Effect of highly purified urinary follicle-stimulating hormone on oocyte and embryo quality. A prospective randomized clinical trial comparing recombinant follicle stimulating hormone (Puregon) and human menopausal gonadotrophins (Humegon) in non-down-regulated in-vitro fertilization patients. Efficacy of recombinant human follicle-stimulating hormone in improving oocyte quality in assisted reproductive techniques. HMG is as good as recombinant human FSH in terms of oocyte and embryo quality: a prospective randomized trial. A prospective and randomized study of ovarian stimulation for ICSI with recombinant FSH versus highly purified urinary FSH. Effectiveness of highly purified human menopausal gonadotropin vs. recombinant follicle-stimulating hormone in first-cycle in vitro fertilization-intracytoplasmic sperm injection patients. Clinical outcome following stimulation with highly purified hMG or recombinant FSH in patients undergoing IVF: a randomized assessor-blind controlled trial. A prospective, randomized clinical trial comparing 150 IU recombinant follicle stimulating hormone (Puregon((R))) and 225 IU highly purified urinary follicle stimulating hormone (Metrodin-HP((R))) in a fixed-dose regimen in women undergoing ovarian stimulation. The effect of HMG and recombinant human FSH on oocyte quality: a randomized single-blind clinical trial. Clinical efficacy of highly purified urinary FSH versus recombinant FSH in volunteers undergoing controlled ovarian stimulation for in vitro fertilization: a randomized, multicenter, investigator-blind trial. Efficacy of recombinant versus human derived follicle stimulating hormone on the oocyte and embryo quality in IVF-ICSI cycles: Randomised, controlled, multi-centre trial. Urinary follicle-stimulating hormone (FSH) is more effective than recombinant FSH in older women in a controlled randomized study. Comparison of recombinant and urinary follicle-stimulating hormone preparations in short-term gonadotropin releasing hormone agonist protocol for in vitro fertilization-embryo transfer. A prospective, randomized, assessor-blind, multicentre study comparing recombinant and urinary follicle stimulating hormone (Puregon versus Metrodin) in in-vitro fertilization. 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. Efficacy and safety of recombinant follicle stimulating hormone (Puregon) in infertile women pituitary-suppressed with triptorelin undergoing in-vitro fertilization: a prospective, randomized, assessor-blind, multicentre trial. Induction of ovulation in women undergoing assisted reproductive techniques: recombinant human FSH (follitropin alpha) versus highly purified urinary FSH (urofollitropin HP). Recombinant human follicle stimulating hormone (r-hFSH; Gonal-F) versus highly purified urinary FSH (Metrodin HP): results of a randomized comparative study in women undergoing assisted reproductive techniques. A prospective, randomized, controlled trial comparing highly purified hMG with recombinant FSH in women undergoing ICSI: ovarian response and clinical outcomes. Impact of recombinant follicle-stimulating hormone and human menopausal gonadotropins on in vitro fertilization outcome. Ovarian responses to recombinant FSH or HMG in normogonadotrophic women following pituitary desensitization by a depot GnRH agonist for assisted reproduction. 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. Highly purified hMG versus recombinant FSH in ovarian hyperstimulation with GnRH antagonists--a randomized study. A randomized prospective assessor-blind evaluation of luteinizing hormone dosage and in vitro fertilization outcome. Recombinant FSH vs. urinary FSH for ovarian stimulation in in vitro fertilization.
To determine the effects of ovarian stimulation with highly purified urofollitropin on oocyte and embryo quality.
                Parallel randomized open-label clinical study.
                Assisted reproduction centers.
                Two hundred sixty-seven infertile couples undergoing IVF/ICSI.
                All participants underwent standard down-regulation with GnRH analogue. One hundred thirty-three participants received highly purified urinary FSH and 134 controls received recombinant FSH.
                Primary end points were number of morphologically mature oocytes retrieved, embryo quality, and pregnancy and implantation rates. Secondary end points were: total number of days of FSH stimulation, total dose of gonadotropin administered, fertilization rate per number of retrieved oocytes, embryo cleavage rate, live birth and miscarriage rates, endometrial thickness and estradiol level on the day of hCG administration, cancellation rate, and incidence of moderate or severe ovarian hyperstimulation syndrome.
