il1r2. Further exploration revealed the abnormal expression of 42 and 5 epigenetic modifiers in the heart and spleen, respectively. The expression of the imprinted genes Dhcr7, Igf2, Mest and Smoc1 decreased in the hearts of ART offspring, and the DNA methylation levels of Igf2- and Mest-imprinting control regions (ICRs) increased abnormally.ConclusionIn the mouse model, ART can interfere with the gene expression pattern in the heart and spleen of the adult offspring and that these changes are related to the aberrant expression of epigenetic regulators.

IntroductionInsulin resistance (IR) may play a central role in the pathophysiology of polycystic ovary syndrome (PCOS). Controlled ovarian stimulation (COS) in PCOS women in the setting of assisted reproductive technology (ART) is always a challenge for clinicians. However, it remains unclear whether IR in women with PCOS correlates with reduced ovarian sensitivity to exogenous gonadotropin (Gn). This study aimed to explore the association between homeostasis model assessment of insulin resistance (HOMA-IR) and ovarian sensitivity index (OSI).MethodsIn this retrospective cohort study, we explored the association between Ln HOMA-IR and Ln OSI based on smoothing splines generated by generalized additive model (GAM). Then the correlation between HOMA-IR and OSI was further tested with a multivariable linear regression model and subgroup analysis.Results1508 women with PCOS aged 20-39 years undergoing their first oocyte retrieval cycle were included consecutively between 2018 until 2022. We observed a negative association between Ln HOMA-IR and Ln OSI by using smoothing splines. In multivariable linear regression analysis, the inverse association between Ln HOMA-IR and Ln OSI was still found in PCOS women after adjustment for potential confounders (β = -0.18, 95% CI -0.25, -0.11). Compared with patients with the lowest tertile of HOMA-IR, those who had the highest tertile of HOMA-IR had lower OSI values (β = -0.25, 95% CI -0.36, -0.15).DiscussionOur study provided evidence for the inverse correlation between IR and the ovarian sensitivity during COS in PCOS women. Herein, we proposed new insights for individualized manipulation in PCOS patients with IR undergoing ART.

Plain Language summary Infertility prevalence rate has increased in the past 30 years. Infertility plagues thousands of women of childbearing age. Although not life-threatening, the detrimental influence of infertility to patients, their families, and society should not be underestimated, especially in China. In order to investigate the prevalence of infertility, determine the associated factors, and promote disease prevention and treatment, we conducted a cross-sectional study among 20–49 year old women in Henan, one of the central provinces of China. This study distributed 920 questionnaires and collected 803 completed questionnaires. Interviews, questionnaires, and physical and ultrasound examinations were done. Among all the 765 participants in this study, the prevalence of infertility was 24.58%. The prevalence of primary infertility was 6.54%, and the secondary infertility was 18.04%. Age, history of gynecological surgeries and DOR may increase the risk of infertility. In conclusion, among women aged 20–49 years in Henan Province, China, the prevalence of infertility in 2019 was 24.58% and 61.17% of infertile women sought medical help.

Abstract Background Abdominal ectopic pregnancy (AEP) is a rare form of ectopic pregnancy. As the number of in-vitro fertilization (IVF) procedures continues to increase, the incidence of AEP will also rise. However, the rarity and atypical presentation of AEP make early diagnosis challenging. Case presentation Herein, we report an AEP following frozen-thawed embryo transfer (FET) in an artificial cycle. The patient was misdiagnosed with implantation failure when the serum human chorionic gonadotropin (hCG) level was detected as 2.59mIU/ml at fourteenth day after embryo transfer. Therefore, she was suggested to stop luteal phase support. However, a ruptured AEP was developed 33 days following embryo transfer, which was diagnosed by laparoscopic surgery. Conclusions The case highlighted the delayed serum β-hCG and massive intraperitoneal hemorrhage may be clues to make early diagnosis of AEP. Clinicians must attach great importance to close monitoring and bear in mind the possibility of abdominal pregnancy.

