Effect of medroxyprogesterone acetate dose in progestin-primed ovarian stimulation on pregnancy outcomes in poor ovarian response patients with different body mass index levels.

Background: For the poor ovarian response (POR) population, the relationship between medroxyprogesterone acetate (MPA) dose in progestin-primed ovarian stimulation (PPOS) and clinical outcome is still unclear. This study aims to explore the effect of MPA dose in PPOS on clinical outcomes in POSEIDON group 3 and 4 patients with different body mass index (BMI) levels, hoping to provide clinical doctors with better options for controlled ovarian hyperstimulation (COH) programs. Methods: This is a retrospective analysis of 253 oocyte retrieval cycles of POSEIDON group 3 and 4 patients who underwent PPOS protocol in IVF/ICSI treatment at the Reproductive Medical Center of Renmin Hospital of Wuhan University from March 2019 to April 2022. The effects of different MPA doses (8 mg/d or 10 mg/d) on pregnancy outcomes were compared in normal BMI (18.5-24 kg/m2) and high BMI (≥24 kg/m2) patients, and multivariate logistic regression analysis was performed to analyze the factors affecting pregnancy outcomes. Results: For normal BMI patients, the 8-mg/d MPA group had a higher embryo implantation rate (33.78% vs. 18.97%, P = 0.012). For high BMI patients, the 10-mg/d MPA group had a higher HCG positive rate (55.00% vs. 25.00%, P = 0.028), clinical pregnancy rate (50.00% vs. 20.00%, P = 0.025), and cumulative pregnancy rate (37.74% vs. 13.79%, P = 0.023) compared with the 8-mg/d MPA group. There was no significant difference in cumulative live birth rate between the 8-mg/d and 10-mg/d MPA groups in patients with normal or high BMI. The results of multivariate logistic regression showed a significant correlation between MPA dose and cumulative pregnancy in the high BMI population (OR = 0.199, 95% CI: 0.046~0.861, P = 0.031). Conclusions: For POR patients with high BMI, 10 mg/d of MPA in the PPOS protocol had a higher cumulative pregnancy rate than 8 mg/d of MPA, but it had no significant effect on the cumulative live birth rate.

Berberine alleviates inflammation in polycystic ovary syndrome by inhibiting hyaluronan synthase 2 expression.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a heterogeneous metabolic and endocrine disorder that causes anovulatory infertility and abnormal folliculogenesis in women of reproductive age. Several studies have revealed inflammation in PCOS follicles, and recent evidence suggests that Berberine (BBR) effectively reduces inflammatory responses in PCOS, however, the underlying mechanisms remain unclear. PURPOSE: To determine the underlying mechanisms by which BBR alleviates inflammation in PCOS. STUDY DESIGN: Primary human GCs from healthy women and women with PCOS, and KGN cells were used for in vitro studies. ICR mice were used for in vivo studies. METHODS: Gene expression was measured using RT-qPCR. HAS2, inflammatory cytokines, and serum hormones were assayed by ELISA. Protein expression profiles were assayed by Western blot. Chronic low-grade inflammatory mouse models were developed by intraperitoneal injection with LPS, and PCOS mouse models were established by subcutaneous intraperitoneal injection of DHEA. BBR and 4-MU were administered by gavage. Ovarian morphologic changes were evaluated using H&E staining. HAS2 expression in the ovary was assayed using Western blot and immunohistochemistry. RESULTS: Our results confirmed that HAS2 expression and hyaluronan (HA) accumulation are closely associated with inflammatory responses in PCOS. Data obtained from in vitro studies showed that HAS2 and inflammatory genes (e.g., MCP-1, IL-1ß, and IL-6) are significantly upregulated in PCOS samples and LPS-induced KGN cells compared to their control groups. In addition, these effects were reversed by blocking HAS2 expression or HA synthesis using BBR or 4-MU, respectively. Furthermore, HAS2 overexpression induces the expression of inflammatory genes in PCOS. These results were further confirmed in LPS- and DHEA-induced mouse models, where inflammatory genes were reduced by BBR or 4-MU, and ovarian morphology was restored. CONCLUSIONS: Our results define previously unknown links between HAS2 and chronic low-grade inflammation in the follicles of women with PCOS. BBR exerts its anti-inflammatory effects by down-regulating HAS2. This study provides a novel therapeutic target for alleviating ovarian inflammation in women with PCOS.

