Objective To test the hypothesis that a freeze-all strategy would increase the chance of live birth compared with fresh embryo transfer in women with low prognosis for in vitro fertilisation (IVF) treatment. Design Pragmatic, multicentre, randomised controlled trial. Setting Nine academic fertility centres in China. Participants 838 women with a low prognosis for IVF treatment defined by ≤9 oocytes retrieved or poor ovarian reserve (antral follicle count <5 or serum anti-Müllerian hormone level <8.6 pmol/L). Interventions Eligible participants were randomised (1:1) to undergo either frozen embryo transfer or fresh embryo transfer on the day of oocyte retrieval. Participants in the frozen embryo transfer group had all of their embryos cryopreserved and underwent frozen embryo transfer later. Participants in the fresh embryo transfer group underwent fresh embryo transfer after oocyte retrieval. Main outcome measures The primary outcome was live birth, defined as the delivery of neonates with a heartbeat and respiration at ≥28 weeks’ gestation. Secondary outcomes were clinical pregnancy, singleton or twin pregnancy, pregnancy loss, ectopic pregnancy, birth weight, maternal and neonatal complications, and cumulative live birth after embryo transfers within one year after randomisation. Results In an intention-to-treat analysis, the rate of live birth was lower in the frozen embryo transfer group than in the fresh embryo transfer group (32% (132 of 419) v 40% (168 of 419); relative ratio 0.79 (95% confidence interval 0.65 to 0.94); P=0.009). The frozen embryo group had a lower rate of clinical pregnancy than the fresh embryo group (39% (164 of 419) v 47% (197 of 419); 0.83 (0.71 to 0.97)). The cumulative live birth rate was lower in the frozen embryo transfer group compared with the fresh embryo transfer group (44% (185 of 419) v 51% (215 of 419), 0.86 (0.75 to 0.99)). No difference was observed in birth weight, incidence of obstetric complications, or risk of neonatal morbidities. Conclusions Fresh embryo transfer may be a better choice for women with low prognosis in terms of live birth rate compared with a freeze-all strategy. The treatment strategies that prevent fresh embryo transfers, such as accumulating embryos with back-to-back cycles or performing routine preimplantation genetic testing for aneuploidy, warrant further studies in women with a low prognosis. Trial registration Chinese Clinical Trial Registry ChiCTR2100050168.

STUDY QUESTION:Can pregnancy outcomes following fresh elective single embryo transfer (eSET) in gonadotropin-releasing hormone (GnRH) antagonist protocols increase using a gonadotropin (Gn) step-down approach with cessation of GnRH antagonist on the day of hCG administration (hCG day) in patients with normal ovarian response? SUMMARY ANSWER:The modified GnRH antagonist protocol using the Gn step-down approach and cessation of GnRH antagonist on the hCG day is effective in improving live birth rates (LBRs) per fresh eSET cycle. WHAT IS KNOWN ALREADY:Currently, there is no consensus on optimal GnRH antagonist regimens. Studies have shown that fresh GnRH antagonist cycles result in poorer pregnancy outcomes than the long GnRH agonist (GnRHa) protocol. Endometrial receptivity is a key factor that contributes to this phenomenon. STUDY DESIGN, SIZE, DURATION:An open label randomized controlled trial (RCT) was performed between November 2021 and August 2022. There were 546 patients allocated to either the modified GnRH antagonist or the conventional antagonist protocol at a 1:1 ratio. PARTICIPANTS/MATERIALS, SETTING, METHODS:Both IVF and ICSI cycles were included, and the sperm samples used were either fresh or frozen from the partner, or from frozen donor ejaculates. The primary outcome was the LBRs per fresh SET cycle. Secondary outcomes included rates of implantation, clinical and ongoing pregnancy, miscarriage, and ovarian hyperstimulation syndrome (OHSS), as well as clinical outcomes of ovarian stimulation. MAIN RESULTS AND THE ROLE OF CHANCE:Baseline demographic features were not significantly different between the two ovarian stimulation groups. However, in the intention-to-treat (ITT) population, the LBRs in the modified antagonist group were significantly higher than in the conventional group (38.1% [104/273] vs. 27.5% [75/273], relative risk 1.39 [95% CI, 1.09-1.77], P = 0.008). Using a per-protocol (PP) analysis which included all the patients who received an embryo transfer, the LBRs in the modified antagonist group were also significantly higher than in the conventional group (48.6% [103/212] vs. 36.8% [74/201], relative risk 1.32 [95% CI, 1.05-1.66], P = 0.016). The modified antagonist group achieved significantly higher implantation rates, and clinical and ongoing pregnancy rates than the conventional group in both the ITT and PP analyses (P < 0.05). The two groups did not show significant differences between the number of oocytes retrieved or mature oocytes, two-pronuclear zygote (2PN) rates, the number of embryos obtained, blastocyst progression and good-quality embryo rates, early miscarriage rates, or OHSS incidence rates (P > 0.05). LIMITATIONS, REASONS FOR CAUTION:A limitation of our study was that the subjects were not blinded to the treatment allocation in the RCT trial. Only women under 40 years of age who had a good prognosis were included in the analysis. Therefore, use of the modified antagonist protocol in older patients with a low ovarian reserve remains to be investigated. In addition, the sample size for Day 5 elective SET was small, so larger trials will be required to strengthen these findings. WIDER IMPLICATIONS OF THE FINDINGS:The modified GnRH antagonist protocol using the Gn step-down approach and cessation of GnRH antagonist on hCG day improved the LBRs per fresh eSET cycle in normal responders. STUDY FUNDING/COMPETING INTEREST(S):This project was funded by grant 2022YFC2702503 from the National Key Research & Development Program of China and grant 2021140 from the Beijing Health Promotion Association. The authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER:The RCT was registered in the Chinese Clinical Trial Registry; Study Number: ChiCTR2100053453. TRIAL REGISTRATION DATE:21 November 2021. DATE OF FIRST PATIENT’S ENROLLMENT:23 November 2021.

