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. IVF/ICSI outcomes between cycles with luteal estradiol (E2) pre-treatment before GnRH antagonist protocol and standard long GnRH agonist protocol: a prospective and randomized study. Comparison of multiple dose GnRH antagonist and minidose long agonist protocols in poor responders undergoing in vitro fertilization: a randomized controlled trial. GnRH agonist protocol administration in the luteal phase in ICSI-ET cycles stimulated with the long GnRH agonist protocol: a randomized, controlled double blind study. [Can the type of GnRH used during long in vitro fertilization protocols influence the pregnancy rate?]. The long protocol of administration of gonadotropin-releasing hormone agonist is superior to the short protocol for ovarian stimulation for in vitro fertilization. A randomized comparison of two ovarian stimulation protocols with gonadotropin-releasing hormone (GnRH) antagonist cotreatment for in vitro fertilization commencing recombinant follicle-stimulating hormone on cycle day 2 or 5 with the standard long GnRH agonist protocol. Comparison of stimulation with clomiphene citrate in combination with recombinant follicle-stimulating hormone and recombinant luteinizing hormone to stimulation with a gonadotropin-releasing hormone agonist protocol: a prospective, randomized study. Efficiency of follicle-stimulating hormone, commenced in the luteal phase, for overcoming a poor response in assisted reproduction. GnRH antagonist versus long GnRH agonist protocol in poor responders undergoing IVF: a randomized controlled trial. Comparison of short 7-day and prolonged treatment with gonadotropin-releasing hormone agonist desensitization for controlled ovarian hyperstimulation. The use of long- and short-acting forms of gonadotrophin-releasing hormone analogues in women undergoing oocyte donation.
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. To study if luteal E(2) pre-treatment before GnRH antagonist protocol improves IVF/ICSI outcomes compared with standard long GnRH agonist protocol.
                A prospective, randomized and controlled study.
                ART center of a state public hospital
                Two hundred twenty infertile women underwent IVF/ICSI treatments.
                Participants received oral Estradiol Valerate 4 mg/day preceding the IVF cycle from day 21 until day 2 of next cycle before GnRH antagonist protocol (E(2) pre-treatment group n=109) or received standard long GnRH agonist protocol as control group (n=111).
                Number of oocytes collected, MII oocytes, fertilization, implantation, live birth and early pregnancy rate, and hormone profiles.
                E(2) pre-treatment exerted a significant suppressive effect on FSH but not LH secretion compared with basal FSH and LH levels. In E(2) pre-treatment group serum LH level was significantly higher during COH and serum P was also significantly higher on the day of HCG injection compared with control group. Five patients from E(2) pre-treatment group had elevated LH at all time (>or= 10 IU/L) and also a concomitantly high P (>1 ng/mL). Two of the five women achieved pregnancy but had early pregnancy loss. Overall, IVF/ICSI outcomes such as implantation, clinical pregnancy and live birth rates were similar between E(2) pre-treatment and control groups.
                Luteal E(2) pre-treatment before GnRH antagonist protocol significantly increases serum LH level and incidence rate of premature LH but no significant effect is observed on implantation, clinical pregnancy, live birth and early pregnancy loss rates compared with long GnRH agonist protocol. However, more studies in large numbers of cycles are needed to confirm that increased serum LH level by E(2) pre-treatment during COH has no negative effect on the IVF/ICSI outcomes. To investigate the efficacy of gonadotropin releasing hormone antagonist (GnRH) in poor responders undergoing in vitro fertilization.
                Ninety-six patients with poor ovarian response in previous treatment cycles were prospectively randomized into two groups. Forty-four patients were stimulated with GnRH antagonist multidose protocol and 45 patients received a standard long agonist protocol. Ovarian response was evaluated by transvaginal ultrasound and hormonal parameters. Cycle characteristics and treatment outcomes were statistically compared between groups.
                There was significantly reduced duration of stimulation and consumption of gonadotrophins in the antagonist group when compared to the agonist group. The estradiol concentrations on the day of human chorionic gonadotropin (hCG) injection, the number of oocytes retrieved, and the number of embryos transferred were similar for both groups. In the antagonist group, eight (18.1%) ongoing pregnancies were achieved and in the agonist group, ten (22.2%) clinical pregnancies were achieved but the difference was not statistically significant.
                The present study was not powered to detect clinically relevant differences between two protocols in outcomes such as pregnancy rate, with confidence. GnRH agonist administration in the luteal phase was reported to beneficially affect the clinical outcome of intracytoplasmic sperm injection (ICSI) and embryo transfer (ET) cycles. This double blind, randomized, placebo controlled trial evaluates whether a single dose GnRH agonist administered 6 days after ICSI increases ongoing pregnancy rates following ET in cycles stimulated with the long GnRH agonist protocol.
                Five hundred and seventy women undergoing ET following controlled ovarian stimulation with a long GnRH agonist protocol were included. In addition to routine luteal phase support with progesterone, women were randomized to receive a single 0.1 mg dose of triptorelin or placebo 6 days after ICSI. Randomization was done on the day of ET according to a computer generated randomization table. Ongoing pregnancy rate beyond 20th week of gestation was the primary outcome measure. The trial was powered to detect a 12% absolute increase from an assumed 38% ongoing pregnancy rate in the placebo group, with an alpha error level of 0.05 and a beta error level of 0.2.
                There were 89 (31.2%) ongoing pregnancies in the GnRH agonist group, and 84 (29.5%) in the control group (absolute difference +1.7%, 95% confidence interval -5.8% to +9.2%). Implantation, clinical pregnancy and multiple pregnancy rates were likewise similar in the GnRH agonist and placebo groups.