Association of SARS-CoV-2 Infection During Controlled Ovarian Stimulation With Oocyte- and Embryo-Related Outcomes.

Importance: SARS-CoV-2 infection has had significant effects on the health of people worldwide. Whether SARS-CoV-2 infection during controlled ovarian stimulation (COS) is associated with laboratory outcomes in assisted reproductive technology remains unclear. Objective: To investigate the association between SARS-CoV-2 infection during COS with oocyte- and embryo-related outcomes. Design, Setting, and Participants: A multicenter cohort study was conducted of couples undergoing assisted reproductive technology treatments in 7 reproductive centers in 4 provinces in China from October 1, 2022, to December 31, 2022. All couples received nucleic acid testing for SARS-CoV-2 during COS. The SARS-CoV-2-positive group included couples in which either partner was infected with SARS-CoV-2. The SARS-CoV-2-negative group comprised couples without infection. Exposure: In the SARS-CoV-2-positive group, either partner was infected with SARS-CoV-2 during COS, defined as a positive test result for the SARS-CoV-2 antigen. Main Outcomes and Measures: Primary outcomes were the available embryo and blastocyst and top-quality embryo and blastocyst rates. Secondary outcomes were the number of oocytes retrieved, the mature oocyte rate, normal fertilization (2 pronuclei observed on day 1 after insemination [2PN]), oocyte degeneration, 2PN cleavage, and blastocyst formation rates. Results: A total of 585 heterosexual couples with infertility participated in the study (median [IQR] age for female partners, 33 [30-37] years), with 135 couples in the SARS-CoV-2-positive group and 450 in the SARS-CoV-2-negative group. The characteristics of the groups were similar. The SARS-CoV-2-positive group had a significantly lower top-quality embryo rate (odds ratio [OR], 0.83; 95% CI, 0.71-0.96), top-quality blastocyst rate (OR, 0.59; 95% CI, 0.45-0.77), available blastocyst rate (OR, 0.70; 95% CI, 0.59-0.82), and blastocyst formation rate (OR, 0.61; 95% CI, 0.52-0.71) than the SARS-CoV-2-negative group. Analysis of the associations of infection by sex showed that the female positive group had impaired oocyte and embryo quality regarding mature oocyte rate, 2PN cleavage rate, top-quality embryo rate, blastocyst formation rate, available blastocyst rate, and top-quality blastocyst rate compared with the SARS-CoV-2-negative group. Compared with the SARS-CoV-2-negative group, the male positive group and the group of couples with both positive partners had significantly decreased available blastocyst rate, top-quality blastocyst rate, and blastocyst formation rate compared with the SARS-CoV-2 negative group. Conclusions and Relevance: In this cohort study, SARS-CoV-2 infection during COS was negatively associated with embryo and blastocyst quality. Reproductive physicians should be more attentive to patients with SARS-CoV-2 infection during COS and should give couples who have been infected adequate counseling.

Preparation of the Chitosan/Poly-γ-Glutamic Acid/Glabrid in Hybrid Nanoparticles and Study on its Releasing Property.

