Comparison between depot leuprorelin and daily buserelin in IVF. Comparison between depot and standard release triptoreline in in vitro fertilization: pituitary sensitivity, luteal function, pregnancy outcome, and perinatal results. A randomized prospective study of early follicular or midluteal initiation of long protocol gonadotropin-releasing hormone in an in vitro fertilization program. Comparison of short 7-day and prolonged treatment with gonadotropin-releasing hormone agonist desensitization for controlled ovarian hyperstimulation. Failure to preserve fertility in patients with Hodgkin's disease. Subcutaneous goserelin versus intranasal buserelin for pituitary down-regulation in patients undergoing IVF: a randomized comparative study. High doses of gonadotrophins combined with stop versus non-stop protocol of GnRH analogue administration in low responder IVF patients: a prospective, randomized, controlled trial. Cessation of gonadotropin-releasing hormone analogue (GnRH-a) upon down-regulation versus conventional long GnRH-a protocol in poor responders undergoing in vitro fertilization. GnRH antagonist versus long GnRH agonist protocol in poor responders undergoing IVF: a randomized controlled trial. A comparison of three gonadotrophin-releasing hormone analogues in an in-vitro fertilization programme: a prospective randomized study. The use of long- and short-acting forms of gonadotrophin-releasing hormone analogues in women undergoing oocyte donation. Effect of prolonged gonadotropin-releasing hormone agonist therapy on the outcome of in vitro fertilization-embryo transfer in patients with endometriosis. Extension of GnRH agonist through the luteal phase to improve the outcome of intracytoplasmic sperm injection. The long protocol of administration of gonadotropin-releasing hormone agonist is superior to the short protocol for ovarian stimulation for in vitro fertilization. Comparison of mild stimulation and conventional stimulation in ART outcome.
To compare the effects of depot and daily forms of GnRH analogs in IVF programs.
                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.
                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.
                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. To compare the effects of depot and standard release form of triptoreline in superovulation induction in IVF programs.
                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.
                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.
                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. To determine the optimum menstrual cycle time to initiate a long-protocol gonadotropin-releasing hormone agonist (GnRH-a) down-regulation regimen before hMG stimulation before IVF.
                Randomized, prospective, single, first cycle study.
                University teaching hospital.
                Eighty-six infertile couples undergoing IVF-ET attempt under rules for Ireland.
                Gonadotropin-releasing hormone agonist administered intranasally from day 1 or 21 of menstrual cycle. Human menopausal gonadotropin commenced when pituitary down-regulation was confirmed.
                Ovarian response, cancellation, fertilization, and pregnancy rates.
                No significant differences found between day 1 and day 21 initiation. But starting on day 1 is more easily recognizable by patients and avoids the possibility of administering GnRH-a in the presence of an unsuspected pregnancy.
                Both follicular and luteal phase initiation of GnRH-a long-protocol down-regulation are equally efficacious. In our clinical context, patients and management favor commencing on day 1. To compare two treatment regimens associating a gonadotropin-releasing hormone agonist (GnRH-a) and human menopausal gonadotropin (hMG) for controlled ovarian hyperstimulation (COH).
                A prospective randomized trial.
                The outpatient fertility clinic of a university tertiary care center, the Hôpital A. Béclère, Clamart, France.
                One hundred eighty-two in vitro fertilization (IVF) candidates undergoing new or repeat IVF cycles at Hôpital A. Béclère over a 4-month period.
                Group 1 (7-day protocol): A short-acting preparation of GnRH-a (Tripteriline 0.1) was administered daily for 7 days, starting on cycle day 2. Ovarian stimulation with hMG was started on cycle day 4. Group 2 (long protocol): A timed release preparation of GnRH-a (Tripteriline 3.75 mg) was administered on cycle day 2. Ovarian stimulation with hMG was started after documented ovarian suppression.
                Response to COH, pregnancy rate (PR), tolerance.
