Autophagy activity is increased in the cumulus cells of women with poor ovarian response.

OBJECTIVE: To evaluate the autophagy status of cumulus cells (CCs) in women with poor ovarian response (POR). MATERIALS AND METHODS: CCs were divided into normal ovarian response (NOR) group and POR group. The ultrastructure of autophagy was analyzed by transmission electron microscopy (NOR: n = 18, POR: n = 26). The mRNA and protein of autophagy markers were detected by Quantitative real-time polymerase chain reaction (NOR: n = 15, POR: n = 19) and Western blotting (NOR: n = 41, POR: n = 38), respectively. RESULTS: Transmission electron microscopy demonstrated abundant autophagosomes and even autophagic death in the POR group. There were no differences in LC3 and P62 mRNA expression between the two groups (p > 0.05). The BCL2 mRNA expression was lower in the POR group (p < 0.05). Moreover, the LC3 II/I ratio and the P62 protein expression were significantly higher in the POR group (p < 0.05). CONCLUSIONS: Autophagy in CCs of POR women is activated and the autophagic flux is blocked. The up-regulation of autophagy in CCs may be related to the pathogenesis of POR.

Elevated estradiol levels on hCG trigger day adversely effects on the clinical pregnancy rates of blastocyst embryo transfer but not cleavage-stage embryo transfer in fresh cycles: a retrospective cohort study.

Background: Elevated estradiol (E2) levels are an inevitable outcome of the controlled ovulation hyperstimulation. However, the effect of this change on pregnancy is still uncertain. Our study aimed to analyze the impact of increased serum E2 at the day of human chorionic gonadotropin (hCG) administration on the clinical outcomes of women with fresh embryo transfer (ET) cycles. Methods: This study included 3,009 fresh ET cycles from October 2015 to September 2021. Based on the stage of embryos transferred, these cycles were categorized into the cleavage group and blastocyst group. Both groups were then divided into four sets according to E2 levels when hCG was administered: set 1 (E2 ≤ 2,000 pg/ml), set 2 (E2 = 2,001-3,000 pg/ml), set 3 (E2 = 3,001-4,000 pg/ml), and set 4 (E2 > 4,000 pg/ml). The primary outcome was the clinical pregnancy rate (CPR). Binary logistics regression analysis was established to explore the association between CPR and E2 levels. Specifically, the threshold effect of serum E2 on CPR was revealed using the two-piecewise linear regression analyses. Results: The multivariate regression model in the cleavage group showed that patients' CPR in set 4 was 1.59 times higher than those in reference set 1, but the statistical difference was insignificant (P = 0.294). As for the blastocyst group, patients in set 4 had a lower CPR with adjusted ORs of 0.43 (P = 0.039) compared to patients in set 1. The inflection point for the blastocyst group was 39.7 pg/dl according to the results of the two-piecewise linear regression model. When E2 levels were over the point, the CPR decreased by 17% with every 1 pg/dl increases in serum E2 (adjusted OR = 0.83, 95% CI [0.72-0.96], P = 0.012). Conclusions: Elevated E2 levels (>39.7 pg/dl) on hCG trigger day were associated with decreased CPR in patients with fresh blastocyst ET. However, it had no similar effect on the CPR of patients with fresh cleavage-stage ET.

Comparison of perinatal outcomes and pregnancy complications between fresh embryo transfer and frozen embryo transfer in singleton pregnant women. / é²œèƒšç§»æ¤ä¸Žå†»èƒšç§»æ¤å•èƒŽå¦Šå¨ å­•å¦‡å¦Šå¨ ç»“å±€å’Œå¦Šå¨ å¹¶å‘ç—‡æ¯”è¾ƒ.

