Ovarian stimulation in 2007: the evolving role of GNRH analogues at a large, university-based fertility center (original) (raw)
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Fertility and Sterility, 2013
The aim of this study was to assess ignoring of the GnRH antagonists on the day of hCG effect the pregnancy and live birth rate during GnRH-antagonist protocol. DESIGN: A retrospective observational study. MATERIALS AND METHODS: A total of 209 eligible IVF cycles in 188 women who underwent gonadotropin-releasing hormone (GnRH) antagonist protocols were evaluated retrospectively. The patients were divided into two groups according to the administration of the GnRH antagonists until the day of hCG (Group A, 135 cycles) or abandoning on the day of hCG (Group B, 74 cycles). The differences between Group A and Group B were tested by Student's t test or Mann Whitney U test. Pearson Chi-square test was applied for categorical comparisons. RESULTS: No differences were found in peak serum estradiol levels, serum progesterone levels, endometrial thickness on the day of hCG, number of oocytes retrieved and number of mature (MII) oocytes among the groups. Total doses of gonadotropins used was less in Group B (1945.1AE942.9 IU) than Group A (2551.8AE1432.8 IU) (p<0.05). No significant differences were found regarding fertilization rates between the groups. The number of Grade A embryos (2.01AE0.7, 1.41AE0.5; p<0.05), rate of blastocyst (63.26AE23.2, 41.57AE20.7; p<0.05) and the number of transferred embryos (2.3AE0.7, 1.4AE0.5; p<0.05) were higher in Group B compared to group A. Although implantation rates were less in Group B (14%) compared to Group A (28%) (p<0.05), clinical pregnancy rates (Group A: 33%, Group B: 30%) and live birth rates (Group A: 26%, Group B 26%) were similar between the groups (p>0.05) whereas no significant differences were found regarding cancellation rates between the groups (10%,12%;p>0.05). CONCLUSION: During a flexible multiple-dose GnRH antagonist protocol, abandoning of the GnRH antagonist on the day of hCG administration does not compromise IVF results in terms of clinical pregnancy and live birth rates.
Frontiers in Endocrinology, 2022
IntroductionThe choice of trigger drug for the controlled ovarian hyperstimulation (COH) protocol correlates with the outcome of in vitro fertilization/intracytoplasmic sperm injection embryo transfer (IVF/ICSI-ET). The co-administration of gonadotropin releasing hormone agonist (GnRH-a) and human chorionic gonadotropin (hCG), i.e., dual trigger, for final oocyte maturation, has received much attention in recent years. This trial was designed to determine whether a dual trigger approach by lengthening the time between trigger and ovum pick-up (OPU) improves the quantity and quality of mature oocytes/top-quality embryos and pregnancy outcomes in expected normal responders with a high immature oocyte rate.Methods and AnalysisWe propose a study at the Affiliated Hospital of Shandong University of Chinese Medicine. A total of 90 individuals undergoing COH use a fixed GnRH antagonist protocol. They will be assigned randomly into two groups according to the trigger method and timing: reco...
Human Reproduction, 2011
This prospective study was designed to assess whether the use of GnRH antagonists can improve the success rate of controlled ovarian stimulation (COS) in intrauterine insemination (IUI) treatments. PATIENTS AND METHODS: Eighty patients were divided into two groups: GnRH antagonist group (Group A, n=40) and control group (Group B, n=40). Patients in Group B underwent COS with recombinant Follicle Stimulating Hormone (r-FSH, 50-75 IU/d) only, while patients in Group A were administered r-FSH (50-75 IU/d) plus cetrorelix (0.25 mg/d, starting when ≥ 2 follicles ≥ 14 mm were detected on ultrasound scan). In both groups a single insemination was performed 36 hours after human Chorionic Gonadotropin (hCG, 250 mcg) administration. The primary outcome was clinical Pregnancy Rate (PR). Secondary outcomes were ongoing PR, incidence of Premature Luteinization (PL), number of follicles with mean diameter ≥ 16 mm and between 11 and 15 mm on the day of hCG administration, miscarriage rate, cycle cancellation rate, total amount of r-FSH used and duration of treatment. Student's t test and Chi-square test were used (p < .05 statistically significant). RESULTS: A total of 146 cycles were performed (Group A: n=72; Group B: n=74). A trend towards higher PR in Group A was detected, although it was not statistically significant (Clinical PR: 18.05% vs 10.81%). The number of follicles ≥ 16 mm was significantly increased in Group A. The incidence of both premature LH surge and premature luteinization (PL) was significantly higher in Group B. No significant differences were found in the duration of the stimulation protocol, and in the total amount of r-FSH administered. CONCLUSIONS: The addition of GnRH antagonist in COS/IUI protocol significantly increases the number of mature follicles. However, this multifollicular recruitment is not linked to a significantly higher PR.
