This study was performed to analyze retrospectively outcomes of stimulated in vitro fertilization (IVF) cycles where the gonadotropin-releasing hormone (GnRH) antagonist was omitted on ovulation triggering day. A total of 92 consecutive IVF cycles were included in 65 women who are undergoing ovarian stimulation with recombinant FSH. A GnRH antagonist, cetrorelix 0.25 mg/day, was started when leading follicle reached 14 mm in diameter until the day of hCG administration (Group A, 66 cycles) or until the day before hCG administration (Group B, 26 cycles). The duration of ovarian stimulation, total dose of gonadotropins, serum estradiol levels on hCG administration day, and the number of oocytes retrieved were not significantly different between the two groups. The total dose of GnRH antagonist was significantly lower in Group B compared to Group A (2.7+/-0.8 vs. 3.2+/-0.9 ampoules). There was no premature luteinization in the subjects. The proportion of mature oocytes (71.4% vs. 61.7%) and fertilization rate of mature (86.3+/-19.7% vs. 71.8+/-31.7%) was significantly higher in Group B. There were no significant differences in embryo quality and clinical pregnancy rates. Our results suggest that cessation of the GnRH antagonist on the day of hCG administration during a flexible multiple-dose protocol could reduce the total dose of GnRH antagonist without compromising IVF results.
Adult ; Chorionic Gonadotropin/administration & dosage ; Drug Administration Schedule ; Estradiol/blood ; Female ; Fertilization in Vitro ; Follicle Stimulating Hormone/administration & dosage/blood ; Gonadotropin-Releasing Hormone/*antagonists & inhibitors ; Hormone Antagonists/*administration & dosage ; Humans ; Ovulation Induction/*methods ; Recombinant Proteins/therapeutic use ; Retrospective Studies

OBJECTIVETo analyze the clinical characteristics and cycle outcome of Chinese women with gonadotropin-releasing hormone (GnRH) antagonist treatment during controlled ovarian hyperstimulation (COH) for in vitro fertilization and embryo transfer (IVF-ET).

METHODSA retrospective review was conducted in patients who completed 54 consecutive cycles of IVF-ET with GnRH antagonist treatment for luteinizing hormone (LH) surge prevention. Descriptive statistics were recorded for the patients' age, GnRH treatment duration (days) and dose, timing and duration of GnRH antagonist treatment, serum E2 and LH level on the day of antagonist use and hCG injection, number of oocytes retrieved, and clinical pregnancy rate.

RESULTSThe clinical pregnancy rate was 46.2% per ET cycle for GnRH antagonist group and 56.8% in GnRH agonist group, showing no significant difference between the two protocols. The age of the patients with GnRH antagonist averaged 35.7-/+3.8 years. Gn and GnRH antagonist treatment lasted for 8.5-/+1.6 and 4.5-/+1.1 days, respectively. On the day of ovulation triggered by hCG, the serum estradiol level was 1616.7-/+721.1 pg/ml, and a mean of 7.4-/+4.6 oocytes was collected per retrieval. The number of the embryos transferred was 2.4-/+0.6, with an implantation rate of 27.7%, resulting in a clinical pregnancy rate of 50.0% in the fixed protocol (antagonist initiation on day 4 or 5 of stimulation) and 37.5% in the flexible protocol (antagonist treatment initiated for a follicle of 12-15 mm, on day 6 to 9 of stimulation).

CONCLUSIONSGnRH antagonists treatment results in good outcomes and can be safe, short, convenient and effective for Chinese women undergoing COH for IVF. GnRH antagonist treatment can be initiated on day 4 to 9 of Gn stimulation to obtain comparable pregnancy rate.

Adult ; China ; Embryo Transfer ; Female ; Fertilization in Vitro ; Follicle Stimulating Hormone, Human ; administration & dosage ; Gonadotropin-Releasing Hormone ; administration & dosage ; antagonists & inhibitors ; Hormone Antagonists ; administration & dosage ; Humans ; Ovarian Hyperstimulation Syndrome ; drug therapy ; prevention & control ; Pregnancy ; Pregnancy Rate ; Retrospective Studies ; Time Factors

