A randomized prospective study of gonadotrophin with or without gonadotrophin-releasing hormone agonist for treatment of unexplained infertility. 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. Comparison of recombinant and urinary follicle-stimulating hormone preparations in short-term gonadotropin releasing hormone agonist protocol for in vitro fertilization-embryo transfer. The routine use of gonadotropin-releasing hormone agonists for all patients undergoing in vitro fertilization. Is there any medical advantage? A prospective randomized study. A combination of norethindrone acetate and leuprolide acetate blocks the gonadotrophin-releasing hormone agonistic response and minimizes cyst formation during ovarian stimulation. Comparison of multiple dose GnRH antagonist and minidose long agonist protocols in poor responders undergoing in vitro fertilization: a randomized controlled trial. Human chorionic gonadotrophin is a better luteal support than progesterone in ultrashort gonadotrophin-releasing hormone agonist/menotrophin in-vitro fertilization cycles. Effects of gonadotrophin-releasing hormone agonists on human ovarian steroid secretion in vivo and in vitro-results of a prospective, randomized in-vitro fertilization study. The use of gonadotrophin-releasing hormone analogues in women receiving oocyte donation does not affect implantation rates. Comparison of mild stimulation and conventional stimulation in ART outcome. Ovarian responses to recombinant FSH or HMG in normogonadotrophic women following pituitary desensitization by a depot GnRH agonist for assisted reproduction. Consequences on gonadotrophin secretion of an early discontinuation of gonadotrophin-releasing hormone agonist administration in short-term protocol for in-vitro fertilization. Intrauterine insemination with recombinant or urinary human chorionic gonadotropin: A prospective randomized trial. Treatment with a gonadotrophin releasing hormone agonist before endometrial resection: a multicentre, randomised controlled trial. A prospective, randomized, controlled, double-blind, double-dummy comparison of recombinant and urinary HCG for inducing oocyte maturation and follicular luteinization in ovarian stimulation. Prospective randomized study of D-Trp6-LHRH versus buserelin in long desensitization protocols for medically assisted conception cycles. A comparison of three gonadotrophin-releasing hormone analogues in an in-vitro fertilization programme: a prospective randomized study. Ovarian stimulation during assisted reproduction treatment: a comparison of recombinant and highly purified urinary human FSH. On behalf of The Feronia and Apis study group. Recombinant versus urinary follicle-stimulating hormone in intrauterine insemination cycles: a prospective, randomized analysis of cost effectiveness. Simplified ultralong protocol of gonadotrophin-releasing hormone agonist for ovulation induction with intrauterine insemination in patients with endometriosis. Ovulation induction with urinary FSH or recombinant FSH in polycystic ovary syndrome patients: a prospective randomized analysis of cost-effectiveness. Human menopausal gonadotropin versus recombinant follicle-stimulating hormone in normogonadotropic women down-regulated with a gonadotropin-releasing hormone agonist who were undergoing in vitro fertilization and intracytoplasmic sperm injection: a prospective randomized study. Ultrasonic control without hormone determination for ovulation induction in in-vitro fertilization/embryo transfer with gonadotrophin-releasing hormone analogue and human menopausal gonadotrophin. Comparison of short 7-day and prolonged treatment with gonadotropin-releasing hormone agonist desensitization for controlled ovarian hyperstimulation. The hormonal flare-up following gonadotrophin-releasing hormone agonist administration is influenced by a progestogen pretreatment.
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. 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 compare the efficiency and efficacy of two recombinant human FSH (r-FSH) and urinary (u-FSH) preparations in patients undergoing superovulation for IVF-ET using a short-term gonadotropin releasing hormone agonist (GnRH-a) (Triptorelin) protocol.
                A total of 88 women undergoing IVF-ET were included in this prospective study. They were randomized to receive u-FSH (150 IU/d), follitropin-alpha (100 IU/d), or follitropin-beta (100 IU/d) for 2 days, and dosages were subsequently adjusted according to the ovarian response.
                The FSH dose required for the overall stimulation was significantly lower in patients treated with r-FSH than in those treated with u-FSH while serum FSH values were higher in the latter group. There were no statistically significant differences in ovarian response and IVF outcome between r-FSH preparations.
