A randomized prospective study on the effect of short and long buserelin treatment in women with repeated unsuccessful in vitro fertilization (IVF) cycles due to inadequate ovarian response. 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. Growth hormone co-treatment within a GnRH agonist long protocol in patients with poor ovarian response: a prospective, randomized, clinical trial. Simplified ultralong protocol of gonadotrophin-releasing hormone agonist for ovulation induction with intrauterine insemination in patients with endometriosis. Extension of GnRH agonist through the luteal phase to improve the outcome of intracytoplasmic sperm injection. Is long-protocol gonadotropin releasing hormone agonist administration superior to the short protocol in ovarian stimulation for in vitro fertilization? Comparison between flare up and down regulation effects of luteinizing hormone-releasing hormone agonists in an in vitro fertilization program. A comparison of three gonadotrophin-releasing hormone analogues in an in-vitro fertilization programme: a prospective randomized study. Human chorionic gonadotrophin is a better luteal support than progesterone in ultrashort gonadotrophin-releasing hormone agonist/menotrophin in-vitro fertilization cycles. A randomized prospective study of gonadotrophin with or without gonadotrophin-releasing hormone agonist for treatment of unexplained infertility. A modified gonadotropin-releasing hormone (GnRH) antagonist protocol failed to increase clinical pregnancy rates in comparison with the long GnRH protocol.
Fifty four women with repeated unsuccessful in vitro fertilization (IVF) cycles due to inadequate ovarian response to stimulation with human menopausal gonadotropins (hMG) participated in this study. They were randomized to receive either gonadotropin releasing hormone agonist (GNRHa), Buserelin, prior to and during induction of ovulation by hMG (Group I--long protocol), or GnRHa starting on the first day of the cycle together with induction of ovulation by hMG (Group II--short protocol). Mean follicular phase serum luteinizing hormone (LH) and progesterone (P) levels were significantly lower in Group I than in Group II (P less than 0.01). Cancellation rate was significantly lower in Group I than in Group II (P less than 0.01). The long GNRHa protocol resulted in statistically significant lower cancellation rates, more oocytes per pickup (OPU), more embryos transferred per patient, and a higher pregnancy rate. Significantly more hMG ampoules and more treatments days were required in the long GNRHa protocol. Our data demonstrate that the use of GNRHa prior to and during ovarian stimulation with hMG offers a very good alternative for patients with repetitive unsuccessful IVF cycles due to inadequate response. 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. The efficacy of growth hormone co-stimulation to long luteal GnRHa regimen in poor responders to COH for IVF was assessed.
                This prospective, randomized, clinical trial was performed in a private assisted reproduction center. The study involved 61 patients who responded poorly to high dose gonadotropin treatment in their first cycles in the same center. Study group of 31 patients were given growth hormone co-treatment, daily subcutaneous injection of 4 mg from day 21 of preceding cycle along with GnRHa, until the day of hCG. Control group of 30 patients received the same treatment protocol except the growth hormone cotreatment. Primary end-point of the study was the number of oocytes fertilized whereas the pregnancy rate was the secondary end-point.
                Patients' demographic characteristics did not differ significantly between the two groups. 2PNs in growth hormone co-treatment group was significantly higher than the control group (4.4 +/- 1.8 vs 1.5 +/- 0.9, p < 0.001). Although more pregnancies and more clinical pregnancies with fetal heart beat were achieved in growth hormone group (12/31), compared to the control group (6/30), the difference did not reach to statistical significance.
                Poor responder women undergoing repeated assisted reproduction treatment and co-stimulated with GH achieve more oocytes, higher fertilization rate if growth hormone started in the luteal phase of previous cycle, as compared with women of the same status treated with GnRHa long protocol. The study was unable to show that clinical pregnancy rate was increased significantly. The present study was designed to assess the usefulness of the simplified ultralong protocol of gonadotrophin-releasing hormone agonist (GnRHa) for ovulation induction with intrauterine insemination (IUI) in patients with various stages of endometriosis. A prospective randomized trial was set up to compare the simplified ultralong protocol (ULP) and the long protocol (LP) of GnRHa for ovulation induction with IUI in patients with endometriosis. There was no evidence of other factors in infertility in any patient. In the ULP group (39 patients), 4 weeks after a single injection of 3.75 mg Decapeptyl had been given, daily s.c. administration of 0.1 mg Decapeptyl was initiated and continued for at least 2 weeks prior to ovarian stimulation. In the LP group (41 patients), daily s.c. administration of 0.1 mg Decapeptyl was initiated from the mid-luteal phase of the cycle preceding the stimulation cycle. After 14 days of administration, ovarian stimulation was started if pituitary desensitization had been achieved. The amount of gonadotrophins required, number of days of gonadotrophin administration, serum oestradiol response, and the number of mature follicles were comparable in both groups. The clinical pregnancy rate per cycle was significantly higher in the ULP group at 48.7% (19/39) compared with 26.8% (11/41) in the LP group. The miscarriage rates were 21.1% (4/19) in the ULP group and 18.2% (2/11) in the LP group. In patients with stage I or II endometriosis, there was no significant difference between the two groups with respect to clinical pregnancy rate per cycle (47.4 versus 35.0%). In patients with stage III or IV endometriosis, the clinical pregnancy rate per cycle was significantly higher in the ULP group at 50.0% (10/20) compared with 19.0% (4/21) in the LP group. This study suggests that a simplified ULP of GnRHa could give better chances of achieving pregnancy in endometriosis patients undergoing assisted reproductive technologies and that this protocol may be more useful in patients with an advanced stage of endometriosis. 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 compare the long and short protocols of gonadotropin releasing hormone agonist (GnRH-a) administration for ovarian stimulation.
