Insulin resistance (IR) is a common pathophysiologic feature in patients with polycystic ovary syndrome (PCOS). However, there have been no studies investigating the association of IR surrogates with pregnancy outcomes in women with PCOS undergoing in vitro fertilization (IVF). Therefore, we explored the association between these factors among PCOS patients. We conducted a retrospective study that included patients with PCOS who underwent IVF at a university-affiliated hospital. Blood samples and physical examinations are collected at reproductive center on fasting in the morning of the 2nd to 4th day of the menstrual cycle prior to medication. We categorized participants into “Non-IR group” (HOMA-IR < 2.2) and “IR group” (HOMA-IR ≥ 2.2). The association of IR surrogates [triglyceride-glucose-body mass index (TyG-BMI), triglyceride-glucose (TyG) and homeostasis model assessment (HOMA-IR)] with IVF outcomes was evaluated by regression model analysis. Moreover, we also performed sensitivity analyses with stratification and interaction tests. The primary outcome variable was the live birth rate. A total of 543 PCOS patients were finally included in the study. In all three regression models for the fresh embryo transfer (ET) cycles, all three IR surrogates showed stable negative correlations with live birth rate (in Model III: TyG-BMI OR = 0.99, 95

Blood transfusions save lives and improve health every day. Despite the matching of blood types being stricter than it ever has been, emergency transfusions among incompatible blood types are still inevitable in the clinic when there is a lack of acceptable blood types for recipients. Here to overcome this, a counter measure nanoplatform consisting of a polymeric core coated by a red blood cell (RBC) membrane is developed. With A-type or B-type RBC membrane camouflaging, the nanoplatform is capable of specifically capturing anti-A or anti-B IgM antibodies within B-type or A-type whole blood, thereby decreasing the corresponding IgM antibody levels and then allowing the incompatible blood transfusions. In addition to IgM, the anti-RBC IgG antibody in a passive immunization murine model can likewise be neutralized by this nanoplatform, leading to prolonged circulation time of incompatible donor RBCs. Noteworthily, nanoplatform made by expired RBCs (>42 days stored hypothermically) and then subjected to lyophilization does not impair their effect on antibody neutralization. Most importantly, antibody-captured RBC-NP do not exacerbate the risk of inflammation, complement activation, and coagulopathy in an acute hemorrhagic shock murine model. Overall, this biomimetic nanoplatform can safely neutralize the antibody to enable incompatible blood transfusion.

Background The basal luteinizing hormone (LH) and the prior LH to follicle-stimulating hormone (FSH) ratio (LH/FSH) in polycystic ovarian syndrome (PCOS) are generally higher than those in non-PCOS patients and the general population. The potential negative effects of elevated LH on human reproductive function are highly controversial, as are the effects of down-regulation of LH on reproductive function. The purpose of this study was to evaluate the effect of the basal LH/FSH ratio on the live birth rate of PCOS patients undergoing in vitro fertilization (IVF) cycles. Methods A retrospective analysis was conducted on 698 patients with polycystic ovary syndrome undergoing IVF treatments with a mild stimulation protocol (n = 95) and a gonadotropin-releasing hormone (GnRH) agonist protocol (n = 603). The basal LH/FSH ratio of 2 was used as the cut-off value for further subgroup analysis. The demographic properties, controlled ovarian hyperstimulation (COH) processes, and clinical pregnancy outcomes were compared between groups under each ovulation stimulation protocol. Results The live birth rate for patients with a LH/FSH ratio ≥ 2 group (56.38%, n = 149) was not statistically different from that of the ones with a ratio < 2 (53.74%, n = 454) in the GnRH agonist protocol (P = 0.576). Correspondingly, the live birth rate for the LH/FSH ratio ≥ 2 group (43.48%, n = 23) also showed no statistical difference from the ratio < 2 group (48.61%, n = 72) in the mild stimulation protocol (P = 0.668). Additionally, LH/FSH ratios had no significant effect on the live birth rate after adjusting for confounders both in the GnRH agonist protocol (adjusted OR: 1.111; 95% CI [0.467–2.642], P = 0.812) and in the mild stimulation protocol (adjusted OR: 4.057; 95% CI [0.431–38.195], P = 0.221). Furthermore, there was no significant difference in the live birth rate between different ovulation stimulation protocols in PCOS patients with the LH/FSH ratio ≥ 2. Conclusions The live birth rate in IVF outcomes was not affected by an elevated basal LH/FSH ratio in patients with polycystic ovary syndrome. The choice of the GnRH agonist protocol or mild stimulation protocol for ovulation stimulation does not affect the final clinical outcomes either for PCOS patients with a basal LH/FSH ratio ≥ 2.