                In the 7-day protocol, the amount of hMG required was markedly lower at 24 +/- 7 than in the long protocol group requiring 42.5 +/- 9.75 vials (75 IU) (mean +/- SD). No elevation of plasma LH occurred in either group. The number of oocytes retrieved was 7.3 +/- 1 and 10.7 +/- 1.2 (mean +/- SD) in the 7-day and long protocols, respectively. Yet, the number of embryos obtained and the PRs were similar in the two treatment groups.
                We observed that in COH, GnRH-a treatment could be interrupted safely several days before human chorionic gonadotropin administration without risking a premature increase of plasma luteinizing hormone. Moreover, the number of embryos available for fresh transfer and the ongoing PRs were similar in the new 7-day and in the classic long GnRH-a/hMG protocols, despite the smaller number of oocytes suggesting a greater efficiency of the 7-day protocol. The peak estradiol level and the hMG requirement were also lower in the 7-day GnRH-a/hMG protocol. The hypothesis that the "down-regulated" gonad is less vulnerable to the effects of cytotoxic chemotherapy for advanced Hodgkin's disease has been investigated. Thirty men and eighteen women were randomly allocated to receive an agonist analogue of gonadotrophin-releasing hormone prior to, and for the duration of, cytotoxic chemotherapy. Buserelin (d-Ser-[TBU]6 LHRH ethylamide) was prescribed in two different dosage schedules to twenty men, and in a single dosage schedule to eight women. A standard gonadotrophin-releasing hormone test (GnRH 100 micrograms) was performed 1 week prior to and on day 1 of each cycle of chemotherapy. In all patients peak luteinizing hormone responses to GnRH were suppressed throughout treatment. The higher of the two dosage schedules used in the men caused more effective suppression of luteinizing hormone, and both regimens led to an initial suppression of peak follicle-stimulating hormone responses to GnRH, which was not maintained. At follow-up assessment up to 3 years from the completion of treatment, all men treated with buserelin were profoundly oligospermic and four of the eight women were amenorrhoeic. All ten male controls were profoundly oligospermic, and six of nine female controls were amenorrhoeic. In the dosages and schedules investigated, buserelin was ineffective in conserving fertility. One-hundred women undergoing ovarian stimulation with gonadotrophin-releasing hormone agonist (GnRH-a) and a human menopausal gonadotrophin (HMG) for in-vitro fertilization (IVF) participated in this randomized comparative study. The effectiveness of long-acting s.c. goserelin (Zoladex depot; 49 patients) and intranasally (i.n.) administered buserelin acetate (Suprefact; 51 patients) for pituitary down-regulation was compared. Treatment with s.c. goserelin (3.6 mg) or i.n. buserelin acetate (200 micrograms; 6 times/day) was started on day 21-23 of the cycle. Stimulation with 150 IU of HMG/day was started after at least 11 days of GnRH-a treatment. There were no differences in the time required for follicular development nor in the clinical outcome between groups treated with either goserelin or buserelin. The number of oocytes recovered in the goserelin group was 6.7 +/- 5.0 versus 6.3 +/- 4.9 in the buserelin group. There were 11 pregnancies after the use of goserelin (22.4%) and 12 pregnancies in those given buserelin (24.0%). The number of HMG ampoules needed for follicular maturation was higher in the goserelin group (27.9 +/- 7.8) than in the buserelin group (24.6 +/- 7.8, P < 0.05). The patients given buserelin suffered significantly more from tiredness, depression, headache and abdominal pain than those receiving goserelin, whereas there were no differences between the groups in experiencing mental irritability, nausea and swelling. Subcutaneous goserelin depot injection offers a useful alternative for pituitary down-regulation in IVF stimulation. Recent evidence suggests that early cessation of gonadotrophin releasing hormone