Women with polycystic ovary syndrome (PCOS) have a high incidence of pregnancy and obstetric complications. Anti-Müllerian hormone (AMH) is closely related to reproductive outcomes. The potential relationship between AMH levels and the occurrence of late miscarriage in these patients remains unclear. This study enrolled 1,831 patients diagnosed with PCOS who achieved clinical pregnancy following their first frozen-thawed embryo transfer cycles. The patients were categorized into miscarriage group and live birth group according to their pregnancy outcomes. The relationship between AMH levels and the occurrence of late miscarriage in this population was assessed before and after propensity score matching. PCOS patients with late miscarriage exhibited elevated AMH levels compared with those who had a live birth. According to univariate logistic regression analysis, each 1 ng/mL elevation in AMH level was related to a 6.3

Adenomyosis is a chronic gynecological condition commonly affecting women of reproductive age, with its etiology still unclear. In clinical practice, gonadotropin-releasing hormone agonists (GnRH-a), often combined with other drugs, are used to treat mild to moderate cases. This meta-analysis aimed to evaluate the therapeutic efficacy of dienogest combined with GnRH-a in managing adenomyosis and explore related obstetric risk factors. A systematic search was conducted for relevant studies published up to 2024, with 5 studies involving 520 patients included in the meta-analysis. Results showed that compared to monotherapy, the combination of dienogest and GnRH-a significantly improved visual analogue scale scores, hemoglobin levels, CA-125 levels, and uterine volume, with no significant difference in adverse event rates. Additionally, 11 studies with 15,015 participants analyzed obstetric risk factors, revealing that women with adenomyosis had significantly higher risks of spontaneous abortion, premature rupture of membranes, preterm birth, small-for-gestational-age fetuses, and cesarean section. These findings suggest that dienogest combined with GnRH-a can improve therapeutic outcomes for adenomyosis, while also highlighting increased obstetric risks associated with the condition.

Abnormality of granulosa cells (GCs) is the critical cause of follicular atresia in premature ovarian failure (POF). RIPK3 is highly expressed in GCs derived from atretic follicles. We focus on uncovering how RIPK3 contributes to ovarian GC senescence. Primary GCs were treated with H2O2 to induce senescence. ROS was detected via DCFH-DA staining. Levels of senescence-related molecules and SA-beta-Gal activity were examined. Cyclophosphamide was administered to mice to induce POF. The impact of RIPK3 on atretic follicles and sex hormones was evaluated through HE staining and ELISA, respectively. The acRIP-qPCR analysis of RIPK3 ac4C levels, RIP detection for interaction between RIPK3 and NAT10, and actinomycin D treatment to detect RIPK3 degradation were conducted. In H2O2-treated GCs and POF mouse ovaries, levels of RIPK3, ROS, senescence-related molecules, as well as SA-beta-Gal activity, were all up-regulated, and this effect was suppressed by RIPK3 inhibition. RIPK3 interference reduced atretic follicles and FSH levels while increasing AMH and E2 levels. Nrf2 and HO-1 content were diminished in the models, whereas si-RIPK3 facilitated their expression. The effect of si-RIPK3 on decreased levels of ROS and senescence-related molecules was reversed by ML385. H2O2 decreased RIPK3 mRNA degradation and increased its ac4C modification. The ac4C modifying enzyme NAT10 was up-regulated in the models, and NAT10 enhanced RIPK3 mRNA stability through ac4C modification. NAT10 knockdown mitigated ovarian GC senescence by inhibiting RIPK3 expression. The promotion of RIPK3 mRNA stability through ac4C modification by NAT10, in turn, affects the Nrf2/HO-1 pathway and promotes ovarian GC senescence.

Premature ovarian insufficiency (POI) seriously affects women's reproductive health. This study aims to explore the mechanism of Klotho-mediated autophagy in alleviating POI. Cyclophosphamide (CTX) treated COV434 cells and CTX injection induced POI mouse models were established. Klotho overexpression alleviates the apoptosis of COV434 cells induced by CTX and promotes autophagy related protein expressions. Autophagy inhibitors attenuated the effect of Klotho, promoted the apoptosis of CTX treated COV434 cells, increased the number of atretic follicles in CTX-POI mice, decreased E2 levels and increased follicle-stimulating hormone levels in serum, and increased c-caspase-3 expression. Klotho overexpression promotes p-adenosine 5'-monophosphate-activated protein kinase (AMPK) and p-Unc51-like kinase 1 (ULK1) expression. Interference with AMPK reversed the effect of Klotho, promoting apoptosis and inhibiting autophagy. Furthermore, YTHDF2 regulates the mRNA stability of Klotho by recognizing METTL3-mediated N6-methyladenosine (m6A) modification. In conclusion, Klotho overexpression promoted autophagy through activating AMPK/ULK1 signal pathway to alleviate CTX-induced ovarian granulocyte injury.

