Association between blood lead levels and unfavorable IVF outcomes: potential involvement of endoplasmic reticulum stress response in granulosa cells.

PURPOSE: To investigate the relationship between blood lead levels (BLLs) and IVF clinical outcomes in infertile females and to further explore the possible involvement of granulosa cell (GC) endoplasmic reticulum (ER) stress in the process. METHODS: One hundred twenty-three infertile women undergoing IVF cycles were included in the current study. All participants were divided into three (low, medium, and high) groups determined by BLL tertiles. Gonadotropin releasing hormone (GnRH) agonist regimen for ovarian stimulation was used for all patients, with follicular fluids being collected on the day of oocyte retrieval. Lactate dehydrogenase (LDH) levels in follicular fluid and the endoplasmic reticulum stress-signaling pathway of granulosa cells (GCs) were examined. RESULTS: The oocyte maturation rate and high-quality embryo rate on cleaved stage decreased significantly as BLL increased. For lead levels from low to high, live birth rate (68.29%, 56.10%, 39.02%; P=0.028) showed negative correlations with BLLs. Also, follicular fluid Pb level and LDH level was significantly higher in the high lead group versus the low group. Binomial regression analysis revealed significant negative correlation between BLLs and live birth rate (adjusted OR, 0.38; 95% CI, 0.15-0.95, P=0.038). Further analysis of the endoplasmic reticulum stress (ER stress) signaling pathway of GCs found that expressions of GRP78, total JNK, phosphorylated JNK, and CHOP increased and BCL-2 decreased with increasing BLLs. CONCLUSIONS: BLLs are negatively associated with final clinical outcomes in IVF patients that may be related to increased ER stress response and GC apoptosis. Thus, reducing Pb exposure before IVF procedures may improve final success rates.

Perfluorotetradecanoic acid exposure to adult male rats stimulates corticosterone biosynthesis but inhibits aldosterone production.

Perfluorotetradecanoic acid (PFTeDA) is a novel perfluoroalkyl substance that ubiquitously exists in the environment. However, whether PFTeDA affects adrenal cortex function remains unclear. Male Sprague-Dawley rats (age of 60 days) were daily administered with PFTeDA (0, 1, 5, and 10 mg/kg body weight) through gavage for 28 days. PFTeDA did not change body and adrenal gland weights. PFTeDA markedly elevated serum corticosterone level at 10 mg/kg but lowering serum aldosterone level at this dosage without influencing serum adrenocorticotropic hormone level. PFTeDA thickened zona fasciculata without affecting zona glomerulosa. PFTeDA remarkably upregulated the expression of corticosterone biosynthetic genes (Mc2r, Scarb1, Star, Cyp21, Cyp11b1, and Hsd11b1) and their proteins, whereas downregulating aldosterone biosynthetic enzyme Cyp11b2 and its protein, thereby distinctly altering their serum levels. PFTeDA markedly downregulated the expression of antioxidant genes (Sod1 and Sod2) and their proteins at 10 mg/kg. PFTeDA significantly decreased SIRT1/PGC1α and AMPK signaling while stimulating AKT1/mTOR signaling. Corticosterone significantly inhibited testosterone production by adult Leydig cells at >0.1 µM in vitro; however aldosterone significantly stimulated testosterone production at 0.1 nM. In conclusion, exposure to PFTeDA at male rat adulthood causes corticosterone excess and aldosterone deficiency via SIRT1/PGC1α, AMPK, and AKT1/mTOR signals, which in turn additively leads to testosterone deficiency.

Comparison of structure-activity relationship for bisphenol analogs in the inhibition of gonadal 3ß-hydroxysteroid dehydrogenases among human, rat, and mouse.

