Immediate versus delayed frozen embryo transfer in women following a failed IVF-ET attempt: a multicenter randomized controlled trial.

BACKGROUND: The optimal time at which to perform a frozen-thawed embryo transfer (FET) following a failed in-vitro fertilization-embryo transfer (IVF-ET) attempt remains elusive to most reproductive experts. Physicians often delay the introduction of FET due to concerns related to potential residual effects of ovarian hyperstimulation which may interfere with the regular menstrual cycle. Moreover, given that most of the published studies on the topic are retrospective and have inconsistent findings, it is crucial to develop evidence-based randomized control guides for clinical practice. Therefore, this well-designed randomized controlled trial (RCT) was conducted to determine whether it is necessary to delay FET for at least one menstrual cycle after the failure of fresh embryo transfer. METHODS: Infertile women eligible for IVF-ET were invited to participate in this multicenter, randomized, non-inferiority, parallel-group, unblinded, controlled trial at the academic fertility centers of four public hospitals in Chinese Mainland. Infertile women scheduled to receive their first FET cycle after a failed IVF-ET attempt were randomly assigned to either (a) the immediate FET group in which FET was performed in the first menstrual cycle following the failed IVF-ET cycle (n = 366) or (b) the delayed FET group in which FET was performed in the second or subsequent menstrual cycle following the failed IVF-ET cycle (n = 366). All FET cycles were performed during hormone replacement cycles for endometrial preparation. The primary outcome was the ongoing pregnancy, defined as a detectable fetal heart beat beyond twelve weeks of gestation. Secondary outcomes were other pregnancy-related outcomes, maternal and neonatal complications. Analysis was performed by both intention-to-treat and per-protocol principles. RESULTS: A total of 646 FETs were completed. The frequency of moderate to severe depression and high stress level prior to FET in delayed FET group were significantly higher than that in immediate FET group (10.6% vs 6.1%, p = 0.039; 30.3% vs 22.4%, p = 0.022, respectively). Immediate FET resulted in a higher frequency of clinical pregnancy than did delayed FET (41.7% vs 34.1%), for a relative risk (RR) of 1.23 (95% confidence interval [CI], 1.00-1.50; p = 0.045). Women who underwent immediate FET also had a lower frequency of biochemical pregnancy loss (11.7% vs. 30.6%), with a RR of 0.28 (95% CI 0.23-0.63, p < 0.001), and a higher frequency of embryo implantation (25.2% vs. 20.2%), with a RR of 1.25 (95% CI 1.01-1.53; p = 0.038). Although the ongoing pregnancy and live birth rates did not differ significantly between the immediate FET and delayed FET groups (37.1% vs 30.3%, RR 1.22, 95% CI 0.99-1.52, p = 0.067; 36.5% vs 30.0%, RR 1.22, 95% CI 0.98-1.52, p = 0.079, respectively), a multivariate logistic regression analysis adjusted for potential confounders such as depression and stress levels revealed that the immediate FET group had a significantly higher ongoing pregnancy and live birth rates than the delayed FET group (odds ratio 0.68, 95% CI 0.47-0.99, p = 0.041; odds ratio 0.67, 95% CI 0.46-0.96, p = 0.031). The risks of maternal and neonatal complications were comparable between the two groups. CONCLUSIONS: In women with a previous failed IVF-ET attempt, immediate FET resulted in higher ongoing pregnancy and live birth rates than delayed FET. These findings warrant caution in the indiscriminate application of a delayed FET strategy when apparent risk of high stress level is perceived. TRIAL REGISTRATION: ChiCTR2000033313 .

Effect of cetyltrimethyl-ammonium bromide on the properties of hydroxyapatite nanoparticles stabilized Pickering emulsion and its cured poly(L-lactic acid) materials.

Hydroxyapatite (HAp) nanoparticles stabilized Pickering emulsions were prepared by dichloromethane (CH2 Cl2 ) dissolved poly(L-lactic acid) (PLLA) as the oil phase and the deionized water with different concentrations of cetyltrimethyl-ammonium bromide (CTAB) as the aqueous phase. Effect of CTAB concentration on emulsions type and stability were studied. The emulsion type underwent a two-phase inversion, and emulsion stability increased first and then decreased with increasing CTAB concentrations. Besides, effect of CTAB concentration on zeta potential, aggregate size, contact angle of HAp nanoparticles and the oil-water interfacial tension were studied. The results indicated that zeta potential value of HAp nanoparticles changed from negative to positive, and the contact angle increased to over 80° initially and then decreased to below 40° rapidly. The distribution of HAp nanoparticles on the surface of emulsion droplets with different concentrations of CTAB (5 and 20 mM) was characterized using laser-induced confocal microscope. It revealed the distribution of HAp nanoparticles changed with different CTAB concentrations. The cured PLLA materials were obtained after the solvent being volatilized using as-received emulsions as templates. Scanning electron microscope images showed both microspheres and porous materials with interconnected pore structure were obtained. In conclusion, the microstructure of microspheres or porous PLLA materials is controllable by adjusting the property of HAp nanoparticles stabilized Pickering emulsions with appropriate amount of CTAB.