AMH is a dependable indicator of ovarian reserve function and assessment of ovarian responsiveness. The relationship between reduced ovarian reserve and pregnancy loss remains poorly understood and requires further investigation. Currently, it has not been systematically evaluated in populations with PGT which could exclude the influence of embryonic chromosomal abnormalities on the outcomes. This study enrolled 1982 non-PCOS patients who underwent PGT and had their first frozen-thawed embryo euploidy blastocyst transfer between January 2016 and August 2023. Primary outcomes included early pregnancy loss rates (defined as spontaneous miscarriage during the early first trimester) with secondary outcomes encompassing clinical pregnancy rates and live birth rates. The cohort was divided into three subgroups using quintile-based categorization of AMH levels: low (≤ 1.872 ng/mL, n = 260); medium (1.873–5.276 ng/mL, n = 779); high (≥ 5.277 ng/mL, n = 258). After propensity score matching, 143 patients in each group were ultimately included in the current research. The matched data revealed a higher rate of EPL in the low AMH level group and a lower rate of clinical pregnancy and live births (P < 0.05). Compared to the medium AMH level group, the low AMH group had a considerably higher risk of EPL, with an unadjusted OR of 1.76 (95

STUDY QUESTION: Does the morphological quality on Day 3 influence the pregnancy outcomes of euploid blastocysts? SUMMARY ANSWER: The morphological quality on Day 3 affects the clinical pregnancy rate (CPR) and live birth rate (LBR) of low-quality euploid blastocysts. WHAT IS KNOWN ALREADY: The morphological grading of Day 3 embryos affects the pregnancy outcome of cleavage-stage embryos and is an excellent indicator to predict embryo development potential. However, it is still unclear whether morphological quality on Day 3 is associated with pregnancy outcomes of the euploid blastocyst. STUDY DESIGN, SIZE, DURATION: This retrospective cohort study comprised 1275 patients who received single euploid blastocyst transfer between January 2016 and August 2021 at a tertiary teaching hospital. PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients were grouped into two groups according to the morphological grading on Day 3 of transferred blastocysts: high-quality (HQ, including Grades I and II) Day 3 embryos and low-quality (LQ, Grade III) Day 3 embryos. The primary outcomes were CPR and LBR. Interactions of development days (Day 5 and Day 6) and morphological quality (high- and low-quality) of blastocysts with morphological quality of Day 3 embryos on pregnancy outcomes were tested in the stratified analysis and logistic regression models. The multivariate logistic regression analysis was conducted to investigate the independent effect of the morphological quality of Day 3 embryos on pregnancy outcomes after adjusting for potentially confounding factors. MAIN RESULTS AND THE ROLE OF CHANCE: The CPR and LBR of the HQ Day 3 embryos group were statistically higher than those of the LQ Day 3 embryos group (CPR: 59.73% versus 49.70%, respectively, P = 0.015; LBR: 49.73% versus 41.21%, respectively, P = 0.041). The development days of blastocysts did not exhibit a multiplicative interaction with the morphological quality of Day 3 embryos on the CPR (P for interaction = 0.648) and LBR (P for interaction = 0.925). The morphological quality of blastocysts exhibits a multiplicative interaction with the morphological quality of Day 3 embryos on the CPR (P for interaction = 0.020) and LBR (P for interaction = 0.012). After adjusting for potential confounders, the HQ Day 3 embryo group was positively associated with the CPR (adjusted odds ratio (aOR): 2.10, 95% CI: 1.31-3.36, P = 0.002) and LBR (aOR: 1.97, 95% CI: 1.20-3.25, P = 0.008) of LQ blastocysts. However, the morphological quality on Day 3 was not significantly associated with the CPR (aOR: 0.95, 95% CI: 0.58-1.55, P = 0.835) and LBR (aOR: 0.86, 95% CI: 0.53-1.40, P = 0.550) of HQ blastocysts. LIMITATIONS, REASONS FOR CAUTION: Selection and confounding bias introduced by the retrospective design cannot be completely eliminated in this study, although multivariable logistic analysis was conducted to adjust for potential confounders. Also, some subgroups had small sample sizes, which may reduce statistical power. Moreover, participants in our study only received single euploid blastocyst transfer, and whether the results could apply to blastocysts with unknown ploidy status is unclear. WIDER IMPLICATIONS OF THE FINDINGS: This study found that the morphological quality on Day 3 was significantly associated with the CPR and LBR of LQ blastocysts; Therefore, when only LQ euploid blastocysts are available for transfer, blastocysts derived from HQ Day 3 embryos are recommended.