Myocardial ischemia/reperfusion (I/R) decreases cardiac function and efficiency. Accumulating evidence suggests that long noncoding RNAs (lncRNAs) have been linked to the cellular processes of myocardial I/R injury. The present investigation elucidated the function of lncRNA colon cancer -associated transcript 2 (CCAT2) in myocardial I/R injury and the related mechanisms. AC16 cardiomyocytes were exposed to hypoxia (16 hours)/reoxygenation (6 hours) (H/R) to mimic myocardial I/R models in vitro . CCAT2 and microRNA (miR)-539-3p expressions in AC16 cardiomyocytes were measured using real-time quantitative polymerase chain reaction. B -cell -specific Moloney murine leukemia virus insertion region 1 (BMI1) protein levels in AC16 cardiomyocytes were determined by western blotting. Cell viability, lactate dehydrogenase (LDH) leakage, reactive oxygen species (ROS) levels, mitochondrial membrane potential, and apoptosis were detected using Counting Kit -8, LDH Assay Kit, dihydroethidium assay, 5,5',6,6'tetrachloro1,1',3,3'-tetramethylbenzimidazolylcarbocyanine iodide staining, flow cytometry, and western blotting, respectively. The interactions between the molecules were confirmed using the dual-luciferase gene reporter. The wingless/integrated/beta-catenin (Wnt/(3-catenin) pathway under the H/R condition was detected by western blotting. CCAT2 and BMI1 mRNA expressions were reduced in H/R-exposed AC16 cardiomyocytes. CCAT2 overexpression exerted protective effects against H/R-induced cardiomyocyte injury, as demonstrated by increased cell viability and mitochondrial membrane potential and decreased LDH leakage, ROS levels, and apoptosis. In addition, CCAT2 positively regulated BMI1 expression by binding to miR-539-3p. CCAT2 knockdown or miR539-3p overexpression restrained the protective effects of BMI1 against H/R-induced cardiomyocyte injury. In addition, miR-539-3p overexpression reversed the protective effects of CCAT2. Furthermore, CCAT2 activated the Wnt/(3-catenin pathway under the H/R condition via the miR-539-3p/BMI1 axis. Overall, this investigation showed the protective effects of the CCAT2/miR-539-3p/BMI1/Wnt/(3-catenin regulatory axis against cardiomyocyte injury induced by H/R.

