Half-dose depot triptorelin in pituitary suppression for multiple ovarian stimulation in assisted reproduction technology: a randomized study.

BACKGROUND: Pituitary suppression by depot GnRH agonist may be excessive for ovarian stimulation in assisted reproduction technology. This study compares the efficacy of standard and half-dose depot triptorelin in a long protocol. METHODS: A total of 180 patients were randomized into two groups using sealed envelopes. Pituitary desensitization was obtained in group 1 (90 patients) with half-dose (1.87 mg) triptorelin depot in the mid-luteal phase of their menstrual cycle, and in group 2 (90 patients) with full-dose (3.75 mg) triptorelin. RESULTS: There was no premature LH surge, with LH levels being lower in the full-dose group (1.04+/-0.05 versus 0.7+/-0.06 IU/l on the day of hCG). The number of FSH ampoules used was lower in group 1 (42+/-2 versus 59+/-3). The numbers of mature oocytes (10.1+/-0.54 versus 7.4+/-0.55), of fertilized oocytes (8.24+/-0.35 versus 6.34+/-0.37) and of embryos (7.8+/-0.36 versus 5.9+/-0.37) were significantly higher in group 1. No significant differences were found in pregnancy (38.8 versus 25.3%), implantation (22.6 versus 13.8%) or abortion (6.1 versus 5.0%) rates. Cumulative pregnancy (fresh plus frozen embryo transfers: 56.8 versus 35.4%) rate was significantly higher in group 1. CONCLUSION: A half-dose of depot triptorelin can be successfully used in ovarian stimulation for IVF and produce a higher number of good quality embryos with a good chance of implantation.

GnRH analogs: depot versus short formulations.

Gonadotropin releasing hormone agonists (GnRH-a) are widely used in controlled ovarian hyperstimulation (COH) for assisted reproduction (ART). Two different formulations are now available: short formulations and depot formulation. Some authors have suggested that depot GnRH-a induce a too high pituitary suppression and have put forward protocols using reduced GnRH-a doses. A reduced dose of daily triptorelin is enough for pituitary suppression during ovarian stimulation but provides no significant improvement in IVF cycle outcome when compared with depot formulation in normally responding women. However, it seems to improve ovarian response and overall results in poor responding patients. Low doses of short GnRH-a allow shorter treatment, requiring lower amounts of gonadotropins. This possibility should be considered in view of its economic advantage.

Effect of duration of estradiol replacement on the outcome of oocyte donation.

PURPOSE: To investigate if duration of estrogenic endometrial stimulation can affect recipient pregnancy rate in an ovum donation program. METHODS: Each recipient received micronized 17 beta-estradiol orally in a steadily increasing dosage from 2 to 6 mg daily over a period of time varying from 5 to 76 days until oocyte were available for donation. Recipients (520 patients for a total of 835 transfer cycles) were retrospectively divided into five groups depending on the duration of E2 administration. RESULTS: No significant difference was seen in pregnancy and implantation rates between groups. There was a higher number of miscarriages in Group A (41%), p < 0.05 vs. Group B (15%), and vs. Group E (1%). Age, number of pregnancies and miscarriages, or implantation rate in donors (327 women aged < 35 years) were similar in all the five groups. CONCLUSIONS: Endometrial receptivity is tolerant to a wide duration of E2 treatment (until 2 months), while waiting for oocytes available for donation, but best results are achieved with a treatment range of 11 to about 40 days.

Effect of reduced dose of triptorelin at the start of ovarian stimulation on the outcome of IVF: a randomized study.