                Recombinant FSH preparations have a higher efficiency than urinary ones in patients undergoing IVF-ET using a short-term GnRH-a protocol. In this situation, the two recombinant follitropins have comparable effectiveness. To determine if the routine use of gonadotropin-releasing hormone agonists (GnRH-a) for all patients undergoing in vitro fertilization (IVF) produces any significant medical advantage.
                Prospective randomized study.
                Three hundred eight patients having their first ever IVF attempt.
                Patients were randomly divided into four groups and received either human menopausal gonadotropin (hMG) alone for ovarian simulation (group A, n = 81); clomiphene citrate and hMG (group B, n = 77); a 3-day ultrashort course of GnRH-a and hMG (group C, n = 74); or pituitary desensitization with GnRH-a followed by hMG (group D, n = 76).
                The indications for IVF and mean age of all four groups of patients were comparable. There was a significant difference in the number of embryos cleaved and transferred among the groups, but there were no significant differences in the cancellation rate, mean number of oocytes collected or fertilized, and number of cases of failed fertilization. There were also no significant differences in the pregnancy and live birth rates per cycle commenced or per embryo transfer.
                The routine use of GnRH-a for all patients undergoing IVF has practical but no significant medical advantages. A protocol utilizing both leuprolide acetate (LA) and norethindrone acetate (NETA) in subjects undergoing ovarian suppression prior to follicle aspiration proved more effective than LA alone in reducing the incidence of ovarian cyst formation without affecting clinical outcome. Patients (n = 105) undergoing ovarian stimulation followed by follicle aspiration and in-vitro fertilization (IVF) were prospectively randomized and studied. Study measures included ovarian suppression days, days of human menopausal gonadotrophin (HMG) stimulation, serum oestradiol concentrations, number of cycles developing de novo cysts (>15 mm), number of induced flare responses (day 8 oestradiol >=50 pg/ml), number of office visits, total dose exogenous gonadotrophins, number oocytes retrieved, and clinical pregnancy and delivery rates per retrieval. Patients undergoing IVF received either LA alone (n = 58; controls) or LA and NETA (n = 47; study group) for the first 8 days of their cycle. Results comparing NETA/LA versus LA demonstrated: serum oestradiol 20.7 +/- 3.9 versus 57.3 +/- 9.4 pg/ml respectively on day 8 of ovarian suppression (P P < 0.01); and only three individuals (6.4%) using NETA/LA developed ovarian cysts >15 mm compared to 15 (25.9%) controls (P < 0.01). No differences were observed for days of stimulation, peak oestradiol attained, total dosage of exogenous gonadotrophins, or number of aspirated oocytes. Neither were there differences in the clinical pregnancy (26.8 versus 22.6%) nor in delivery rates (19.5 versus 20. 8%). We conclude that the addition of NETA to LA enhances ovarian suppression and lessens ovarian cyst formation, thereby significantly decreasing the overall cost per cycle. 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. 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 aim of this prospective randomized study was to compare the effects of two gonadotrophin-releasing hormone (GnRH) agonists, buserelin and triptorelin, on human ovarian follicular steroidogenesis, oocyte fertilization and IVF treatment outcome. Ovulatory, healthy women undergoing IVF were treated either with human menopausal gonadotrophin (HMG) alone or with HMG and one of the two GnRH agonists. Serum and follicular fluid hormonal concentrations and cultures of luteinizing granulosa cells obtained during follicular aspiration were analysed. GnRH agonist treatment significantly affected steroidogenesis both in serum and follicular fluid. In follicular fluid, progesterone and oestradiol concentrations were significantly elevated while testosterone concentrations were significantly lower in the triptorelin group. The ratios of testosterone/progesterone, oestradiol/progesterone but not oestradiol/testosterone concentrations were significantly affected by GnRH agonist administration. Similarly, the steroidogenic activity of luteinizing granulosa cells in vitro was significantly decreased in women treated with GnRH agonists. Women treated with GnRH agonists had significantly more fertilized oocytes and cleaving embryos. The results indicate a marked effect of GnRH agonists on the pattern of ovarian follicular steroidogenesis that cannot be explained solely by changes in gonadotrophin concentrations. There is conflicting clinical evidence suggesting a positive role for gonadotrophin-releasing hormone analogues (GnRHa) on implantation in humans. This potential effect was evaluated in this study taking the oocyte donation programme as a model. Patients were randomly allocated into one of the two treatment groups: group I received simultaneous treatment with GnRHa and steroids, and group II only received exogenous steroid replacement. An analysis of the donors and semen quality showed similarity between recipient groups. There was no significant difference between groups in the number and quality of embryos replaced, clinical pregnancy and implantation rates. In summary, using a model in which the endometrium can be analysed independently of the embryos, the results suggest that GnRHa are neither effective nor detrimental for embryo implantation in humans. 