PurposePropofol, a widely utilized anesthetic, is employed to alleviate pain and anxiety in outpatient oocyte retrieval procedures. However, its potential impact and safety profile in the context of in vitro fertilization and embryo transfer (IVF-ET) remain unclear.MethodsThis retrospective study enrolled 1187 patients undergoing IVF-ET, and divided into two groups depending on whether they received propofol (propofol group, n=140) or not (control group, n=1047) for anesthesia during oocyte retrieval.ResultsThe baseline characteristics were comparable between the groups. Compared with control group, the number of oocytes retrieved in propofol group was more (p=0.012), while both the estradiol (E2) level on the trigger day and the pre-ovulatory follicle count were higher in propofol group ((p<0.01). Additionally, the rate of preterm delivery was significantly higher in the propofol group (p<0.001). To further analyze the effect of propofol on the oocyte retrieval rate, patients were divided into three subgroups depending on the pre-ovulatory follicle count (≤10, 11–20, and >20) to eliminate the influence of inconsistency in the estimation of the pre-ovulatory follicle count between the two groups. Analysis revealed that the use of propofol during oocyte retrieval was particularly advantageous in the subgroup with a pre-ovulatory follicle count of 11–20, yielding a higher oocyte retrieval rate (p<0.001).ConclusionThe use of propofol in oocyte retrieval did not adversely affect fertilization, embryo quality, or clinical outcomes. Moreover, it was found to increase the oocyte retrieval rate among patients with an estimated pre-ovulatory follicle count of 11–20. These findings offer valuable evidence supporting the clinical application of propofol in oocyte retrieval procedures.

Background: Severe congenital neutropenia (SCN) is an autoimmune disease clinically characterized by persistent and severe neutropenia. It is typically caused by a heterozygous mutation in the ELANE gene, which encodes neutrophil elastase. Procedure: Using one 3-year-old male diagnosed with severe congenital neutropenia, we aimed to assess the clinical and genetic characteristics of SCN caused by ELANE mutations and test whether the mutation can be corrected by CRISPR/Cas9-mediated gene editing. The proband underwent extensive clinical assessments, with exome sequencing and bioinformatics analysis to identify pathogenic genes. In addition, Sanger sequencing was used to verify the pedigrees. The cell line, 293-ELANE, harboring ELANE mutation was generated by lentiviral transduction and selection with puromycin from HEK-293. And the mutation was corrected by CRISPR/Cas9-mediated homology-directed repair (HDR). Results: The ELANE gene test in the proband unveiled a heterozygous de novo missense mutation: c. 248T>A (p.V83D), which is not detected in his asymptomatic parents with peripheral blood samples. Surprisingly, we found that 46.01% of his father’s sperm cells had the same mutation. These results demonstrated that the proband inherited the ELANE mutation from his father, who had a normal neutrophil count but was germline mosaic. In this study, the highest repair efficiency of CRISPR/Cas9-mediated HDR for 293-ELANE is 4.43%. Conclusions: We identified a missense mutation (p.V83D) in ELANE causing SCN, the first report on paternal semen mosaicism of an ELANE mutation. Our study also paves the way for preimplantation genetic diagnosis (PGD) based on ELANE mutation prevention and clinical treatment of congenital disabilities.