OBJECTIVES: To compare perinatal outcomes and the incidence of pregnancy complications between fresh embryo transfer and frozen embryo transfer in singleton pregnant women. METHODS: The clinical data of 3161 in vitro fertilization-embryo transfer cycles conducted in Center for Reproductive Medicine of the Third Affiliated Hospital of Sun Yat-sen University from October 2015 to May 2021 were retrospectively analyzed, among which 1009 cases were fresh embryo transfer (fresh embryo group) and 2152 cases were frozen embryo transfer (frozen embryo group). The baseline characteristics were compared between two groups, and logistic regression was used to analyze the effect of fresh embryo transfer and frozen embryo transfer on pregnancy outcome and complications. RESULTS: Compared with the fresh embryo group, the frozen embryo group had an increased gestational age (P<0.01), increased birth weight (P<0.01), higher cesarean section rate (65.1% vs. 50.7%, AOR=1.791, 95%CI: 1.421-2.256, P<0.01), higher risk of large for gestational age infant (12.7% vs. 9.4%, AOR=1.487, 95%CI: 1.072-2.064, P<0.05) and macrosomia (5.4% vs. 3.2%, AOR=2.126, 95%CI: 1.262-3.582, P<0.01). The incidences of early abortion (18.5% vs. 16.2%, AOR=1.377, 95%CI: 1.099-1.725, P<0.01) and gestational hypertension (3.1% vs. 1.9%, AOR=1.862, 95%CI: 1.055-3.285, P<0.05) in the frozen embryo group were significantly higher than those in the fresh embryo group. Stratified analyses by stage of embryo transfer showed that during blastocyst transfer, the gestational weeks of delivery, birth weight and risk of cesarean section in frozen embryo group were significantly higher than those in fresh embryo group. During cleavage stage embryo transfer, frozen embryo transfer was associated with a higher risk of cesarean section, macrosomia, miscarriage and early miscarriage, and the birth weight of newborns was also significantly increased. CONCLUSIONS: Compared with fresh embryo transfer, frozen embryo transfer is associated with a higher risk of abortion, early abortion, large for gestational age infant, macrosomia, cesarean section, and pregnancy induced hypertension. The birth weight of newborns after frozen embryo transfer is also significantly increased.

Electrochemical PINOylation of Methylarenes: Improving the Scope and Utility of Benzylic Oxidation through Mediated Electrolysis.

A mediated electrosynthetic method has been developed for selective benzylic oxidation of methylarenes. Phthalimide-N-oxyl (PINO) radical generated by proton-coupled electrochemical oxidation of N-hydroxypthalimide serves as a hydrogen atom-transfer (HAT) mediator and as a radical trap for the benzylic radicals generated in situ. This mediated electrolysis method operates at much lower anode potentials relative to direct electrolysis methods for benzylic oxidation initiated by single-electron transfer (SET). A direct comparison of SET and mediated-HAT electrolysis methods with a common set of substrates shows that the HAT reaction exhibits a significantly improved substrate scope and functional group compatibility. The PINOylated products are readily converted into the corresponding benzylic alcohol or benzaldehyde derivative under photochemical conditions, and the synthetic utility of this method is highlighted by the late-stage functionalization of the non-steroidal anti-inflammatory drug celecoxib.

GnRH Antagonist Protocol Versus GnRH Agonist Long Protocol: A Retrospective Cohort Study on Clinical Outcomes and Maternal-Neonatal Safety.

Objective: To evaluate the clinical outcomes and maternal-neonatal safety of gonadotropin releasing hormone antagonist (GnRH-ant) and gonadotropin releasing hormone agonist (GnRH-a) protocols. Methods: A total of 2505 women undergoing their first in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) were retrospectively analyzed. Patients were divided into GnRH-ant group (n = 1514) and GnRH-a group (n = 991) according their stimulation protocol. Propensity Score Matching (PSM) was used for balancing the baseline of two groups. The pregnancy outcomes were analyzed in fresh transfer cycles, and the obstetric and perinatal outcomes were calculated in singleton live births of fresh cycles. The primary outcome was the live birth rate. The secondary outcome measures were maternal complications, preterm birth rate, low birthweight rate, multiple pregnancy rate, and moderate-severe OHSS rate. Results: After 1:1 PSM, baseline characteristics of the GnRH-ant group and GnRH-a group were matched and assigned 991 cycles in each group. Before PSM, there were 700 fresh cycles including 237 singleton live births in the GnRH-ant group and 588 fresh cycles including 187 singleton live births in the GnRH-a group. After PSM, there were 471 fresh cycles including 166 singleton live births in the GnRH-ant group and 588 fresh cycles including 187 singleton live births in the GnRH-a group. No significant differences were observed in the live birth rate (44.6% vs 48.8%), maternal complications, preterm birth rate (9.0% vs 6.4%), and low birthweight rate (17.5% vs 24.1%) between two groups after PSM (P > 0.05). The moderate-severe OHSS rate (2.9% vs 6.0%, P = 0.002) and multiple pregnancy rate (24.5% vs 33.1%, P = 0.025) was significantly lower in the GnRH-ant group than that in the GnRH-a group after PSM. Conclusion: GnRH-ant protocol was comparable with GnRH-a protocol in clinical outcomes, obstetric and perinatal outcomes, and with a lower risk of OHSS. For those who want to get an effective and safe outcome, and a shorter treatment period, GnRH-ant is a suitable choice.