BackgroundOptimal protocols for frozen-thawed embryo transfer (FET) after preimplantation genetic testing (PGT) remain unclear. This study compared Day 5 (D5) and Day 6 (D6) blastocysts and evaluated predictors of FET success.MethodsA total of 870 patients with genetic diseases or chromosomal translocations who received PGT at the First Affiliated Hospital of Zhengzhou University from January 2015 to December 2019 were recruited. All patients underwent at least one year of follow-up. Patients were divided into groups according to the blastocyst development days and quality. Univariate and multivariate logistic regression were applied to identify risk factors that affect clinical outcomes and to construct a predictive nomogram model. Area under the curve (AUC) of the subject’s operating characteristic curve and GiViTI calibration belt were conducted to determine the discrimination and fit of the model.ResultsD5 blastocysts, especially high-quality D5, resulted in significantly higher clinical pregnancy (58.4% vs 49.2%) and live birth rates (52.5% vs 45%) compared to D6. Multivariate regression demonstrated the number of blastocysts, endometrial preparation protocol, days of embryonic development and the quality of blastocysts independently affected live birth rates (P<0.05). A nomogram integrating these factors indicated favorable predictive accuracy (AUC=0.598) and fit (GiViTI, P=0.192).ConclusionsTransferring high-quality D5 euploid blastocysts after PGT maximizes pregnancy outcomes. Blastocyst quality, blastocyst development days, endometrial preparation protocols, and number of blastocysts, independently predicted outcomes. An individualized predictive model integrating these factors displayed favorable accuracy for counseling patients and optimizing clinical management.

PurposeTo investigate potential differences in pregnancy outcomes among patients with regular menstruation who underwent frozen-thawed embryo transfer using natural cycle (NC) or hormone replacement therapy (HRT).MethodsThis study retrospectively analyzed 2672 patients with regular menstruation who underwent FET from November 2015 to June 2021 at the single reproductive medical center. A one-to-one match was performed applying a 0.02 caliper with propensity score matching. Independent factors influencing the live birth and clinical pregnancy rates were screened and developed in the nomogram by logistic regression analysis. The efficacy of live birth rate and clinical pregnancy rate prediction models was assessed with the area under the ROC curve, and the live birth rate prediction model was internally validated within the bootstrap method.ResultsThe NC protocol outperformed the HRT protocol in terms of clinical pregnancy and live birth rates. The stratified analysis revealed consistently higher live birth and clinical pregnancy rates with the NC protocol across different variable strata compared to the HRT protocol. However, compared to the HRT treatment, perinatal outcomes indicated that the NC protocol was related to a higher probability of gestational diabetes. Multifactorial logistic regression analysis demonstrated independent risk factors for live birth rate and clinical pregnancy rate. To predict the two rates, nomogram prediction models were constructed based on these influencing factors. The receiver operating characteristic curve demonstrated moderate predictive ability with an area under curve (AUC) of 0.646 and 0.656 respectively. The internal validation of the model for live birth rate yielded an average AUC of 0.646 implying the stability of the nomogram model.ConclusionThis study highlighted that NC yielded higher live birth and clinical pregnancy rates in comparison to HRT in women with regular menstruation who achieved successful pregnancies through frozen-thawed embryo transfer. However, it might incur a higher risk of developing gestational diabetes.

PurposeThis study aims to retrospectively estimate cumulative reproductive outcomes in women with primary ovarian insufficiency (POI) in assisted reproductive technology (ART) therapy.MethodsA total of 139 patients diagnosed with POI were reviewed in this study. Firstly, they were divided into two groups according to oocyte origin: using their own oocytes (OG group) or accepting oocyte donations (OD I group). Secondly, the patients were split depending on the pregnancy outcome. In the OG group, nine patients decided to use others’ oocytes after a failure of attempting to use their own, and this population was the oocyte donation II group (OD II group).ResultsThere were 88 patients who used their own oocytes, while 51 patients accepted oocyte donations. In the OG group, there are only 10 (7.2%) patients who got pregnant, and patients in the OD group had worse hormone levels (FSH 71.37 ± 4.18 vs. 43.98 ± 2.53, AMH 0.06 ± 0.04 vs. 1.15 ± 0.15, and AFC 0.10 ± 0.06 vs. 1.15 ± 0.15) and more years of infertility (5.04 ± 0.48 vs. 3.82 ± 0.30), which explained why they choose oocyte donation. In all the three groups, baseline characteristics were comparable between pregnant women and non-pregnant women. Of the 10 pregnant patients in the OG group, four of them used luteal-phase short-acting long protocol and had pregnancies successfully in their first cycles.ConclusionOvarian stimulation in POI women requires more cost and time. For those with a stronger desire to have genetic offspring, luteal-phase short-acting long protocol may help them obtain pregnancy rapidly.