Bisphenol A (BPA) is a widely used plastic material and its potential endocrine disrupting effect has restricted its use and increasing use of BPA alternatives has raised health concerns. However, the effect of bisphenol alternatives on steroidogenesis remains unclear. The objective of this study was to compare inhibitory potencies of 10 BPA alternatives in the inhibition of gonadal 3ß-hydroxysteroid dehydrogenase (3ß-HSD) in three species (human, rat and mouse). The inhibitory potency for human 3ß-HSD2, rat 3ß-HSD1, and mouse 3ß-HSD6 ranged from bisphenol FL (IC50, 3.32 µM for human, 5.19 µM for rat, and 3.26 µM for mouse) to bisphenol E, F, and thiodiphenol (ineffective at 100 µM). Most BPA alternatives were mixed inhibitors of gonadal 3ß-HSD and they dose-dependently inhibited progesterone formation in KGN cells. Molecular docking analysis showed that all BPA analogs bind to steroid and NAD+ active sites. Lipophilicity of BPA alternatives was inversely correlated with IC50 values. In conclusion, BPA alternatives mostly can inhibit gonadal 3ß-HSDs and lipophilicity determines their inhibitory strength.

Carbon chain length of perfluoroalkylated carboxylic acids determines inhibitory strength on gonadal 3ß-hydroxysteroid dehydrogenases in humans, rats, and mice.

Perfluoroalkylated carboxylic acids (PFCAs) are a subclass of man-made chemicals that have been widely used in industrial production and consumer products. As a result, PFCAs have been found to accumulate in the environment and bioaccumulate in organisms, leading to potential health and environmental impacts. This study investigated the inhibition of 11 PFCAs on gonadal 3ß-hydroxysteroid dehydrogenases in humans, rats, and mice. We observed a V-shaped inhibition pattern against human granulosa (KGN) cell 3ß-HSD2 starting from C9 (half-maximal inhibitory concentration, IC50, 100.8 µM) to C11 (8.92 µM), with a V-shaped turn. The same V-shaped inhibition pattern was also observed for PFCAs against rat testicular 3ß-HSD1 from C9 (IC50, 50.43 µM) to C11 (6.60 µM). Mouse gonadal 3ß-HSD6 was insensitive to the inhibition of PFCAs, with an IC50 of 50.43 µM for C11. All of these PFCAs were mixed inhibitors of gonadal 3ß-HSDs. Docking analysis showed that PFCAs bind to the nicotinamide adenine dinucleotide (NAD+)/steroid binding sites of these enzymes and bivariate correlation analysis showed that molecular length determines the inhibitory pattern of PFCAs on these enzymes. In conclusion, the carbon chain length determines the inhibitory strength of PFCAs on human, rat, and mouse gonadal 3ß-HSDs, and the inhibitory strength of PFCAs against human and rat 3ß-HSD enzymes shows V-shaped turn.

Leydig cell development in pubertal male rats is blocked by perfluorotetradecanoic acid through decreasing AMPK-mTOR-autophagy pathway.

Perfluorotetradecanoic acid (PFTeDA) is a type of perfluoroalkyl acid that has been linked to various health effects in animals and humans. The study aimed to investigate the potential impact of PFTeDA exposure on Leydig cell development in rats during puberty. Understanding the effects of PFTeDA on Leydig cells is crucial as these cells play a significant role in male reproductive function. Male Sprague-Dawley rats were gavaged with PFTeDA at doses of 0, 1, 5, and 10 mg/kg/day from postnatal day 35-56. The serum hormone levels were measured and testicular transcriptome changes were analyzed by RNA-seq and verified by qPCR, and the levels of steroidogenesis-related proteins and energy regulators were measured. PFTeDA significantly reduced serum testosterone levels while slightly increasing LH levels. RNA-seq and qPCR analysis showed that genes responsive to oxidative phosphorylation (Naufa1 and Ndufs6) and steroidogenesis (Ldlr, Star, Cyp11a1) were markedly downregulated at ≥ 5 mg/kg, while those related to ferroptosis (Alox15) and cell senescence (Map2k3 and RT1-CE3) were significantly upregulated. PFTeDA markedly reduced SIRT1 (silent information regulator 1) /PGC-1α (peroxisome proliferator-activated receptor gamma coactivator-1α) and AMPKA (AMP activated kinase A), LC3B and Beclin1 (biomarkers for autophagy) levels while increasing phosphorylated mTOR. In vitro treatment of PFTeDA at 5 µM significantly reduced androgen output of Leydig cells from 35-day-old male rats while ferrostatin 1 (10 µM) reversed PFTeDA-mediated inhibition. In conclusion, the inhibitory effects of PFTeDA on pubertal rat Leydig cell development are possibly regulated by inducing ferroptosis thereby downregulating SIRT1/AMPKA/ autophagy pathways, eventually resulting in reduced steroidogenesis.