Inhibition of bacterial adhesion and biofilm formation by a textured fluorinated alkoxyphosphazene surface.

The utilization of biomaterials in implanted blood-contacting medical devices often induces a persistent problem of microbial infection, which results from bacterial adhesion and biofilm formation on the surface of biomaterials. In this research, we developed new fluorinated alkoxyphosphazene materials, specifically poly[bis(octafluoropentoxy) phosphazene] (OFP) and crosslinkable OFP (X-OFP), with improved mechanical properties, and further modified the surface topography with ordered pillars to improve the antibacterial properties. Three X-OFP materials, X-OFP3.3, X-OFP8.1, X-OFP13.6, with different crosslinking densities were synthesized, and textured films with patterns of 500/500/600 nm (diameter/spacing/height) were fabricated via a two stage soft lithography molding process. Experiments with 3 bacterial strains: Staphylococcal epidermidis, Staphylococcal aureus, and Pseudomonas aeruginosa showed that bacterial adhesion coefficients were significantly lower on OFP and X-OFP smooth surfaces than on the polyurethane biomaterial, and surface texturing further reduced bacterial adhesion due to the reduction in accessible surface contact area. Furthermore the anti-bacterial adhesion effect shows a positive relationship with the crosslinking degree. Biofilm formation on the substrates was examined using a CDC biofilm reactor for 7 days and no biofilm formation was observed on textured X-OFP biomaterials. The results suggested that the combination of fluorocarbon chemistry and submicron topography modification in textured X-OFP materials may provide a practical approach to improve the biocompatibility of current biomaterials with significant reduction in risk of pathogenic infection.

New cross-linkable poly[bis(octafluoropentoxy) phosphazene] biomaterials: Synthesis, surface characterization, bacterial adhesion, and plasma coagulation responses.

Biomaterial-associated microbial infection and thrombosis represent major issues to the success of long-term use of implantable blood-contacting medical devices. The development of new poly[bis(octafluoropentoxy) phosphazene (OFP) biomaterials provides new routes for combatting microbial infection and thrombosis. However, the limited mechanical properties of OFP to date render them unsuitable for application in medical devices and inhibit any attempts at subsequent surface topography modification. In this study, we synthesized cross-linkable OFPs (X-OFPs) with the different degrees of cross-linking in an effort to improve the mechanical properties. The results showed that the surface chemistry and surface topography of X-OFPs do not change significantly, but the surface mechanical stiffness increased after cross-linking. Atomic force microscopic phase images showed that the polymer phase separation structures changed due to cross-linking. Experiments with three bacterial strains: Staphylococcal epidermidis, Staphylococcal aureus, and Pseudomonas aeruginosa showed that bacterial adhesion was significantly decreased on the OFP and X-OFPs for both the pre-cross-linked and cross-linked as compared to polyurethane biomaterials. Furthermore, bacterial adhesions were lower on X-OFP surfaces than on pre-cross-linked materials, suggesting that mechanical stiffness is an important parameter influencing bacterial adhesion. Blood plasma coagulation responses revealed longer coagulation times for OFP and X-OFP materials than on polyurethanes, indicating that the new cross-linked OFPs are resistant to plasma coagulation compared to currently used polyurethane biomaterials.

Chronological age vs biological age: a retrospective analysis on age-specific serum anti-Müllerian hormone levels for 3280 females in reproductive center clinic.