Phototherapy is an effective strategy to control Candida albicans (C. albicans) infection without raising the concern of drug resistance. Despite its effectiveness, a higher dose of phototherapeutic power is required for C. albicans elimination compared to bacteria that have to be used, which is readily accompanied by off-target heat and toxic singlet oxygen to damage normal cells, thus limiting its usefulness for antifungal applications. Here to overcome this, we develop a "three-in-one" biomimetic nanoplatform consisting of an oxygen-dissolved perfluorocarbon camouflaged by a photosensitizer-loaded vaginal epithelial cell membrane. With a cell membrane coating, the nanoplatform is capable of specifically binding with C. albicans at the superficial or deep vaginal epithelium, thereby centering the phototherapeutic agents on C. albicans. Meanwhile, the cell membrane coating endows the nanoplatform to competitively protect healthy cells from candidalysin-medicated cytotoxicity. Upon candidalysin sequestration, pore-forming on the surface of the nanoplatform accelerates release of the preloaded photosensitizer and oxygen, resulting in enhanced phototherapeutic power for improved anti-C. albicans efficacy under near-infrared irradiation. In an intravaginal C. albicans-infected murine model, treatment with the nanoplatform leads to a significantly decreased C. albicans burden, particularly when leveraging candidalysin for further elevated phototherapy and C. albicans inhibition. Also, the same trends hold true when using the nanoplatform to treat the clinical C. albicans isolates. Overall, this biomimetic nanoplatform can target and bind with C. albicans and simultaneously neutralize the candidalysin and then transform such toxins that are always considered a positive part in driving C. albicans infection with the power of enhancing phototherapy for improved anti-C. albicans efficacy.

With its well-documented toxicity, the use of doxorubicin (Dox) for cancer treatment requires trade-offs between safety and effectiveness. This limited use of Dox also hinders its functionality as an immunogenic cell death inducer, thus impeding its usefulness for immunotherapeutic applications. Here, we develop a biomimetic pseudonucleus nanoparticle (BPN-KP) by enclosing GC-rich DNA within erythrocyte membrane modified with a peptide to selectively target healthy tissue. By localizing treatment to organs susceptible to Dox-mediated toxicity, BPN-KP acts as a decoy that prevents the drug from intercalating into the nuclei of healthy cells. This results in significantly increased tolerance to Dox, thereby enabling the delivery of high drug doses into tumor tissue without detectable toxicity. By lessening the leukodepletive effects normally associated with chemotherapy, dramatic immune activation within the tumor microenvironment was also observed after treatment. In three different murine tumor models, high-dose Dox with BPN-KP pretreatment resulted in significantly prolonged survival, particularly when combined with immune checkpoint blockade therapy. Overall, this study demonstrates how targeted detoxification using biomimetic nanotechnology can help to unlock the full potential of traditional chemotherapeutics.

ObjectiveTo compare the effects of five different frozen-thaw embryo transfer (FET) strategies in women aged 35–40 years.MethodsData from 1,060 patients were divided into five groups according to the number and quality of transferred blastocysts: a high-quality single blastocyst group (group A, n= 303), a high-quality double blastocysts group (group B, n= 176), a high-quality plus poor-quality double blastocysts group (group C, n= 273), a poor-quality double blastocysts group (group D, n= 189), and a poor-quality single blastocyst group (group E, n= 119). Comparative analyses were then performed between groups with regard to primary conditions, pregnancy, and neonatal outcomes.ResultsGroup A had the lowest twin pregnancy rate (1.97%) and incidence of low-birth-weight infants (3.45%), which were significantly different from groups B, C, and D. In addition, the preterm birth rate (7.89%), neonatal birth weight (3300 g [3000, 3637.5]), and neonatal birth age (39.14 weeks [38.43, 39.61]) in group A were different from those in groups B and C. Double blastocyst transfer (DBT) was associated with a 20.558-fold (Risk Ratio [RR]=20.558, 95% confidence interval [CI], 6.628–63.763) and 3.091-fold (RR=3.091, 95% CI, 1.69–5.653) increased risk of twin pregnancy and preterm delivery in unadjusted analysis, respectively, when compared with single blastocyst transfer (SBT). In the adjusted analysis, we observed similar risk estimates (adjusted RR=26.501, 95% CI, 8.503–82.592; adjusted RR=3.586, 95% CI, 1.899–6.769).ConclusionAlthough, high-quality SBT resulted in a lower live birth rate than high-quality DBT, it also significantly reduced the risk of adverse pregnancies, thus resulting in more benefits for both the mother and baby. Collectively, our data indicate that high-quality SBT remains the optimal FET strategy for women aged 35–40 years and warrants further clinical application.