Pubertal lead exposure affects ovary development, folliculogenesis and steroidogenesis by activation of IRE1α-JNK signaling pathway in rat.

Epidemic studies showed that lead exposures are associated with various female reproductive dysfunctions, including infertility, miscarriage, preterm delivery, and early menopause. However, the mechanism involved is still unclear. In the current study, SD rats were exposed to lead at doses of 0, 5, 25, 50 or 250 mg/L through drinking water from postnatal day 21-56. Lead exposures did not affect the body weight or ovary weight. However, the puberty initiation (ages by which vagina opens and estrous cycle occurs) was significantly delayed by as many as 5.8 and 6.8 days respectively (P < 0.05). Also, lead exposures disrupted the estrous cycles, reduced the numbers of primordial and primary follicles and increased the number of atretic follicles by adult. Furthermore, for the highest does group, serum levels of progesterone and testosterone decreased by 80.2% (P < 0.01) and 49.9% (P < 0.05) respectively, while estradiol level increased by 69.8% (P < 0.01). Western blot analyses indicated that lead exposures specifically down-regulated the expressions of steroidogenic protein STAR, CYP17A1, and HSD3B1, while up-regulated FSHR and CYP19A1. Also, the exposure stimulated the endoplasmic reticulum stress (ERS)-related IRE1α-JNK signaling pathway members. Such activation may also result in apoptosis since the death-signaling molecules CHOP and cleaved-CASP3 were up-regulated while BCL2 was down-regulated. In conclusion, lead exposure during juvenile and puberty significantly affected ovary development and functions. The effects may relate to ERS response since the 6 members related to the pathway were all consistently activated.

Comparison of recombinant human FSH biosimilar QL1012 with Gonal-f® for ovarian stimulation: a phase-three trial.

RESEARCH QUESTION: Are QL1012 and Gonal-f® equivalent in women undergoing ovarian stimulation for assisted reproductive technology (ART)? DESIGN: This multicentre, randomized, assessor-blinded, phase-three trial was conducted at 13 centres in China. Eligible patients were infertile women; age 20-39 years; body mass index 18-30 kg/m2; regular menstrual cycles; and indication for ART. After successful pituitary downregulation, patients were randomly assigned (1:1) to receive QL1012 or Gonal-f®, stratified by age (initial dose of 75-150 IU for women younger than 30 years, 150-225 IU for women aged 30-34 years and 225-300 IU for women aged ≥35 years, subcutaneously, once daily). The primary end point was the number of oocytes retrieved. RESULTS: Between October 2018, and June 2019, 341 patients were included in the per-protocol set. The mean numbers of oocytes retrieved were 14.7 ± 7.0 in the QL1012 group (n = 169) and 13.4 ± 6.1 in the Gonal-f® group (n = 172). Adjusted by analysis of covariance model, the least-squares mean difference was 1.3 oocytes (95% CI -0.1 to 2.7; P = 0.0650), within the pre-defined equivalence margins of ±3.0. Similar results were observed in the full analysis set. Additionally, no statistical differences were found in secondary end points except oestradiol concentration (median 3948.0 pg/ml versus 3545.3 pg/ml; P = 0.0015). Ovarian hyperstimulation syndrome (12.4% versus 13.1 %) and other adverse events were similar between the two groups. CONCLUSIONS: Therapeutic equivalence and similar safety profiles were demonstrated between QL1012 and Gonal-f® in women undergoing ovarian stimulation for ART.

Leydig cell function in adult male rats is disrupted by perfluorotetradecanoic acid through increasing oxidative stress and apoptosis.