The aim of the present study was to determine the correlation between chronological age and biological age by characterizing age-specific serum anti-Müllerian hormone (AMH) values for 3280 Chinese women. A retrospective analysis including 3280 females between 10 to 52 years old was conducted from January 2016 to December 2016 in the clinical laboratory of Center for Reproductive Medicine, The Third Affiliated Hospital of Sun Yat-sen University, China. All included women were divided into several groups by age. Distribution and Statistical description of age-specific AMH levels was provided. Our results showed that serum AMH levels were negatively correlated with age (r = -0.606, p < .001). AMH concentrations approximately 31.1% depended on age and descended by an average of 6.2% per year. Around 25, 35 and 40 years, the decrease of AMH values accelerated. In conclusion, biological age was inversely correlated with chronological age. The present data can provide information for evaluating the fertility potential and ovarian reserve of infertile patients, as well as facilitate clinicians to decide individual treatment options.

[Cost-effectiveness analysis of two breast cancer screening modalities in Shanghai, China].

OBJECTIVE: To evaluate the cost-effectiveness of two breast cancer screening modalities conducted in Minhang district of Shanghai, China. METHODS: An organized and an opportunistic breast screening programs were implemented among women aged 35-74 years in Minhang district of Shanghai between May 2008 and Oct 2010, and were compared with the results obtained without screening. Costs related to screening were obtained by access to finance data of the screening programs, and costs of first treatment were collected through patient survey and medical reimbursement system query. Information on breast cancer stage was obtained from Shanghai Cancer Registry and confirmed by medical chart review. The effectiveness of screening was evaluated by breast cancer stage improvement.Cost-effectiveness ratios (CERs) were computed as costs of gaining a stage improvement from a specified screening strategy when compared with the results obtained without screening. Incremental cost-effectiveness (ICER) which compares the two screening strategies was calculated by dividing the difference in total net costs and the difference in stages improved between the two screening strategies. RESULTS: Thirty-five, one hundred and ninety-three and four hundred and seventy-nine breast cancer cases were identified in the organized screening, opportunistic screening and control groups, with an early detection rate of 46.9%, 40.7% and 38.9%, respectively. The costs of screening were 208 yuan per person or 72 453 yuan per case detected in the organized screening group and were 21 yuan per person or 11 640 yuan per case detected in the opportunistic screening group. The total cost was 103 650 yuan per case in the organized screening group, significantly higher than 50 712 yuan in the opportunistic screening group and 35 413 yuan in the control group. However, the average direct medical cost was significantly lower in the organized screening group than that in the opportunistic screening group and control group, with median costs of 11 024 yuan, 13 465 yuan and 14 243 yuan per case, respectively (P<0.001). The additional cost per case detected was 68 237 yuan for the organized screening and 15 299 yuan for opportunistic screening. The CERs were 135 291 yuan and 152 179 yuan per stage improved in the organized screening and opportunistic screening relative to the control group, with ICER of organized versus opportunistic screening being 131 086 yuan per stage improved. CONCLUSIONS: The organized screening modality and the opportunistic one are both effective in early detecting breast cancer in Chinese women. The organized screening costs more than opportunistic screening, but with a better cost-effectiveness. It may be used as an option in economically developed areas of China.

Performance of breast cancer screening methods and modality among Chinese women: a report from a society-based breast screening program (SBSP) in Shanghai.

To evaluate the screening performance of individual and combined use of clinical breast examination, ultrasonography and mammography in Chinese women, we conducted a biennial breast cancer screening program among 14,464 women aged 35 to 74 years old who lived in Qibao County, Minhang district of Shanghai, China, between May 2008 and Sept 2012. All participants were submitted to clinical breast examination, and then women with positive results and all women at age of 45-69 years old were preformed breast ultrasonography and mammography. The examination results were compared against pathological findings as the gold standard of reference. A total of 66 women were diagnosed with breast cancer in the two rounds of the screening, yielding an incident rate of 194 per 100,000 person-years. The sensitivity of clinical breast examination, ultrasonography and mammography alone were 61.4%, 53.7% and 67.3%, respectively. While mammography performed better in elder age groups and hormone receptor positive disease groups, ultrasonography had a higher sensitivity in younger age group and did not differ in sensitivity by estrogen receptor or progesterone receptor status. Combined use of the two imaging examinations increased the sensitivity in almost all age groups, but had a higher sensitivity in hormone receptor positive cancers than in those negative. Our results suggest that the Qibao modality is an effective strategy for breast cancer screening among Chinese women, especially for early detection of elder and hormone receptor positive breast cancer.