                Pregnancy and implantation rates were nonsignificantly higher in the urinary FSH group than the recombinant FSH group (46.5% vs. 36.8% and 22.1% vs. 15.8%, respectively). The grade 1 embryo score was significantly higher in the urinary FSH group than the recombinant FSH (42.1% vs. 33.5%), and the live birth rate was nonsignificantly higher in the former group.
                Highly purified urinary FSH is as effective, efficient, and safe for clinical use as recombinant FSH. A randomized clinical trial was performed comparing recombinant follicle stimulating hormone (rFSH, Puregon, n = 54) and human menopausal gonadotrophin (HMG, Humegon, n = 35) in infertile women undergoing in-vitro fertilization without the use of a gonadotrophin-releasing hormone (GnRH) agonist. Most patients had a tubal or idiopathic infertility, the latter always longer than 4 years' duration. Patients with sperm abnormalities were excluded. None of the between-group differences in treatment outcome was statistically significant. In the rFSH group, a mean number of 11.2 oocytes was retrieved compared with 8.3 in the HMG group. Ongoing pregnancy rates per started cycle were higher in the rFSH group (22.2%) than in the HMG group (17.1%). Implantation rates were 27.5% in the rFSH group in comparison with 16.7% in the HMG group. In the rFSH group, a mean total dose of 1410 IU during 6.2 days was administered compared with 1365 IU in 6.0 days in the HMG group. Oestradiol concentrations on the day of human chorionic gonadotrophin administration were 3889 pmol/l in the rFSH group and 3145 pmol/l in the HMG group. In 15 subjects (rFSH: n = 9, 16.7%; HMG: n = 6, 17.1%) luteinizing hormone concentrations higher than 10 IU/l were seen during stimulation. In two of them, both from the rFSH group, ongoing pregnancies were achieved. The results indicate that rFSH (Puregon) is at least as efficacious as HMG and that acceptable pregnancy rates can be achieved without the use of a GnRH agonist. To estimate the efficacy of recombinant human follicle-stimulating hormone (rFSH) versus highly purified urinary human FSH (uFSH) in women undergoing controlled ovarian hyperstimulation (COH) for in vitro fertilization and embryo transfer (IVF-ET).
                This prospective, randomized, quality of retrieved double-blind study compared uFSH with rFSH in IVF-ET rFSh cycles. A total of 254 cycles from 241 patients who attended the infertility clinic at Samsung Cheil Hospital from January to August 2001 were included in the study. With pituitary desensitization using gonadotropin-releasing hormone agonist and a short protocol, rFSH was administered in 131 cycles; uFSH was administered in 123 cycles. We analyzed ovarian response, oocyte quality, fertilization rate, embryo quality, pregnancy rate and live birth rate in the uFSH and rFSH groups.
                Total FSH dosage (1322.3 +/- 526.2 vs. 2124.4 +/- 881.9 i.u.) and dosage per retrieved oocyte (90.6 +/- 36.0 vs. 138.0 +/- 57.2 i.u.) were significantly lower in the rFSH group than those in the uFSH group (P < .001). The proportion of good-quality oocytes (grade 1 and 2) was higher in the rFSH group (68.2% vs. 64.8%, P = .024). Moreover, the proportion of atretic oocytes (grade 5) was lower in the rFSH group (7.5% vs. 10.3%, P = .002). The fertilization rate, quality of transferred embryos, clinical pregnancy rate and live birth rate were not significantly differ between the 2 groups.
