[Systematic inhibition of the luteinizing hormone with a gonadoliberin analog, triptorelin, during ovarian stimulation for fertilization in vitro. Choice of protocol]. Good results of milder form of ovarian stimulation in an in vitro fertilization/intracytoplasmic sperm injection program. Should gonadotropin-releasing hormone down-regulation therapy be routine in in vitro fertilization? Evaluation of ovulation induction protocols for poor responders undergoing assisted reproduction techniques. Randomized, prospective comparison of luteal leuprolide acetate and gonadotropins versus clomiphene citrate and gonadotropins in 408 first cycles of in vitro fertilization. Luteal phase consequences of low-dose gonadotropin-releasing hormone agonist therapy in nonluteal-supported in vitro fertilization cycles. Comparison of stimulation with clomiphene citrate in combination with recombinant follicle-stimulating hormone and recombinant luteinizing hormone to stimulation with a gonadotropin-releasing hormone agonist protocol: a prospective, randomized study. Comparison of outcome of clomiphene citrate/human menopausal gonadotropin/cetrorelix protocol and buserelin long protocol--a randomized study. Comparison of mild stimulation and conventional stimulation in ART outcome. The routine use of gonadotropin-releasing hormone agonists for all patients undergoing in vitro fertilization. Is there any medical advantage? A prospective randomized study.
The quality of ovarian stimulation for in vitro fertilization with or without an LH-RH analogue was investigated in a randomized trial involving 30 women divided into 3 groups. Group I women were treated with the conventional clomiphene citrate-human menopausal gonadotropin combination without LH-RH analogue. Group II women (long regimen) received a slow-release preparation of triptorelin (DTRp6-LH-RH), an LH-RH analogue, and human menopausal gonadotropin. Group II women (short regimen) were given triptorelin with human menopausal gonadotropin. Inhibition of the endogenous luteinizing hormone using triptorelin improved the results of in vitro fertilization in group II and group III women, but the short regimen was distinctly less compelling and less expensive than the long regimen. In a prospective study, we compared two protocols of ovulation stimulation, the clomiphene citrate and human menopausal gonadotropin (hMG) versus D-triptorelin, a long-acting gonadotropin-releasing hormone (GnRH) agonist and hMG in 324 couples having their first in vitro fertilization or intracytoplasmic sperm injection (IVF/ICSI) program, in terms of pregnancy rates and cost-effectiveness of drugs used. The GnRH agonist/hMG group was characterized by a greater mean number of ampoules of hMG used (31.7 versus 10.2), a larger number of oocytes collected (10.4 versus 4.2), and a larger number of embryos obtained (5.8 versus 2.9). With the policy of transferring only two of the best quality embryos, the mean number of embryos replaced were comparable (1.8 in clomiphene citrate/hMG and 1.9 in GnRH agonist/hMG group). The percentage of patients reaching embryo transfer was lower in the clomiphene citrate/hMG than in the GnRH agonist/hMG group (84.1% versus 93.1%, respectively). However, the combined results of the IVF and ICSI procedure in terms of pregnancy rate, both per patient and per embryo transfer were better, though not significantly in the clomiphene citrate/hMG than in GnRH agonist/hMG group (25.0% and 29.7% versus 23.7% and 25.5%, respectively). Similarly, the implantation rate was better (19.0% versus 13.5%, respectively). With the use of clomiphene citrate/hMG, a fivefold less costly drug regimen, we obtained pregnancy rates equivalent to those gained using GnRH agonist/hMG in our IVF/ICSI program. To compare the classic clomiphene citrate (CC) and hMG regime for ovarian stimulation before IVF in women who received hMG post-long protocol down-regulation with either 3 mg triptorelin [INN] IM or 150 mg buserelin acetate four times daily intranasally. Furthermore, if possible, to determine the preferred method of down-regulation.
                A prospective study of 150 women randomized blind to the clinician to one of three alternative ovarian stimulation regimes when passing for the first time through an IVF program during 1992.
                Triptorelin [INN] down-regulated significantly more quickly than buserelin acetate. The non-down-regulated group CC and hMG used significantly less hMG in a shorter time. In these women LH levels at hCG administration were significantly higher. No other intergroup differences were found. Pregnancy and take-home baby rates for the overall study were, respectively, 32%:25% (per cycle) and 42%:33%; (per ET) for the triptorelin [INN] group 28%:22% and 39%:31%; the CC group 32%:24% and 46%:34%; and the buserelin acetate group 34%:28% and 42%:34%.
                Triptorelin [INN] and buserelin acetate were comparable in all parameters except down-regulation. The former was significantly quicker and more sure. In none of the clinical end points measured, however, was the classic CC and hMG non-down-regulation regime significantly less effective or troublesome than where down-regulation was used. These results therefore show that although indications for down-regulation before IVF exist, it should not be used on all patients. To compare 3 stimulation protocols in poor ovulation responders undergoing in-vitro fertilization (IVF).
                The study was a randomized, prospective clinical trial from June 2003 to July 2004, in Royan Institute, Tehran, Iran. One hundred and fifty-four patients, who had poor responses to ovulation induction in at least one previous IVF attempt, were randomly divided into 3 groups. In the first group, human menopausal gonadotropin (HMG) was administered from day 3 of the cycle at a dose rate of 150 IU/day. In the second group, gonadotropin-releasing hormone (GnRH) agonist was started at a dose rate of 800 microg/day by nasal spray or 500 microg/day subcutaneously in the mid-luteal phase, followed by a standard HMG dose after pituitary down regulation was confirmed. In the third group, clomiphene at a dose rate of 100 mg/day was given from day 3 and HMG from day 6. Our main outcomes were number of mature oocytes, cancellation rate, number of HMG ampoules used and incidence premature luteinizing hormone (LH) surge.