Objective: To investigate the effect of different gestational weeks and psychological intervention on pregnancy outcome in patients with monochorionic twin pregnancy. Methods: The clinical data of 68 patients with monochorionic twin pregnancy in the middle and late pregnancy who were treated with radiofrequency ablation in the First Affiliated Hospital of Zhengzhou University from March 2017 to April 2021 were retrospectively analyzed, including 54 patients with single chorionic and single amniotic sac and 14 patients with single chorionic and double amniotic sac. Patients were divided into three groups according to the gestational weeks:<20 weeks (n=36), 20-23 weeks (n=17) and ≥24 weeks (n=15); and were divided into intervention group (n=40) and control group (n=28) according to the preoperative psychological intervention. The pregnancy outcome of patients with different pregnancy reduction and the effect of psychological intervention on pregnancy outcome was analyzed. Results: The age of 68 patients was (30.2±4.6) years old, the gestational age was (22.2±3.2) weeks, and 60 cases (88.2%) were live births after fetal reduction. There were no significant difference in age [(31.8±4.7),(28.3±5.0),(30.3±4.0) years old] (P=0.098), abortion rate, preterm birth rate, live birth rate, delivery mode, gestational week of preterm birth, gestational week of delivery, and neonatal weight between the two groups at different gestational weeks (all P>0.05). The ages of the intervention group and the control group were (30.6±4.7) and (29.4±4.0) years old (P=0.352). After psychological intervention for 40 patients in the intervention group, the anxiety score after pregnancy reduction was reduced from (54.8±6.8) to (37.3±7.3) (P<0.001), while the depression score decreased from (62.7±7.2) to (33.2±2.4) (P<0.001). Compared with patients in the control group (12.5%, n=5), the proportion of postoperative discomfort in the intervention group was higher (53.6%, n=15) (P<0.001). Compared with the control group, there were no statistically significant difference in the postoperative preterm birth rate, abortion rate, live birth rate, delivery mode, gestational week of preterm birth, gestational week of delivery, and neonatal weight in the intervention group (all P>0.05). Conclusions: Radiofrequency ablation is a safe and effective minimally invasive technique. For complex monochorionic twin pregnancies, early fetal reduction (<20 weeks) and preoperative psychological intervention can provide a solid guarantee for a good postoperative pregnancy outcome.