Metabolomic Analysis Of Human Follicular Fluid: Potential Follicular Fluid Markers Of Reproductive Aging.

OBJECTIVE: To assess the difference in the metabolomics profiles of follicular fluid between older and younger reproductive-aged women. METHODS: The retrospective study was conducted at the Centre of Reproduction and Genetics, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China and comprised patient data related to the period between July and October 2015. Follicular fluid was obtained from male-factor infertility women aged 28-35 years as the younger group A, and those aged 35-42 years as the older group B. The subjects were undergoing in vitro fertilization / intracytoplasmic sperm injection and were retrospectively analysed by ultra-performance liquid chromatography-high-resolution mass spectrometry. The fragments were structurally identified using debris' information obtained from fragmented ion scans to identify the different compounds. RESULTS: Of the 55 cases studied, 28(51%) were in group A with a mean age of 29.57 ± 2.92 years, and 27(49%) were in group B with a mean age of 39.19±2.95 years. Compared with the group A, four types of compounds, hormones, licithin, lysophospholipids, and protein degradation fragments, were expressed significantly differentially in group B (p<0.05 each). Nicotine glucuronide and phosphatidylcholine were found only in Group B follicular fluid. CONCLUSIONS: The components of follicular fluid and relative contents were found changed with ageing.

Study on influencing factors of Pickering emulsions stabilized by hydroxyapatite nanoparticles with nonionic surfactants.

Emulsions were prepared using hydroxyapatite nanoparticles and nonionic surfactant sorbitan monooleate (Span 80) as emulsifier. Effects of Span 80 concentration, emulsification time, emulsification rate, poly(l-lactic acid) (PLLA) concentration and the surface chemical properties of hydroxyapatite nanoparticles on emulsion properties were systematically studied. The results showed that emulsion would undergo a phase inversion from oil-in-water (O/W) type to water-in-oil (W/O) type with an increase in Span 80 concentration. All of the above factors are closely related to emulsion type and stability. SEM results indicated that cured materials with different structures were obtained using these emulsions as templates via in situ evaporation; especially, open-cell porous structures were obtained by a mixture of hydroxyapatite and a moderate concentration of Span 80. The mechanism of this emulsion system is proposed in relation to the emulsion properties and cured material structure, which should be attributed to the formation of hydrogen bonds between hydroxyapatite and Span 80 by hydroxyl groups as well as their location changes in the emulsion.

Effect of stearic acid modified HAp nanoparticles in different solvents on the properties of Pickering emulsions and HAp/PLLA composites.

Stearic acid (Sa) was used to modify the surface properties of hydroxyapatite (HAp) in different solvents (water, ethanol or dichloromethane(CH2Cl2)). Effect of different solvents on the properties of HAp particles (activation ratio, grafting ratio, chemical properties), emulsion properties (emulsion stability, emulsion type, droplet morphology) as well as the cured materials (morphology, average pore size) were studied. FT-IR and XPS results confirmed the interaction occurred between stearic acid and HAp particles. Stable O/W and W/O type Pickering emulsions were prepared using unmodified and Sa modified HAp nanoparticles respectively, which indicated a catastrophic inversion of the Pickering emulsion happened possibly because of the enhanced hydrophobicity of HAp particles after surface modification. Porous materials with different structures and pore sizes were obtained using Pickering emulsion as the template via in situ evaporation solvent method. The results indicated the microstructures of cured samples are different form each other when HAp was surface modified in different solvents. HAp particles fabricated using ethanol as solvent has higher activation ratio and grafting ratio. Pickering emulsion with higher stability and cured porous materials with uniform morphology were obtained compared with samples prepared using water and CH2Cl2 as solvents. In conclusion, surface modification of HAp in different solvents played a very important role for its stabilized Pickering emulsion as well as the microstructure of cured samples. It is better to use ethanol as the solvent for Sa modified HAp particles, which could increase the stability of Pickering emulsion and obtain cured samples with uniform pore size.

Factors influencing the stability and type of hydroxyapatite stabilized Pickering emulsion.

Hydroxyapatite (HAp) nanoparticle stabilized Pickering emulsion was fabricated with poly(l-lactic acid) dissolved in dichloromethane (CH2Cl2) solution as oil phase and HAp aqueous dispersion as aqueous phase. Pickering emulsion was cured via in situ solvent evaporation method. Effect of PLLA concentrations, pH value, HAp concentrations, oil-water ratio, emulsification rates and times were studied on emulsion stability and emulsion type, etc. The results indicated emulsion stability increased with the increase of HAp concentration, emulsification rate and time; it is very stable when pH value of aqueous phase was adjusted to 10. Stable W/O and O/W emulsions were fabricated successfully using as-received HAp particles as stabilizer by adjusting the fabricating parameters. The interaction between HAp and PLLA played an important role to stabilize Pickering emulsions. SEM results indicated that both microsphere and porous materials were fabricated using emulsion stabilized by unmodified HAp nanoparticles, implying that both W/O and O/W emulsion type were obtained.