STUDY QUESTION:How do the types and frequency of chromosome aberrations in couples in central China affect fertility and ART treatment? SUMMARY ANSWER:Men with chromosome aberrations or polymorphisms have an increased risk of semen quality impairment and infertility, and couples affected by reciprocal translocations had a lower pregnancy rate compared with other chromosome aberrations. WHAT IS KNOWN ALREADY:Karyotyping is crucial for patients affected by infertility as chromosome aberrations play an important role in the etiology of male infertility. However, the influence of chromosome aberrations and polymorphisms on sperm motility and morphology remains controversial. Data on ART treatment outcomes in infertile couples affected by chromosome aberrations are insufficient. STUDY DESIGN, SIZE, DURATION:We conducted a retrospective study involving 17 054 patients affected by infertility who underwent karyotyping in our center between January 2020 and May 2022. PARTICIPANTS/MATERIALS, SETTING, METHODS:Karyotyping was performed on 17 054 patients with reproductive failure. All patients were from the central regions of China. The following data were collected from a medical records system using patient identification numbers: couples' ages, history of pregnancy and childbirth, type of infertility, years of infertility, cause of infertility, chromosome karyotypes, semen analysis results, assisted reproductive techniques performed, and treatment outcomes of ART. MAIN RESULTS AND THE ROLE OF CHANCE:The incidence of chromosome aberrations was 2.04%; 2.49% in men and 1.57% in women. By analyzing the relationships between chromosome aberrations/polymorphisms and abnormal semen parameters, we found that there were significantly higher rates of asthenozoospermia, oligospermia, and teratozoospermia among men with Robertsonian translocations and sex chromosomal structural aberrations compared with those with normal karyotypes. Higher rates of asthenozoospermia and teratozoospermia were also observed among men with autosomal reciprocal translocations. The incidence of chromosome aberrations in azoospermic men (13.75%), and in men with cryptozoospermia or severe oligospermia (6.97%) was significantly higher than that in men with mild oligospermia or normospermia (0.88-2.12%). In addition, we found that the progressive movement of sperm is impaired in men with Chromosome 21 polymorphisms compared with men with normal karyotypes (39.46% ± 20.51% vs 48.61% ± 18.76%, P = 0.026). The percentage of morphologically normal forms was lower in the chromosomal polymorphism group than in the normal karyotype group (5.01% ± 2.41% vs 5.59% ± 2.14%, P = 0.001), especially in men with polymorphisms on Chromosome 9 (enlarged Chromosome 9 heterochromatin [9qh+]: 4.48% ± 2.22% vs 5.59% ± 2.14%, P = 0.006; pericentric inversion of Chromosome 9 [inv(9)]: 5.09% ± 3.11% vs 5.59% ± 2.14%, P = 0.008). ART treatment was successful in 36.00% of couples affected by chromosome aberrations. However, couples affected by reciprocal translocations achieved a lower pregnancy rate (24.07%), which may be due to the lower euploidy rates (27.31%) when compared with that in other chromosome aberrations. LIMITATIONS, REASONS FOR CAUTION:First, although the initial cohort was large, chromosome aberrations were identified in a small number of patients. Second, the observational nature of the study design is limiting. Third, the couples affected by infertility in this study were all outpatients that did not undergo identical comprehensive examinations except for karyotyping, leading to the incomplete collection of medical records. Also, the population included in this study mainly focused on couples affected by infertility, which may not be included in the European Association of Urology (EAU) recommendation on male infertility. WIDER IMPLICATIONS OF THE FINDINGS:Men with chromosome aberrations or polymorphisms have an increased risk of semen quality impairment and infertility. Constitutional chromosome analysis is recommended for men affected by infertility and severe oligospermia or azoospermia to facilitate early and appropriate guidance for the most suitable treatment. Carriers of chromosome aberrations can achieve acceptable pregnancy outcomes through IVF. However, couples affected by reciprocal translocations have lower pregnancy rates, and more treatment cycles are needed before a successful pregnancy. A possible explanation may be the fewer euploid embryos obtained. STUDY FUNDING/COMPETING INTEREST(S):This work was supported by Grant 2021YFC2700603 from the National Key Research & Development Program of China. The authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER:N/A.

Objective:To explore the pregnancy outcomes of frozen-thawed embryo transfer (FET) after antibiotic treatment in patients with recurrent implantation failure (RIF) and chronic endometritis (CE).Methods:A retrospective cohort study was conducted to analyze 496 women with RIF undergoing hysteroscopy and endometrial biopsy before the next FET in Reproductive Medicine Center of Tongji Hospital, Tongji Medicine College, Huazhong University of Science and Technology from January 2018 to December 2021. According to the pathological results of endometrial biopsy and subsequent treatment, the patients were divided into cured CE group (strong positive CD138 was converted to negative after antibiotic treatment, n=103), suspected CE group (weak positive CD138, n=76), non-CE group (negative CD138, n=230) and control group (hysteroscopy and diagnostic only, no CE-related histopathological screening, n=85). The pregnancy outcomes after FET were compared among the four groups. Results:The prevalence of CE in the patients with RIF was 25.5% (105/411), and the sensitivity of hysteroscopy for the diagnosis of CE was 55.2% and the specificity was 83.0%. The conversion rate of patients with CE was 86.7% (91/105) after 1 cycle of antibiotic treatment and 98.1% (103/105) after 2 cycles of treatment. After removing the confounding factors of age, ovarian reserve function, number of previous transfer cycles, number and type of embryos transferred in FET cycle, and number of high-quality embryos, multivariate regression analysis showed that the clinical pregnancy rate of the cured CE group improved significantly after antibiotic treatment ( OR=1.841, 95% CI: 1.123-3.020, P=0.029). Conclusion:Patients with RIF should be screened for CE, and if CE is diagnosed, pharmacological treatment is recommended prior to embryo transfer, which is beneficial to improve pregnancy outcomes in FET cycles.