Objective To investigate the feasibility of switching from in vitro fertilization (IVF) to in vitro maturation (IVM) combined with all-blastocyst-culture and transfer as a supplementary infertility treatment in patients with ovarian hyperstimulation syndrome (OHSS) tendency Methods Retrospective cohort study including 184 patients who switched from IVF and underwent 192 IVM cycles between January 2016 and December 2020. The outcomes were compared between cleavage-stage embryo transfer (group A, n = 74) and blastocyst-stage transfer (group B, n = 52) groups. Results The OHSS rate is 0%. 66 cycles were canceled for transfer. Among the 126 transfer cycles, number of retrieved oocytes, proportion of metaphase II oocytes, cleavage rate, and proportion of high-quality embryos on day 3 post-fertilization are significantly lower in group A than that in group B. On the contrary, number of transferred embryos is significantly lower in group B than that in group A, whereas the rates of implantation, clinical pregnancy, and live births are significantly higher in group B than that in group A. Conclusion Timely switching to IVM combined with all-blastocyst-culture and transfer for patients undergoing controlled ovarian hyperstimulation and exhibiting characteristics of OHSS tendency is feasible as a supplementary infertility treatment.

Abstract Purpose Propofol is a common anesthetic agent used for oocyte retrieval procedures to reduce the pain and fear in outpatients. However, the potential effects and safety of propofol on in vitro fertilization and embryo transfer (IVF-ET) is not clear yet. Methods A total of 1187 patients undergoing IVF-ET were recruited in this retrospective study and divided into two groups depending on whether they received propofol (propofol group, n = 140) or not (control group, n = 1047) for anesthesia during oocyte retrieval. Results Baseline information did not differ between the two groups (p > 0.05). Compared with control group, the number of oocytes retrieved in propofol group was more (p = 0.012), while both the estradiol (E2) level on the trigger day and the pre-ovulatory follicle count were higher in propofol group ((p < 0.01). Furthermore, the preterm delivery rate was higher in the propofol group (p < 0.001). To further analyze the effect of propofol on the oocyte retrieval rate, patients were divided into three subgroups depending on the pre-ovulatory follicle count (≤ 10, 11–20, and > 20) to eliminate the influence of inconsistency in the estimation of the pre-ovulatory follicle count between the two groups. Data showed that oocyte retrieval with propofol was beneficial for getting more oocytes in the pre-ovulatory follicle count 11–20 subgroup (p < 0.001). Conclusion Oocyte retrieval with propofol had no negative effect on fertilization, embryo quality, and clinical outcomes, and could raise the oocyte retrieval rate in patients with an estimated pre-ovulatory follicle count 11–20. These findings provided evidence for further clinical applications of this technique.

Objective To investigate transfer strategies in the frozen-thawed embryo transfer (FET) cycle.Methods The clinical data of 1,652 FET patients were divided into five groups according to the number and quality of the transferred blastocyst: high-quality single blastocyst group (group A, n = 558), high-quality plus poor-quality double blastocyst group (group B, n = 435), poor-quality double blastocyst group (group C, n = 241), high-quality double blastocyst group (group D, n = 298), and poor-quality single blastocyst group (group E, n = 120).Inter-group comparison analyses of primary conditions, pregnancy outcomes and neonatal outcomes were then performed.Results Group A had the highest embryo implantation rate (67.38%), significantly different from the implantation rates of the other four groups.The gemellary pregnancy rate (1.60%), preterm birth rate (5.58%), neonatal birth weight (3,350g [3,000g, 3,650g]), neonatal birth age (39.57weeks [38.71, 40.34]), and incidence of low birth weight (7.02%) in group A were different from those in groups B, C, and D, but did not significantly differ from those in group E.Moreover, the proportions of male infants born in groups A (56.86%) and D (59.41%) were significantly higher than those in the other three groups.Double blastocyst transfer (0.528, 95% CI: 0.410-0.680,P<0.001) and high-quality blastocyst transfer (0.609, 95% CI: 0.453-0.820,P=0.001) were found to be protective factors for live birth.In addition, double blastocyst transfer was also the largest risk factor for pregnancy complications (3.120, P<0.001) and neonatal complications (2.230, P<0.001), especially for gemellary pregnancy (59.933,P<0.001) and preterm birth (3.840, 95% CI: 2.272-6.489,P<0.001).Based on the ROC curves, a double blastocyst transfer could predict gemellary pregnancy reliably with a high area under the curve (AUC = 78.53%).Additionally, a double blastocyst transfer could effectively predict a high risk of pregnancy complications (AUC = 65.90%), neonatal