Perfluorotetradecanoic acid (PFTeDA) is a long-chain perfluoroalkyl compound with increased applications. Its effect on Leydig cell function and its underlying mechanism remain unclear. Male Sprague-Dawley rats (60 days old) were gavaged with PFTeDA at doses of 0, 1, 5, and 10 mg/kg/day from 60 to 87 days after birth. PFTeDA significantly reduced serum testosterone levels at 1 mg/kg and higher doses, while markedly increasing serum luteinizing hormone level at 10 mg/kg and follicle-stimulating hormone at ≥1 mg/kg. PFTeDA significantly reduced the sperm number at the cauda of epididymis at ≥1 mg/kg. PFTeDA also reduced the number of CYP11A1-positive Leydig cells due to increased apoptosis shown by the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. PFTeDA significantly repressed the expression of Cyp17a1 and Star and their proteins at 1-10 mg/kg, while it increased the expression of Srd5a1 and its protein (an immature Leydig cell biomarker) at 10 mg/kg. PFTeDA markedly increased testicular malondialdehyde level, while inhibiting antioxidants (SOD1, SOD2, and CAT), triggering oxidative stress, thereby further inducing BAX and CASP3 while inhibiting BCL2, which led to cell apoptosis. PFTeDA also reduced DHH level secreted by Sertoli cells, which indirectly affected Leydig cell function. PFTeDA inhibited testosterone secretion in primary Leydig cells in vitro by increasing reactive oxygen species and inducing apoptosis at 50 µM. In conclusion, PFTeDA inhibits the function of Leydig cells by inducing oxidative stress and subsequently stimulating cell apoptosis.

Metformin Alleviates Endometriosis and Potentiates Endometrial Receptivity via Decreasing VEGF and MMP9 and Increasing Leukemia Inhibitor Factor and HOXA10.

Background: Endometriosis affects endometrial receptivity, a key factor for successful embryo implantation. Metformin treatment is associated with alleviating the symptoms of endometriosis; however the mechanism of metformin action is unclear. Neoangiogenesis plays an important role in the development and recurrence of endometriosis. In addition, the leukemia inhibitor factor (LIF) and HOXA10 genes are also distinguishing markers of endometriosis (decrease) and endometrial receptivity (increase). This study investigated the therapeutic potentials of metformin and the underlying mechanism using an in vivo rat endometriosis model. Methods: Female Wistar albino mature rats with experimentally induced endometriosis were used in this study. Metformin was administered at doses of 100 mg/kg/d and 200 mg/kg/d. The volume of endometriotic implants was assessed. The protein and mRNA expression of the vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9), the endometrial receptivity markers, LIF and HOXA10, were measured in the endometrium of rats with endometriosis. Results: Metformin treatment significantly suppressed the growth of endometriotic implants. Further, the expression of VEGF and MMP-9 protein and mRNA in endometriotic implants were significantly reduced. Metformin also significantly upregulated LIF and HOXA10 expression in endometrium from rats with endometriosis. The inhibitory effect of metformin on the growth of endometriotic implants, VEGF and MMP-9, and upregulating effect on LIF and HOXA10, was optimal at a dose of 100 mg/kg/d. Conclusion: Our in vivo data demonstrates that metformin treatment alleviates endometriosis and potentiates endometrial receptivity. The underlying mechanisms are associated with decreased expression of VEGF and MMP-9 genes and upregulation of the LIF and HOXA10 genes. The effect of metformin was optimal at 100 mg/kg/d. These findings provide a potential alternative for women with endometriosis with the potential to increase fertility. Metformin is an approved drug by FDA for diabetes and this study may add another potential clinical use for metformin.

Androgens impair ß-cell function in a mouse model of polycystic ovary syndrome by activating endoplasmic reticulum stress.

BACKGROUND: Androgens excess results in endoplasmic reticulum (ER) stress, which is an important cause of ß cells dysfunction. Here, we investigated the molecular regulation of androgens excess, ER stress, and ß-cell function in polycystic ovary syndrome (PCOS). METHODS: PCOS mouse model was established by injection of DHEA. Primary cultured mouse islets were used to detect testosterone (TE)-induced ER stress. The response of ER stress, apoptosis, and hyperinsulinemia were analyzed in INS-1 cells with or without TE exposure. Androgen receptor (AR) antagonist and ER stress inhibitor treatment was performed to evaluate the role of TE in ER stress and proinsulin secretion of PCOS mice. RESULTS: PCOS mice had higher ER stress in islets. TE exposure induced ER stress and apoptosis significantly through sustaining insulin overexpression in ß cells, which in turn impaired proinsulin maturation and secretion. Blocking this process could significantly relieve ER stress and apoptosis and improve insulin homeostasis. CONCLUSION: ER stress activated by androgens excess in PCOS contributes to ß cell dysfunction and hyperinsulinemia.