Background Oocyte maturation arrest and early embryonic arrest are important reproductive phenotypes resulting in female infertility and cause the recurrent failure of assisted reproductive technology (ART). However, the genetic etiologies of these female infertility-related phenotypes are poorly understood. Previous studies have mainly focused on inherited mutations based on large pedigrees or consanguineous patients. However, the role of de novo mutations (DNMs) in these phenotypes remains to be elucidated. Results To decipher the role of DNMs in ART failure and female infertility with oocyte and embryo defects, we explore the landscape of DNMs in 473 infertile parent–child trios and identify a set of 481 confident DNMs distributed in 474 genes. Gene ontology analysis reveals that the identified genes with DNMs are enriched in signaling pathways associated with female reproductive processes such as meiosis, embryonic development, and reproductive structure development. We perform functional assays on the effects of DNMs in a representative gene Tubulin Alpha 4a ( TUBA4A ), which shows the most significant enrichment of DNMs in the infertile parent–child trios. DNMs in TUBA4A disrupt the normal assembly of the microtubule network in HeLa cells, and microinjection of DNM TUBA4A cRNAs causes abnormalities in mouse oocyte maturation or embryo development, suggesting the pathogenic role of these DNMs in TUBA4A . Conclusions Our findings suggest novel genetic insights that DNMs contribute to female infertility with oocyte and embryo defects. This study also provides potential genetic markers and facilitates the genetic diagnosis of recurrent ART failure and female infertility.

ABSTRACT Several recent studies have suggested an association between children conceived by assisted reproductive technology (ART) and a distinct growth pattern in early life, which has been linked to diseases of older age. Telomere shortening, specifically a shorter leukocyte telomere length (LTL), has also been linked to age-related diseases including cardiometabolic diseases and cancer. Initial telomere length is shaped by a telomere reset process during gamete fertilization and the early stages of preimplantation development. Given that ART involves the in vitro manipulation of oocytes and embryos, this study aimed to evaluate the association between ART-related factors and LTL in children. Whole genome-sequencing (WGS) data from the Nanjing and Suzhou centers of the China National Birth Cohort (CNBC) were obtained from 1137 individuals from 365 parent-children families, including 202 children conceived using ART and 205 conceived spontaneously. The association was determined between blastocyst-stage transfer and shorter telomere length in 180 children conceived by ART in the same centers. In addition, qPCR was used to perform validation on fingerstick blood samples from 406 children conceived using ART at 3 different centers in China. Data from qPCR were then compared with data obtained from WGS in 70 children in the discovery cohort with sufficient DNA samples. Associations between parental factors and demographics with LTL were examined in the discovery cohort. LTL attribution with aging was calculated using data from the discovery cohort, 1185 individuals aged 40–69 years from healthy controls in the Nanjing Lung Cancer Cohort with LTL measured using WGS, and 1452 East Asian adults aged 40–69 years in the UK biobank with LTL measured using qPCR. Results of association analyses found paternal LTL (β = 0.27, P = 3.26 × 10 −8 ), maternal LTL (β = 0.26, P = 2.41 × 10 −7 ), plurality (twins vs singletons; β = −0.34, P = 0.010), sex of children (male vs female; β = −0.22, P = 0.032), gestational age (β = 0.05, P = 0.026), and conception type (ART-conceived pregnancy vs spontaneously conceived, β = −0.35, P = 5.98 × 10 −4 ) were all significantly associated with LTL in children. Multivariate regression analysis revealed that children conceived by ART had a significantly shorter LTL than those conceived spontaneously, even when adjusting for parental age at conception (adjusted β = −0.41, P = 3.33 × 10 −4 ). Transfer of blastocyst-stage embryos was found to be significantly associated with shorter LTL (β = −0.54, P = 2.69 × 10 −3 ). In addition, when LTL in children from spontaneous pregnancies was compared with LTL in children from ART pregnancies through cleavage-stage versus blastocyst-stage transfer, the LTL of the cleavage-stage group was comparable to the spontaneous pregnancy group, whereas the LTL of the blastocyst-stage group was shorter (β = −0.67, P = 7.81 × 10 −8 ). This result suggests that the difference in LTL between transfer stages might explain the difference between the ART-conceived and spontaneous pregnancy groups. No associations between COS protocols, fertilization methods, or embryo transfer cycles on shorter LTL in children were observed. The multicenter validation cohort had similar associations between blastocyst-stage transfer and shorter LTL. Shortened LTL associated with blastocyst transfer was equivalent to 13.93 years (95% CI, 4.64–23.22 years), 13.42 years (95% CI, 4.52–22.21 years), and 10.85 years (95% CI, 1.03–20.67 years) of aging between 40–69 years in the discovery and 2 validation cohorts, respectively. The results of this study demonstrate that children conceived by ART are associated with a shorter LTL compared with those conceived spontaneously, and transfer of blastocyst-stage embryos was associated with shorter LTL in children than is the transfer of cleavage-stage embryos.

