Induction of final follicular maturation and early luteinization in women undergoing ovulation induction for assisted reproduction treatment--recombinant HCG versus urinary HCG. The European Recombinant Human Chorionic Gonadotrophin Study Group. Recombinant HCG for triggering ovulation increases the rate of mature oocytes in women treated for ICSI. Comparison of serum and follicular fluid hormone levels with recombinant and urinary human chorionic gonadotropin during in vitro fertilization. Triggering ovulation with gonadotropin-releasing hormone agonists does not compromise embryo implantation rates. Human recombinant luteinizing hormone is as effective as, but safer than, urinary human chorionic gonadotropin in inducing final follicular maturation and ovulation in in vitro fertilization procedures: results of a multicenter double-blind study. A prospective, randomized, controlled, double-blind, double-dummy comparison of recombinant and urinary HCG for inducing oocyte maturation and follicular luteinization in ovarian stimulation. A lower ongoing pregnancy rate can be expected when GnRH agonist is used for triggering final oocyte maturation instead of HCG in patients undergoing IVF with GnRH antagonists. Hemodynamic changes induced by urinary human chorionic gonadotropin and recombinant luteinizing hormone used for inducing final follicular maturation and luteinization.
This multicentre, double-blind, double-dummy, randomized, parallel-group study compared the efficacy and safety of recombinant human chorionic gonadotrophin (rHCG) (Ovidrel((R))) and urinary HCG (uHCG) (Profasi((R))) for inducing final follicular maturation and early luteinization in women undergoing ovulation induction for assisted reproduction treatment. Following long down-regulation and stimulation with recombinant human FSH (rFSH) (Gonal-F((R))), a total of 190 women received a single, s.c. injection of either 250 microg rHCG or 5000 IU uHCG. For evaluable patients (n = 172), the mean number of oocytes retrieved per patient (primary efficacy endpoint) was 11.6 for rHCG and 10.6 for uHCG (not significant). The mean number of mature oocytes was statistically higher (P = 0.027) for the rHCG group than the uHCG (9.4 versus 7.1). Serum progesterone concentrations on day 1 and days 6-7 post-HCG, and serum HCG concentrations at all post-HCG time points were statistically significantly in favour of rHCG. The clinical pregnancy rate was somewhat higher (not significant) in the rHCG group (33 versus 25%) as was the live birth rate (27 versus 23%, not significant). Both treatments were well tolerated, though the incidence of adverse events was significantly higher in the uHCG group (45.1 versus 22.7%, P = 0.0004). The incidence of injection-site reactions was significantly lower in the rHCG group (P = 0.0001). In conclusion, for triggering ovulation, rHCG seems to have significant advantages compared with uHCG in terms of number of mature oocytes retrieved, luteal progesterone and local tolerance. To conduct a prospective randomized study in order to investigate the effect of recombinant HCG (rHCG) on oocyte nuclear and cytoplasm maturity compared to urinary HCG (uHCG), for inducing ovulation in women treated with ICSI for male factor infertility.
                We compared 89 patients randomly assigned to one of the two study groups. Group A consisted of 42 women who received a subcutaneous (s.c.) injection of 250 microg rHCG and group B consisted of 47 patients receiving an intramuscular (i.m.) injection of 10,000 IU uHCG.
                Patients treated with rHCG showed a rate of metaphase II oocytes, a number of metaphase II oocytes with mature cytoplasm and a rate of metaphase II oocytes with mature cytoplasm calculated from total MII oocytes statistically higher than in patients treated with uHCG. However this differences were not associated with a significantly better clinical outcome.
                Our data show that in women treated with ICSI for male factor infertility, rHCG increases the rate of metaphase II oocytes, the number and the rate of MII oocytes with mature cytoplasm compared to uHCG. A larger study comparing transfer cycles of embryos all derived from oocytes with mature cytoplasm and transfer cycles of embryos all derived from oocytes with immature cytoplasm may be needed to clarify clinical correlations. To study serum and follicular fluid (FF) hormone levels after the administration of urinary or recombinant hCG to initiate the final stages of oocyte maturation during IVF.