                Single 0.1 mg triptorelin administration 6 days after ICSI following ovarian stimulation with the long GnRH agonist protocol does not seem to result in an increase >or=12% in ongoing pregnancy rates. Luteal defect is common during IVF cycles using GnRH agonist. It could be interesting to make up for this problem by using short acting GnRH agonist (effective for 24 hours), more handy at the end of the stimulation. 160 patients included in a long IVF protocol at the Bordeaux CHRU FIV center have been randomized, from September 1993 to August 1994, for the analog's choice (long or short) at the beginning of the stimulation. The stimulation's parameters, the hormonal dosages and the pregnancy rate are independent of the galenic form used. In close, the use of long-acting GnRH analog (sympler to use) sems preferable. 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. Extending the FSH window for multifollicular development by administering FSH from the midfollicular phase onward constitutes a novel mild protocol for ovarian stimulation for in vitro fertilization (IVF) based on the physiology of single dominant follicle selection in normo-ovulatory women. We compared outcomes from this protocol with two other stimulation protocols. One hundred and forty-two normo-ovulatory patients with an indication for IVF (or IVF/ICSI) were randomized to a GnRH agonist long protocol (group A; n = 45) or one of two GnRH antagonist protocols commencing recombinant FSH on cycle d 2 (group B; n = 48) or cycle d 5 (group C; n = 49). A fixed dose (150 IU/d) of rFSH was used for ovarian stimulation, and GnRH antagonist cotreatment was initiated on the day when the leading follicle reached 14 mm diameter. Group C showed a shorter duration of stimulation (median duration, 11, 9, and 8 d for groups A, B, and C, respectively; P < 0.001), reflected in a significantly lower total dose of rFSH used (median amount of rFSH, 1650, 1350, and 1200 IU for groups A, B, and C, respectively; P < 0.001). In group C more cycles were cancelled during the stimulation phase due to insufficient response, resulting in a lower percentage of oocyte retrievals (84%, 73%, and 63% for groups A, B, and C; P = 0.02). However, women in group C obtained better quality embryos (percentage of embryo score of 1 for best embryo, 29%, 37%, and 61% for groups A, B, and C, respectively; P = 0.008), resulting in more transfers per oocyte retrieval (68%, 71%, and 90% for groups A, B, and C, respectively; P = 0.04). After profound ovarian stimulation (groups A and B) only 7% of the patients who retrieved four oocytes or less conceived, whereas after mild stimulation (group C) 67% of these patients conceived (P < 0.01). Overall, no differences were found among the three groups comparing pregnancy rate per started IVF cycle. In conclusion, application of the described mild ovarian stimulation protocol resulted in pregnancy rates per started IVF cycle similar to those observed after profound stimulation with GnRH agonist cotreatment despite shorter stimulation and a 27% reduction in exogenous FSH. A higher cancellation rate before oocyte retrieval was compensated by improved embryo quality concomitant with a higher chance of undergoing embryo transfer. A relatively low number of oocytes retrieved after mild ovarian stimulation distinctly differs from the pathological reduction in the number of oocytes retrieved after profound ovarian stimulation (poor response) associated with poor IVF outcome. The relatively small number of oocytes obtained after mild ovarian stimulation may represent the best of the cohort in a given cycle. To compare IVF-ET outcome with a new stimulation protocol using clomiphene citrate (CC) with recombinant FSH and LH to stimulation with the standard long GnRH-a protocol.
                Prospective randomized study.
                Outpatient infertility clinic in Vienna, Austria.
                Two hundred ninety-four infertile women undergoing IVF-ET; 154 IVF cycles stimulated with CC + recombinant FSH + recombinant LH (group A) and 140 cycles with long GnRH-a suppression + recombinant FSH (group B).
                Controlled ovarian hyperstimulation, egg retrieval, and ET.
                Cycle parameters (number of oocytes, fertilization, number of embryos) and outcome (pregnancy rate, cancellation rate, ovarian hyperstimulation syndrome [OHSS]).
                Pregnancy rate per ET was 42.9% (implantation rate, 21.3%) in group A and 36.6% (17.4%) in group B. Cancellation rates were similar. The OHSS occurred in four cases (3%) in group A and 12 cases (10%) in group B.
                Stimulation with CC + recombinant FSH + recombinant LH leads to comparable pregnancy rates vs. the long protocol. With this new stimulation, less gonadotropins are used and there is less need for monitoring (lower cost for patient and clinic). The risk of OHSS is reduced as well. Therefore, this protocol should be regarded as the first-line treatment. The efficacy of commencement of recombinant follicle-stimulating hormone (recFSH) during the luteal phase in the long-protocol gonadotropin-releasing hormone (GnRH) agonist regimen in poor responders was compared with the conventional protocol in a prospective, randomized, controlled study.
                Forty-two women who responded poorly to previous conventional controlled ovarian hyperstimulation were included in the study. Recombinant FSH (150 IU) was started simultaneously with the GnRH agonist long protocol in the study group. The control group was started recFSH on Day 2 of menstruation in the long-protocol GnRH agonist regimen. The number of metaphase (M) II oocytes, the number of embryos transferred, and the pregnancy rate were analyzed as main outcome measures.
                Patients in the study group had a higher number of MII oocytes compared with the control group (6.8 vs 3.2, respectively; P < 0.005), received a higher number of embryos (2.7 vs 1.2, respectively; P < 0.05), and had higher pregnancy rates (38% vs 15%, respectively; P < 0.005).
                Commencement of recFSH during the luteal phase simultaneously with the long-protocol GnRH agonist regiment in poor responder women produces better results compared with the conventional long-protocol GnRH agonist plus high-dose recFSH regimen. 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. 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. 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.
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.