对于要求在肿瘤手术前进行生育力保存的复发性卵巢癌患者而言,由于卵巢储备功能低下可能需要不止一次的促排卵,目前尚无临床证据表明两次促排卵及收集卵母细胞是否会对卵巢肿瘤的预后造成影响.本文报道了 1例寻求生育力保存的复发性卵巢上皮内癌患者,通过两次促排卵冻存了 4枚胚胎.完成全面分期手术(保留子宫)后,该患者复苏并移植了一枚囊胚,成功获得临床妊娠.两次促排卵后,随访1年余未见肿瘤复发及转移.

Some concern has been expressed regarding the negative effects of low-level ionizing radiation exposure in the context of radiological evaluation prior to IVF/ICSI treatment, but the available evidence is limited and conflicting. The aim of this study is to evaluate pregnancy and neonatal outcomes of couples who did chest computed tomography (CT) prior to IVF/ICSI. This was a retrospective cohort study of 2680 IVF/ICSI fresh embryo transfer cycles conducted from January 2019 – August 2020. Fertility outcomes were compared between couples that had or had not undergone CT examination within 3 months prior to the date of oocyte retrieval and sperm collection. Miscarriage was the primary study outcome, while secondary outcomes included the number of oocytes collected, oocyte maturation, normal fertilization, number of good quality cleavage stage embryos, blastocyst formation, implantation, clinical pregnancy, ectopic pregnancy, live birth, multiple birth, Cesarean section rates, gestational weeks, maternal obstetric complications, birth weight, newborn sex ratio, and birth defect incidence. Propensity score matching was used to control for potential confounding variables. Of the 2680 cycles included in this study, couples underwent CT examination in 731 cycles. After 1:1 propensity score matching, 670 cycles were included in each group. When comparing demographic and fertility-related variables between groups that had and had not undergone CT examination after propensity score matching, we detected no significant differences in miscarriage rates (16.99

BackgroundIt has been demonstrated that a thin endometrium is associated with a lower chance of pregnancy, but there is a paucity of research into whether a thin endometrium adversely affects perinatal outcomes.MethodsThis was a retrospective cohort study on 10098 frozen cycles with single blastocyst transfer, resulting in 5505 singleton clinical pregnancies, and 4314 singleton live births. Patients were divided into a thin endometrium group (<8 mm) and a normal endometrium group (≥8 mm). Multivariable logistic regression with restricted cubic splines, receiver operating characteristic curve, and multivariable linear model were used for statistical analysis.ResultsThe incidences of preterm birth (15.65 vs. 9.80%, aOR=1.69 [1.19-2.42]), low birth weight (8.40 vs. 4.10%, aOR=2.05 [1.27-3.30]) and gestational diabetes (6.87 vs. 4.17%, aOR=1.74 [1.05-2.90]) were all higher in the endometrial thickness (EMT) <8 mm group. The miscarriage rate was higher in the EMT <8 mm group than the EMT ≥8 mm group (27.91 vs. 20.39%, aOR=1.40 [1.10-1.79]).ConclusionA thin endometrium may be associated with a higher incidence of preterm birth, low birth weight, and miscarriage. Therefore, embryo transfer should be performed with caution in these patients, and postponing to a later cycle with a thicker endometrium should be considered.

阿司匹林作为经典的非甾体类抗炎药,具有解热镇痛、消炎抗风湿的作用;此外,阿司匹林具有明确的抗血小板聚集作用,广泛应用于心血管系统疾病的预防和治疗.近年来,阿司匹林的应用领域不断拓展,本文就阿司匹林在围助孕期的应用进行综述.