ObjectiveTo investigate the effects of blastocyst quality and morphological grade on the perinatal outcomes in patients undergoing frozen-thawed single blastocyst transfer cycles.MethodsThis single-center retrospective cohort study included 2648 singleton neonates resulting from frozen-thawed single blastocyst transfers performed between January 2017 and September 2021. Multivariate logistic regression was performed to evaluate perinatal outcomes for their association with blastocyst quality and morphological parameters.ResultTransfer of a good-quality blastocyst in a frozen-thawed cycle was associated with a lower rate of preterm delivery (PTD, adjusted OR =0.7, 95% CI 0.5-0.9; P=0.020) and a higher likelihood of a male neonate (adjusted OR =1.2, 95%CI 1.0-1.5; P=0.048). Compared with grade C inner cell mass (ICM) blastocyst transfer, grade B ICM (adjusted OR =0.5, 95%CI 0.2-0.9; P=0.027) and grade A ICM (adjusted OR =0.6, 95%CI 0.3-1.5; P=0.290) blastocyst transfers were associated with a lower rate of PTD, which was more evident for grade B ICM. After adjusting for confounders, the likelihood of a male neonate (grade B TE, OR =1.2, 95%CI 1.0-1.5, P=0.037; grade A TE OR =1.9, 95%CI 1.3-28, P=0.002) increased with increasing trophectoderm (TE) quality. Compared with expansion stage 4, the likelihood of a male neonate was 1.5 times greater with transfer of a stage 6 blastocyst (OR =1.5, 95%CI 1.0-2.3; P=0.06), and the risk of small for gestational age (SGA) was greater with transfer of a stage 5 blastocyst (adjusted OR =3.5, 95%CI 1.5-8.0; P=0.004). The overall grading of the blastocyst, expansion stage, ICM grade, and TE grade were not associated with length at birth, birthweight, large for gestational age (LGA), or birth defects (all P>0.05).ConclusionsIn frozen-thawed single blastocyst transfer cycles, transfer of a good-quality blastocyst was associated with a lower rate of PTD and a greater likelihood of a male neonate. Transfer of grade B ICM blastocysts decreased the rate of PTD, and TE quality was positively correlated with the likelihood of a male neonate.

Summary: Background: Polycystic ovary syndrome (PCOS) has become a major international public health concern. However, because of controversy about the diagnostic criteria and patient selection, estimates of its absolute prevalence and change with time vary greatly. Methods: We conducted two consecutive nationwide epidemiological surveys of the prevalence of PCOS in representative samples of reproductive-aged women in China in 2010 and 2020. Face-to-face interviews were performed by trained interviewers in each survey. All participants completed a questionnaire and underwent a physical examination, blood sampling, and transvaginal pelvic ultrasound. We assessed hyperandrogenism (H), chronic anovulation (O), and polycystic ovaries (P) to classify the presence of PCOS using the Rotterdam criteria. The prevalence of PCOS among reproductive-aged women was estimated after consideration of differential probabilities of selection and population distribution. We conducted a logistic regression analysis by using the probability of PCOS as a function of the survey year to acquire the trend information across the years. Findings: 28,739 respondents completed the survey, including 15,924 in the previously published 2010 survey and 12,815 in the new 2020 survey. In 2020, 826 participants could be diagnosed as having PCOS, with a weighted prevalence of 7.8% (95%CI: 7.0%, 9.0%) among women aged 20-49 years, leading to an estimate of 24.0 million women of reproductive age affected by this condition in China as a whole. The estimated prevalence in 2020 was higher than that of a decade ago despite identical research methods suggesting a two-thirds increase over the study period. Women with PCOS in 2020 also appeared to have a more severe phenotype overall than those of a decade ago, possibly reflecting a significantly higher prevalence of obesity, hyperandrogenism, and infertility. Interpretation: The prevalence of PCOS in Chinese women has increased significantly over the past 10 years. PCOS is a significant public health problem in women of reproductive age in China and national policy and guidelines should be re-examined in the light of the current data. Funding: National Key R&D Program of China and the National Natural Science Foundation of China.