STUDY QUESTION:Can emergency vitrification protect embryos and oocytes during natural disasters or other events that prevent normal practice to achieve satisfactory embryonic development and clinical outcomes at a later time? SUMMARY ANSWER:Emergency vitrification of oocytes and Day 0-Day 5 (D0-D5) embryos during disasters is a safe and effective protective measure. WHAT IS KNOWN ALREADY:When some destructive events such as floods, earthquakes, tsunamis, and other accidents occur, emergency vitrification in embryo laboratories to protect human embryos, oocytes, and sperm is one of the important measures of an IVF emergency plan. However, there are few detailed reports on emergency vitrification in a state of disaster, especially about oocytes and D0 zygotes. Therefore, the effectiveness and safety of emergency vitrification of oocytes and D0-D5 embryos in disaster states are still unclear. STUDY DESIGN, SIZE, DURATION:A retrospective study was made in the Reproductive Medicine Center of the First Affiliated Hospital of Zhengzhou University from January 2018 to November 2022. The record rainstorms in Zhengzhou, China, caused severe flooding, traffic disruptions, and power outages. From 17:30, 20 July 2021 to 17:30, 21 July 2021, 1246 oocytes and D0-D5 embryos of 155 patients were vitrified whilst the laboratory had only an emergency power supply. PARTICIPANTS/MATERIALS, SETTING, METHODS:As of 21 December 2021, 1149 emergency vitrified oocytes and D0-D5 embryos of 124 patients underwent frozen-thawed embryo transfer (FET). They were divided into the following four groups according to the days of embryo culture in vitro: oocyte group, Day 0-Day 1 (D0-D1) group, Day 2-Day 3 (D2-D3) group, and Day 4-Day 5 (D4-D5) group. Control groups for each were selected from fresh cycle patients who underwent IVF/ICSI from January 2018 to October 2021. Control and emergency vitrification patients were matched on criteria that included age, fertilization method, days of embryonic development, and number and grade of transferred embryos. A total of 493 control patients were randomly selected from the eligible patients and matched with the emergency vitrification groups in a ratio of 4:1. The results of assisted reproduction and follow-up of pregnancy were analyzed. The embryonic development, clinical outcomes, and birth outcomes in each group were statistically analyzed. MAIN RESULTS AND THE ROLE OF CHANCE:A significant difference was observed in fertilization rate (81% versus 72%, P = 0.022) between the oocyte group and the control group. Significant differences were also observed in the monozygotic twin pregnancy rate (10% versus 0%, P = 0.038) and ectopic pregnancy rate (5% versus 0%, P = 0.039) between the D0-D1 group and the control group. No significant differences (P > 0.05) were observed between vitrified oocytes/D0-D1 embryos/D2-D3 embryos and the control group on the number of high-quality embryos (3.17 ± 3.00 versus 3.84 ± 3.01, P = 0.346; 5.04 ± 3.66 versus 4.56 ± 2.87, P = 0.346; 4.85 ± 5.36 versus 5.04 ± 4.64, P = 0.839), the number of usable blastocysts (1.22 ± 1.78 versus 1.21 ± 2.03, P = 0.981; 2.16 ± 2.26 versus 1.55 ± 2.08, P = 0.090; 2.82 ± 3.23 versus 2.58 ± 3.32, P = 0.706), clinical pregnancy rate (56% versus 57%, P = 0.915; 55% versus 55%, P = 1.000; 40% versus 50%, P = 0.488), miscarriage rate (30% versus 15%, P = 0.496; 5% versus 11%, P = 0.678; 17% versus 20%, P = 1.000), and live birth rate (39% versus 49%, P = 0.460; 53% versus 50%, P = 0.772; 33% versus 40%, P = 0.635). No significant differences (P > 0.05) were observed between the D4-D5 group and the control group on clinical pregnancy rate (40% versus 55%, P = 0.645), miscarriage rate (0% versus 18%, P = 1.000), and live birth rate (40% versus 45%, P = 1.000). LIMITATIONS, REASONS FOR CAUTION:The retrospective study design is a limitation. The timing and extent of natural disasters are unpredictable, so the sample size of vitrified oocytes, zygotes, and embryos is beyond experimental control. WIDER IMPLICATIONS OF THE FINDINGS:This study is the first study analyzing embryonic development, clinical outcomes, and birth outcomes of large samples of oocytes, D0 zygotes, and D1-D5 embryos after emergency vitrification under the disaster conditions. The results show that emergency vitrification is a safe and effective protective measure applicable to oocytes and D0-D5 embryos. The embryology laboratories need to be equipped with an emergency uninterrupted power supply capable of delivering for 6-8 h at full load. STUDY FUNDING/COMPETING INTEREST(S):This work was supported by the National Natural Science Foundation of China (grant 81871206). The authors declare that they have no conflicts of interest. All authors have completed the ICMJE Disclosure form. TRIAL REGISTRATION NUMBER:N/A.

Background:In vitro fertilization-embryo transfer (IVF-ET) is a crucial assisted reproductive technology for treating infertility. However, recurrent implantation failure (RIF), a significant challenge in IVF-ET success, remains unresolved. This study aimed to explore the role and mechanism of FLI1 in endometrial receptivity and RIF.Methods:Differential endometrial cell proportions between patients with RIF and control subjects were assessed using single-cell RNA sequencing (scRNA-seq) analysis. The chromatin accessibility of FLI1 in the luteal endometrial tissue of patients with RIF and control subjects was examined using the single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq). FLI1 mRNA and protein levels were gauged by quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting. Cell viability and migration were examined via cell counting kit (CCK)-8 and scratch healing assays. Epithelial-mesenchymal transition markers were analyzed using western blotting. Mechanisms underlying FLI1's regulation of PART1 transcription and expression in endometrial epithelial cells were explored using chromatin immunoprecipitation and dual-luciferase reporter assays. Adeno-associated virus (AAV) carrying epithelial cell-specific FLI1/PART1 overexpression sequences was uterinely injected in mice to assess FLI1/PART1 effects.Results:scRNA-seq revealed diminished endometrial epithelial cell proportions in RIF patients. Meanwhile, scATAC-seq indicated enhanced chromatin accessibility of FLI1 in these cells. FLI1 exhibited specific expression in RIF patients' endometrial epithelial cells. Specific FLI1 overexpression inhibited embryo implantation, while knockdown enhanced it. Pregnant mice injected with AAV encoding FLI1 overexpression had significantly lower implantation than AAV-negative controls. FLI1 binding to PART1 promoter heightened PART1 transcription and expression in endometrial epithelial cells. Rescue experiments illustrated FLI1's role in embryo implantation by boosting PART1 expression. PART1 was notably elevated in RIF patients' luteal endometrial tissue and non-receptive endometrial epithelial cells (HEC-1-A). Specific PART1 overexpression dampened embryo implantation, whereas knockdown promoted it. Pregnant mice injected with AAV encoding PART1 had lower implantation than negative controls. PART1 knockdown mitigated FLI1's inhibitory impact on HEC-1-A cell viability and migration.Conclusions:FLI1 overexpression in the endometrial epithelial cells of patients with RIF inhibited embryo implantation by binding to the PART1 promoter region to promote PART1 expression. These findings can aid in the development of novel therapeutic targets for RIF.