                In women undergoing COH, rFSH revealed more efficient ovarian response and better quality of oocytes than did uFSH. Previous studies have demonstrated that the use of recombinant human follicle stimulating hormone (rhFSH) for ovarian stimulation may be associated with a better outcome than human menopausal gonadotrophin (HMG), probably due to the absence of LH, higher FSH bioactivity and better quality of oocytes and embryos when rhFSH is used. Very few studies have examined the effects of different gonadotrophins on oocyte and embryo quality. In this prospective study, 40 women undergoing ovarian stimulation for intracytoplasmic sperm injection were randomized to receive a standard protocol of either HMG or rhFSH in down-regulated cycles. Prior to microinjection, each denuded oocyte was videotaped to assess nuclear maturity, morphology of zona pellucida, oocyte and polar body and the zona thickness, and diameters of oocyte and ooplasma. Fertilization and subsequent embryo development of each oocyte were followed. The embryologists were blind to the type of gonadotrophin each patient had received for stimulation. No significant differences were found between the two groups with regard to the demographic data, the ovarian responses and pregnancy/implantation rates. The percentage of metaphase II oocytes in the HMG and rhFSH groups were similar (86.9 versus 87.4% respectively). All other parameters assessing oocyte and embryo quality were also comparable between the two groups. A prospective and randomized study of ovarian stimulation with human recombinant follicle-stimulating hormone (r-FSH; Gonal-F) versus highly purified urinary FSH (u-FSH-HP; Metrodin-HP) was conducted on patients submitted to an intracytoplasmic sperm injection (ICSI) program. A total of 120 patients aged 37 years or less were stimulated in a randomized manner with r-FSH (group I = 60 patients) or u-FSH-HP (group II = 60 patients). All received a fixed dose of FSH for 7 days and on the 8th day of stimulation the doses started to be adapted according to ovarian response. Human chorionic gonadotropin (hCG) at the dose of 5000 IU to 10,000 IU was administered to both groups when at least one follicle presented a diameter > or = 17 mm. The ovarian response did not differ significantly between groups I and II in terms of number of follicles > or = 16 mm (group I = 6.2 +/- 3.2; group II = 6.7 +/- 2.9; p = 0.26), number of oocytes collected (group I = 10.7 +/- 6.8; group II = 10.5 +/- 5.7; p = 0.91), number of oocytes in metaphase II (group I = 9.2 +/- 5.8; group II = 8.2 +/- 4.8; p = 0.56) or number of immature oocytes (group I = 1.8 +/- 0.9; group II = 1.9 +/- 1.7; p = 0.62). The normal fertilization rate after ICSI did not differ significantly between treatments (group I = 69.4 +/- 25; group II = 66.5 +/- 23; p = 0.38). No cases of cancellation of ovarian stimulation or of severe ovarian hyperstimulation syndrome occurred in either group. The total number of embryos obtained from patients who used r-FSH (group I = 6.3 +/- 4.5) was similar (p = 0.46) to the number obtained from patients who used u-FSH-HP (group II = 5.5 +/- 3.7), as also was the number of transferred embryos (group I = 2.8 +/- 0.8; group II = 2.6 +/- 0.9; p = 0.27). Implantation rate (26.1%) and clinical pregnancy rates per puncture (36.7%) and per embryo transfer (37.9%) were higher in patients who used r-FSH than in patients who used u-FSH-HP (19.5%, 31.7% and 32.2%, respectively), but the differences were not statistically significant. The abortion rate (p = 0.32) did not differ between groups (group I = 4.5%, n = 1 versus group II = 15.7%, n = 3). Thus far, the data do not demonstrate significant differences in ovary stimulation with r-FSH versus u-FSH in patients whose indication for assisted reproduction was the male factor. To compare the effectiveness of highly purified hMG with recombinant FSH (rFSH) in IVF-intracytoplasmic sperm injection patients who were treated with a GnRH agonist.
                An open-label, prospective, randomized comparison of fixed gonadotropin regimens.
                Eighteen Dutch IVF centers.
                Six hundred twenty-nine patients who were selected for IVF-intracytoplasmic sperm injection.
                Patients were randomized to receive either highly purified hMG or rFSH in a fixed dosage of 150 IU/d after GnRH-agonist suppression (long protocol).
                Ongoing pregnancy rate per started cycle. Difference between the two treatment groups was tested by using odds ratios, including the 95% confidence limits (intention-to-treat sample), and by using the Fisher's exact test (per-protocol sample).
                The ongoing pregnancy rates per started cycle were 26.3% and 25.2% for highly purified hMG and rFSH, respectively (no statistically significant difference). Treatment with highly purified hMG resulted in statistically significantly fewer oocytes (n = 7.8) than did treatment with rFSH (n = 10.6). There were no differences with respect to fertilization rates and implantation rates. Cycles with highly purified hMG were statistically significantly less often canceled as a result of ovarian hyperresponse (2.0% vs. 6.0% for highly purified hMG and rFSH, respectively).
                Compared with rFSH, highly purified hMG did not result in superiority in ongoing pregnancy rates in first-cycle IVF-intracytoplasmic sperm injection patients who were treated with a fixed dosage of 150 IU of gonadotropin per day. Compared with rFSH, treatment with highly purified hMG resulted in retrieval of fewer oocytes, a lower incidence of hyperresponse, and comparable pregnancy rates. LH activity may influence treatment response and outcome in IVF cycles.