                There was a high incidence of premature LH surge in all groups except in the GnRH group (p=0.0001) and there were significant differences between groups in HMG requirements (p=0.004). There were no significant differences between groups in number of mature oocytes recovered and cancellation rate.
                Results showed no advantage in the use of GnRH agonist compared to the older regimens of clomiphene plus HMG and HMG alone. The cancellation rate was similar for 3 protocols and HMG requirement was higher with the use of GnRH agonist. The treatment of poor responders in assisted reproductive technologies remains a challenge. To compare luteal phase leuprolide acetate (LA) initiated pituitary down regulation followed by human menopausal gonadotropins (hMG) versus clomiphene citrate (CC) and hMG for follicular recruitment and oocyte maturation before in vitro fertilization (IVF).
                Randomized, prospective comparison in first cycles of IVF.
                University Hospital, a tertiary referral center offering assisted reproductive technologies.
                Participants were couples undergoing their first ever cycle of IVF and consenting to participation in the trial.
                Luteal phase initiated LA/hMG was associated with a lower probability of cycle cancellation, improved folliculogenesis, and a higher probability of embryo transfer (ET) compared with CC/hMG alone. Implantation rates were not different.
                A higher rate of ET with LA/hMG suggests that gonadotropin-releasing hormone agonist for the induction of folliculogenesis before IVF may be appropriate. To determine the follicular and luteal phase impact of low-dose GnRH agonist (GnRH-a) treatment during follicular stimulation for IVF.
                A randomized prospective study compared patients receiving low-dose GnRH-a and hMG therapy to clomiphene citrate (CC) and hMG cycles.
                Patients were treated through a university-based IVF-ET program.
                Thirty-six patients underwent follicular stimulation with low-dose GnRH-a and hMG and were compared with 34 patients undergoing ovulation induction with CC and hMG.
                Significantly shorter luteal phase length occurred with GnRH-a and hMG therapy; however, there was no statistically significant difference in luteal P levels. Follicular parameters were the same (peak E2, number of follicles, and number of oocytes), suggesting that folliculogenesis was not altered. There were no statistical differences in pregnancy rates.
                Sustained low-dose GnRH-a therapy during follicular stimulation does not have a clinical effect on luteal function. To compare IVF-ET outcome with a new stimulation protocol using clomiphene citrate (CC) with recombinant FSH and LH to stimulation with the standard long GnRH-a protocol.
                Prospective randomized study.
                Outpatient infertility clinic in Vienna, Austria.
                Two hundred ninety-four infertile women undergoing IVF-ET; 154 IVF cycles stimulated with CC + recombinant FSH + recombinant LH (group A) and 140 cycles with long GnRH-a suppression + recombinant FSH (group B).
                Controlled ovarian hyperstimulation, egg retrieval, and ET.
                Cycle parameters (number of oocytes, fertilization, number of embryos) and outcome (pregnancy rate, cancellation rate, ovarian hyperstimulation syndrome [OHSS]).
                Pregnancy rate per ET was 42.9% (implantation rate, 21.3%) in group A and 36.6% (17.4%) in group B. Cancellation rates were similar. The OHSS occurred in four cases (3%) in group A and 12 cases (10%) in group B.
                Stimulation with CC + recombinant FSH + recombinant LH leads to comparable pregnancy rates vs. the long protocol. With this new stimulation, less gonadotropins are used and there is less need for monitoring (lower cost for patient and clinic). The risk of OHSS is reduced as well. Therefore, this protocol should be regarded as the first-line treatment. This study evaluates the efficacy of a stimulation protocol with clomiphene citrate (CC)/human menopausal gonadotropin (hMG)/cetrorelix and its effects on oocyte quality and endometrium. One hundred and twenty couples with male-factor infertility who were about to undergo their first intracytoplasmic sperm injection cycles were randomized into two groups. Sixty women were stimulated with the CC/hMG/cetrorelix protocol (cetrorelix group) and 60 received the buserelin long protocol (buserelin group). Fewer oocytes were recovered in the cetrorelix group than in the buserelin group (mean +/- standard deviation (SD): 11.1 +/- 4.0 vs. 17.3 +/- 5.8, p < 0.001); however, the percentages of metaphase II, metaphase I and germinal vesicle oocytes were similar between the two groups. Serum estradiol level was significantly lower in the cetrorelix than in the buserelin group (mean +/- SD: 2600.58 +/- 1189.11 vs. 3293.46 +/- 1221.49 pg/ml, p = 0.006), but the endometrial thickness was similar. The implantation rates (19.2% vs. 17.7%) and the pregnancy rates (41.7% vs. 40.0%) were similar between groups. The ampoules (mean +/- SD: 18.9 +/- 3.0 vs. 38.9 +/- 12.2, p < 0.001) and injections (mean +/- SD: 6.8 +/- 1.1 vs. 15.7 +/- 3.1, p < 0.001) of gonadotropin used were significantly lower in the cetrorelix group than in the buserelin group. No patients in either group developed a premature luteinizing hormone surge. The present study found no statistically significant difference between the two treatment modalities with regard to pregnancy rates. 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. 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.
There was no evidence to indicate that clomiphene with gonadotropins (with or without GnRH antagonist) differed significantly from gonadotropins in GnRH agonist protocols for women undergoing IVF treatment, in terms of live births or pregnancy rates. Meanwhile, use of clomiphene led to a reduction in the incidence of OHSS. However, these results were based on data from a small number of underpowered randomised trials with few participants. Hence there was insufficient evidence to recommend use of clomiphene citrate in routine IVF practice. Larger trials with adequate power are required.