ObjectiveTo assess whether progesterone (P) levels on the trigger day during preimplantation genetic testing (PGT) cycles are associated with embryo quality and pregnancy outcomes in the subsequent first frozen-thawed blastocyst transfer (FET) cycle.MethodsIn this retrospective analysis, 504 eligible patients who underwent ICSI followed by frozen-thawed embryo transfer (FET) with preimplantation genetic test (PGT) between December 2014 and December 2019 were recruited. All patients adopted the same protocol, namely, the midluteal, short-acting, gonadotropin-releasing hormone agonist long protocol. The cutoff P values were 0.5 and 1.5 ng/ml when serum P was measured on the day of human chorionic gonadotropin (HCG) administration, and cycles were grouped according to P level on the day of HCG administration. Furthermore, the effect of trigger-day progesterone on embryo quality and the subsequent clinical outcome of FET in this PGT population was evaluated.ResultsIn total, 504 PGT cycles were analyzed. There was no significant difference in the number of euploid blastocysts, top-quality blastocysts, euploidy rate, or miscarriage rate among the three groups (P>0.05). The 2PN fertilization rate (80.32% vs. 80.17% vs. 79.07%) and the top-quality blastocyst rate (8.71% vs. 8.24% vs. 7.94%) showed a downward trend with increasing P, and the between-group comparisons showed no significant differences (P>0.05). The clinical pregnancy rate (41.25% vs. 64.79%; P<0.05) and live birth rate (35.00% vs. 54.93%; P<0.05) in subsequent FET cycles were substantially lower in the high-P group than in the P ≤ 0.5 ng/ml group. After adjustments were made for confounding variables, multivariate logistic regression analysis revealed that the high-P group had a lower clinical pregnancy rate (adjusted OR, 0.317; 95% CI, 0.145–0.692; P=0.004) and live birth rate (adjusted OR, 0.352; 95% CI, 0.160–0.773; P=0.009) than the low-P group in subsequent FET cycles, and the differences were significant.Conclusion(s)This study demonstrates that in the PGT population, elevated P on the trigger day may diminish the top-quality blastocyst rate (although there is no difference in the euploidy rate). Trigger-day P is an important factor influencing clinical outcomes in subsequent FET cycles.

Objective:To explore the impact of female body mass index (BMI) on clinical outcomes in patients treated with intrauterine insemination (IUI).Methods:This study was a retrospective cohort study. A total of 21 137 patients who visited the Reproductive Medical Center, the First Affiliated Hospital of Zhengzhou University from January 2010 to December 2021 were recruited. The patients underwent the first IUI cycles, including artificial insemination by husband (AIH) and artificial insemination by donor (AID). According to clinical pregnancy or not, it is divided into pregnancy group and non-pregnancy group. The basic parameters between clinical pregnancy group and non-clinical pregnancy group were compared. According to the BMI, patients were divided into 4 groups, group A: BMI≤18.5 kg/m 2, group B: 18.6-23.9 kg/m 2, group C: 24.0-27.9 kg/m 2and group D: BMI≥28.0 kg/m 2. Patients' basic parameters and clinical outcomes were compared among the four groups. Multivariate logistic regression analysis was used to explore the impact of BMI on pregnancy outcomes. Results:In all IUI cycles, BMI was significantly different between pregnant patients and non-pregnant patients [(24.58±3.52) kg/m 2vs. (23.35±4.20) kg/m 2, P<0.001]. In AIH cycles, clinical pregnancy rate [18.21% (877/4 815), 17.12% (222/1 297)] and early spontaneous miscarriage rate [17.10% (150/877), 21.62% (48/222)] were significantly higher in patients of group C and group D than in group A [11.24% (130/1 157), 10.77% (14/130)] and group B [13.40% (1 229/9 174), 15.30% (188/1 229)]. The differences among the 4 groups were statistically significant ( P=0.012, P=0.003). However, BMI was not associated with clinical pregnancy rate in multivariate logistic analysis, but obesity was a predictor for early spontaneous miscarriage ( OR=1.63, 95% CI: 1.25-1.95, P=0.003). In AID cycles, pregnancy outcomes were comparable among the four BMI groups. Obesity significantly increased early spontaneous miscarriage rate ( OR=1.58, 95% CI: 1.14-1.87, P=0.016). Conclusion:Female BMI is not associated with clinical outcomes in IUI cycles. Obesity is a predictor for early spontaneous miscarriage in both AIH and AID cycles.