STUDY QUESTION Do cumulative live birth rates (CLBRs) after one complete ART cycle differ between the three commonly used controlled ovarian stimulation (COS) protocols (GnRH antagonist, depot GnRHa (GnRH agonist) and long GnRHa) in normal responders undergoing IVF/ICSI? SUMMARY ANSWER There were similar CLBRs between the GnRH antagonist, depot GnRHa and long GnRHa protocols. WHAT IS KNOWN ALREADY There is no consensus on which COS protocol is the most optimal in women with normal ovarian response. The CLBR provides the final success rate after one complete ART cycle, including the fresh and all subsequent frozen-thawed embryo transfer (ET) cycles. We suggest that the CLBR measure would allow for better comparisons between the different treatment protocols. STUDY DESIGN, SIZE, DURATION A prospective controlled, randomized, open label trial was performed between May 2016 and May 2017. A total of 819 patients were allocated to the GnRH antagonist, depot GnRHa or long GnRHa protocol in a 1:1:1 ratio. The minimum follow-up time from the first IVF cycle was 2 years. To further investigate the potential effect of COS with the GnRH antagonist, depot GnRHa or long GnRHa protocol on endometrial receptivity, the expression of homeobox A10 (HOXA10), myeloid ecotropic viral integration site 1 (MEIS1) and leukemia inhibitory factor (LIF) endometrial receptivity markers was evaluated in endometrial tissue from patients treated with the different COS protocols. PARTICIPANTS/MATERIALS, SETTING, METHODS Infertile women with normal ovarian response (n=819) undergoing IVF/ICSI treatment were randomized to the GnRH antagonist, depot GnRHa or long GnRHa protocol. Both IVF and ICSI cycles were included, and the sperm samples used were either fresh or frozen partner ejaculates or frozen donor ejaculates. The primary outcome was the live birth rate (LBR) per fresh ET cycle, and the CLBR after one complete ART cycle, until the birth of a first child (after 28 weeks) or until all frozen embryos were used, whichever occurred first. Pipelle endometrial biopsies from 34 female patients were obtained on Days 7-8 after oocyte retrieval or spontaneous ovulation in natural cycles, respectively, and HOXA10, MEIS1 and LIF mRNA and protein expression levels in the human endometrium was determined by quantitative real-time PCR and western blot, respectively. MAIN RESULTS AND THE ROLE OF CHANCE There were no significant differences in CLBRs between the GnRH antagonist, depot GnRHa or long GnRHa protocol (71.4 versus 75.5 versus 72.2%, respectively). However, there was a significantly higher LBR per fresh ET cycle in the depot GnRHa protocol than in the long GnRHa and GnRH antagonist protocols (62.6 versus 52.1% versus 45.6%, P<0.05). Furthermore, HOXA10, MEIS1 and LIF mRNA and protein expression in endometrium all showed significantly higher in the depot GnRHa protocol than in the long GnRHa and GnRH antagonist protocols (P<0.05). LIMITATIONS, REASONS FOR CAUTION A limitation of our study was that both our clinicians and patients were not blinded to the randomization for the randomized controlled trial (RCT). An inclusion criterion for the current retrospective cohort study was based on the 'actual ovarian response' during COS treatment, while the included population for the RCT was 'expected normal responders' based on maternal age and ovarian reserve test. In addition, the analysis was restricted to patients under 40 years of age undergoing their first IVF cycle. Furthermore, the endometrial tissue was collected from patients who cancelled the fresh ET, which may include some patients at risk for ovarian hyperstimulation syndrome, however only patients with 4-19 oocytes retrieved were included in the molecular study. WIDER IMPLICATIONS OF THE FINDINGS The depot GnRH agonist protocol improves the live birth rate per fresh ET cycle, but not the cumulative live birth rate in normal responders. A possible explanation for the improved LBR after fresh ET in the depot GnRHa protocol could be molecular signalling at the level of endometrial receptivity.

Background Adverse obstetric outcomes are correlated with altered circulating hormone levels at the time implantation by the trophectoderm. What’ more, embryo freezing process may also have adverse effect on perinatal outcomes. This study aims to evaluate whether increasing interval time between a freeze-all cycle and a subsequent frozen-thawed single blastocyst transfer could have any effect on pregnancy and perinatal outcomes. Methods This was a retrospective cohort study included the first single blastocyst transfer in artificially cycles of all patients who underwent a freeze-all cycle between January 1 st , 2016 and September 30 th , 2018. All patients were divided into two groups according to the time interval between oocyte retrieval and the day of first frozen-thawed embryo transferred (FET): Group 1 (immediate FET cycles) and Group 2 (delayed FET cycles). Results No significant differences were reported between the two groups regarding the rates of clinical pregnancy, live birth, biochemical pregnancy and pregnancy loss even after adjusting for measured confounding. When accounting for perinatal outcomes, gestational age, birth weight, delivery mode, fetus gender, preterm birth, gestational hypertension, GDM, placenta previa, fetal malformation and low birthweight also did not vary significantly between the two groups. Only the incidence of macrosomia was more frequently in the Group 2 compared with the Group 1 (AOR 3.886, 95%CI 1.153–13.103, P = 0.029) after adjusting with a multiple logistic regression model. Conclusions We found delayed FET cycles for blastocyst transfer following freeze-all cycles may not improve the pregnancy outcomes. On the contrary, postponement of FET cycles may increase the risk of macrosomia. Therefore, FET cycles for blastocyst transfer should be done immediately to avoid adverse effects of delayed time on perinatal outcomes.