Efficacy and safety of recombinant human follicle-stimulating hormone in patients undergoing in vitro fertilization-embryo transfer.

To compare the ovarian responses after administration of two recombinant follicle-stimulating hormone (r-FSH) preparations under gonadotropin-releasing hormone (GnRH) analogue downregulation, we conducted a phase 3, randomized, multicenter, assessor-blind, active-controlled, parallel group study. The primary outcome was the number of oocytes retrieved. The secondary outcomes included total dose and duration of r-FSH administered, oocyte quality, blood estradiol levels, follicular development, fertilization rates, implantation rates, and pregnancy rates (biochemical, clinical, and ongoing). A total of 451 patients with infertility were randomized to receive either Follitrope™ Prefilled Syringe or Gonal-F® Pen for ovarian stimulation. The mean number of oocytes retrieved was 14.9 in the FollitropeTM Prefilled Syringe group, and 12.8 in the Gonal-F® Pen group. The 95% confidence interval in the oocyte number difference between the groups was [-0.1, 4.2], demonstrating that FollitropeTM Prefilled Syringe was not inferior to Gonal-F® Pen. The clinical pregnancy rates (FollitropeTM Prefilled Syringe vs. Gonal-F® Pen: 55.4% vs. 51.9%) and ongoing pregnancy rates (44.1% vs. 43.0%) were similar between the groups. No clinically significant adverse events were observed in either group. In summary, our study indicates that FollitropeTM Prefilled Syringe is safe and efficacious for ovarian stimulation.

Multiple facilitated glucose transporters SLC2As are required for normal mouse preimplantation embryo development.

BACKGROUND: Glucose metabolism is an essential energy source for mammalian preimplantation embryonic development. Therefore, we aimed to analyze the expression of all 12 known glucose transporters (facilitated solute carrier family 2, Slc2a) during early mouse embryo development. METHODS: Gene and protein expression of Slc2a transporters in oocytes and embryos were assessed by the TaqMan gene expression assay and confocal immunofluorescence, respectively. RESULTS: Except for Slc2a2, the other 11 Slc2a transcripts were detected in oocytes. Transcripts of Slc2a1, Slc2a3, Slc2a4, and Slc2a8 were the most enriched and detected in preimplantation embryos. The transcription of other Slc2a isoforms was barely detectable or absent after fertilization; however, they were detected in blastocysts, except for Slc2a10 and Slc2a13. Embryo culture in the simple defined medium caused a reduction in transcription of Slc2a1, Slc2a3, Slc2a4, and Slc2a8 in blastocyst; yet, amino acids partially reversed this impaired transcription of Slc2a1 and Slc2a4. SLC2A1 and SLC2A4 proteins were detected at all embryonic stages with nuclear accumulation in the embryos at the early cleavage stage. SLC2A3 and SLC2A8 were not detected in embryos until the eight-cell stage. The cellular membrane localization of SLC2A1, SLC2A3, and SLC2A8 occurred after compaction and was characterized in blastocysts. SLC2A4 was evenly distributed in the cytoplasm and nuclei without its characteristic membrane localization. Indinavir sulfate (a SLC2A4 inhibitor) decreased the rate of development and prevented glucose utilization in embryos after compaction. These inhibitory activities were partially reversed by exogenous insulin. CONCLUSION: The results unveil distinct expression patterns of individual Slc2a glucose transporters during early embryo development. Taken together, they provide novel insights into the understanding and management of glucose metabolic infertility in assisted-reproductive technologies (ART).

Obstetric and perinatal outcomes of dizygotic twin pregnancies resulting from in vitro fertilization versus spontaneous conception: a retrospective study.

This study was designed to to assess perinatal and neonatal outcomes of dizygotic twin pregnancies conceived naturally or by in vitro fertilization (IVF). After strict selection, the study included 470 dizygotic twin pregnancies. There were 249 resulting from IVF treatments and 221 conceiving spontaneously. After adjusting maternal age and primiparity, the results showed that there were no significant differences between the two groups (P > 0.05) in terms of maternal antenatal complications and neonatal outcomes. In conclusion, our study does not reveal increased risks for pregnancy-related complications and adverse neonatal outcomes in dizygotic twin pregnancies following IVF treatments. With these fundamental data, this study could provide a reference for perinatal care and clinical assisted reproductive technology (ART) treatment and help to inform infertile parents about the potential risks of IVF treatments.