目的 探讨血脂异常对非多囊卵巢综合征(PCOS)不孕患者体外受精/卵胞浆内单精子注射-胚胎移植(IVF/ICSI-ET)妊娠结局的影响.方法 回顾性分析2017年1月至2021年7月在郑州大学第一附属医院生殖医学中心采用卵泡期长效促性腺激素释放激素激动剂(GnRH-a)长方案进行第一周期IVF/ICSI-ET助孕的10 424例非PCOS不孕患者的临床资料,根据血清中总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)水平将患者分为血脂异常组(2 607例)及血脂正常组(7 817例),比较两组间的基础资料、促排卵和移植情况、不同年龄层间的妊娠结局,Logistic回归分析血脂异常对妊娠结局的影响.结果 基础资料:两组患者间的年龄、体质量指数(BMI)、不孕年限、不孕类型、基础卵泡刺激素(FSH)、基础雌二醇(E2)、基础孕酮(P)、促甲状腺激素(TSH)、空腹血糖(FBG)、血脂四项(TC、TG、LDL-C、HDL-C)均存在显著差异(P＜0.05),余项均无显著性差异(P＞0.05).促排卵及移植情况:血脂异常组的HCG日E2水平、HCG日P水平、获卵数、2PN胚胎数、种植率显著低于血脂正常组(P＜0.05),Gn启动量、Gn天数、Gn总量显著高于血脂正常组(P＜0.05),余项均无显著性差异(P＞0.05).妊娠结局:按年龄分层分析,年龄＜35岁时两组的晚期流产率及活产率有显著差异(P＜0.05),年龄≥35岁时两组的早期流产率有显著差异(P＜0.05);未校正年龄的影响时,总体两组间临床妊娠率、早期及晚期流产率、活产率均有显著差异(P＜0.05);校正年龄的影响后,总体两组间临床妊娠率无显著差异(P＞0.05),早期流产率、晚期流产率及活产率仍有显著差异(P＜0.05).多因素Logistic回归分析结果显示,校正混杂因素后,血脂异常是早期流产率[OR=1.267,95％CI(1.037,1.550),P=0.021]、晚期流产率[OR=1.394,95％CI(1.021,1.903),P=0.037]及活产率[OR=0.895,95％CI(0.811,0.989),P=0.029]的独立影响因素.结论 血脂异常增加非PCOS不孕患者流产的风险并降低其活产率,对其IVF/ICSI-ET妊娠结局具有负面影响.

Objective:To analyze the subsequent assisted pregnancy outcomes of recurrent implantation failure (RIF) and find out the key influencing factors.Methods:A case-control study was conducted to analyze the clinical data of 640 patients who received embryo transfer assisted fertility in the Center for Reproductive Medicine of the First Affiliated Hospital of Zhengzhou University from January 2016 to June 2019 and were diagnosed with RIF and received subsequent assisted fertility treatment. The main outcome measures were the live birth rate and the time to pregnancy after diagnosis of RIF.Results:The live birth rate, the biochemical pregnancy rate, the clinical pregnancy rate and the abortion rate of the first cycle, the second cycle, the third and above cycle after a diagnosis of RIF were not significantly different (all P>0.05). The time to pregnancy after diagnosis of RIF of 344 patients who achieved live births was 5.00(3.13, 8.52) months. After adjusting for confounding factors by using multivariate logistic regression, the results showed that the cumulative live birth probability of blastocyst transfer was significantly higher than that of cleavage embryo transfer [ P=0.002, RR (95% CI)=1.492(1.158-1.923)]; the cumulative live birth probability of patients less than 35 years old was significantly higher than older patients (≥35 years old)[ P=0.013, RR (95% CI)=0.694(0.521-0.925)]; the cumulative live birth probability of patients with endometrial thickness ≥8 mm on the embyro transfer day was significantly higher than that of patients with endometrial thickness <8 mm [ P=0.016, RR (95% CI)=1.943(1.132-3.335)]; compared with patients with 0 [ P=0.001, RR (95% CI)=0.625(0.474-0.825)] or 2 and more [ P=0.003, RR (95% CI)=0.414(0.233-0.736)] biochemical pregnancy in the RIF cycles, the cumulative live birth probability of patients with history of only 1 biochemical pregnancy in the RIF cycles was significantly higher. Conclusion:The type of embryos transferred, age, endometrial thickness on the embyro transfer day and the history of biochemical pregnancy in the RIF cycles are independent factors for subsequent cumulative live birth probability in RIF patients. Blastocyst transfer should be selected as much as possible, and fertility treatment should be performed as soon as possible through reasonable cycle management, the history of only 1 biochemical pregnancy in the RIF cycles heralds a better live birth outcome in the subsequent cycles of RIF.