Immunotherapy has become the breakthrough strategies for treatment of cancer in recent years. The application of messenger RNA in cancer immunotherapy is gaining tremendous popularity as mRNA can function as an effective vector for the delivery of therapeutic antibodies on immune targets. The high efficacy, decreased toxicity, rapid manufacturing and safe administration of mRNA vaccines have great advantages over conventional vaccines. The unprecedent success of mRNA vaccines against infection has proved its effectiveness. However, the instability and inefficient delivery of mRNA has cast a shadow on the wide application of this approach. In the past decades, modifications on mRNA structure and delivery methods have been made to solve these questions. This review summarizes recent advancements of mRNA vaccines in cancer immunotherapy and the existing challenges for its clinical application, providing insights on the future optimization of mRNA vaccines for the successful treatment of cancer.

Abstract Background Spent culture medium (SCM) as a source of DNA for preimplantation genetic tests aneuploidy (PGT-A) has been widely discussed. Methods Seventy-five blastocysts that were donated for research provided a unique possibility in which multiple specimens, including trophectoderm (TE) biopsy, SCM, and paired corresponding whole blastocyst (WB) specimens from the same blastocyst source, could be utilized for the purpose of this preclinical validation. Results To conduct a validation ploidy concordance assessment, we evaluated the full chromosomal concordance rates between SCM and WB (SCM-to-WB), and between TE and WB (TE-to-WB) as well as sensitivity, specificity and overall diagnostic accuracy. 78.67% (59/75) of NGS results in the SCM group were interpretable, a significantly lower percentage than their corresponding TE and WB groups. This discrepancy manifests itself in intrinsically low quantity and poor integrity DNA from SCM. Subsequently, remarkable differences in full concordance rates (including mosaicism, and segmental aneuploidies) are seen as follows: 32.2% (SCM-to-WB, 19/59) and 69.33% (TE-to-WB, 52/75), (p

ObjectiveThe objective of the study was to explore the effect of insulin resistance on pregnancy outcomes in patients with polycystic ovary syndrome (PCOS) from the first embryo transfer cycle.DesignThis was a single-center, retrospective, observational cohort study.PatientsIncluded in the study were women with PCOS for the first embryo transfer.Main Outcome MeasuresEarly miscarriage rate and macrosomia rate were the main outcome measures.ResultsWith increased HOMA-IR, the early miscarriage rate (7.14, 13.21, and 16.22%, respectively; P = 0.039), macrosomia rate (5.78, 11.79, and 17.58%, respectively; P = 0.026) and the incidence of gestational diabetes (GDM) (10.00, 14.50, and 25.67% respectively; P = 0.002) significantly increased, while the live birth rate markedly decreased (63.03, 55.27, and 47.88%, respectively; P = 0.004). No significant difference was found in clinical pregnancy rate, late miscarriage rate, low birthweight rate and baby gender ratio (all P >0.05). After adjusting for confounding factors, HOMA-IR was an independent risk factor of early miscarriage rate and macrosomia rate.ConclusionInsulin resistance is an independent risk factor for early miscarriage and macrosomia in PCOS patients during the first embryo transfer cycle. It is essential to give more attention before and after pregnancy for PCOS women with high HOMA-IR.