AIM: The aim of this study was to encapsulate glabridin (GB) into nanoparticles, prepared by an ionic-gelation method blended with chitosan (CS) and poly-γ-glutamic acid (γ-PGA) to address the issue of poor stability and low water solubility of glabridin. METHODS: The physicochemical properties of nanoparticles were investigated by transmission electron microscope (TEM), dynamic light scattering (DLS) and fourier-transform infrared (FT-IR) spectroscopy. RESULTS: FT-IR results indicated that the spontaneous interaction between CS, γ-PGA and GB can form a cross linked network-structure, leading to the spontaneous formation of nanoparticles. Morphology of the complex particles was nano-scale spherical shape. Furthermore, particle size was decreased according to the decrease of γ-PGA contents and CS, accompanying with the increase of mixed solution transmittance. The mγ-PGA : mGB = 1: 1 and mCS: (mγ-PGA + mGB) =1: 1 were considered to be a proper preparation condition of CS/γ-PGA/GB hybrid nanoparticles, which produced the smaller nanoparticles with the satisfactory encapsulation efficiency (EE), loading content (LC) and sustained GB release. With the increase of pH values, the potential, EE, and LC decreased gradually, while the particle size increased. The nanoparticles prepared with higher molecular weight γ-PGA had larger particle size and less loading capacity on GB. Additionally, moderate weight ratio of CS/γ-PGA/GB, low pH, and high molecular weight of γ-PGA were favorable for sustained release. CONCLUSION: It can be concluded that the physicochemical properties of nanoparticles and GB release behaviors were affected by several factors including the weight ratio of CS/γ-PGA/GB, pHvalues, and γ-PGA molecular weight (MW). Nanoencapsulation using CS, γ-PGA and GB has a potential application for the development of functional cosmetic products with skin-whitening effect.

Role of Transforming Growth Factor-ß1 in Regulating Fetal-Maternal Immune Tolerance in Normal and Pathological Pregnancy.

Transforming growth factor-ß (TGF-ß) is composed of three isoforms, TGF-ß1, TGF-ß2, and TGF-ß3. TGF-ß1 is a cytokine with multiple biological functions that has been studied extensively. It plays an important role in regulating the differentiation of immune cells and maintaining immune cell functions and immune homeostasis. Pregnancy is a carefully regulated process. Controlled invasion of trophoblasts, precise coordination of immune cells and cytokines, and crosstalk between trophoblasts and immune cells play vital roles in the establishment and maintenance of normal pregnancy. In this systematic review, we summarize the role of TGF-ß1 in regulating fetal-maternal immune tolerance in healthy and pathological pregnancies. During healthy pregnancy, TGF-ß1 induces the production of regulatory T cells (Tregs), maintains the immunosuppressive function of Tregs, mediates the balance of M1/M2 macrophages, and regulates the function of NK cells, thus participating in maintaining fetal-maternal immune tolerance. In addition, some studies have shown that TGF-ß1 is dysregulated in patients with recurrent spontaneous abortion or preeclampsia. TGF-ß1 may play a role in the occurrence and development of these diseases and may be a potential target for the treatment of these diseases.

Phase Behavior of Polyglycerol Ester-Based Nanoemulsions.

Nanoemulsions were prepared using polyglycerol esters as emulsifiers. The effects of emulsifiers, oils, and polyols on the phase behavior of nanoemulsions were analyzed by phase diagram method using caprylic acid capric triglyceride (318), mineral oil, and squalane (Squ) as oils respectively. Various factors affecting the area of the oil-in-water (O/W) nanoemulsion were investigated. The results showed that hydrophilic polyglyceryl-4 laurate was beneficial to the formation of translucent nanoemulsions, while lipophilic polyglyceryl-4 oleate could synergize the emulsification performance and was more conducive to the formation of nanoemulsions; the type of oil could affect the emulsifying ability of the emulsifier. It was found that it was beneficial to form translucent nanoemulsion when caprylic acid capric triglyceride was adopted as oil. However, it was almost impossible to form translucent nanoemulsions when mineral oil and squalane were used as oils. The addition of water-soluble jojoba ester was beneficial to the formation of O/W emulsion. In addition, glycerin can improve the polarity of the aqueous medium, enhance the affinity between emulsifiers and aqueous medium, and help to form a translucent nanoemulsion.