Expression and localization of nuclear factor erythroid 2-related factor 2 in the ovarian tissues of mice at different ages.

The aim of the present study was to investigate the expression and localization of nuclear factor erythroid 2-related factor 2 (Nrf2) in the ovaries of mice in different age groups, and to explore the association between Nrf2 and premature ovarian aging. The present study identified the localization of Nrf2 protein by performing immunohistochemical assay of ovarian tissues obtained from mice in different age groups. The mRNA expression levels of Nrf2 were detected via reverse transcription-quantitative polymerase chain reaction, while the expression levels of Nrf2 protein and apoptosis-associated proteins, including Caspase3 and B-cell lymphoma 2 (Bcl-2), were evaluated by western blot analysis. The results revealed that Nrf2 protein was mainly localized in granulosa cells, as well as in the secondary follicles and antral follicles of oocytes. Nrf2 expression levels were significantly lower in mice aged 4 days compared with 12-week-old mice (P<0.05), and the level of Nrf2 was lower in mice aged 40 weeks compared with those aged 12 weeks (P<0.05). In addition, the expression of the apoptosis protein Caspase3 in the ovarian tissue of mice aged 3, 8 and 12 weeks remained markedly greater when compared with those aged 4 days and 40 weeks. Bcl-2, an anti-apoptotic protein, was also significantly expressed in the ovarian tissues of juvenile (4-day-old) mice when compared with mice aged >40 weeks (P<0.05). In conclusion, Nrf2 was highly expressed in the ovarian tissues of mice of childbearing age (8-12 weeks old) and may possibly be involved in ovarian regulatory functions. The results indicated that Nrf2 expression and localization may have important implications in the prevention of ovarian aging.

MicroRNA-1 inhibits ovarian cancer cell proliferation and migration through c-Met pathway.

In this study, we investigated the differential expression of microRNAs in an ovarian cancer cell line HO-8910PM with increased migration and invasiveness activities. miR-1 was found to be one of the microRNA species most significantly downregulated in HO-8910PM compared with the control cell line HO-8910. We demonstrated that ovarian cancer tissues expressed decreased levels of miR-1 compared to non-neoplastic tissues. In vitro experiments showed that overexpression of miR-1 in HO-8910PM led to an inhibition of cell proliferation, blocking of cell cycle progression by G1 phase arrest, and decreased migration and invasiveness of HO-8910PM cells. Moreover, we confirmed that the expression of c-Met, a potential target of miR-1, was significantly inhibited following overexpression of miR-1 in HO-8910PM cells. Further analyses indicated that expression of factors including p-Akt, p-ERK1/2, CDK4, and p-Rb in HO-8910PM cells were affected by manipulation of c-Met expression. Infection of HO-8910PM cells with lentivirus vector expressing miR-1 led to a significant inhibition of tumor growth in the tumor subcutaneous nude mouse model. Taken together, these results indicated that miR-1 is downregulated in ovarian cancer tissues, and may play a tumor suppressive role by inhibiting c-Met expression and its effects on the regulation of cell proliferation, migration and invasion.

Identification of a peptide specifically targeting ovarian cancer by the screening of a phage display peptide library.

Ovarian cancer is the most common cause of cancer-associated mortality in terms of gynecological malignancies, and is difficult to diagnose due to the absence of reliable biomarkers. To identify ovarian cancer-specific biomarkers, the present study used a Ph.D.-7™ Phage Display Peptide Library to screen for ligands that selectively target HO-8910 ovarian cancer cells. Following 5 rounds of biopanning, the phage clone P2 was selected by enzyme-linked immunosorbent assay and DNA sequencing, and its characteristics were additionally validated by immunofluorescence and immunohistochemical assays. The results revealed the positive phage were enriched 92-fold following 5 rounds of biopanning, and the DNA sequence AAC CCG ATG ATT CGC CGC CAG (amino acid sequence, NPMIRRQ) was repeated most frequently (phage clones, P2, P3, P15, P30 and P54). Immunofluorescence and immunohistochemical assays revealed that the phage clone P2 was able to bind to ovarian cancer cells and tissues, and not those of cervical cancer. In conclusion, the peptide NPMIRRQ may be a potential agent for the diagnosis of ovarian cancer.