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. At present, there is considerable debate about the utility of supplemental LH in assisted reproduction treatment. In order to explore this, the present authors used a depot gonadotrophin-releasing hormone agonist (GnRHa) protocol combined with recombinant human FSH (rhFSH) or human menopausal gonadotrophin (HMG) in patients undergoing intracytoplasmic sperm injection (ICSI). The response to either rhFSH (75 IU FSH/ampoule; group rhFSH, 25 patients) or HMG (75 IU FSH and 75 IU LH/ampoule; group HMG, 25 patients) was compared in normo-ovulatory women suppressed with a depot triptorelin injection and candidates for ICSI. A fixed regimen of 150 IU rhFSH or HMG was administered in the first 14 days of treatment. Treatment was monitored with transvaginal pelvic ultrasonographic scans and serum measurement of FSH, LH, oestradiol, androstenedione, testosterone, progesterone, inhibin A, inhibin B and human chorionic gonadotrophin (HCG) at 2-day intervals. Although oestradiol serum concentrations on the day of HCG injection were similar, both the duration of treatment and the per cycle gonadotrophin dose were lower in group HMG. In the initial 16 days of gonadotrophin treatment, the area under the curve (AUC) of LH, oestradiol, androstenedione and inhibin B were higher in group HMG; no differences were seen for the remaining hormones measured, including the inhibin B:inhibin A ratio. The dynamics of ovarian follicle development during gonadotrophin treatment were similar in both study groups, but there were more leading follicles (>17 mm in diameter) on the day of HCG injection in the rhFSH group. The number of oocytes, mature oocytes and good quality zygotes and embryos obtained were significantly increased in the rhFSH group. It is concluded that in IVF patients undergoing pituitary desensitization with a depot agonist preparation, supplemental LH may be required in terms of treatment duration and gonadotrophin consumption. However, both oocyte, embryo yield and quality were significantly higher with the use of rhFSH. Administration of gonadotrophin-releasing hormone (GnRHa) agonists, used in IVF short-term protocols to initiate follicular recruitment, may be restricted to the early follicular phase without any further risk of LH surge. However, consequences of an early discontinuation upon residual endogenous gonadotrophin secretion are still unknown. Here, the effects of early cessation of GnRH agonist upon gonadotrophin secretion and ovarian parameters of IVF cycles were investigated. A total of 230 normo-ovulatory women were prospectively allocated to one of the two regimens: decapeptyl-GnRH (100 microgram) was daily injected either from day 1 to the triggering of ovulation (group 1) or for the first 7 days (group 2). Exogenous gonadotrophins (150 IU) were administered on day 4 and 5 with a subsequent adjustment. Detections of free alpha subunit and dimeric LH were performed by highly specific 'two site' monoclonal immunoradiometric assays. The results show that early discontinuation of GnRH agonist administration was associated with a sharp decrease in both plasma free alpha subunit and dimeric LH concentrations while plasma oestradiol response to exogenous gonadotrophins was reduced. Other ovarian parameters and pregnancy rate were unchanged. These data indicate that endogenous LH secretion is maintained by a daily administration of GnRH agonist and may contribute to the final follicular maturation. Our aim was to compare the efficacy and safety of recombinant and urinary human chorionic gonadotropin (rhCG and uhCG, respectively) for the induction of follicle maturation in women undergoing intrauterine insemination (IUI).
                Patients were randomized to receive rhCG or uhCG. IUI was carried out 24 h (day 1) and 48 h (day 2) after hCG administration, except for all cases in which ovulation occurred after 24 h.
                The two treatments were comparable in terms of progesterone levels on day 7 and day 12. Pregnancy rates were comparable between the treatment groups. Of the 64 women who received rhCG, 29.7% became pregnant; there were 16.7% clinical pregnancies and 3.1% biochemical pregnancies per started cycle, and an ongoing pregnancy rate of 93.7% was reported. Of the 61 patients who received uhCG, 24.6% became pregnant; there were 15.9% clinical pregnancies and 1.1% biochemical pregnancies per started cycle, and ongoing pregnancy rate was 92.9%. No adverse effects were noted in either group.