                A randomized, assessor-blind, multinational trial compared ongoing pregnancy rates (primary end-point) in 731 women undergoing IVF after stimulation with highly purified menotrophin (HP-hMG) (n = 363) or recombinant FSH (rFSH) (n = 368) following a long GnRH agonist protocol. Patients received identical pre- and post-randomization interventions. One or two embryos were transferred on day 3.
                More oocytes were retrieved (P < 0.001) after rFSH treatment (11.8) compared with HP-hMG treatment (10.0), but a higher proportion developed into top-quality embryos (P = 0.044) with HP-hMG (11.3%) than with rFSH (9.0%). At the end of stimulation, lower estradiol (E(2)) (P = 0.031) and higher progesterone (P < 0.001) levels were found with rFSH, even after adjusting for follicular response. The distribution of hypo-, iso- and hyper-echogenic endometrium showed a significant (P = 0.023) shift towards the hyperechogenic pattern after rFSH treatment. The ongoing pregnancy rate per cycle was 27% with HP-hMG and 22% with rFSH [odds ratio (95% confidence interval): 1.25 (0.89-1.75)].
                Superiority of HP-hMG over rFSH in ongoing pregnancy rate could not be concluded from this study, but non-inferiority was established. Pharmacodynamic differences in follicular development, oocyte/embryo quality, endocrine response and endometrial echogenicity exist between HP-hMG and rFSH preparations, which may be relevant for treatment outcome. A prospective, randomized, open, multicentre (n = 3) study was conducted to compare the efficacy and efficiency of a fixed daily dose of 150 IU (3x50 IU) recombinant follicle stimulating hormone (recFSH, Puregon((R))) and 225 IU (3x75 IU) highly purified urinary FSH (uFSH-HP, Metrodin-HP((R))) in women undergoing ovarian stimulation prior to in-vitro fertilization treatment. A total of 165 women were treated with FSH, 83 subjects with recFSH and 82 subjects with uFSH-HP. In the recFSH group a mean number of 8.8 oocytes were retrieved, compared with 9.8 in the uFSH-HP group (not statistically significant). In the recFSH group, a significantly lower total dose was required compared to the uFSH-HP group, 1479 versus 2139 IU, respectively (P < 0.0001; 95% confidence interval -747 to -572). Treatment with recFSH resulted in a significantly higher embryo development rate (69.6 versus 56.2%; P = 0.003) and more embryos accessible for the embryo freezing programme (3.3 versus 2.0; P = 0.02) compared to uFSH-HP. The vital pregnancy rate per cycle started was 30.2 versus 28.3% in the recombinant and urinary FSH group, respectively. It is concluded that treatment outcome of a fixed daily dose of 150 IU recFSH is comparable to a fixed daily dose of 225 IU uFSH-HP. However, a significantly lower total dose was needed in the recFSH group (nearly 700 IU less). To compare the effect of HMG and rhFSH on oocyte quality in ICSI cycle.
                Vali-e-Asr university teaching hospital.
                Prospective single-blind randomized clinical trial.
                Sixty women undergoing ovarian stimulation for ICSI were randomized to receive a standard protocol of either HMG or rhFSH in down-regulation cycles.
                Prior to microinjection, each oocyte was assessed regarding the nuclear maturity, morphology of zona plucida, cytoplasmic appearance and polar body morphology. Fertilization rate was followed.
                The percentage of metaphase II oocytes in HMG and rhFSH groups.
                Statistical analyses were carried out by the Mann-Whitney, Fisher's exact, chi2 tests and Student's t-test.
                No significant differences were found between two groups in regard to the demographic data, the ovarian response and pregnancy/implantation rates (P>0.05). The percentage of metaphase II oocytes in HMG and rhFSH groups were 81.3% versus 80.6%, respectively.
                There were no significant differences between parameters such as, oocyte quality and percentage of metaphase II oocytes between these two groups. To compare the efficacy of highly purified human urinary follicle stimulating hormone (HP-hFSH) versus human recombinant follitropin-alpha (rFSH) in volunteers undergoing controlled ovarian stimulation for IVF.
                A randomized, controlled, investigator-blind trial.
                Four assisted reproductive technology centers.
                One hundred fifty-two IVF patients.
                Volunteers, aged 18-39, were randomized to HP-hFSH (n = 76) versus rFSH (n = 76) at a starting dose of 300 IU in down-regulated cycles.
