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

The association of anosmia with gonadal failure was first described by Kallmann et al. and reviewed by Nawakouski and Lenz. This hypogonadotropic hypogonadism is due to a defect of the hypothalamic level. We reported a case of Kallmann`s syndrome who was visited our department for evaluation of undescended testis. The patient was 15 year old male with anosmia and underdeveloped external genitalia. Hormonal study was done. On basal state. FSH was 1.1 mIU/ml, LH and testosterone were undetectable. 24 hours urine 17-OH CS is 4.5 mg/dl. After LH-RH 100 microgram was intravenous administration. LH value was 3.9mIU/ml. 2.0mIU/ml. 1.7mIU/ml. 1.0mIU/ml on 30', 60', 90', 120', respectively and FSH value was 3.8mIU/ml, 4.0mIU/ml, 4.9mIU/ml, 4.0mIU/ml on 30', 60', 90'. 120', respectively.
Administration, Intravenous ; Adolescent ; Cryptorchidism ; Genitalia ; Gonadotropin-Releasing Hormone ; Gonads ; Humans ; Hypogonadism ; Kallmann Syndrome* ; Male ; Olfaction Disorders ; Testosterone

OBJECTIVETo evaluate the effects of levonorgestrel-releasing intrauterine system (LNG-IUS) combined with GnRH analogue (GnRH-a) in the treatment of adenomyosis with uterine body enlargement.

METHODSTwelve women (mane age 40.3 years) with adenomyosis and uterine cavity depth over 11 cm received injections of GnRH-a every 4 weeks, and after the uterine cavity depth was reduced to below 10 cm, LNG-IUS was deployed. VAS pain score, PBAC bleeding score, uterine volume, and hemoglobin levels of the women were measured before the treatment and at 6 and 12 months after LNG-IUS placement.

RESULTSThe VAS pain score was significantly lowered at 6 and 12 month after LNG-IUS placement (P<0.05), and the PBAC bleeding score also showed significant reductions (P<0.05). The uterine volume decreased significantly at 6 and 12 months after LNG-IUS placement as compared with that before the treatment, but was significantly greater at 6 month in comparison with that at the time of LNG-IUS placement (P<0.05). Serum hemoglobin levels underwent significant increments after LNG-IUS placement (P<0.05).

CONCLUSIONLNG-IUS combined with GnRH analogue injection can be effective in the treatment of adenomyosis with dysmenorrhea and hypermenorrhea.

Adult ; Delayed-Action Preparations ; administration & dosage ; Drug Therapy, Combination ; Endometriosis ; drug therapy ; Female ; Gonadotropin-Releasing Hormone ; analogs & derivatives ; therapeutic use ; Humans ; Levonorgestrel ; administration & dosage ; Uterine Diseases ; drug therapy

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

OBJECTIVETo investigate the value of serum estradiol increment and serum estradiol/follicles on the day of hCG administration in predicting the clinical outcomes of in vitro fertilization-embryo transfer (IVF-ET).

METHODSA retrospective analysis of the IVF-ET data was conducted involving 121 patients who received a long gonadotrophin-releasing hormone agonist (GnRHa) protocol. According to the increment of serum estradiol on the day of hCG administration (relative to the level on the day before hCG administration), the patients were divided into 3 groups (A1, A2 and A3) with a increment ratio below 30%, between 30% and 50%, and over 50%, respectively. In addition, according to the ratio of serum estradiol level on hCG day to mature follicle (diameter ≥ 14 mm) number, these patients were divided into three groups (B1, B2 and B3) with the ratio below 250 pg/ml, between 250 and 350 gp/ml, and over 350 pg/ml, respectively. The hormonal characteristics and clinical outcomes of the IVF-ET cycles were analyzed comparatively.

RESULTSBoth the clinical pregnancy rate (71.05%) and embryo implantation rate (52.63%) were significantly higher in group A3 than in groups A1 and A2 (P<0.05). The best clinical pregnancy rate (67.86%) and embryo implantation rate (49.14%) were significantly higher in group B2 than in groups B1 and B3 (P<0.05).

CONCLUSIONThe variation of serum estradiol shows an important impact on the clinical outcomes of IVF-ET in patients receiving long GnRH-a protocol. Favorable outcomes can be expected with a hCG day serum estradiol increment ratio above 50% and E(2)/follicle ratio between 250 and 350 pg/ml.