BACKGROUND: Partial pituitary desensitization using gonadotrophin-releasing hormone (GnRH) agonists may be sufficient in women undergoing controlled ovarian hyperstimulation for assisted reproduction. However, the minimal effective agonist dose remains to be determined. The aim of the study was to investigate the effect of a reduced daily dose of triptorelin, administered at the start of ovarian stimulation, on the results of IVF and intracytoplasmic sperm injection. METHODS: A total of 132 patients was randomized in two groups. Pituitary desensitization was obtained in group 1 (66 patients) with a single 3.75 mg injection (i.m.) of triptorelin. In group 2, 66 patients received 100 microg triptorelin daily, which was then reduced to 50 microg at the start of follicle-stimulating hormone (FSH) stimulation. RESULTS: No significant differences were found in terms of pregnancy rate per transfer (38% in group 1 versus 34.9% in group 2), implantation rate (20.2 versus 18%) and abortion rate (8.3 versus 9.1%). The number of FSH ampoules used, as well as the number of days stimulation required, was significantly reduced in group 2 (41 +/- 26 versus 46.6 +/- 25.3, P < 0.03 and 11 +/- 1.3 versus 11.8 +/- 1.5, P < 0.002 respectively). No significant differences were seen in oestradiol concentrations and in follicle number, in the quantity of oocytes collected and fertilized, or in the number of embryos obtained or transferred. CONCLUSION: A reduced dose of triptorelin is enough for pituitary suppression during ovarian stimulation but provides no significant improvement in IVF cycle outcome when compared with depot formulation. The possibility of a shorter treatment protocol requiring lower amounts of gonadotrophins should be considered in view of its economic advantage.

Births after transcervical gamete intrafallopian transfer with a falloposcopic delivery system.

OBJECTIVE: To evaluate the safety and efficiency of a new delivery system to perform transcervical GIFT. DESIGN: Evaluation of pregnancy rate (PR), miscarriage rate, ectopic pregnancy rate, and delivery rate. SETTING: Institute of Obstetrics and Gynecology, Reproductive Endocrinology Unit, Infertility and IVF Center. PATIENT(S): Twenty-five patients with patent tubes documented by laparoscopy plus falloposcopy. INTERVENTION(S): Superovulation was induced with GnRH analogue and FSH. Under laparoscopic control, transcervical cannulation of the tube was done using a linear everting catheter incorporating direct falloposcopic vision of the tubal lumen. Two lengths of everting catheter (3 and 6 cm) were used providing either isthmic-ampullary or midampullary placement of the inoculum. A comparison was done in terms of ease of access and transfer, falloposcopic observations, and PRs between the groups. MAIN OUTCOME MEASURE(S): Efficacy was established by evaluating the PR, miscarriage rate, ectopic pregnancy rate, and delivery rate. RESULT(S): The PR was 28% (with no differences between the lengths of everting catheters). No ectopic pregnancies occurred. The abortion rate was 28.6% and the delivery rate was 20%. Neither tubal perforation nor other complications occurred during the procedure. CONCLUSION(S): Falloposcopic GIFT is safe and efficient and may be a less invasive alternative than laparoscopic transfer.

Comparison between depot leuprorelin and daily buserelin in IVF.

OBJECTIVES: To compare the effects of depot and daily forms of GnRH analogs in IVF programs. METHODS: One hundred seventeen patients undergoing IVF, with no severe male factor, were randomized between two treatment groups. Pituitary desensitization was obtained in group 1 (60 patients) with a single IM injection of leuprorelin (3.75 mg), and in group 2 (57 patients) with buserelin (0.3 mg SC twice daily). In a subgroup of 10 patients (5 for the depot form and 5 for the daily form) several GnRH tests were performed to investigate pituitary desensitization. RESULTS: No differences were found in the time to reach desensitization. Resumption of pituitary activity occurred in 7 days with the daily form and in about 2 months with the depot form. No significant differences were found in the stimulation pattern, oocyte quality, percentage of fertilization. The pregnancy rate per transfer was slightly, but not significantly, better in the depot group (29.4% vs 25.9%). Implantation rate (11.9% vs 12.3%) and the percentage of miscarriages (26.6% vs 28.5%) were similar. CONCLUSION: Depot and daily forms of GnRH analogs are equally effective in superovulation induction for IVF. Considering improved patient compliance and preference, depot forms are advantageous.