                Number of oocytes, clinical pregnancy rate, and live birth rate with HP-hFSH versus rFSH.
                The total IU of gonadotropin used did not differ between the two groups. There was no difference in number of oocytes retrieved with HP-hFSH (mean = 16.3) compared with rFSH (mean = 17.1), confidence interval (CI) of difference = -3.79 to +2.18. Clinical pregnancy rate, as defined by the presence of a gestational sac, was 48.7% (CI = 37.0%-60.4%) with HP-hFSH versus 44.7% (CI = 33.3%-56.6%) with rFSH (CI of difference = -11.9% to +19.8%). Live birth rate was 38.2% (29 of 76) in both groups (CI = 27.2%-50.0%), for a difference between groups of 0.0% (CI of the difference = -15.4% to +15.4%).
                There were no statistically significant differences in mean oocyte number, clinical pregnancy rate, or live birth rate between HP-hFSH versus rFSH. The aim of this trial, comparing human follicle stimulating hormone (hFSH) and recombinant FSH (rFSH) was to evaluate the efficacy on oocyte and embryo quality in in vitro fertilisation/intracytoplasmic sperm injection cycles. Four-hundred and one women were randomised in two groups to receive or hFSH or rFSH in stimulation protocols. The primary end point of this study was the oocyte/embryo quality. No significant difference in oocyte/embryo quality was observed between the two groups. The number of oocytes retrieved was significantly higher in the hFSH group (6 +/- 2.8 in hFSH group vs. 5 +/- 2.6 in rFSH group; P = 0.003). A less amounts of gonadotropins consumed (2106 +/- 719 IU in hFSH group vs. 3536 +/- 1099 IU in rFSH group; P < 0.0001) and shorter duration of stimulation (human chorionic gonadotropin day of administration: Day 12.3 +/- 1.0 in hFSH and Day 13.3 +/- 1.2 in rFSH group, respectively; P < 0.0001) was registered in hFSH group. Fertilisation, cleavage and implantation rates, pregnancy and abortion rates were similar in both groups. However, lower clinical abortion rate (not significant) in hFSH group might be noteworthy. In our study, we demonstrated that hFSH and rFSH products are equivalent in terms of clinical efficacy. The following study was conducted to determine which FSH, recombinant or urinary, works better in older women.
                We conducted a controlled randomized study in a single university IVF center.
                University IVF center.
                Women (N = 257) over 39 years old undergoing IVF.
                The patients were randomized into two study groups at their first IVF cycle: 121 patients were treated with recombinant FSH, and 120 patients were treated with urinary FSH. Both groups were suppressed with a long GnRH analog protocol.
                Days of stimulation, E2 at the day of hCG, total amount of FSH administered, number of oocytes collected, amount of FSH per oocyte, and number of embryos obtained.
                Patients treated with urinary FSH required a significantly lower total amount of FSH, and a lower amount of FSH per oocyte than women treated with recombinant FSH. The other measures evaluated did not show any statistically significant differences.
                Our study showed that urinary FSH performed better in older women than recombinant FSH when associated with the long protocol. 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. Urinary follicle stimulating hormone (FSH) is being used for the treatment of human infertility. Recently, FSH manufactured by means of recombinant DNA technology with a much higher purity (> 99%) has become available. A prospective, randomized, assessor-blind, multicentre (n = 18) study was conducted in infertile women undergoing in-vitro fertilization comparing recombinant FSH (Org 32489, Puregon) and urinary FSH (Metrodin). Eligible subjects were randomized (recombinant versus urinary FSH = 3:2) and pretreated with buserelin for pituitary suppression. FSH was given until three or more follicles with a diameter of at least 17 mm were seen. After oocyte retrieval, fertilization routines were applied according to local procedures. No more than three embryos were replaced. In all, 585 subjects received recombinant FSH and 396 urinary FSH. Significantly more oocytes were retrieved after recombinant FSH treatment (mean adjusted for centre 10.84 versus 8.95, P < 0.0001). Ongoing pregnancy rates per attempt and transfer in the recombinant FSH group were 22.17 and 25.97% respectively, and in the urinary FSH group, 18.22 and 22.02% respectively (not significant). Ongoing pregnancy rates including pregnancies resulting from frozen-thawed embryo cycles were 25.7% for recombinant and 20.4% for urinary FSH (P = 0.05). Compared to urinary FSH, the total dose of FSH was significantly lower with recombinant FSH (2138 versus 2385 IU, P < 0.0001) in a significantly shorter treatment period (10.7 versus 11.3 days, P < 0.0001). No clinically relevant differences between recombinant and urinary FSH were seen with respect to safety variables. It is concluded that recombinant FSH (Puregon) is more effective than urinary FSH in inducing multifollicular development and achieving an ongoing pregnancy. 