The application of clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated proteins (Cas) can be limited due to a lack of compatible protospacer adjacent motif (PAM) sequences in the DNA regions of interest. Recently, SpRY, a variant of Streptococcus pyogenes Cas9 (SpCas9), was reported, which nearly completely fulfils the PAM requirement. Meanwhile, PAMs for SpRY have not been well addressed. In our previous study, we developed the PAM Definition by Observable Sequence Excision (PAM-DOSE) and green fluorescent protein (GFP)-reporter systems to study PAMs in human cells. Herein, we endeavored to identify the PAMs of SpRY with these two methods. The results indicated that 5′-NRN-3′, 5′-NTA-3′, and 5′-NCK-3′ could be considered as canonical PAMs. 5′-NCA-3′ and 5′-NTK-3′ may serve as non-priority PAMs. At the same time, PAM of 5′-NYC-3′ is not recommended for human cells. These findings provide further insights into the application of SpRY for human genome editing.

Background: Clinical and genetic characteristics of ELANE mutation of a 3-year-old male who had a severe congenital neutropenia (SCN) were examined. We then investigated whether CRISPR/Cas9-mediated gene editing could correct the mutation. Procedure: The proband underwent extensive clinical assessments, such as exome sequencing and bioinformatics analysis, so that pathogenic genes could be identified. Sanger sequencing was also utilized for confirmation. The cell line, 293-ELANE, harboring ELANE mutation was generated, and the mutation was then corrected by CRISPR/Cas9-mediated homology-directed repair (HDR). Results: The ELANE gene test in the proband unveiled a heterozygous de novo missense mutation: c. 248T > A (p. V83D), which was not detected in his asymptomatic parents who had provided peripheral blood samples. We found that 46.01% of his father's sperm cells had the same mutation. These results demonstrate that the proband inherited the ELANE mutation from his father, who had an average neutrophil count but had a germline mosaicism. The highest repair efficiency of CRISPR/Cas9-mediated HDR for 293-ELANE is 4.43%. Conclusions: We identified a missense mutation (p.V83D) in ELANE that causes SCN. This is the first report on paternal semen mosaicism of an ELANE mutation. Our study paves the way for preimplantation genetic diagnosis (PGD) based on ELANE mutation prevention and clinical treatment of congenital disabilities.

Objective To investigate transfer strategies in the frozen-thawed embryo transfer (FET) cycle. Methods The clinical data of 1,652 FET patients were divided into five groups according to the number and quality of the transferred blastocyst: high-quality single blastocyst group (group A, n = 558), high-quality plus poor-quality double blastocyst group (group B, n = 435), poor-quality double blastocyst group (group C, n = 241), high-quality double blastocyst group (group D, n = 298), and poor-quality single blastocyst group (group E, n = 120). Inter-group comparison analyses of primary conditions, pregnancy outcomes and neonatal outcomes were then performed. Results Group A had the highest embryo implantation rate (67.38%), significantly different from the implantation rates of the other four groups. The gemellary pregnancy rate (1.60%), preterm birth rate (5.58%), neonatal birth weight (3,350g [3,000g, 3,650g]), neonatal birth age (39.57 weeks [38.71, 40.34]), and incidence of low birth weight (7.02%) in group A were different from those in groups B, C, and D, but did not significantly differ from those in group E. Moreover, the proportions of male infants born in groups A (56.86%) and D (59.41%) were significantly higher than those in the other three groups. Double blastocyst transfer (0.528, 95% CI [0.410–0.680], P < 0.001) and high-quality blastocyst transfer (0.609, 95% CI [0.453–0.820], P = 0.001) were found to be protective factors for live birth. In addition, double blastocyst transfer was also the largest risk factor for pregnancy complications (3.120, 95% CI [2.323–4.190], P < 0.001) and neonatal complications (2.230, 95% CI [1.515–3.280], P < 0.001), especially for gemellary pregnancy (59.933, 95% CI [27.298–131.58], P < 0.001) and preterm birth (3.840, 95% CI [2.272–6.489], P < 0.001). Based on the ROC curves, a double blastocyst transfer could predict gemellary pregnancy reliably with a high area under the curve (AUC = 78.53%). Additionally, a double blastocyst transfer could effectively predict a high risk of pregnancy complications (AUC = 65.90%), neonatal complications (AUC = 64.80%) and preterm birth (AUC = 66.20%). Conclusion The live birth rate of frozen-thawed high-quality single blastocyst transfer is lower than that of double high-quality blastocyst transfer, which can significantly increase the embryo implantation rate. High-quality single blastocyst transfer also significantly lowers the risk of gemellary pregnancy, preterm birth, and low birth weight, and can significantly improve maternal and infant outcomes. After weighing the pros and cons of live birth with pregnancy and neonatal complications, the authors believe that high-quality single blastocyst transfer is the optimal FET strategy for young women and is worthy of further clinical application. Despite this recommendation, high-quality single blastocyst transfer can increase the risk of monozygotic twins, as well as significantly increase the proportion of male infants born.

