Equivalence of the 3-month and 28-day formulations of triptorelin with regard to achievement and maintenance of medical castration in women with endometriosis.

OBJECTIVE: The present study aims at demonstrating the equivalence of the 28-day and 3-month formulations of triptorelin SR (sustained release) in terms of percentage of patients achieving castration levels of estradiol (<==50 pg/mL) 84 days after treatment initiation. DESIGN: A phase II, prospective, randomized, multicenter, open study was conducted in two parallel groups of women with endometriosis. SETTING: Academic hospitals. PATIENT(S): Seventy-two women with endometriosis. were treated with a single intramuscular injection of 3-month triptorelin SR, and 74 patients were treated with one intramuscular injection of 28-day triptorelin SR every 28 days for 3 months. INTERVENTION(S): As part of two parallel treatment groups, 72 women were given a single intramuscular injection of 3-month triptorelin SR, and 74 women were given one intramuscular injection of 28-day triptorelin SR every 28 days for 3 months. MAIN OUTCOME MEASURE(S): Percentage of patients achieving castration levels of estradiol at the end of the treatment period. RESULT(S): Patients participated in the study until resumption of menses. Ninety-seven percent of patients given the 3-month formulation and 94% of those given the 28-day formulation were in a state of medical castration on day 84. The mean time to achieve castration was shorter for the 3-month formulation, and the duration of castration was significantly longer. The FSH and LH parameters were comparable, though not always identical. CONCLUSION(S): The pharmacodynamic effects of the Decapeptyl SR 3-month formulation are equivalent to those of the 28-day formulation. The 3-month formulation provides the added advantage of a longer maintenance of medical castration in women who have endometriosis

Recombinant Human Luteinizing Hormone is as effective as, but safer than urinary human chorionic gonadotropin in inducing final follicular maturation and ovulation in in vitro procedures: results of a multicenter double-blind study

n a prospective, comparative, dose-finding study, the minimal effective dose of recombinant human LH (rhLH) required to induce final follicular maturation and early luteinization in patients undergoing in vitro fertilization and embryo transfer was determined. In addition, the efficacy and safety of rhLH were compared with urinary human CG (u-hCG). A total of 259 infertile women, aged 18-39 yr, were enrolled in the study. After pituitary desensitization using a GnRH agonist, rhFSH was administered for ovarian stimulation. Patients then received either rhLH or u-hCG to achieve final follicular maturation. The doses of rhLH administered were 5,000, 15,000, 30,000, or 15,000 + 10,000 IU (second injection administered 3 days after the first injection; 129 patients), and those of u-hCG were consistently 5,000 IU (121 patients). Ovum pick-up was performed 34--38 h after rhLH or u-hCG injection. After fertilization in vitro, up to three embryos were replaced in the uterine cavity. The numbers of oocytes retrieved after u-hCG or rhLH administration were not significantly different between the four different doses of rhLH, when compared with each corresponding u-hCG group, nor when compared with the pool of all u-hCG groups. Similarly, there were no statistically significant differences in: the number of oocytes retrieved per follicle with a diameter of over 10 mm on the day of u-hCG or rhLH administration; the number of patients with at least one oocyte retrieved; oocyte nuclear maturity; oocyte potential for fertilization; the number of embryos; the number of total, biochemical, and clinical pregnancies; and the embryo implantation rate. However, in many of these parameters, the lowest dose of rhLH seemed suboptimal when compared with the higher dose. In terms of safety, rhLH was well tolerated at a dose of up to 30,000 IU. Moderate ovarian hyperstimulation syndrome (OHSS) was reported in 12.4% of patients who received u-hCG and 12.0% of patients who received two injections of rhLH. No moderate or severe OHSS was reported in patients who received a single dose of rhLH up to 30,000 IU. The results show that a single dose of rhLH is effective in inducing final follicular maturation and early luteinization in in vitro fertilization and embryo transfer patients and is comparable with 5,000 IU u-hCG. A single dose of rhLH results in a highly significant reduction in OHSS compared with hCG. The dose of rhLH giving the highest efficacy to safety ratio was between 15,000 and 30,000 I

The use of a decremental dose regimen in patients treated with a chronic low-dose step-up protocol for WHO Group II anovulation: a prospective randomized multicentre study

BACKGROUND: In women with chronic anovulation, the choice of the FSH starting dose and the modality of subsequent dose adjustments are critical in controlling the risk of overstimulation. The aim of this prospective randomized study was to assess the efficacy and safety of a decremental FSH dose regimen applied once the leading follicle was 10-13 mm in diameter in women treated for WHO Group II anovulation according to a chronic low-dose (CLD; 75 IU FSH for 14 days with 37.5 IU increment) step-up protocol. METHODS: Two hundred and nine subfertile women were treated with recombinant human FSH (r-hFSH) (Gonal-f) for ovulation induction according to a CLD step-up regimen. When the leading follicle reached a diameter of 10-13 mm, 158 participants were randomized by means of a computer-generated list to receive either the same FSH dose required to achieve the threshold for follicular development (CLD regimen) or half of this FSH dose [sequential (SQ) regimen]. HCG was administered only if not more than three follicles >or=16 mm in diameter were present and/or serum estradiol (E(2)) values were or=16 mm in size at the time of hCG administration. RESULTS: Clinical characteristics and ovarian parameters at the time of randomization were similar in the two groups. Both CLD and SQ protocols achieved similar follicular growth as regards the total number of follicles and medium-sized or mature follicles (>/=16 mm: 1.5 +/- 0.9 versus 1.4 +/- 0.7, respectively). Furthermore, serum E(2) levels were equivalent in the two groups at the time of hCG administration (441 +/- 360 versus 425 +/- 480 pg/ml for CLD and SQ protocols, respectively). The rate of mono-follicular development was identical as well as the percentage of patients who ovulated and achieved pregnancy. CONCLUSIONS: The results show that the CLD step-up regimen for FSH administration is efficacious and safe for promoting mono-follicular ovulation in women with WHO Group II anovulation. This study confirms that maintaining the same FSH starting dose for 14 days before increasing the dose in step-up regimen is critical to adequately control the risk of over-response. Strict application of CLD regimen should be recommended in women with WHO Group II anovulation