Objective: The aim of this study was to evaluate the impact of male infertility or intracytoplasmic sperm injection (ICSI) technique on perinatal outcomes. Materials and methods: A retrospective cohort study included patients with singleton live births after fresh-cycle embryo transfer that occurred between 1(st) January 2016 and 31(st) May 2018. The patients were divided into four groups: (1) IVF treatment without male infertility; (2) ICSI treatment without male infertility; (3) ICSI treatment with male infertility; and (4) IVF treatment with male infertility. Result: In total, 2118 patients were analyzed. When comparing perinatal outcomes between the four groups, there were significant differences with regard to gender proportions of offspring and GDM. No statistically significant differences were reported in the incidence of preterm birth, gestational hypertension, placenta previa, fetal malformation, macrosomia, or low birthweight. A separate multiple logistic regression model was performed for each abnormal perinatal outcome to eliminate confounding factors, with the exception of GDM, the above abnormal perinatal outcomes still did not differ significantly when comparing the four groups. However, the incidence of GDM was higher in the third group than it was in the first group. The proportion of male births was significantly decreased in the third and fourth groups. Conclusion: The results showed that ICSI may be associated with the risk of GDM in abnormal perinatal outcomes, but the risk is not due to male infertility. However, male infertility may reduce the proportion of male births.

Objective: To investigate the risk of abnormal perinatal outcomes in young patients with diminished ovarian reserve (DOR). Design: A retrospective cohort study. Setting: Reproductive medicine center in a hospital. Patients: A total of 5,649 young patients (<= 35 years) undergoing assisted reproductive technology for fresh -cycle ET between January 1, 2016, and January 31, 2019, were included. The patients were divided into two groups: the non-DOR group (n = 5,295) and the DOR group (n = 354). Intervention(s): None. Main Outcome Measure(s): Singleton live births were assessed for obstetrical complications and adverse birth outcomes. Result(s): There were signi fi cantly lower rates of clinical pregnancy, live birth, and singleton live birth among young patients with DOR, without an increase in the rates of clinical pregnancy loss, biochemical pregnancy, and multiple live births compared with young patients without DOR. For young patients with singleton live births, there were no signi fi cant differences in the incidence of gestational hypertension, gestational diabetes mellitus, placenta previa, fetal malformation, macrosomia, low birth weight, or preterm birth be- tween the two groups after adjusting with a multiple logistic regression model. Conclusion(s): We found that young patients with DOR still had acceptable pregnancy outcomes and similar risks of biochemical preg- nancy, pregnancy loss, multiple live births, and abnormal perinatal outcomes compared with young patients with normal ovarian reserve. (Fertil Steril (R) 2020;114:118-24. (C) 2020 by American Society for Reproductive Medicine.)

To characterize the clinical features of a female patient with isolated follicle-stimulating hormone (FSH) deficiency and to investigate the underlying mechanisms of FSH inactivation. The proband was a 29-year-old woman with primary amenorrhea, impaired pubertal development, and infertility. Subsequently, reproductive endocrine was screened. DNA sequencing was conducted for the identification of FSHβ mutation. RT-PCR, western blots, in vitro immunometric assay, and bioassay were performed to confirm the impact of the mutation on FSH expression and biological activity. Molecular model consisting of FSHα and mutant FSHβ subunit was built for the structural analysis of FSH protein. The evaluation of reproductive endocrine revealed undetectable basal and GnRH-stimulated serum FSH. Sequencing of the FSHβ gene identified a homozygous nonsense mutation at codon 97 (Arg97X). RT-PCR and western blot analysis revealed the mutation Arg97X did not affect FSHβ mRNA and protein expression. But in vitro immunometric assay and bioassay demonstrated the production of normal bioactive FSH protein was disturbed by the mutation Arg97X. Structural analysis showed the surface structure of the resulting mutant FSH presented with lock-and-key, mosaic binding pattern, while the native structure was an encircling binding mode. The mutation Arg97X could disturb structural stability of the resulting FSH protein consisting of FSHα and mutant FSHβ subunit, which may lead to FSH deficiency.