Comparison between depot and standard release triptoreline in in vitro fertilization: pituitary sensitivity, luteal function, pregnancy outcome, and perinatal results.

OBJECTIVE: To compare the effects of depot and standard release form of triptoreline in superovulation induction in IVF programs. DESIGN: One hundred ninety-six patients undergoing IVF were randomized between two treatment groups. Pituitary desensitization was obtained in group 1 (102 patients) with a single IM injection of 3.75 mg D-Trp-6-luteinizing hormone-releasing hormone (LH-RH) and, in group 2 (94 patients), with daily SC administration of 0.1 mg D-Trp-6-LH-RH. In a subgroup of 11 patients, a series of GnRH tests was performed to investigate pituitary desensitization and, in another subgroup of 12 patients, a study of luteal phase steroid profile was performed. In an additional 23 patients, a series of GnRH tests were performed to investigate pituitary desensitization during the late follicular and midluteal phases. RESULTS: No differences were found in the time necessary to reach desensitization (11.3 +/- 1.03 versus 11.3 +/- 1.45 days; mean +/- SEM), whereas resumption of pituitary activity takes place in 7 days after the discontinuation of the daily form and in about 2 months after discontinuation of the depot form. No differences were found in the duration of stimulation, number of FSH ampules, E2 levels, and number of follicles (11.7 +/- 0.68, versus 12.2 +/- 0.68) on hCG administration day and the total oocytes collected (9.1 +/- 0.6 versus 9.2 +/- 0.64). Oocyte quality, percentage of fertilization and cleavage, pregnancy rate per transfer (28.7% versus 25.6%), and miscarriages (about 30%) were similar in the two protocols. No difference was found in hormonal levels during the luteal phase. In both groups there was a high incidence of multiple pregnancy. CONCLUSION: Comparable results can be achieved with both long-acting and standard-release forms of GnRH analogs in patients undergoing assisted reproduction in terms of follicular stimulation and abortion rates despite differences in the duration of pituitary suppression.

Frequency and treatment of ovarian cysts in adolescence.

Ultrasound examination of the ovaries was performed monthly in the follicular phase of 139 healthy adolescents for one year. In 17 girls (12.2%) ovarian cysts spontaneously disappeared within 3 months of first observation. In 6 subjects, treatment with the combined estrogen/progestogen pill was given. The treatment was effective in 4 girls after 2-6 months while 2 subjects required surgical intervention for a cystic teratoma and a simple follicular cyst respectively. A spell of serial sonographic observation of ovarian cysts would seem appropriate in adolescents.

Ketoconazole therapy for women with acne and/or hirsutism.

The effects of ketoconazole, a synthetic imidazole derivate, were evaluated in 42 women affected by acne (17 cases) and/or hirsutism (36 cases) treated with 400 mg/day for 3-6 months. Androstenedione, total and free testosterone, 5 alpha dihydrotestosterone and dehydroepiandrosterone levels progressively dropped during treatment while 17 alpha hydroxyprogesterone, estradiol, ACTH, cortisol, LH and FSH levels increased. Dehydroepiandrosterone sulfate decreased only towards the end of treatment, while estrone, sex hormone binding globulin, and PRL remained unchanged. Daily mean +/- SD rate of hair growth, measured by a special image analysis processor, decreased within 3 months of therapy from 0.258 +/- 0.058 to 0.184 +/- 0.039 mm/day (P less than 0.02) and mean +/- SD hair diameter from 0.123 +/- 0.015 to 0.110 +/- 0.013 mm (P less than 0.05) together with decreasing hormone levels. The therapeutic effects of ketoconazole on hirsutism was evident at 6 months in only 14 subjects, while no significant change in hirsutism score was recorded in 22 women who failed to complete the therapy. Acne improved in all cases. Several side effects and complications arose during treatment, such as headache, nausea, loss of scalp hair, hepatitis, and biochemical changes. Even though ketoconazole improves hyperandrogenism, only selected patients are eligible for treatment as scrupulous monitoring is required.