The effect of protein supplement concentration in embryo transfer medium on clinical outcome of IVF/ICSI cycles: a prospective, randomized clinical trial.

The aim of this prospective, randomized clinical trial (RCT) was to evaluate whether the supplemental protein concentration in embryo transfer (ET) medium affects the clinical outcomes in IVF-ET. A total of 750 patients undergoing IVF-ET who met the inclusion criteria were randomly divided into three groups, according to the concentration of synthetic serum substitute (SSS) in ET medium as follows: 10% (Group A), 20% (Group B) and 50% (Group C). The patient characteristics and embryology data were all similar among the groups. The rates of implantation, clinical pregnancy and live birth were compared. Clinical pregnancy (44.61%, 48.79% and 45.49%), multiple pregnancy (24.18%, 28.71% and 25.0%), implantation (28.21%, 30.68% and 29.86%) and live birth (41.67%, 43.96% and 41.70%) rates in the three groups (A, B and C, respectively) showed no significant differences. This RCT demonstrates that supplemental protein concentration in the ET medium does not affect the treatment outcomes in IVF-ET. There was no statistical evidence to support the hypothesis that supplemental protein concentration in the ET medium influences treatment outcomes in IVF-ET.

Blastocyst-stage versus cleavage-stage embryo transfer in the first frozen cycles of OHSS-risk patients who deferred from fresh embryo transfer.

Elective cryopreservation of all embryos has been the most effective means to avoid developing ovarian hyperstimulation syndrome (OHSS). However, it is still unknown which stage is optimal for freezing and transferring into uterus in OHSS-risk patients. This study was undertaken to evaluate whether OHSS-risk patients could benefit from transferring blastocysts. A total of 162 women were allocated to cleavage-stage embryo transfer (ET) (group A = 70) and blastocysts transfer (group B = 92) on the basis of patients' voluntary in their first frozen cycles. Although the mean number of transferred embryos in group A was significantly more than those in group B (2.37 ± 0.52 versus 2.11 ± 0.52, p < 0.05), the clinical pregnancy rates, implantation rates and live birth rates in group B were significantly higher than those in group A (47.83% versus 31.43%, p < 0.05; 31.44% versus 18.67%, p < 0.05; 40.21% versus 27.14%, p < 0.05), and the multiple pregnancy rates in both groups were comparable (34.09% versus 36.36%, p > 0.05). The observed results in OHSS-risk population allow us to take a position in favor of blastocyst transfer, thus pregnancy and live birth could be achieved with fewer ETs and in a shorter time frame.

Dual-color labeled anti-mucin 1 antibody for imaging of ovarian cancer: A preliminary animal study.

To investigate the feasibility of the anti-mucin 1 (anti-MUC1/CD227) antibody in the fluorescent imaging of ovarian cancer, the CD227 antibody and a control IgG antibody were labeled with a near-infrared dye [Cy5.5-N-hydroxysuccinimide (NHS)] and a green dye (fluorescein-NHS). In vivo fluorescence images were obtained at 4, 12 and 36 h after injection of the probes into OVCAR3 tumor-bearing mice. The tumor to background ratios were calculated for both probes. Ex vivo fluorescence images were obtained following sacrifice at 36 h. After conjugation to Cy5.5 and fluorescein, the dual-color labeled CD227 probe (Ab-FL-Cy5.5) could be visualized by both green and near-infrared fluorescence. Uptake by the tumors was higher for the Ab-FL-Cy5.5 than for the IgG-Cy5.5 probe. All tumors could be visualized by in vivo imaging with an acceptable tumor to background ratio. Ex vivo studies demonstrated the advantages of using green fluorescence imaging to guide the resection of tumor tissues. These preliminary data indicate that the Ab-FL-Cy5.5 probe is promising for further tumor imaging applications and clinical translation.