                The recombinant products can be effectively used instead of urinary products; moreover, apart from the equivalent efficacy in ovulation induction and safety described in this study, it is necessary to consider the advantages provided by the recombinant form. To ascertain whether treatment with a gonadotrophin releasing hormone agonist before endometrial resection reduces absorption of distension fluid and operating time and facilitates the procedure.
                A multicentre, prospective, randomised controlled study.
                Seventy-one premenopausal women with established menorrhagia.
                Eight weeks of goserelin depot treatment before endometrial resection of immediate surgery in the early proliferative phase of the cycle.
                Irrigation fluid deficit, operating time and degree or difficulty of the procedure.
                After randomisation eight women withdrew from the study, leaving 33 women in the goserelin arm and 30 in the immediate surgery arm. Mean (SD) operating time was 15.1 (9.0) min in the goserelin group versus 16.9 (9.5) min in the controls; mean difference + 1.8 min, 95% CI, -2.9 to + 6.4. Mean (SD) distension medium deficit was, respectively, 422 (287) ml versus 564 (291 ml); mean difference + 142 ml, 95% CI -4 to + 288. The goserelin effect was restricted to the 29 women with adenomyosis as the mean (SD) fluid deficit was considerably less in the 19 treated women than in the 10 controls (299 (206) ml versus 597 (135) ml; mean difference + 298 ml, 95% CI + 149 to + 447). The surgeons classified the intraoperative difficulties as none in 6, minimal in 20, moderate in 7, and severe in no cases in the goserelin group; corresponding figures in the group without pretreatment were 2, 14, 13, and 1.
                Goserelin administration before endometrial resection may reduce absorption of fluid at surgery in women with adenomyosis and may facilitate intrauterine operating conditions. A randomized, controlled, double-blind, double-dummy, phase III clinical trial was conducted in 84 women to compare the efficacy of a s.c. injection of 250 microg recombinant human chorionic gonadotrophin (rHCG; Ovidrel) to an i.m. injection of 5000 IU urinary HCG (uHCG; Profasi) in inducing folliculogenesis, resumption of oocyte meiosis and luteinization after ovulation induction with recombinant follicle stimulating hormone (Gonal-F). The study primary endpoint was comparison of the number of oocytes retrieved per patient receiving either compound. Secondary comparisons included the number of oocytes retrieved per follicles aspirated; the number of mature oocytes; normally fertilized oocytes; and cleaved embryos. There were no statistically significant differences between groups for the primary endpoint (mean +/- SD oocytes retrieved 10.8 +/- 4.5 for rHCG versus 10.3 +/- 5.1 for uHCG) or each of the secondary endpoints except for increased concentrations of progesterone 6-7 days after rHCG administration (353.2 +/- 215.1 versus 234.1 +/- 129.4 nmol/l; P < 0. 004) and for HCG during the luteal phase following rHCG (P < 0.02). There were also no significant side-effects for either drug. Since the confidence intervals for the difference of the number of oocytes retrieved between the two treatment groups were within the bounds defined by the multi-trial protocol equivalence between rHCG and uHCG could be declared. In a prospective, controlled, randomized study where two different agonists were used, we compared three different long desensitization protocols for induction of multiple follicular growth in medically assisted conception cycles. In protocol A, 30 patients were injected with buserelin twice a day for 15 days prior to ovarian stimulation until human chorionic gonadotrophin (HCG) administration. In protocol B, 30 patients were injected with a single dose of long acting Triptorelin (3.75 mg) 15 days before the ovarian stimulation onset. In protocol C, 30 patients were injected with the long acting Triptorelin 4 weeks before ovarian stimulation followed by daily administration of 0.1 mg of the same agonist until HCG injection. There was no difference in the ovarian response to exogenous gonadotrophin stimulation, except for the presence of premature luteinization in two patients in group B. A significantly higher number of mature oocytes was collected from patients with protocol A; however, the fertilization and cleavage rate demonstrated no significant difference among the three groups of patients. The ongoing pregnancy rate and the implantation rate per treatment cycle were very similar in the three study groups. When the convenience, cost and side-effects for the patient are being considered, protocol B should be selected as the first choice when the agonist is utilized for the purpose of inducing pituitary desensitization before and during ovarian stimulation. 