Embryo Transfer ; Estradiol ; blood ; Female ; Fertility Agents, Female ; administration & dosage ; Fertilization in Vitro ; Gonadotropin-Releasing Hormone ; administration & dosage ; agonists ; Humans ; Pregnancy ; Pregnancy Rate ; Retrospective Studies ; Treatment Outcome

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

OBJECTIVETo investigate the efficacy and side-effects of long-acting gonadotropin-releasing hormone analogue (GnRHa) in treatment of idiopathic central precocious puberty (ICPP) in girls.

METHODSThirty six ICPP girls were treated with GnRHa. The secondary sexual characteristics, uterus volume, ovary volume, follicle development, bone age/chronological age (BA/CA), predicted adult height (PAH), serum inhibitor A (INHA) and inhibitor B (INHB), body mass index (BMI) and growth rate were compared before and after treatment. Bone age was assessed using the Greulich-Pyle method, PAH was calculated by the Payley-Pinneau method, serum INHA and INHB were measured by ELISA, and serum LH and FSH were measured by chemoluminescence.

RESULT(1) Breast development was reduced after 3 to approximately 6 months of treatment, and no continued development were observed. In 12 girls the breast development returned from Tanner II to B1. (2) Both uterus and ovary volume were decreased after 6 months [(3.28 +/-2.20)ml comrade with (1.27 +/-0.69)ml and (3.62 +/-1.94)ml compared with (1.24 +/-0.50)ml, respectively]; the follicle was reduced or even disappeared; and the serum INHA and INHB were decreased from Log(0.93 +/-0.35)ng/L and Log(1.95 +/-0.37)ng/L to Log(0.60 +/-0.32)ng/L and Log(1.46 +/-0.32)ng/L, respectively. (3) BA/CA was decreased from 1.40 +/-0.20 to 1.26 +/-0.15; PAH was increased from (149.12 +/-4.04)cm to (152.84 +/-3.72)cm after one-year treatment; BMI showed no significant changes (16.04 +/-1.68 compared with 15.93 +/-1.69).

CONCLUSIONGnRHa can effectively inhibit the development of sex gland and the secondary sexual characteristics, stabilize or delay bone maturation, improve the predicted adult height, and has no observed side-effects in the short-term treatment for ICPP girls.

Child ; Delayed-Action Preparations ; therapeutic use ; Female ; Gonadotropin-Releasing Hormone ; administration & dosage ; analogs & derivatives ; Humans ; Puberty, Precocious ; drug therapy ; Treatment Outcome

Several case reports have indicated that a small subgroup of patients may develop ovarian hyperstimulation following the administration of gonadotropin-releasing hormone agonists (GnRHa) without gonadotropins. However, since only few such cases have been published, it is unclear what course to follow in subsequent cycles after ovarian hyperstimulation in the first cycle using only GnRHa. A 33-yr-old woman was referred to in vitro fertilization for oocyte donation. A depot preparation (3.75 mg) of tryptorelin without gonadotropins induced ovarian multifollicular enlargement with high estradiol level, and was followed by human chorionic gonadotropin administration and oocyte retrieval. In a subsequent cycle of the same patient, a low dose of tryptorelin (0.05 mg) did not induce ovarian hyperstimulation, and resulted in clinical pregnancy. This report shows potential management of ovarian hyperstimulation following the administration of GnRHa without gonadotropins.
Adult ; Chorionic Gonadotropin/administration & dosage ; Female ; Fertilization in Vitro ; Gonadotropin-Releasing Hormone/*agonists ; Humans ; *Oocyte Donation ; Oocyte Retrieval ; Ovarian Hyperstimulation Syndrome/*chemically induced ; Ovary/*drug effects ; Ovulation Induction/methods ; Pregnancy ; Triptorelin Pamoate/*administration & dosage/adverse effects