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. The objective of this study was to compare the efficacy and safety of a recombinant follicle stimulating hormone (FSH) preparation (Org 32489, Puregon) with a urinary FSH preparation (Metrodin) in infertile women undergoing in-vitro fertilization (IVF and embryo transfer and who were pituitary-suppressed with triptorelin. In an assessor-blind, group-comparative, multicentre study, 60 women were randomized to Org 32489 and 39 to urinary FSH. An evaluation of the main parameter, the mean total number of oocytes recovered, indicated a similar efficacy for the two preparations: 9.7 with Org 32489 versus 8.9 with urinary FSH. In addition, there were no significant between-group differences with respect to other efficacy variables such as the total dose used, the duration of the treatment, the number of follicles > or = 17 mm in diameter and embryo quality. The ongoing pregnancy rates per attempt (30.2 versus 17.4%) and per transfer (34.0 versus 18.8%) were higher with Org 32489, but this difference was not statistically significant. No clinically relevant differences between Org 32489 and urinary FSH were seen with respect to safety variables. Serum antibodies were not detected in any of the subjects. It is concluded that Org 32489 compares favourably with urinary FSH in the treatment of infertile pituitary-suppressed women undergoing IVF and embryo transfer. This multicentre, open, randomized, study compared the efficacy and safety of recombinant follicle stimulating hormone (rFSH; follitropin alpha) with highly purified urinary human FSH (uFSH; urofollitropin HP) in women undergoing ovulation induction for assisted reproductive techniques. Following long down-regulation with buserelin, patients received two ampoules of 75 IU (150 IU) s.c. rFSH or highly purified uFSH for 6 days, after which the dose could be increased until they fulfilled the criteria for human chorionic gonadotrophin (HCG) administration. Of 168 patients recruited, 155 received at least one dose of FSH, and 137 received HCG [68: rFSH (85%); 69: uFSH (92%)]. Following oocyte retrieval and fertilization, up to three embryos were replaced/patient and luteal support was given. The mean number of oocytes retrieved/patient was 10.2 +/- 6.0 for rFSH patients compared with 10.8 +/- 6.1 in the uFSH group (not significant). There was a trend towards fewer ampoules used (22.3 +/- 6.5 versus 24.3 +/- 6.5), higher pregnancy (44.3 versus 41.4%) and live birth rates (33.8 versus 26.7%), as well as a lower miscarriage rate (0.0 versus 16.7%) in favour of rFSH. However, no significant differences in efficacy parameters were recorded. Ovarian hyperstimulation syndrome occurred in 8.6% and 7.9% of rFSH and uFSH patients respectively. In conclusion, this protocol was effective in inducing multiple follicular development and high numbers of oocytes were retrieved with both drugs. A prospective, randomized, comparative, assessor-blind study was carried out in two centres to compare the efficacy and safety of recombinant human follicle stimulating hormone (r-hFSH; Gonal-F) versus highly purified urinary FSH (u-hFSH HP; Metrodin HP), both administered s.c. in women undergoing ovarian stimulation for in-vitro fertilization including intracytoplasmic sperm injection (ICSI). A total of 235 patients started a long gonadotrophin-releasing hormone agonist protocol: 119 received r-hFSH and 114 received u-hFSH HP (150 IU/day) for the first 6 days. Two patients were excluded from the study because they mistakenly received the incorrect treatment combination. Human chorionic gonadotrophin (HCG; 10000 IU, s.c.) was administered once there was at least one follicle 18 mm in diameter and two others > or = 16 mm. In all, 119 (100%) and 102 (89%) of the patients respectively in the r-hFSH and u-hFSH HP groups achieved the criteria for HCG. The mean numbers (+/- SD) of oocytes