A Microstructural Study of the O/W Primary Emulsion on the Formation of Oil-in-Water-in-Oil Multiple Emulsion.

AIM: This study aimed to investigate the influence of the preparation process and composition on the microstructure of the O/W primary emulsions and the corresponding impact on the formation of oil-in-water-in-oil (O/W/O) multiple emulsions. OBJECTIVES: Multiple emulsions were prepared by a two-step emulsification method and the microstructure was characterized by the microscope. METHODS: The primary emulsion was prepared by four kinds of preparation methods, which include both high-energy and low-energy emulsification, and then the primary emulsion was re-emulsified by stirring in the outer phase. RESULT: Through the theoretical investigation and the corresponding verification experiments of the interfacial film, the geometric reason for O/W/O multiple emulsion which was relatively difficult to prepare has been found. The microstructure of O/W particles was more obvious, and the particle size became smaller with the increase of the hydrophilic emulsifier amount beneficial to the formation and stability of O/W/O structures. However, the excess emulsifier that existed in the water phase could interfere the stability of the W/O interface. Moreover, the viscosity of inner oil phase had a large influence on the formation of O/W/O emulsion by affecting the particle size of the primary emulsion and the dynamic equilibrium between the inner and outer oil phase. CONCLUSION: It can be concluded that fine multiple emulsions were formed when the particle size of the primary emulsion was moderate since the large particles would break through the outer interface membrane and small particles would combine with the outer oil phase due to the Ostwald ripening.

Effect of solid lipid's structure on nanostructured lipid carriers encapsulated with sun filter: characterisation, photo-stability and in vitro release.

Three series of solid lipid are formulated in nanostructured lipid carriers (NLC) system, which encapsulated with sun filter to evaluate the effect on the physicochemical properties of the nanocarriers. Production is performed by ultrasonication-homogenisation, analysis by particle size, zeta potential (ZP), transmission electron microscope, Fourier transform infrared spectroscopy, differential scanning calorimetry (DSC), X-ray diffraction (XRD). Moreover, the encapsulation efficiency, ultraviolet performance and in vitro release are also investigated. The particle sizes of NLCs are between 185 and 225 nm and the polydispersity index is lower than 0.4, ZP from -56.4 to -78.6 mV, and the particles are spherical and in homogenous shading. All prepared NCLs encapsulated the sun filter and the EE are higher than 73%. DSC analysis revealed α- to ß-polymorphic modification existed in the system of fatty alcohol and fatty acid. However, α, ß and ß'-polymorphic modifications are exist in the system of cetyl palmitate (PC). Compared with conventional emulsion, all NLCs displayed perfect photo-protective property, especially for the alcohol system. The photo-stability studies showed that the all NLCs have the ability to improve the photo-stability of sunscreens. The in vitro release study suggested all three NLCs displayed sustained release profile and they were fit well with Higuchi equation.

Preparation and Characterization of Silver Nanoparticles from the Super-Heated Water Degraded Keratin Solutions.

This research demonstrates that silver nanoparticles can be prepared from the chicken feathers keratin solution obtained by superheated water treatment. Feathers are inexpensive and renewable resources but have limited applications. In this study, a facile method was described for synthesis of silver nanoparticles by the super-heated water degradation of chicken feathers keratin without using any additional chemicals. Stable and well-dispersed silver nanoparticles of about 3.24 nm were biosynthesized. The prepared nanoparticles were characterized using UV-Vis spectroscopy, transmission electron microscopy, FTIR-ATR spectroscopy and X-ray diffract. Prepared silver nanoparticles were stable on keeping at room temperature for more than 6 months and also stable in the presence of NaCl. The agglomerates caused by the decrease of pH value can easily be re-dispersed in alkaline aqueous media with no obvious change in their optical properties. The as-prepared silver nanoparticles have excellent antibacterial property reducing the bacterial population with more than 99.99%.