Abstract Background Poor ovarian response (POR), a manifestation of low ovarian reserve and ovarian aging, leads to a significant reduction in the pregnancy rate after in vitro fertilization-embryo transfer. Acupuncture has increasingly been used to improve the ovarian reserve. The purpose of this study will be to evaluate the effect of acupuncture on increasing the number of retrieved oocytes after controlled ovarian hyperstimulation in women with POR. Methods This will be a multicenter randomized controlled trial. A total of 140 women with POR will be randomly assigned to receive acupuncture or nontreatment for 12 weeks before controlled ovarian hyperstimulation. The primary outcome will be the number of retrieved oocytes. The secondary outcomes will be antral follicle counts, serum levels of anti-Müllerian hormone, basal serum levels of follicle stimulating hormone, luteinizing hormone and estradiol levels, scores from the self-rating anxiety scale, fertilization rates, cleavage rates, available embryo rates, and high-quality embryo rates. The safety of acupuncture will also be assessed. Discussion The results of this trial will help to determine the effectiveness of acupuncture in the treatment of POR. This may provide a new treatment option for patients with POR and their physicians. Trial registration AMCTR-IPR-18000198 . Registered on 10 August 2018.

ObjectiveTo investigate the effects of endometrial thickness (EMT) on pregnancy outcomes on hCG trigger day in fresh in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) cycles.MethodsA total of 42,132 fresh cycles between 1 January 2013 and 31 December 2019 were included in this retrospective cohort study. Data were collected from five reproductive centers of large academic or university hospitals in China. All patients were divided into different groups according to their endometrial thickness on hCG trigger day. Multivariate regression analysis, curve fitting and threshold effect analysis were performed.ResultsAfter adjusting for age, body mass index, infertility type, number of embryos transferred, number of retrieved oocytes and COS (controlled ovarian stimulation) protocols, significant associations were found between endometrial thickness and clinical pregnancy rate (adjusted odds ratio [aOR]: 1.05; 95% confidence interval [CI]: 1.06–1.08, P < 0.0001), live birth rate (aOR: 1.04; 95% CI: 1.03–1.05, P < 0.0001) as well as miscarriage rate(aOR: 0.96; 95% CI: 0.94 – 0.98, P < 0.0001). When the endometrial thickness was less than 12mm, the clinical pregnancy rate and live birth rate were increased significantly by 10% and 9%(OR:1.10; 95%CI: 1.08-1.12, OR:1.09; 95%CI: 1.07-1.11), respectively, along with the increase of each millimeter increment of endometrial thickness. However, when the EMT ranged from 12-15 mm, were stable at the ideal level, that were not significantly associated with EMT growth. Additionally, clinical pregnancy rate and live birth rate were slightly reduced by 6% and 4% when EMT was ≥15mm. Meanwhile, the miscarriage rate was significantly declined by 8% (OR:0.92; 95%CI: 0.90-0.95)with each millimeter increment of EMT. And when EMT was thicker than 12mm, the miscarriage rate didn’t change any more significantly.ConclusionsEndometrial thickness exhibits a curvilinear relationship with pregnancy outcomes in fresh embryo transfer cycles. Clinical pregnancy rate, live birth rate and miscarriage rate may achieve their optimal level when EMT ≥ 12 mm, but some adverse pregnancy outcomes would be observed when EMT ≥15 mm especially for clinical pregnancy.

(1) Background: The genetic etiology of most patients with cerebral folate deficiency (CFD) remains poorly understood. KDM6B variants were reported to cause neurodevelopmental diseases; however, the association between KDM6B and CFD is unknown; (2) Methods: Exome sequencing (ES) was performed on 48 isolated CFD cases. The effect of KDM6B variants on KDM6B protein expression, Histone H3 lysine 27 epigenetic modification and FOLR1 expression were examined in vitro. For each patient, serum FOLR1 autoantibodies were measured; (3) Results: Six KDM6B variants were identified in five CFD patients, which accounts for 10% of our CFD cohort cases. Functional experiments indicated that these KDM6B variants decreased the amount of KDM6B protein, which resulted in elevated H3K27me2, lower H3K27Ac and decreased FOLR1 protein concentrations. In addition, FOLR1 autoantibodies have been identified in serum; (4) Conclusion: Our study raises the possibility that KDM6B may be a novel CFD candidate gene in humans. Variants in KDM6B could downregulate FOLR1 gene expression, and might also predispose carriers to the development of FOLR1 autoantibodies.