JBRA Assisted Reproduction
Objective: The aim of the present study is to investigate embryo quality (score) after controlled ovarian stimulation for IVF using rFSH or hMG with the GnRH antagonist protocol. Methods: Open, randomized, single center study. The patients were randomized to receive rFSH or hMG according to randomized cards inside a black envelope with the name of the respective treatment following a computer generated list (85 patients were allocated to rFSH group and 83 patients to hMG group). Inclusion criteria were patients with IVF indication and normal ovarian reserve. Embryo evaluation was performed on day three, after fertilization based on the Graduated Embryo Score (GES). Results: There were no relevant differences in demographic characteristics. There was no difference in pregnancy rates with 27 (31%) and 25 (30.1%) pregnancies for rFSH and hMG, respectively (p=0.87). The total embryo score was the same for both groups, but the best embryo score was significant higher for the rFSH group (77.33±34.0 x 65.07±33.2 p=0.03). The total number of embryos was statistical different, also in favor of the rFSH group (4.17±3.1 x 3.26±2.4 p=0.04). Conclusion: The total embryo score was the same for both groups, but the best embryo score was significantly higher for the rFSH group. Moreover, rFSH was associated with an increased number of embryos.
Fertility and Sterility, 2010
Objective: To assess whether GnRH agonist administration in the luteal phase improves pregnancy outcome in intrauterine insemination (IUI) cycles. Design: Single-center, randomized, single-blind, placebo-controlled trial. Setting: University-affiliated infertility clinic, between February 2005 and December 2007. Patient(s): Three hundred forty-four women undergoing IUI owing to mild to moderate male factor or donor sperm indication. Intervention(s): Random administration to either a single subcutaneous injection of 0.1 mg triptorelin (group A; n ¼ 172) 8 days after hCG administration, or solvent only (group B; n ¼ 172) at the same time. Main Outcome Measure(s): Pregnancy rate was the primary outcome measure considered for assessing the role of triptorelin administration at the time of implantation. Clinical pregnancy, miscarriage, and ongoing pregnancy rates were the secondary outcome measures. Result(s): No differences were detected between the groups regarding clinical, seminal, or ovarian stimulation parameters. Pregnancy rate per randomized patient was similar in both groups (22.7% vs. 22.1%), as were clinical pregnancy, miscarriage, and ongoing pregnancy rates. There was a significant increase in the proportion of multiple pregnancies in the placebo group (10.3% vs. 36.8%). Conclusion(s): Administration of GnRH agonist at the time of implantation does not improve the reproductive outcome of IUI cycles. (Fertil Steril Ò 2010;94:1065-71.
Human Reproduction, 2020
STUDY QUESTION Do cumulative live birth rates (CLBRs) after one complete ART cycle differ between the three commonly used controlled ovarian stimulation (COS) protocols (GnRH antagonist, depot GnRHa (GnRH agonist) and long GnRHa) in normal responders undergoing IVF/ICSI? SUMMARY ANSWER There were similar CLBRs between the GnRH antagonist, depot GnRHa and long GnRHa protocols. WHAT IS KNOWN ALREADY There is no consensus on which COS protocol is the most optimal in women with normal ovarian response. The CLBR provides the final success rate after one complete ART cycle, including the fresh and all subsequent frozen–thawed embryo transfer (ET) cycles. We suggest that the CLBR measure would allow for better comparisons between the different treatment protocols. STUDY DESIGN, SIZE, DURATION A prospective controlled, randomized, open label trial was performed between May 2016 and May 2017. A total of 819 patients were allocated to the GnRH antagonist, depot GnRHa or long GnRHa protocol in...