Photocurable high internal phase emulsions (HIPEs) containing hydroxyapatite for additive manufacture of tissue engineering scaffolds with multi-scale porosity.

Porous composites containing hydroxyapatite (HA) were templated from high internal phase emulsions (HIPEs) and were further structured using direct-write UV stereolithography to produce composite scaffolds with multi-scale porosity. FTIR, TGA and SEM analyses confirmed that HA was retained after photocuring and subsequent treatments and was incorporated within the polymerised HIPE (polyHIPE). The addition of HA particles to the polyHIPE caused changes in the mechanical properties of the material. An increase in both the Young's modulus and maximum stress at yield was observed compared with the pure polyHIPE from 1.544±0.231 to 4.614±0.775 and 0.177±0.009 to 0.267±0.034MPa, respectively. Except at very high concentrations, adding HA did not adversely cause the phase separation of the HIPE or the porous microstructure of the resulting polyHIPE. In combination with a photoinitiator, the HIPE emulsion containing HA was investigated as a photocurable resin for stereolithography-based additive manufacturing. The material was readily processable into "woodpile" structures via direct-write UV stereolithography, producing scaffolds with multi-scale porosity which may be useful for medical applications such as tissue engineering. In conclusion, HA was successfully added into polyHIPEs, producing a similar porous structure to that of the pure polyHIPE whilst improving the mechanical performance.

Effect of raw material ratios on the compressive strength of magnesium potassium phosphate chemically bonded ceramics.

The compressive strength of magnesium potassium phosphate chemically bonded ceramics is important in biomedical field. In this work, the compressive strength of magnesium potassium phosphate chemically bonded ceramics was investigated with different liquid-to-solid and MgO-to-KH2PO4 ratios. X-ray diffractometer was applied to characterize its phase composition. The microstructure was imaged using a scanning electron microscope. The results showed that the compressive strength of the chemically bonded ceramics increased with the decrease of liquid-to-solid ratio due to the change of the packing density and the crystallinity of hydrated product. However, with the increase of MgO-to-KH2PO4 weight ratio, its compressive strength increased firstly and then decreased. The low compressive strength in lower MgO-to-KH2PO4 ratio might be explained by the existence of the weak phase KH2PO4. However, the low value of compressive strength with the higher MgO-to-KH2PO4 ratio might be caused by lack of the joined phase in the hydrated product. Besides, it has been found that the microstructures were different in these two cases by the scanning electron microscope. Colloidal structure appeared for the samples with lower liquid-to-solid and higher MgO-to-KH2PO4 ratios possibly because of the existence of amorphous hydrated products. The optimization of both liquid-to-solid and MgO-to-KH2PO4 ratios was important to improve the compressive strength of magnesium potassium phosphate chemically bonded ceramics.

Effect of liquid-to-solid ratios on the properties of magnesium phosphate chemically bonded ceramics.

The temperature variation, setting time, phase compositions and compressive strength of magnesium phosphate chemically bonded ceramics were important for its application in biomedical field. Different amounts of liquid were added into the premixed acid phosphate and oxide powders in order to study the effect of liquid-to-solid ratios on the properties of magnesium phosphate chemically bonded ceramics. The results indicated that the setting time increased and the maximum temperature decreased as the liquid-to-solid ratio increases. The hydrated product was mainly composed of magnesium potassium phosphate hexahydrate, which was not affected by the liquid-to-solid ratios. Besides, magnesia was also found because it was an obvious excess of the hydrated reaction. The compressive strength decreased as the liquid-to-solid ratios increase possibly because of the higher porosity caused by the superfluous liquid. According to the performed study, results indicated that the properties of MPCBC could be adjusted by changing the liquid-to-solid ratios.

Effect of sintering on porosity, phase, and surface morphology of spray dried hydroxyapatite microspheres.

This article deals with the effect of sintering temperature on the physical and chemical characteristics of hydroxyapatite microspheres (HAMs) obtained by spray drying method. A set of specimens were sintered in a conventional furnace at 500-1100 degrees C. The surface morphology, phase composition, size distribution, specific surface area, and porosity were characterized by scanning electron microscope, X-ray diffractometer, laser diffraction particle size analyzer, and specific surface area analyzer, respectively. The results indicated that at 800 degrees C, hydroxyapatite crystals began to grow and were sintered together, which caused a drastic decrease in both the specific surface area and the pore volume. Great changes took place on the surfaces of HAMs during sintering. When the samples were sintered at the temperature of 500 and 600 degrees C, no obvious changes can be found on the surfaces of the samples, but at 800 degrees C, open-micropore surfaces came forth. Besides, the dispersibility of the samples decreased at high temperature (1100 degrees C) because small particles tended to aggregate together.