ObjectiveTo compare the cumulative live birth rate (CLBR) of a gonadotropin-releasing hormone (GnRH) antagonist regimen and a progestin-primed ovarian stimulation (PPOS) regimen in low-prognosis patients according to POSEIDON criteria.DesignSingle-center, retrospective, observational study.SettingHenan Provincial People’s Hospital, Zhengzhou, ChinaPatientsWomen aged ≤40 years, with a body mass index

We studied the type of cusps on the caustic in the optical model that the coplanar point light source irradiates a singular planar curvilinear mirror in our last paper. In this paper, we give a oneto-one correspondence between the wavefront (orthotomic) and the caustic. According to this one-toone correspondence, we can derive the property of one of them from that of the other one. To prove it, we formulate the involutes of (n, m)-cusp curves and study their singular properties. Furthermore, we give a duality theorem for evolute-involute pairs. This theorem plays a crucial role in the one-to-one correspondence mentioned earlier.

ObjectiveThe reference range and potential value of inhibin B are still unclear and controversial. This study aimed to define the variation trend of inhibin B in healthy women with age and explore its value in the reflection of ovarian reserve.MethodsA total of 2524 healthy reproductive age women from eight medical institutes nationwide were recruited. The variation tendency of inhibin B with age was primarily established in the first group of 948 women and validated in another 605. We evaluated the relationship between inhibin B and classic ovarian reserve and function markers. The potency of inhibin B in predicting AFC

OBJECTIVE:To investigate factors that influence maternal hCG concentration in early pregnancy and the relationship between hCG concentration in early pregnancy and basal FSH (bFSH) level. DESIGN:Retrospective cohort study. SETTING:Reproductive medical center. PATIENT(S):In total, 482 women aged 22 to 38 years with elevated basal FSH (> 10 IU/L) and who experienced a single live birth after in vitro fertilization-embryo transfer were selected. These 482 women were age-matched with an equal number of women with normal basal FSH (≤10 IU/L) who also experienced a single live birth. INTERVENTION(S):None. MAIN OUTCOME MEASURE(S):HCG concentration. RESULT(S):The hCG concentrations on Day 14 and Day 21 were 560.46 (363.63-842.52) IU/L and 9862.00 (6512.25-14029.50) IU/L, respectively, in the elevated bFSH group, and these values were significantly increased compared with the normal bFSH group. After adjusting for confounding factors, the concentrations of maternal hCG on Day 14 and Day 21 were significantly associated with basal FSH. In addition, crude linear regression analysis demonstrated that hCG concentrations increased as the basal serum levels of FSH increased. CONCLUSION(S):Elevated basal FSH has implications for the interpretation of hCG concentrations in early pregnancy after in vitro fertilization-embryo transfer (IVF-ET) that led to a single live birth.

In order to study the impact of procedures of IVF/ICSI technology on sex ratio in China, we conducted this multi-center retrospective study including 121,247 babies born to 93,895 women in China. There were 62,700 male babies and 58,477 female babies, making the sex ratio being 51.8% (Male: Female = 107:100). In univariate logistic regression analysis, sex ratio was imbalance toward females of 50.3% when ICSI was preformed compared to 47.7% when IVF was used (P