analogue (GnRHa) administration may offer some benefit to low responder patients undergoing IVF. A prospective, randomized controlled trial was designed to evaluate whether early cessation of GnRHa in an ovarian stimulation regimen is more beneficial than just increasing the doses of gonadotrophins. Seventy low responder patients (less than three mature follicles in a previous cycle) with normal basal follicle stimulating hormone concentrations and a previous cancelled IVF cycle were randomly allocated into two protocols: (i) non-stop protocol: long GnRHa suppression with high doses of gonadotrophins, and (ii) stop protocol, in which GnRHa administration is stopped with the onset of menses, while gonadotrophin doses remained similar to the non-stop protocol. A significantly higher number of mature oocytes were obtained in the study group (stop protocol) compared to the control group (non-stop protocol) (8.7 +/- 0.9 versus 6.2 +/- 0.7, P: = 0. 027). The stop protocol reduced the number of ampoules of gonadotrophins required (56.6 +/- 2.7 versus 68.0 +/- 3.5, P: = 0. 013). Both protocols resulted in a similar cancellation rate (2.7 versus 5.8%) (with no cycles cancelled due to ovulation), pregnancy rate (14.3 versus 18.7%), and implantation rate (12.1 versus 8.8%). The early cessation of GnRHa combined with high doses of gonadotrophins permitted the retrieval of a significantly higher number of oocytes. To determine whether a controlled ovarian hyperstimulation (COH) regimen that involves GnRH agonist (GnRH-a) discontinuation before administration of gonadotropins would benefit poor responders.
                A prospective, randomized controlled trial.
                Hospital-based IVF Unit.
                Sixty-three patients with previous poor response to COH and/or high basal FSH level (> or =9 mIU/mL) undergoing 78 IVF-ET cycles.
                In both groups, administration of GnRH-a was started in the midluteal phase. Whereas in the study group (40 cycles), it ended before administration of gonadotropins, in controls (38 cycles) GnRH-a treatment was continued throughout the follicular phase.
                Ovarian stimulation patterns and IVF outcome.
                A significantly higher cancellation rate was noted in the study group than in the controls (22.5% versus 5%, respectively). The new and control regimens resulted in similar stimulation characteristics and clinical pregnancy rates (11% versus 10.3%, respectively). In 13 patients with a basal FSH level that was not persistently high, the new regimen resulted in a significantly higher number of retrieved oocytes compared with the standard protocol (7.6+/-1.03 versus 4.0+/-0.68, respectively).
                Whereas for most low responders, the new COH regimen offers no further advantage, future prospective studies may demonstrate whether it can confer a benefit for a subset of patients with a basal FSH level that is not persistently high. This is the first published report of a prospective, randomized, controlled trial comparing a fixed, multi-dose GnRH antagonist protocol with a long GnRH agonist protocol in poor responders undergoing IVF.
                Sixty-six poor responders were randomized into two groups: the study group received 0.25 mg of cetrorelix daily starting on day 6 of stimulation; the control group received 600 microg of buserelin acetate daily starting in the mid-luteal phase of the preceding cycle. Both groups were given a fixed dose of recombinant FSH (300 IU daily) for stimulation.
                There were no significant differences in the cycle cancellation rates, duration of stimulation, consumption of gonadotrophins, and mean numbers of mature follicles, oocytes and embryos obtained. The implantation rates were similar, but the number of embryos transferred was significantly higher for the antagonist group (2.32 +/- 0.58 versus 1.50 +/- 0.83; P = 0.01). The pregnancy rates were also higher in the antagonist group, but the difference was not statistically significant.