                University hospital.
                90 patients on their first attempt at in vitro fertilization and embryo transfer (IVF-ET).
                The results of two stimulation protocols were compared with respect to number of follicles greater than 17 mm, peak serum estradiol level, number of oocytes retrieved and fertilized, fertilization rate per oocyte, number of embryos transferred, and pregnancy rate per initiated cycle.
                The number of follicles greater than 17 mm and the peak estradiol level were significantly (P < .05) higher in the long protocol than those in the short protocol. The number of oocytes retrieved and fertilized, the number of embryos transferred, and the pregnancy rate per initiated cycle were also significantly (P < .001) higher in the long protocol than those in the short protocol. The fertilization rates per oocyte retrieved did not differ significantly between groups.
                The long protocol of gonadotropin releasing hormone agonist administration for ovarian stimulation in IVF-ET may be the preferred method when GnRH-a is used. Luteinizing hormone-releasing hormone (LH-RH) agonists are being increasingly used in ovulation stimulation protocols in IVF programs. The results of two methods of utilization of LH-RH agonists are compared. In the long protocol, gonadotropin stimulation was commenced only after a preliminary period of pituitary desensitization with LH-RH agonist. In the short protocol, exogenous gonadotropins were administered shortly after the start of LH-RH agonist therapy, benefiting from the gonadotropin flare up effect. One hundred eighty-six patients were equally divided between the two treatments. There was no difference in the ovarian response on the day of human chorionic gonadotropin (hCG) or the number of mature oocytes recovered. The cleavage rate of mature oocytes was higher in the short protocol (70% versus 56% P less than 0.01). The ongoing pregnancy rate per treatment cycle was similar in both groups (18% in the long protocol and 16% in the short protocol). Analysis of the luteal phases revealed a trend for higher progesterone values in the long protocol although this was only significant on the 2nd day following oocyte retrieval. As the clinical results were similar, other factors should be taken into account when deciding therapy. These include patient convenience, cost, and side effects. Other schedules of ovulation stimulation with LH-RH agonists are discussed. 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. In an attempt to determine the best luteal support in in-vitro fertilization (IVF) cycles treated with gonadotrophin-releasing hormone agonist (GnRHa) and human menopausal gonadotrophin (HMG) by the ultrashort protocol, 60 patients were prospectively randomized for either i.m. progesterone or human chorionic gonadotrophin (HCG) luteal support. The two groups did not differ in the mean number of oocytes retrieved and embryos replaced, nor in the mean age of the patients and the amount of HMG used. HCG maintained higher levels of oestradiol and progesterone during the luteal phase. Conception rate was significantly higher in the HCG group. We conclude that HCG is superior to i.m. progesterone as luteal support in IVF cycles in which GnRHa is used in the ultrashort protocol. The use of gonadotrophin-releasing hormone agonist (GnRHa) in combination with human menopausal gonadotrophin (HMG) for ovulation induction has been advocated for the treatment, particularly by in-vitro fertilization (IVF) of various types of infertility. The present study was designed to compare the clinical efficacy of HMG alone with a short protocol of GnRHa/HMG for treatment of unexplained infertility. A total of 91 couples with unexplained infertility were randomly assigned to one of two treatments; either HMG with intra-uterine insemination (IUI) (45 patients, 62 cycles) or GnRHa/HMG with IUI (46 patients, 69 cycles) treatments. Progesterone concentrations on the day of human chorionic gonadotrophin (HCG) administration were significantly higher in HMG (1.5 +/- 0.9 ng/ml) versus GnRHa/HMG (0.8 +/- 0.6 ng/ml; P < 0.05) cycles. Furthermore, GnRHa suppressed the occurrences of premature luteinization (GnRHa/HMG 5.8% and HMG 24.2% respectively). However, there were no significant differences in HMG dose requirements, plasma oestradiol concentrations or follicular development on the day of HCG administration between the two groups. Nor were any significant differences found in the pregnancy rates between the two treatment protocols (GnRHa/HMG 13.0% and HMG 11.3% respectively). Our results suggest no beneficial effect of GnRHa/HMG compared to HMG alone for the treatment of unexplained infertility, based on pregnancy rates. The purpose of this prospective randomized study was to compare stimulation characteristics and IVF outcomes of the standard long GnRH agonist protocol for ovarian stimulation with a modified GnRH antagonist protocol. Starting GnRH antagonist in a flexible protocol according to the size of the leading follicle, with simultaneous augmentation of 75 IU recombinant FSH, failed to increase clinical pregnancy rates.
The pregnancy rate was found to be higher when GnRHa was used in a long protocol as compared to a short or ultrashort protocol. There was no evidence of a difference in live birth rate, but this outcome was only reported by three studies. There was no evidence of a difference in the outcomes amongst various long protocols; nor that stopping or reducing GnRHa at the start of stimulation was associated with a reduced pregnancy rate. For all comparison, except a long versus short protocol, there was a lack of power.