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Objective: To investigate the impact of endometrial thickness on the embryo transfer(ET) day on the clinical pregnancy outcomes of frozen-thawed embryo transfer cycles which have undergone hormone replacement therapy(HRT-FET). Methods: A total of 10,165 HRT-FET cycles performed between January 2013 to December 2017 in the Reproductive Medicine Center of Henan Provincial People's Hospital were studied retrospectively. All patients were grouped according to their endometrial thickness on the ET day (each group having an increment of 1mm between two neighboring groups). Multivariate regression analysis, curve fitting and threshold effect analysis were performed on all data. Results: After adjusting for the age, duration of infertility, body mass index(BMI), infertility type and number and type of embryos transferred, a significant correlation was observed to be between the endometrial thickness and implantation rates (aOR: 1.08; 95% CI: 1.06–1.10, p < 0.0001), clinical pregnancy rate(aOR: 1.10; 95% CI: 1.07–1.14, p < 0.0001)and live birth rate (aOR: 1.09; 95% CI: 1.06–1.12, p < 0.0001). The numerical value of the cut-off point for the endometrial thickness was 8.7 mm. When the endometrial thickness was less than 8.7 mm, with each additional 1 mm of endometrial thickness, the implantation rate increased by 32%, the clinical pregnancy rate increased by 36%, and the live birth rate increased by 45%. Conclusions: In the HRT-FET cycles, the optimal live birth rate would be obtained when the endometrial thickness remains within the range of 8.7–14.5 mm. If the endometrium is too thin or too thick, the live birth rate will be reduced. [ABSTRACT FROM AUTHOR]

Objective To estimate the proportion of married women in China who intend to become pregnant given the country's pronatalist population policy and to investigate fecundity, with an emphasis on the influence of socioeconomic factors. Methods A nationally representative survey of 12 815 married women aged 20 to 49 years (mean: 36.8 years) was conducted during 2019 and 2020. All completed questionnaires, 10 115 gave blood samples and 11 710 underwent pelvic ultrasound examination. Fertility intention was the desire or intent to become pregnant combined with engagement in unprotected sexual intercourse. We defined infertility as the failure to achieve pregnancy after 12 months or more of unprotected intercourse. We considered an anti-Müllerian hormone level < 1.1 ng/ mL and an antral follicular count < 7 as indicating an abnormal ovarian reserve. Findings Fertility intentions were reported by 11.9% of women overall but by only 6.1% of current mothers (weighted percentages). Fertility intention was significantly less likely among women in metropolises (odds ratio, OR: 0.38; 95% confidence interval, CI: 0.31--0.45) and those with a higher educational level (OR: 0.74; 95% CI: 0.62--0.88). Overall, 18.0% had experienced infertility at any time and almost 30% had an abnormal ovarian reserve on assessment. An abnormal ovarian reserve and infertility were less likely in women in metropolises (P < 0.05) but more likely in obese women (P < 0.05). Conclusion The willingness of Chinese married women to give birth remained low, even with relaxation of the one-child policy. [ABSTRACT FROM AUTHOR]

Background Chronic endometritis (CE) refers to chronic inflammatory condition of the endometrium. Recent studies have found that CE is closely associated with infertility, recurrent miscarriage, and recurrent implantation failure. However, there are no studies on CE prevalence in patients with first implantation failure and the outcome of re-pregnancy by assisted reproductive technology in these patients after antibiotic treatment. Objective To investigate CE prevalence in women who used in vitro fertilization & embryo transfer (IVF-ET) to assist in achieving a pregnancy but had failed first implantation and the impact of antibiotic treatment on the outcome of the next frozen-thawed embryo transfer in this group. Methods Women (n=381) who received IVF-ET to assist in achieving a pregnancy but had failed first implantation were selected from Henan Provincial People's Hospital from May 2017 to May 2021. 333 patients without CE were according to hysteroscopic and endometrial histopathological findings. 37 of CE patients were found with reversed (cured) clinical condition, but the other 11 still with unreversed (uncured) condition who were received antibiotic treatment . Clinical data and the outcome of the second assisted conception were compared between cured and uncured CE patients, as well as non-CE patients. Results Cured and uncured CE patients and non-CE patients had no statistical differences in mean age, BMI, endometrial thickness on the day of embryo transfer, years of infertility, and number of embryos transferred, as well as the distribution of infertility type (P>0.05) . But they had statistical differences in success rates of embryo retransfer and pregnancy (P0.05) . Conclusion CE should be treated by standard antibiotic treatment. Uncured CE may negatively influence the outcome of frozen-thawed embryo retransfer. So it is recommended that women with first implantation failure actively undergo hysteroscopy and endometrial histopathology so as to find possible causes of implantation failure.