Purpose Poly(lactic-co-glycolic) acid (PLGA) nanoparticles coated with the membrane of red blood cells (RBC-NP) have been applied in various biomedical fields. Despite the well-documented great biocompatibility, the potential toxicity of RBC-NP on maternal mice or their developing fetuses during pregnancy, or juvenile mice post-birth, remains unclear, which warrants a systematic evaluation. Methods We fabricate an RBC-NP with approximately 50 nm in diameter (RBC-NP-50). Upon RBC-NP-50, pregnant mice are intravenously injected with this nanoparticle either at a single high dose of 400 mg/kg (1HD) or a low dose of 200 mg/kg for 3 times (3LD). Afterwards, the biocompatible assessments are performed at 48 h after the final injection or 21 d post-birth/partum both on maternal and fetal/juvenile mice. Results RBC-NP-50 is capable of accumulating in the placenta and then passing through the blood-fetal barrier (BFB) into the fetus. On 48 h after RBC-NP-50 exposure, no significant dose-dependent toxicity is observed in maternal mice including blood biochemistry, inflammatory factors, progesterone level, histological analysis, etc, whereas fetal brains reveal remarkable differentially expressed genes analyzed by transcriptome sequencing. On 21 d post-birth, those genes’ expression in juvenile mice is alleviated, along with negligible differences in behavioral evaluations including surface righting test, negative geotaxis test, cliff avoidance test, and olfactory orientation test. Conclusion These results indicate that RBC-NP is considered to be generally safe and biocompatible both for maternal mice and fetus during pregnancy, and for the subsequent juvenile mice post-birth, although future studies will need to examine higher dosage or longer-term measurements.

目的 探讨年轻女性行新鲜单囊胚移植与冻融单囊胚移植对妊娠结局的影响.方法 回顾性分析2018年1～12月在温州医科大学附属第二医院生殖中心采用新鲜周期或冻融周期单囊胚移植的901例患者临床资料.根据移植周期不同分为两组,新鲜单囊胚移植周期组(A组)693例,冻融单囊胚移植周期组(B组)208例,比较两组患者的基本情况、实验室及妊娠结局.将两组中满足临床妊娠条件的患者根据是否发生早期流产分为早期流产组69例和活产组483组,分析早期流产的相关因素.结果 B组的获卵数及早期流产率高于A组,差异均有统计学意义(P<0.05);多因素Logistic回归分析结果显示,配偶年龄、冻融胚胎移植是早期流产发生的独立危险因素(P<0.05).结论 在年轻患者(≤35岁)中,冻融单囊胚移植可以获得与新鲜单囊胚移植同样满意的妊娠结局,但需要警惕的是,冻融胚胎移植使早期流产发生风险增加,需要进一步寻找原因和对策解决.

Ovarian aging is associated with depletion of the ovarian follicle reserve, which is the key determinant of fertility potential in females. In this study, we found that the small secreted protein C1QL1 is involved in the regulation of follicle depletion through intraovarian and endocrine control in a multidimensional collaborative manner. C1ql1 was detected to be conserved in the ovary and showed high transcript levels during folliculogenesis. Blockade of C1QL1 by intraperitoneal and ovarian intrabursal injection of C1QL1 antiserum into prepubertal mice impaired folliculogenesis accompanied by reductions in body weight, fat mass and intraovarian lipid accumulation. An elevation of circulating estradiol levels, reduction of hypothalamic KISS1 and GnRH expression and a decrease in serum FSH levels were found in C1QL1-deficient mice. In C1QL1-deficient ovaries, a large number of primordial follicles were recruited and developed into medium follicles, but underwent atresia at the large follicle stages, which resulted in depletion of follicle reserve. Depletion of C1QL1 alleviated the inhibitory effect of C1QL1 on granulosa cell apoptosis and the stimulatory effect of C1QL1 on granulosa cell autophagy, which resulted in accumulation in the preantral and early antral follicles and an increase in the atretic follicles. The abnormal profile of endocrine hormones accelerated the intraovarian effect of C1QL1 deficiency and further led to depletion of ovarian reserve. Altogether, this study revealed the expression patterns and the mechanism of action of C1QL1 during folliculogenesis, and demonstrated that deficiency of C1QL1 caused ovarian follicular depletion.