ObjectiveTo evaluate the effect of polycystic ovary syndrome (PCOS) without hyperandrogenism on pregnancy‐related outcomes.DesignA retrospective cohort study.SettingReproductive Medicine Centre of Tongji Hospital.PopulationWomen without hyperandrogenism undergoing their first single blastocyst transfers in frozen–thawed cycles were divided into a PCOS group and a non‐PCOS group according to the Rotterdam criteria.MethodsThe pregnancy‐related outcomes of women with and without PCOS were compared. Propensity score matching and multiple logistic regression models were used to eliminate essential impacts on pregnancy‐related outcomes.Main outcome measuresPregnancy‐related outcomes included pregnancy loss and abnormal perinatal outcomes.ResultsA total of 4083 women without hyperandrogenism met the study criteria, among whom 557 met the diagnostic criteria for PCOS. Women with PCOS had higher rates of clinical pregnancy (P = 0.035) and cumulative live births (P = 0.023). However, there were no significant differences in the rates of biochemical pregnancy, twins and pregnancy loss between the two groups. Among women with singleton pregnancies, the incidences of preterm birth, hypertensive disorders of pregnancy, gestational diabetes, placenta praevia, fetal malformation, macrosomia and low birthweight did not differ significantly between the two groups. The results remained unchanged even after adjustments were made for propensity score matching and multiple logistic regression analyses.ConclusionWomen with PCOS without hyperandrogenism may achieve higher rates of clinical pregnancy and cumulative live birth than those without PCOS, without increases in their rates of biochemical pregnancy, pregnancy loss or other abnormal perinatal outcomes.Tweetable abstractPCOS without hyperandrogenism was not associated with abnormal pregnancy‐related outcomes.

Objective: To evaluate the elements more likely to be associated with premature rupture of membrane (PROM) in patients that use assisted reproductive technology (ART).Materials and methods: A retrospective case-control study was performed from January 2014 to August 2017. We included 301 patients, 257 patients were without PROM in the non-PROM group and 44 patients with PROM in the PROM group.Results: In the PROM group, the rate of intracytoplasmic sperm injection (ICSI) and BMI were significantly higher than the non-PROM group. Moreover, the rate of preterm birth was significantly higher in the PROM group. When using logistic regression analysis to decrease the impact of confounding factors, it showed that overweight and ICSI were confirmed to be associated with PROM. After matching 1:2 by BMI, the process of controlled ovarian hyperstimulation was all similar in the two groups. What is more, the rate of twin pregnancies was significantly higher in the preterm PROM (PPROM) group compared with the term PROM group and twin pregnancies were associated with preterm birth.Conclusions: ART parameters ICSI may increase the risk of PROM. Single embryo transfer during ART should be supported to decrease the incidence of PPROM and losing weight is essential for patients before embarking on ART.

To investigate risk factors of gestational diabetes mellitus (GDM) during assisted reproductive technology (ART) procedures. A total of 1022 patients were included in this retrospective cohort study from January 1, 2014 to August 31, 2017. While patients were divided into two groups: the non- GDM group and the GDM group. There was no significant difference in basal FSH, AFC, infertility years, gestational age, number of fetus, method of fertilization, and reason of infertility between the two groups. However, age, BMI, and fresh cycle were verified to be association with GDM by using logistic regression model. During the process of controlled ovarian hyperstimulation (COH), estradiol (E-2) was significantly lower in the GDM group. The incidence of GDM was highest when E-2 level less than 200 pg/mL of per oocyte. Our study showed maternal fundamental factors had greater impacts on subsequent GDM.

Advanced maternal age (AMA) was an independent risk factor that affect pregnancy outcome. With the increase of maternal age, the success rate of IVF declined. Even though AMA women conceived with assisted reproductive technology (ART), the risks for obstetric and perinatal complications significantly increased, accompanied by an increased risk of perinatal morbidity and mortality. Especially to the women with very advanced maternal age (VAMA), there was high-quality evidence verified VAMA significantly increased the risk of pregnancy complication, severe maternal complication and adverse fetal/neonatal outcomes, which seriously affected maternal and child health. Meanwhile, a series of ethical issues related to infertility treatments to women with VAMA still existed. ART could be provided to VAMA women after a thorough medical evaluation to eliminate health risks. If women over the age of 52 years, ART should be discouraged. Key words: Very advanced maternal age; Assisted reproductive technology; Obstetric risks; Ethics