                A fixed multi-dose GnRH antagonist protocol is feasible for patients who are poor responders on a long agonist protocol; however, our study failed to demonstrate an overall improvement in ovarian responsiveness. Clinical outcomes may be improved by developing more flexible antagonist regimens, an approach that requires further evaluation. The use of gonadotrophin-releasing hormone analogues (GnRHa) has resulted in improved pregnancy rates in in-vitro fertilization (IVF) treatment cycles. Traditionally, short-acting analogues have been employed because of concerns over long-acting depot preparations causing profound suppression and luteal phase defects adversely affecting pregnancy and miscarriage rates. We randomized 60 IVF patients to receive a short-acting GnRHa, nafarelin or buserelin, or to receive a depot formulation, leuprorelin, all commenced in the early follicular phase and compared their effects on hormonal suppression and clinical outcome. We found that on day 15 of administration there was a significant difference in the suppression of oestradiol from initial concentrations, when patients on buserelin were compared with patients on nafarelin or leuprorelin (54 versus 72 and 65%; P < 0.05) and also in the number of patients satisfactorily suppressed, (80 versus 90 and 90%; P < 0.05), though there were no differences between the analogues by day 21. Similarly there was no difference in hormonal suppression during the stimulation phase or in implantation, pregnancy or miscarriage rates in comparing the three agonists. We conclude that with nafarelin and leuprorelin, stimulation with gonadotrophins may begin after 2 weeks of suppression and that long-acting GnRHa are as effective as short-acting analogues with no detrimental effects on the luteal phase. Evidence accumulated in in-vitro fertilization (IVF) cycles suggests that the use of long-acting forms of gonadotrophin-releasing hormone analogues (GnRHa) for pituitary desensitization may impair the outcome of IVF as compared to classical short-acting formulations. Whether the negative effects are directed against the corpus luteum, the endometrium, or both is unknown. However, the presence of high affinity binding sites for gonadotrophin-releasing hormone (GnRH) in the human endometrium suggests a possible role of these analogues on this target organ, affecting embryo implantation. In the present study, we tested direct effects of two different forms of GnRHa on implantation using the ovum donation model. Patients were prospectively allocated to one of the three study groups: the short-acting form of the analogue leuprolide acetate (group I; n=64), the long-acting form of the same analogue (group II; n=58), and the long-acting preparation of the analogue tryptorelin (group III; n=61). A total of 68 cycles of embryo transfer was carried out in group I, whereas 67 were performed in group II and 65 in group III. Cancellation rates were respectively 18.1, 17.3 and 18.8% because of bleeding while being on the waiting list for anonymous oocyte donation. The number of oocytes donated, fertilization rates and embryos replaced in each group were similar. As a result, pregnancy rate per transfer was 38.2, 49.3 and 44.6% respectively. Implantation rates per embryo replaced were respectively 13.4, 19.1 and 17.0%. These data suggest that the use of a long-acting form of GnRHa provides success rates similar to the short-acting preparations, resulting in more convenient medication for patients with ovarian function included in ovum donation programmes. To evaluate the effect of a 3-month course of GnRH agonist administered immediately before IVF-ET in infertile patients with endometriosis.
                Prospective, randomized trial.
                Three tertiary care assisted reproductive technology programs.
                IVF-ET candidates with surgically confirmed endometriosis.
                Twenty-five patients received three courses of a long-acting GnRH agonist, 3.75 mg i.m. every 28 days, followed by standard controlled ovarian hyperstimulation. Twenty-six patients received standard controlled ovarian hyperstimulation with mid-luteal phase GnRH agonist down-regulation or microdose flare regimens.
                Response to controlled ovarian hyperstimulation, ongoing pregnancy rates per cycle, group implantation rates, and implantation rate per embryo transfer procedure.
                The extent of surgically confirmed endometriosis was greater in patients who received the long-acting GnRH regimen for 3 months before IVF-ET. The groups did not differ significantly in terms of dose or duration of gonadotropin stimulation, number of oocytes retrieved, fertilization rate, or number of embryos transferred. Patients who received the long-acting GnRH regimen had significantly higher ongoing pregnancy rates (80% vs. 53.85%) and a trend toward higher implantation rates (42.68% vs. 30.38%).