Using a simple method to determine the interaction between peptide and lipid bilayer and then deciding how to modify formulation from classic DepoFoam technology, multivesicular liposome of LXT-101 (DepoLXT-101) was prepared and characterized by in vitro evaluation. The electrostatic adsorption between peptide and lipid bilayer was observed by zeta potential and fluorescence spectrum. Anionic surfactants were added to stable the multiple emulsion and minimize the opposite effects resulted from drug. Encapsulation efficiency was determined by RP-HPLC. Morphology, particle size of DepoLXT-101 particles were characterized and their in vitro release was studied in sodium chloride solution. The DepoLXT-101 particles were prepared with good encapsulation efficiency, narrow size distribution and multivesicular construction. Over 95% of the DepoLXT-101 particles were in a size range of 5-20 microm. The in vitro assay in sodium chloride solution at 37 degrees C showed that 70%-90% of the peptide was released from particles slowly over 11 days. Multivesicular liposome sustained delivery of synthetic cationic peptides could be successfully prepared by the method.
Delayed-Action Preparations ; Drug Compounding ; Drug Delivery Systems ; methods ; Gonadotropin-Releasing Hormone ; antagonists & inhibitors ; Liposomes ; administration & dosage ; pharmacokinetics ; Oligopeptides ; administration & dosage ; pharmacokinetics ; Particle Size ; Technology, Pharmaceutical ; methods

Abortifacient Agents, Steroidal ; administration & dosage ; Abortion, Induced ; methods ; Androgen Antagonists ; administration & dosage ; Contraceptives, Oral ; administration & dosage ; Female ; Fertilization in Vitro ; methods ; Gonadotropin-Releasing Hormone ; administration & dosage ; analogs & derivatives ; Hormone Replacement Therapy ; methods ; Hormones ; administration & dosage ; Humans ; Mifepristone ; administration & dosage ; Norpregnenes ; administration & dosage ; Pregnancy

Bipolar androgen therapy (BAT), as a new therapeutic strategy for castration-resistant prostate cancer (CRPC), can significantly reduce the level of prostate-specific antigen (PSA) for prostate cancer patients and has exhibited an excellent safety profile with no serious adverse events. Based on the clinical trials recently published at home and abroad, this article reviews the background, action mechanism, development, and prospect of BAT.
Androgen Antagonists ; therapeutic use ; Hormone Replacement Therapy ; methods ; Humans ; Male ; Prostate-Specific Antigen ; blood ; Prostatic Neoplasms, Castration-Resistant ; blood ; drug therapy ; Receptors, Androgen ; Testosterone ; administration & dosage ; blood

This paper developed a sensitive and specific liquid chromatography-electrospray ionization mass spectrometry (HPLC-MS/MS) method for the determination of decapeptide LXT-101 in Beagle dog plasma. Plasma samples spiked with internal standard (IS) were treated with acetonitrile to precipitate the protein. Selected reaction monitoring (SRM) using the precursor --> product ion combinations of m/z 472.1-->587.9 and m/z 502.8-->633.8 were used to quantify LXT-101 and IS, respectively. The linear calibration curves were obtained in the concentration range of 0.5 - 500.0 ng x mL(-1). The limit of quantification (LOQ) was 0.5 ng x mL(-1). The inter-day and intra-day precision (RSD) across three validation run over the entire concentration range was below 10.9%, and the accuracy (RE) was within +/- 1.8%. The main pharmacokinetic parameters of LXT-101 after muscle injection of 20 microg x kg(-1) were as follows, AUC(0-t): (176.8 +/- 116.7) microg x h x L(-1), MRT(0-t): (2.52 +/- 0.53) h, T(1/2): (1.4 +/- 0.3) h; CL: (0.16 +/- 0.09) L x h(-1) x kg(-1), and Vd: (0.30 +/- 0.16) L x kg(-1), respectively. The method is proved to be specific, sensitive and suitable for the investigation of LXT-101 pharmacokinetics in Beagle dog.
Animals ; Antineoplastic Agents ; administration & dosage ; blood ; pharmacokinetics ; Area Under Curve ; Chromatography, High Pressure Liquid ; Dogs ; Gonadotropin-Releasing Hormone ; antagonists & inhibitors ; Injections, Intramuscular ; Male ; Oligopeptides ; administration & dosage ; blood ; pharmacokinetics ; Spectrometry, Mass, Electrospray Ionization

OBJECTIVETo study the expression of ET receptor and the apoptosis after intervened with ET receptor antagonist in androgen-independent prostate cancer.

METHODSPC3, an androgen-independent prostate cancer cell line, was used. The expression of ETA and ETB receptor in PC3 was measured through RT-PCR. After intervened with selective ETA and ETB receptor antagonist, the apoptosis in PC3 was studied through flow cytometry and electron microscope.

RESULTSClear signal was obtained in PC3 for ETA receptor mRNA transcript, while the signal for ETB receptor mRNA transcript was very weak. The expression of ETA receptor mRNA was obviously reduced and the apoptosis of PC3 cell was observed after intervened with selective ETA receptor antagonist. There was no change after intervened with selective ETB receptor antagonist.

CONCLUSIONET-1 exerts its effects through the ETA receptor subtype and ETB receptor is silenced in PC3. The expression of ETA was reduced and the apoptosis was observed in PC3 when ETA receptor was blocked. It was dose-dependent.