recovered (the primary endpoint) were 12.2 +/- 5.5 and 7.6 +/- 4.4 in the r-hFSH and u-hFSH HP groups respectively (P < 0.0001). However, the number of FSH treatment days (11.0 +/- 1.6 versus 13.5 +/- 3.7) and the number of 75 IU ampoules (21.9 +/- 5.1 versus 31.9 +/- 13.4) used were significantly less (P < 0.0001) in the r-hFSH group than in the u-hFSH HP group. In patients treated using ICSI (63 patients in each group), no difference in oocyte maturation was observed. The mean numbers of embryos obtained were 8.1 +/- 4.2 and 4.7 +/- 3.5 (P < 0.0001), in favour of the r-hFSH group. In the majority of patients (96 and 99% respectively) only one or two embryos were replaced (mean 2.0 +/- 0.2 and 1.9 +/- 0.1 respectively) in the r-hFSH and u-hFSH HP groups. The clinical pregnancy rates per started cycle and per embryo transfer were 45 and 36%, and 48 and 47%, respectively in the r-hFSH and u-hFSH HP groups (not significant). There were six (5.1%) and two (1.7%) cases of ovarian hyperstimulation syndrome respectively. In conclusion, it was found that r-hFSH was more effective than u-hFSH at inducing multiple follicular development. However, the high rate of low ovarian response in the u-hFSH group compared with our general experience was unexpected. The availability of a gonadotrophin with less inter-batch variation would be beneficial for clinicians. r-hFSH seems to fulfil such a requirement. To assess the clinical profile and efficacy in assisted reproductive treatment of a new human-derived highly purified (HP) menotropin, we compared HP hMG and recombinant (r) FSHalpha use in ICSI within a prospective, randomized, controlled study.
                100 infertile women were treated with HP hMG (50 patients) or rFSHalpha (50 patients). All patients received the same daily gonadotrophin dose (150 IU) following GnRH agonist suppression (long regimen) until more than three follicles >17 mm and estradiol (E(2)) levels >600 pg/ml were reached. Patients were monitored with daily LH, FSH, hCG, estradiol (E(2)), progesterone, and testosterone measurements; and alternate day pelvic ultrasound.
                Treatment duration (11.1 +/- 0.4 versus 12.9 +/- 0.5 days, P < 0.05) and gonadotrophin dose (22.4 +/- 1.0 versus 27.0 +/- 1.5 ampoules, P < 0.05) were lower in the HP hMG group. Conversely, peak pre-ovulatory E(2) (1342 +/- 127 versus 933 +/- 109 pg/ml, P < 0.005); and area under the curve of E(2) (3491 +/- 350 versus 2602 +/- 349 pg/ml.day, P < 0.05), immunoreactive serum FSH (65.9 +/- 2.1 versus 48.8 +/- 1.8 IU/l.day, P < 0.001). and hCG (1.7 +/- 0.3 versus 0.0 +/- 0.0 IU/l/day, P < 0.001) during treatment were higher in the HP hMG group. Cycle cancellation rates, transferred embryo number, pregnancy rates per started cycle (30 versus 28%) and per embryo transfer (35 versus 35%) and miscarriage rates (6 versus 6%) were not significantly different.
                HP hMG treatment was associated with: (i) a more efficient patient response, as reflected by reduced treatment duration and gonadotrophin requirements; (ii) increased serum levels of hCG, E(2), and immunoreactive FSH during treatment; (iii) an ICSI outcome indistinguishable from rFSHalpha. To investigate possible differences between using recombinant FSH (rFSH) and hMG for ovarian stimulation in IVF/intracytoplasmic sperm injection (ICSI) cycles.
                Parallel group design. Prospective, randomized clinical study.
                A tertiary care infertility clinic.
                A total of 578 patients of our IVF/ICSI routine were recruited.
                Treatment with hMG was used for 282 patients (282 cycles), whereas 296 patients (296 cycles) were treated with rFSH. The number of cycles leading to an embryo transfer were 248 and 259, respectively.
                Primary: clinical pregnancy rate. Secondary: treatment days, total dose of gonadotropin administered, number of oocytes retrieved, number of mature oocytes, and embryo quality.
                Of the cycles with embryo transfer, the pregnancy rates were 30.1% and 32.3% in the rFSH and the hMG groups, respectively. This difference is not statistically significant (P=0.798). Treatment with rFSH resulted in a significantly higher number of recovered oocytes compared with the hMG group but was also associated with a higher number of ampoules needed to reach the criterion for hCG administration. No significant differences were found with regard to the number of mature oocytes, the number of treatment days, and the embryo quality.