                Prospective randomized study between 250 microg of recombinant hCG and 7,500 IU of urinary hCG as the final trigger of ovulation during IVF.
                Private IVF center.
                Infertile women undergoing IVF/intracytoplasmic sperm injection (ICSI) using the long protocol and recombinant FSH.
                IVF treatment. Serum and FF hormone measurements on the day of oocyte collection.
                Serum and FF E(2), P, hCG, and T levels.
                Stimulation parameters, serum and follicular E(2), P, T, and hCG levels were similar in the recombinant and urinary hCG groups. The number of oocytes retrieved from follicles >14 mm, the proportion of mature oocytes, fertilization rate, and pregnancy rate (PR) were also comparable.
                Recombinant and urinary hCG provided similar serum and follicular hormonal environments during the final stages of oocyte maturation. The IVF outcome parameters were also comparable. The two medications appear to be equally effective. To evaluate the implant capacity of embryos derived from oocytes matured with a bolus of GnRH agonist.
                Donors were randomly assigned to a protocol using either GnRH agonist or recombinant (r) hCG to trigger ovulation. Analysis of variance, Student t test, and Fisher exact test were used where appropriate.
                Private clinical setting.
                Young voluntary donors receiving GnRH agonist (n = 30) or rhCG (n = 30). Eighty-nine patients received oocytes.
                Controlled ovarian stimulation was carried out with GnRH antagonist and FSH/LH in a step-down protocol. Donors received a single bolus of GnRH agonist (0.2 mg) or rhCG (250 microg). The endometrial tissue of recipient patients was prepared with oral E(2) and P.
                Pregnancy and implantation rates and ovarian hyperstimulation syndrome (OHSS) in an IVF donor program.
                No significant differences in the number of retrieved oocytes (327 vs. 288), MII oocytes (70% vs. 76%), fertilization (80% vs. 65%,), pregnancy/transfer (55% vs. 59%), and implantation rates (29% vs. 32%) were found between recipients whose embryos originated from donors in whom final oocyte maturation was triggered with GnRH agonist and those whose donors received hCG. Significant differences in luteal phase length (4.16 + 0.70 days vs. 13.63 + 2.12 days) and in OHSS (0/30 vs. 5/30) were seen between donors ovulated with the agonist and the donors in whom ovulation was triggered with hCG.
                In controlled ovarian stimulation IVF donor cycles, GnRH agonists trigger ovulation and induce luteolysis but do not compromise embryo implantation capacity. In a prospective, comparative, dose-finding study, the minimal effective dose of recombinant human LH (rhLH) required to induce final follicular maturation and early luteinization in patients undergoing in vitro fertilization and embryo transfer was determined. In addition, the efficacy and safety of rhLH were compared with urinary human CG (u-hCG). A total of 259 infertile women, aged 18-39 yr, were enrolled in the study. After pituitary desensitization using a GnRH agonist, rhFSH was administered for ovarian stimulation. Patients then received either rhLH or u-hCG to achieve final follicular maturation. The doses of rhLH administered were 5,000, 15,000, 30,000, or 15,000 + 10,000 IU (second injection administered 3 days after the first injection; 129 patients), and those of u-hCG were consistently 5,000 IU (121 patients). Ovum pick-up was performed 34--38 h after rhLH or u-hCG injection. After fertilization in vitro, up to three embryos were replaced in the uterine cavity. The numbers of oocytes retrieved after u-hCG or rhLH administration were not significantly different between the four different doses of rhLH, when compared with each corresponding u-hCG group, nor when compared with the pool of all u-hCG groups. Similarly, there were no statistically significant differences in: the number of oocytes retrieved per follicle with a diameter of over 10 mm on the day of u-hCG or rhLH administration; the number of patients with at least one oocyte retrieved; oocyte nuclear maturity; oocyte potential for fertilization; the number of embryos; the number of total, biochemical, and clinical pregnancies; and the embryo implantation rate. However, in many of these parameters, the lowest dose of rhLH seemed suboptimal when compared with the higher dose. In terms of safety, rhLH was well tolerated at a dose of up to 30,000 IU. Moderate ovarian hyperstimulation syndrome (OHSS) was reported in 12.4% of patients who received u-hCG and 12.0% of patients who received two injections of rhLH. No moderate or severe OHSS was reported in patients who received a single dose of rhLH up to 30,000 IU. The results show that a single dose of rhLH is effective in inducing final follicular maturation and early luteinization in in vitro fertilization and embryo transfer patients and is comparable with 5,000 IU u-hCG. A single dose of rhLH results in a highly significant reduction in OHSS compared with hCG. The dose of rhLH giving the highest efficacy to safety ratio was between 15,000 and 30,000 IU. 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. Eliciting an endogenous LH surge by GnRH-agonist for the induction of final oocyte maturation may be more physiological compared with the administration of HCG. However, the efficacy of this intervention in patients treated for IVF with GnRH antagonists remains to be assessed.