Androgens ; physiology ; Apoptosis ; drug effects ; physiology ; Endothelin A Receptor Antagonists ; Endothelin B Receptor Antagonists ; Endothelin-1 ; physiology ; Humans ; In Vitro Techniques ; Male ; Neoplasms, Hormone-Dependent ; pathology ; Oligopeptides ; administration & dosage ; Peptides, Cyclic ; administration & dosage ; Piperidines ; administration & dosage ; Prostatic Neoplasms ; pathology ; physiopathology ; Receptor, Endothelin A ; metabolism ; physiology ; Receptor, Endothelin B ; metabolism ; physiology

This paper was aimed to study the minimum dose of human chorionic gonadotropin (hCG) to effectively trigger maturation of oocytes and prevent ovarian hyperstimulation syndrome (OHSS) in a series of hyper-responders treated with a long gonadotropin releasing hormone agonist (GnRHa) protocol. Six women at high risk of developing severe OHSS in a long GnRHa protocol were enrolled into this study. Serum hormone levels on the day of and after hCG administration, antral follicle count, oocyte retrieval number and quality were determined. In total, 6 women aged between 29 and 36 years and at risk of developing severe OHSS, received 2000 U hCG. Five of them were treated with coasting for 1 day and the rest one for 4 days. The mean number of oocytes collected was 19 (range 14-27) and the fertilization rate per collected oocyte was 72.81%. Of the 6 women in the study, only one cancelled embryos transfer and all embryos were frozen, and then she delivered two health boys on term in the subsequent frozen-thawed embryo transfer (FET) cycle. Pregnancies and births were achieved in 3 patients out of 5 in vitro fertilization-embryo transfer (IVF-ET) cycles. No woman developed moderate or severe OHSS. Triggering with 2000 U hCG is feasible to prevent OHSS in unpredicted hyper-responders undergoing IVF in a long GnRHa protocol.
Adult ; Chorionic Gonadotropin ; administration & dosage ; adverse effects ; Dose-Response Relationship, Drug ; Female ; Fertility Agents, Female ; administration & dosage ; Gonadotropin-Releasing Hormone ; antagonists & inhibitors ; Humans ; Infertility, Female ; therapy ; Oocytes ; drug effects ; pathology ; Ovarian Hyperstimulation Syndrome ; etiology ; prevention & control ; Ovulation Induction ; adverse effects ; methods ; Treatment Outcome

OBJECTIVETo determine the influence of maximal androgen blockade (MAB) on bone mineral density (BMD) in men with prostate cancer.

METHODSWe enrolled 40 men with prostate cancer treated by MAB for 7 to 12 months. We obtained the laboratory results of PSA, testosterone, serum calcium and phosphorus, 24-h urine calcium and phosphorus, alkaline phosphatase, and parathyroid hormone, measured the BMD of the lumbar spine and femoral neck by dual energy X-ray absorptiometry, recorded pain scores, and compared the results before and after the treatment.

RESULTSBefore MAB treatment, 5 (12.5%) of the patients met the BMD criteria of lumbar spine (L2-4) osteopenia, 8 (20%) lumbar spine (L2-4) osteoporosis, 13 (32.5%) left femoral neck osteopenia, and 15 (37.5%) left femoral neck osteoporosis. The PSA and testosterone levels were decreased from (52.9 +/- 69.9) microg/L and (18.9 +/- 6.5) nmol/L before MAB to (1.5 +/- 1.6) microg/L and (1.9 +/- 1.3) nmol/L after it (P<0.05). There were no statistically significant differences before and after MAB in the levels of serum calcium and phosphorus, 24-h urine calcium and phosphorus, alkaline phosphatase, and parathyroid hormone (P>0.05), nor in the BMD levels of the lumbar spine ([1.1 +/- 0.1] vs [1.1 +/- 0.2] g/cm2) and femoral neck ([0.8 +/- 0.2] vs [0.8 +/- 0.1] g/cm2), nor in the pain score ([0.6 +/- 0.2] vs [0.7 +/- 0.1], P>0.05).

CONCLUSIONMAB treatment (range from 7 to 12 months) has no significant influence on BMD in men with prostate cancer, but BMD should be measured before MAB.

Aged ; Aged, 80 and over ; Alkaline Phosphatase ; analysis ; Androgen Antagonists ; administration & dosage ; adverse effects ; therapeutic use ; Bone Density ; drug effects ; Bone Diseases, Metabolic ; etiology ; Calcium ; blood ; urine ; Humans ; Male ; Middle Aged ; Osteoporosis ; etiology ; Parathyroid Hormone ; analysis ; Phosphorus ; urine ; Prostatic Neoplasms ; drug therapy ; metabolism ; Testosterone ; blood