                Prolonged use of GnRH agonist before IVF-ET in patients with endometriosis resulted in significantly higher ongoing pregnancy rates than did standard controlled ovarian hyperstimulation regimens. No deleterious effect on ovarian response was observed. To investigate the effect of continuous administration of gonadotropin-releasing hormone agonist (GnRHa) during the luteal phase in an intracytoplasmic sperm injection program.
                One hundred eighty-one women underwent a down-regulation protocol of GnRHa administered from the 21st day of the preceding cycle. Patients were randomized at initiation of stimulation by a computer-generated list. Group 1 patients (n = 90) were continuously administered GnRHa for 12 days after embryo transfer, while in group 2 patients GnRHa was stopped on the day of human chorionic gonadotropin administration.
                Demographic parameters, infertility etiologies, number of gonadotropin ampules used, number of mature oocytes recovered, rates of testicular sperm usage, number of embryos transferred, and cycle and transfer cancellation rates were similar in both groups. Clinical pregnancy rates, implantation rates and live birth rates did not show a significant difference.
                Extending GnRHa treatment through the luteal phase appeared not to have a significant impact on pregnancy or implantation rates in intracytoplasmic sperm injection cycles. To investigate whether pituitary desensitization with the gonadotropin-releasing hormone agonist (GnRH-a), buserelin acetate, before the administration of human menopausal gonadotropin (hMG) for ovarian stimulation in in vitro fertilization (IVF) is superior to the simultaneous administration of both hormones at the beginning of the treatment cycle.
                Prospective randomized study.
                Ninety-one patients having their first attempt at IVF.
                Patients in group 1 (long protocol) were administered subcutaneous (SC) buserelin acetate 200 micrograms/d from day 1 of the menstrual cycle, and hMG was started only after pituitary desensitization had been achieved at least 14 days later. Patients in group 2 (short protocol) were administered SC buserelin acetate 200 micrograms/d from day 2 and the same dose of hMG used in the long protocol from day 3 of the menstrual cycle.
                The median total amount of hMG required in both groups was comparable. There were significantly more follicles (P = 0.0001), oocytes (P = 0.0008), fertilized oocytes (P = 0.0001), and cleaved embryos (P = 0.0001), and a higher fertilization rate (P = 0.0047) in patients in group 1. The pregnancy rates per initiated cycle and per embryo transfer were 19.57% and 25.71% in group 1 compared with 8.89% and 16.67% in group 2.
                The long protocol is superior in terms of significantly greater follicular recruitment, oocyte recovery and fertilization rates, and significantly greater number of embryos available for transfer. In general, it is the preferred method when GnRH-a are used for ovarian stimulation in IVF. To provide a treatment for particular condition that is the most effective treatment with the least risk and cost for the patient we compared the efficacy of using clomiphene 100 mg + delayed low dose gonadotropin + flexible GnRH antagonist administration for ovarian stimulation protocol and GnRH agonist + gonadotropin for stimulation protocol in IVF outcome.
                Clinical outcome of 243 women with regularly menstruation who were candidate for IVF. They had undergone stimulation with GnRH agonist and gonadotropin (group A) or clomiphene citrate, gonadotropin and GnRH antagonist (group B). Main outcome was ongoing pregnancy.
                There were no significant difference in mean age, cause of infertility, basal FSH, BMI, duration of infertility, endometrial thickness on the day HCG administration in two groups. The number of recovered oocytes, obtained embryos, transferred embryos, peak of estradiol on the day HCG administration and OHSS were significantly higher in group A. Significantly more patients in control group had embryos for cryopreservation. There were no significant difference in clinical pregnancy rate and ongoing pregnancy rate between two groups.
                Clomiphene + delayed low dose gonadotropin + flexible GnRH - antagonist stimulation is an acceptable alternative protocol for IVF in patients with regularly menstruation.
We found no evidence of a significant difference between depot and daily GnRHa use for pituitary down regulation in IVF cycles using the long protocol, but substantial differences could not be ruled out. Since depot GnRHa requires more gonadotrophins and a longer duration of use, it may increase the overall costs of IVF treatment.