                106 patients were randomized to receive either 10 000 IU urinary HCG or 0.2 mg Triptorelin for triggering final oocyte maturation. Ovarian stimulation for IVF was performed with a fixed dose of 200 IU recombinant FSH and GnRH antagonist was started on stimulation day 6. Luteal phase was supported with micronized vaginal progesterone and oral estradiol. The study was monitored continuously for safety and stopping rules were established.
                No significant differences were present in the number of cumulus-oocyte complexes retrieved, in the proportion of metaphase II oocytes, in fertilization rates or in the number and quality of the embryos transferred between the two groups. However, a significantly lower probability of ongoing pregnancy in the GnRH agonist arm prompted discontinuation of the trial, according to the stopping rules established (odds ratio 0.11; 95% confidence interval 0.02-0.52).
                Lower probability of ongoing pregnancy can be expected when GnRH agonist is used for triggering final oocyte maturation instead of HCG in patients undergoing ovarian stimulation for IVF with GnRH antagonists. To compare the safety of recombinant human luteinizing hormone (LH) with that of urinary hCG in terms of the hemodynamic changes when they are used to induce final follicular maturation in patients undergoing in vitro fertilization (IVF). A secondary end point was efficacy in terms of IVF outcome.
                Prospective, randomized clinical trial.
                University teaching hospital.
                Thirty IVF patients.
                Ovarian stimulation was induced with FSH under pituitary suppression. Patients were randomized to receive either hCG or recombinant human LH as a trigger of oocyte maturation (5,000 IU) and for luteal phase support (5,000 IU, 2,500 IU, and 2,500 IU on the day of follicular aspiration, 2 days later, and 5 days later, respectively).
                Mean arterial pressure, cardiac output, peripheral vascular resistance, and serum levels of progesterone, plasma concentrations of aldosterone, norepinephrine, and plasma renin activity were measured in all patients on postovulatory day 7 of the spontaneous menstrual cycle preceding IVF (baseline) and 7 days after the hCG/recombinant human LH ovulatory injection during the IVF cycle.
                Ovarian response and IVF outcome (pregnancy rate, 60%) were similar in both treatment groups. On the seventh day after hCG/recombinant human LH administration, the peripheral vascular resistance was significantly lower and serum progesterone concentrations significantly higher in the hCG group as compared with the recombinant human LH group. The percentage change from baseline values during IVF cycles in all hemodynamic and neurohormonal variables investigated was higher (albeit not statistically different) in the group treated with hCG vs. the group treated with recombinant human LH.
                Recombinant human LH is associated with less intense circulatory changes than hCG when it is given to induce final follicular maturation and luteal phase support in IVF procedures.
We conclude that there is no evidence of difference between rhCG or rhLH and uhCG in achieving final follicular maturation in IVF, with equivalent pregnancy rates and OHSS incidence. According to these findings uHCG is still the best choice for final oocyte maturation triggering in IVF and ICSI treatment cycles.