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. This randomized, single-blind, multicentre, multinational study compared recombinant human FSH (rhFSH, Gonal-F) with highly purified urinary human FSH (uhFSH, Metrodin HP) in women undergoing ovarian stimulation for IVF/intracytoplasmic sperm injection (ICSI). Following desensitization in a long gonadotrophin-releasing hormone (GnRH) agonist protocol, patients received s.c. Gonal-F or Metrodin HP, at a fixed dose of 150 IU, until there was adequate follicular development. Of 496 women randomized, 232 and 231 in the Gonal-F and Metrodin HP groups respectively received human chorionic gonadotrophin (HCG). The duration of FSH treatment was significantly shorter with Gonal-F than with Metrodin HP (11.6 +/- 1.9 days versus 12. 4 +/- 2.7 days; P < 0.0001) and significantly fewer ampoules were required (mean 22.6 +/- 5.0 versus 24.3 +/- 5.1, P < 0.0002). There were, however, significantly more follicles > or =10 mm in diameter with Gonal-F (15.6 +/- 8.2 versus 13.6 +/- 7.1, P < 0.01) and oocytes retrieved (13.1 +/- 7.7 versus 11.4 +/- 7.6, P < 0.002). Although no statistical difference in pregnancy rate was recorded, patients receiving Gonal-F had a higher pregnancy rate per cycle than patients given Metrodin HP (25.1 versus 20.1%). Moderate to severe ovarian hyperstimulation syndrome occurred in 2.8 and 1.2% of Gonal-F and Metrodin HP patients respectively (not significant). In conclusion, FSH stimulation in combination with a long GnRH agonist protocol is effective in inducing multiple follicular development and embryos with a high implantation potential. However, Gonal-F is clearly more effective than Metrodin HP in inducing multifollicular development. To compare the clinical results and the cost effectiveness of urinary FSH and recombinant FSH in ovarian stimulation for IUI cycles.
                Prospective, randomized trial.
                University Hospital, Perugia, and A.G.UN.CO. Obstetrics and Gynaecology Centre, Rome, Italy.
                IUI cycles were performed in 67 infertile patients.
                Protocols of ovarian stimulation with urinary FSH or recombinant FSH were randomly assigned, for a total of 138 cycles performed (67 and 71, respectively).
                Number of mature follicles, days of stimulation, number of ampules, and IU used per cycle, biochemical/clinical pregnancy rates and cost-effectiveness ratio.
                Follicular development, length of stimulation, pregnancy and delivery rates were not statistically different. Although in the urinary FSH group a significantly higher number of IU of gonadotropins were used (815.5 +/- 284.9 vs. 596.0 +/- 253.8), the cost per cycle remained significantly lower (220.73 +/- 94.72 vs. 318.50 +/- 125.21). The cost-effectiveness ratio was 1,848.61 euro in the urinary FSH group and 2,512.61 euro in the recombinant FSH group.
                Urinary FSH and recombinant FSH are both effective in ovarian stimulation in IUI cycles. The urinary preparation is more cost effective due to the difference of its cost per IU. 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. The aim of this prospective, randomized trial was to compare the clinical results and the cost-effectiveness of urinary FSH (uFSH) and recombinant FSH (rFSH) in ovarian stimulation for intrauterine insemination (IUI) cycles in polycystic ovary syndrome (PCOS) patients. One-hundred and seventy PCOS infertile patients undergoing IUI were enrolled, and protocols of ovarian stimulation with uFSH or rFSH were randomly assigned. The total number of cycles performed was 379 (182 and 197, respectively). The main outcome measures were the number of mature follicles, the days of stimulation, the number of ampoules and IU used per cycle, the biochemical/clinical pregnancy rates, the number of multiple pregnancies and the cost-effectiveness. No statistically significant differences were found in the follicular development, length of stimulation, pregnancy rates, delivery rates and multiple pregnancies between the two groups. In the uFSH group, the cost per cycle remained significantly lower (218.51 +/- 88.69 versus 312.22 +/- 118.12; P < 0.0001), even though a significantly higher number of IU of gonadotrophins were used (809.3 +/- 271.9 versus 589.1 +/- 244.7; P < 0.0001). The cost-effectiveness (i. e. within a group, the total cost of all cycles divided by no. of clinical pregnancies) was 1729.08 in the uFSH group and 3075.37 in the rFSH group. In conclusion, uFSH and rFSH demonstrated the same effectiveness in ovarian stimulation in IUI cycles in PCOS patients. The urinary preparation is more cost-effective due to the difference of its cost per IU. To evaluate clinical and endocrinological effects of intranasal (IN) vs. subcutaneous (SC) GnRH-a for pituitary down-regulation combined with hMG vs. rFSH.