The objective of this study was to investigate factors that influence the success of resynchronization protocols for bovines with and without progesterone supplementation. Cow synchronized and not found pregnant were randomly assigned to two resynchronization protocols: ovsynch without progesterone (P4) supplementation (n = 66) or with exogenous P4 administered from Days 0 to 7 (n = 67). Progesterone levels were measured on Days 0 and 7 of these protocols as well as 4 and 5 days post-insemination. Progesterone supplementation raised the P4 levels on Day 7 (p < 0.05), but had no overall effect on resynchronization rates (RRs) or pregnancy per artificial insemination (P/AI). However, cows with Body Condition Score (BCS) > 3.5 had increased P/AI values while cows with BCS < 2.75 had decreased P/AI rates after P4 supplementation. Primiparous cows had higher P4 values on Day 7 than pluriparous animals (p = 0.04) and tended to have higher RRs (p = 0.06). Results of this study indicate that progesterone supplementation in resynchronization protocols has minimal effects on outcomes. Parity had an effect on the levels of circulating progesterone at initiation of the protocol, which in turn influenced the RR.
Animals ; Cattle/*physiology ; Dinoprost/administration & dosage/*pharmacology ; Estrus Synchronization/*drug effects/methods ; Female ; Fertility Agents/administration & dosage/pharmacology ; Gonadotropin-Releasing Hormone/administration & dosage/*pharmacology ; Insemination, Artificial/veterinary ; Ovulation/drug effects ; Pregnancy ; Progesterone/administration & dosage/*pharmacology ; Tromethamine/administration & dosage/*pharmacology

OBJECTIVEGonadotropin-releasing hormone agonist (GnRHa) is widely used for the treatment of precocious puberty, but there was no identical regime for the dosage and the interval of administration. The aim of this study was to assess the feasibility of subcutaneous administration of Triptorelin with a prolonged interval (six weeks) for the suppression of pituitary-gonadal axis and clinical signs in girls with idiopathic central precocious puberty (ICPP).

METHODSForty-six girls with ICPP were enrolled in this trial and were divided into two groups at random, with 26 patients in group A and 20 in group B. There were no significantly differences in chronological age, height, weight, age at clinical onset of puberty and bone age between the two groups before treatment. Triptorelin (Decapeptyl, 3.75 mg) was administered subcutaneously (SC) at 6 weeks intervals in group A or intramuscularly (IM) at 4 weeks intervals in group B. Both forms were given for more than 12 months consecutively. During the period of treatment, the clinical parameters including height, weight, pubertal stage, bone age, uterine volume and ovarian size were documented. The serum levels of luteinizing hormone (LH), follicle stimulating hormone (FSH) and estradiol (E(2)) were monitored using immunoenzymometric assay.

RESULTSBoth treatment regimes can completely suppressed the pituitary-gonadal axis. The clinical signs of pubertal development regressed or stabilized in all patients. Breast developments, as reflected by Tanner staging, were regressed. Uterine volume decreased after treatment, however, this decrease did not reach statistical significance. Mean ovarian volume did not change significantly during treatment. The height velocity was significantly decreased from a pretreatment value of 6.3 +/- 1.4 cm/year to 5.8 +/- 1.2 cm/year in group A and 6.7 +/- 1.3 cm/year to 5.4 +/- 1.0 cm/year in group B, respectively. The rate of skeletal maturation was reduced significantly during treatment. The ratio of bone age/chronological age was 1.2 +/- 0.2 or 1.3 +/- 0.3 at the onset of therapy and decreased significantly after the treatment to 0.7 +/- 0.2 or 0.9 +/- 0.1, respectively. The predicted adult height increased significantly and progressively during therapy. The levels of serum LH, FSH and E(2) were returned to the prepubertal condition after 6 - 8 weeks treatment and remained suppressed for the duration of treatment. No significantly side effects of therapy were noted. The most common adverse event during SC treatment was that a non-irritating, 1 cm in diameter mass can be palpated at the site of subcutaneous injection in the abdominal wall of group A patients. It gradually decreased in size, and disappeared after 8 - 12 weeks. Two girls had minimal withdrawal virginal bleeding episodes after the first injection.

CONCLUSIONBoth IM and SC triptorelin administration were clinically effective. They can induce profound suppression of hypothalamic-pituitary-gonadal axis while stabilizing height velocity, slowing bone maturation and increasing predicted adult height. These results suggest that subcutaneous injection of triptorelin in 6 weeks intervals at a dosage of 3.75 mg was a safe and acceptable regime for ICPP with good efficacy.

Body Height ; drug effects ; Breast ; drug effects ; Drug Administration Schedule ; Feasibility Studies ; Female ; Gonadotropin-Releasing Hormone ; administration & dosage ; agonists ; Humans ; Injections, Intramuscular ; Injections, Subcutaneous ; Puberty, Precocious ; drug therapy ; Triptorelin Pamoate ; administration & dosage ; Uterus ; drug effects