BACKGROUD:This study's objectives were to compare the clinical, perinatal, and obstetrical outcomes of patients with different estradiol (E2) levels in fresh single-blastocyst-transfer (SBT) cycles under an early follicular phase prolonged regimen on the day of trigger. METHODS:We recruited patients in fresh SBT cycles (n = 771) undergoing early follicular phase prolonged protocols with β-hCG values above 10 IU/L between June 2016 and December 2018. Patients who met the inclusion and exclusion criteria were divided into four groups according to their serum E2 level percentages on the day of trigger: <25th, 25th-50th, 51st-75th, and >75th percentile groups. RESULTS:Although the rates of clinical pregnancy (85.57% (166/194)), embryo implantation 86.60% (168/194), ongoing pregnancy (71.13% (138/194)), and live birth (71.13% (138/194)) were lowest in the >75th percentile group, we did not observe any significant differences (all P > 0.05). We used this information to predict the rate of severe ovarian hyperstimulation syndrome (OHSS) area under the curve (AUC) = 72.39%, P = 0.029, cut off value of E2 = 2,893 pg/ml with the 75% sensitivity and 70% specificity. The 51st-75th percentile group had the highest rates of low birth weight infants (11.73% (19/162), P = 0.0408), premature delivery (11.43% (20/175), P = 0.0269), admission to the neonatal intensive care unit (NICU) (10.49% (17/162), P = 0.0029), twin pregnancies (8.57% (15/175), P = 0.0047), and monochorionic diamniotic pregnancies (8.57% (15/175); P = 0.001). We did not observe statistical differences in obstetrics complications, including gestational diabetes mellitus (GDM), gestational hypertension, placenta previa, premature rupture of membranes (PROM), and preterm premature rupture of membranes (PPROM). CONCLUSION:We concluded that serum E2 levels on the day of trigger were not good predictors of live birth rate or perinatal and obstetrical outcomes. However, we found that high E2 levels may not be conducive to persistent pregnancies. The E2 level on the day of trigger can still be used to predict the incidence of early onset severe OHSS in the fresh SBT cycle.

目的:探讨剖宫产史对体外受精-胚胎移植(IVF-ET)治疗结局的影响.方法:回顾性分析2019年1月至2019年12月温州医科大学附属第二医院育英儿童医院生殖中心接受IVF-ET的患者,根据患者的分娩史分为仅有阴道分娩史组(292例)和剖宫产史组(311例),比较2组胚胎植入成功率及治疗结局等.结果:剖宫产史组的胚胎植入成功率低于仅有阴道分娩史组(P<0.05).2组间的流产率、双胎率、异位妊娠率差异无统计学意义(P>0.05).2组间早产、死产、出生体质量、出生缺陷、胎盘前置和产后出血等指标差异无统计学意义(P>0.05).结论:剖宫产史影响了IVF-ET再妊娠的胚胎植入成功率,但剖宫产史对患者的流产率等治疗结局无明显影响.

复合妊娠(heterotopic pregnancy,HP)是一种极其危险的异位妊娠,自然受孕者中HP的发生率并不高,但随着近年体外受精-胚胎移植(in vitro fertilization and embryo transfer,IVF-ET)术以及促排卵技术的普及,HP的发生率较前有所上升.HP患者早期一般仅有腹痛、阴道出血等非特异性症状,且由于宫内妊娠囊的存在使得宫外妊娠囊特别容易误诊和漏诊,从而易导致患者宫外妊娠囊继续发展,引起腹腔内大出血甚至休克等危及生命的严重后果.因此,充分了解HP的相关危险因素,在行ET术或促排卵技术前采取相应的预防HP发生的措施、发生HP后尽早进行确诊及确诊后采取有效的治疗对改善患者的预后显得尤为重要.综述近年IVF-ET后HP的诊断及管理措施进展.