                Prospective, randomized study.
                University hospital, IVF unit.
                Three hundred seventy-nine normogonadotropic women eligible for IVF or ICSI.
                Randomization to intranasal (IN) or SC GnRH-a and to hMG or rFSH.
                Oocytes retrieved, embryos developed, clinical pregnancy, and delivery rates. Serum hormone concentrations on stimulation days 1 (S1) and 8 (S8), and oocyte pick-up (OPU) day.
                After randomization, four groups were formed: IN/hMG (n = 100), IN/FSH (n = 98), SC/hMG (n = 89), and SC/FSH (n = 92). Mean number of oocytes retrieved and of transferable and transferred embryos were similar in the four groups. Clinical pregnancy rate per started cycle was significantly higher in the IN/HMG group than in the SC/FSH group (P<.05) and was intermediate in the two remaining groups. Se-LH on S8 in the two SC groups was significantly lower than in the two IN groups. Se-E2 on S8 in the SC/FSH group was significantly lower than in the other three groups.
                The clinical and endocrinological outcome in IVF and ICSI-treated normogonadotropic women is significantly influenced by mode of down-regulation as well as gonadotropin formulation. A total of 114 patients admitted to an in-vitro fertilization-embryo transfer programme for the first time, were randomly assigned to the study group or controls. Gonadotrophin-releasing hormone analogue (GnRHa) and human menopausal gonadotrophin (HMG) were used for ovulation induction. The study patients were followed up merely by ultrasonography and the controls by ultrasonography and serum determinations of oestradiol, progesterone and luteinizing hormone (LH). There was no significant difference in the duration and total amount of HMG used for ovulation induction (10.9 versus 11.5 days and 34.8 versus 37.9 ampoules, respectively). The number of oocytes retrieved (11.7 versus 13.4) and the numbers of embryos replaced (2.6 versus 2.8) and cryopreserved (1.9 versus 3.3) were also similar. Pregnancy rates were similar. Pregnancy rate per ovum retrieval was 22.2 versus 25% and per embryo transfer 27.2 versus 26.5%. Oestradiol patterns were also similar. The rate and severity of ovarian hyperstimulation syndrome were virtually identical. We conclude that 'ultrasound-only' monitoring of ovulation induction in IVF cycles treated by GnRHa-HMG in the long protocol is as effective and safe as the conventional ultrasound and hormone determination, but far simpler, swifter and more cost-effective. 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. In a short-term protocol, the influence of progestogen pretreatment upon the oestradiol flare-up (delta E2) induced by gonadotrophin-releasing hormone agonist (GnRHa) was assessed in relation to in-vitro fertilization (IVF) outcome in 90 cycles programmed (n = 52) or not (n = 38) by norethisterone (10 mg/day for 12-20 days). Patients pretreated by progestogen had a significantly lower delta E2 value than patients without pretreatment (delta E2 = 26 +/- 5 versus 61 +/- 8 pg/ml, P = 0.003). It could be related to a lower gonadotrophic response for luteinizing hormone (LH) (delta LH = 9 +/- 0.8 versus 14.5 +/- 2.2 IU/l, P = 0.01). The IVF outcome (final oestradiol, number of oocytes or embryos) was similar in both groups and delta E2 was well correlated with these final parameters in each group. A significant rise in serum progesterone was observed only in patients without pretreatment (delta P = 1.1 +/- 0.2 versus 0.1 +/- 0.1 ng/ml, P < 0.0001). Thus norethisterone pretreatment decreases the oestradiol flare-up and prevents the early increase of progesterone (by avoiding some rescue of the corpus luteum or some luteinization of small developing follicles) but does not influence the outcome of the IVF cycle. In clinical practice, evaluation of the hormonal flare-up for predicting IVF outcome must take into account any pretreatment prescription.
Clinical choice of gonadotrophin should depend on availability, convenience and costs. Differences between urinary gonadotrophins were considered unlikely to be clinically significant. Further research on these comparisons is unlikely to identify substantive differences in effectiveness or safety.