                In terms of the clinical pregnancy rate, no significant differences between the two stimulation regimens can be stated. 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. 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. Highly purified hMG (hp-hMG) has recently shown better cycle outcome than the recombinant FSH (rFSH) when compared in GnRH agonist long protocol cycles. However, they have not yet been compared in GnRH antagonist cycles.
                A RCT comparing the ongoing pregnancy rate (primary end-point) in 280 patients undergoing IVF/ICSI after stimulation with hp-hMG or rFSH controlled with a GnRH antagonist.
                No significant differences were observed between hp-hMG and rFSH in terms of the ongoing pregnancy rate per started cycle (35.0 versus 32.1%, respectively; P = 0.61); relative risk: 1.09 (95% confidence interval: 0.78-1.51; risk difference: 2.9%). No differences were observed for implantation, clinical pregnancy and pregnancy loss rates. More oocytes were obtained from patients receiving rFSH then hMG (14.4 +/- 8.1 versus 11.3 +/- 6.0, respectively; P = 0.001). Estradiol was higher at the end of stimulation in the hp-hMG group (P = 0.02), whereas progesterone was higher in patients stimulated with rFSH (P < 0.001).
                A similar outcome was observed for hp-hMG and rFSH when used for stimulation in GnRH antagonist cycles. However, some differences were found in ovarian response in terms of oocyte yield and hormonal profile. Clinical Trials.gov Trial registration number: NCT00669786. To determine the effect of exogenous LH dosage on IVF outcome.
                Single-blinded (assessor-blinded) study with random assignment of treatment groups.
                Human Assisted Reproduction Unit, Rotunda Hospital, Dublin, Ireland.
                Infertile normogonadotropic women undergoing their first cycle of IVF were studied.
                Patients were randomized to gonadotropin drugs with varying doses of LH per ampule: recombinant FSH containing no LH (group 0, n = 39), urinary FSH containing <1 IU of LH per ampule (group 1, n = 30), hMG containing 25 IU of LH per ampule (group 25, n = 30), and hMG containing 75 IU of LH per ampule (group 75, n = 29). The FSH dose was kept constant at 75 IU per ampule. A long-protocol GnRH-analog regimen was used.
                Dose and duration of gonadotropin stimulation, follicle and oocyte numbers, implantation rate, and pregnancy rate.
                The median duration of ovarian stimulation; median number of gonadotropin ampules used; serum E2 levels; and numbers of follicles, oocytes, and embryos were similar among the four groups. Median LH levels on the day of hCG administration, however, differed significantly. Live birth rates per cycle differed markedly, but statistical significance was not achieved (23%, 7%, 20%, and 31% for groups 0, 1, 25, and 75, respectively). A significant trend in implantation rates was noted with increasing LH dosage of the urinary preparations (19%, 10%, 18%, and 28% for groups 0, 1, 25, and 75, respectively).
                In the present study, although the residual endogenous LH after down-regulation was adequate for ovarian response and E2 synthesis, the addition of exogenous LH improved implantation. An FSH/LH ratio of 75/75 IU per ampule appeared to be the optimum dose. To compare ovarian stimulation with recombinant FSH (rFSH) vs. urinary FSH (uFSH) in terms of hormonal events within ovarian follicles and the outcome of in vitro fertilization.
                A prospective randomized comparative study of rFSH (n = 70) vs. uFSH (n = 61) ovarian stimulation. Hormone determinations were serum estradiol (E2) on the day of human chorionic gonadotropin (hCG) administration, and E2, androstenedione (A) and testosterone (T) at the time of follicular aspiration in the follicular fluid and serum.
                The total dose of gonadotropins required and the length of ovarian stimulation were the same in the 2 groups. In follicular fluid the E2 and the A levels were significantly higher in the rFSH group (3,065 +/- 1,646 vs. 2,368 +/- 1,240 nmol/L, P = .004, and 103.7 +/- 51.6 vs. 89.0 +/- 42.3 nmol/L, P = .042, respectively), whereas A:E2 and T:E2 ratios were significantly lower (39.6 +/- 22.5 vs. 52.3 +/- 59.6, P = .042, and 9.1 +/- 4.7 vs. 17.6 +/- 26.9, P = .006, respectively). Serum hormonal levels, number of oocytes retrieved and pregnancy rates did not differ significantly between the groups.
                rFSH provides results similar to those of uFSH. rFSH enhances steroidogenesis and provokes different androgen/estrogen ratios than does uFSH without influencing the outcome of in vitro fertilization.
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.