Introduction:Women with diminished ovarian reserve (DOR) have a lower pregnancy rate and higher cancellation rate compared to those without DOR when seeking assisted reproductive technology. However, which factors are associated with reproductive outcomes and whether AMH is a predictor of clinical pregnancy remain unclear.Objective:This retrospective study was designed to find factors associated with reproductive outcomes in DOR patients and then discuss the role of AMH in predicting cycle results among this population.Method:A total of 900 women were included in the study. They were diagnosed with DOR with the following criteria: (i) FSH > 10 IU/L; (ii)AMH < 1.1 ng/ml; and (iii) AFC <7. They were divided into different groups: firstly, based on whether they were clinically pregnant or not, pregnant group vs. non-pregnant group (comparison 1); secondly, if patients had transferrable embryos (TE) or not, TE vs. no TE group (comparison 2); thirdly, patients undergoing embryo transfer (ET) cycles were divided into pregnant I and non-pregnant I group (comparison 3). The baseline and ovarian stimulation characteristics of these women in their first IVF/ICSI cycles were analyzed. Logistic regression was performed to find factors associated with clinical pregnancy.Results:Of the 900 DOR patients, 138 women got pregnant in their first IVF/ICSI cycles while the rest did not. AMH was an independent predictor of TE after adjusting for confounding factors (adjusted OR:11.848, 95% CI: 6.21-22.62, P< 0.001). Further ROC (receiver operating characteristic) analysis was performed and the corresponding AUC (the area under the curve) was 0.679 (95% CI: 0.639-0.72, P< 0.001). Notably, an AMH level of 0.355 had a sensitivity of 62.6% and specificity of 65.6%. However, there was no statistical difference in AMH level in comparison 3, and multivariate logistic regression showed female age was associated with clinical pregnancy in ET cycles and women who were under 35 years old were more likely to be pregnant compared to those older than 40 years old (adjusted OR:4.755, 95% CI: 2.81-8.04, P< 0.001).Conclusion:AMH is highly related to oocyte collection rate and TE rate,and 0.355 ng/ml was a cutoff value for the prediction of TE. For DOR patients who had an embryo transferred, AMH is not associated with clinical pregnancy while female age is an independent risk factor for it.

Background Peutz Jeghers syndrome (PJS) is an autosomal dominant genetic disorder caused by STK11 mutation with a predisposition to gastrointestinal polyposis and cancer. PJS patients suffer poor quality of life and are highly concerned about whether deleterious mutations transmit to their offspring. Therefore, this study aimed to propose feasible clinical management and provide effective preimplantation genetic testing for monogenic defect (PGT-M) strategies to protect offspring from inheriting the disease. Methods A hospital-based clinical retrospective analysis reviewing the clinical characteristics and fertility aspects was first conducted on 51 PJS patients at the First Affiliated Hospital of Zhengzhou University between January 2016 and March 2021. Among the 51 patients, the PGT-M strategy was further carried out in 4 couples, which started with a biopsy of the trophectoderm cells of embryos and whole genome amplification using multiple displacement amplification. Thereafter, single nucleotide polymorphism linkage analyses based on karyomapping were performed with copy number variations of the embryos identified simultaneously. Finally, prenatal diagnosis was used to verify the validity of the PGT-M results. Results A comprehensive management flowchart adopted by the multidisciplinary team model was formulated mainly focusing on clinical genetic and gastrointestinal aspects. Under the guidelines of this management, 32 embryos from 4 PJS pedigrees were diagnosed and 2 couples successfully conceived healthy babies free of the STK11 pathogenic mutation. Conclusions Our comprehensive management could help affected families avoid having children with PJS through preimplantation genetic testing and provide meaningful guidance for multidisciplinary clinical practice on PJS.

Objective To investigate the genetic etiology of a patient with primary infertility and oocyte maturation defect. Methods Whole exome sequencing (WES) was carried out on patient's DNA to detect potential pathologic variants. The positive sites detected by WES were verified by Sanger sequencing, and the bioinformatics analysis of the mutation was analyzed. Results The patient was found to harbor compound heterozygous variants of the PATL2 in exon 14 and 13 c.1 374A＞G (p.Ile458Met) and c.1 289_1 291delTCC (p.Leu430del), which were respectively inherited from her father and mother. Conclusions The compound heterozygous variation of PATL2 may be the genetic mechanism to explain infertility resulted from the disturbance of oocyte maturation.