Basrah Journal of Surgery, 2013
The aim of this study is to compare clinical pregnancy rates in ICSI-ET cycles where GnRH agonist or hCG was used to induce final maturation of the oocytes. A total of 97 women who produced more than 14 follicles following ovulation induction with recombinant FSH and GnRH antagonist were selected for randomization. Human chorionic gonadotropin (hCG, 5.000 IU, IM) or GnRH agonist (triptorelin 0.2 mg, SC) was used for the induction of final maturation. Women in GnRH agonist group received higher dose of progesterone (100 mg vs. 50 mg) and estradiol (6 mg orally per day vs. none) compared to women in hCG group in the luteal phase starting on the day of oocyte pickup. Age, duration of stimulation, dose of gonadotropins, peak estradiol levels were similar in both groups. The mean number of collected oocytes (14.7±2.1 vs. 13.8±4.3) and fertilization rates (70.7 ±18 vs.71.8 ±21) were not significantly different between women allocated to hCG group (n=53) and GnRH agonist group (n=44). Clinical pregnancy rates (37.7 vs. 36.3), miscarriage rates (15% vs. 18.7%) and ongoing pregnancy rates (32% vs. 29.5%) were similar between hCG group and GnRH agonist group, respectively. Two cases of moderate/severe OHSS occurred in the hCG group, and none in the GnRH agonist group. In conclusion, GnRH-agonist triggering together with high dose steroid supplementation in the luteal phase yields similar clinical pregnancy rate to that obtained with lower dose of hCG administration for final maturation. However, lower dose of hCG was associated with a higher incidence of moderate/severe OHSS.
Session 65: Fertility Preservation 3
Human Reproduction, 2010
Oral contraceptive pills (OC) allow an effective scheduling in IVF cycles, using GnRh antagonists for controlled ovarian stimulation. Its influence in cycle outcomes is still controversial. We conducted a prospective, randomized, controlled study to compare IVF performance in antagonist GnRh cycles with and without oral contraceptive pre-treatment. material and methods: 150 patients with IVF indication were randomized to receive either pre-treatment with OC or non-pretreatment. Inclusion criteria for this study were: Age less than 39, first IVF attempt, basal FSH less than 12 mIU/ml. Patients with PCO criteria, prior ovarian surgery and TESE needing were excluded. The OC group (Group A, N = 75) took April ® (0.02 mg etinilestradiol-0.1 mg levonorgestrel) for 21 days in the preceding cycle and follicular development was induced using recombinant FSH of 200 IU/day from menstrual cycle day 2-3. The non-OC group (Group B, N = 75) started with rFSH at same dose from day 2-3 after menses. Both groups received GnRh antagonist (Cetrorelix 0.25 mg subcutaneous) in a flexible protocol starting when the leading follicle reached 14 mm average size continuing daily until the day of hCG administration. Oocyte maturation was triggered by recombinant 250 μg hCG and 34-36 hours later ovum pick up was performed followed by IVF of ICSI and embryo transfer was performed 3 or 5 days later. Clinical pregnancy rate (PR) was the primary endpoint. Secondary endpoints were: Total days of stimulation and gonadotrophin dose, Total and metaphase 2 oocyte number, fertilization rate, good embryo quality and implantation rate. Statistical analysis was performed with chi2 tests for categorical data and t test for continuous parametric data. results: 75 patients were assigned to each group. 4 patients in group A and 3 patients in group B started ovarian stimulation but did not have embryo transfer. There were no difference between total gonadotrophin dose (2360 ± 748 IU vs 2233 ± 499 IU, NS) and stimulation days (10.3 ± 1.7 vs. 10.3 ± 1.4. NS) between both groups. The mean number of oocytes retrieved per cycle in group A was 10.1 ± 6 (7.4 ± 4.7 M2) versus 11.9 ± 7.7 (9.1 ± 5.9 M2) in group B, not significant. Although we found no difference in fertilization rate (72.3 % vs 76.6 %, NS), total number of embryos achieved (5.2 ± 3.6 vs 6.2 ± 3,9, NS) and good embryo quality rate (48.8 % vs 64.9 %, NS) between both groups, clinical pregnancy rate was significantly higher in OC group (40/71, 56.3% group A vs 27/72, 37.5% group B, p < 0.05). Implantation rate did not reached statistical difference between groups (20.7 % group A vs. 15.8 % group B, NS). conclusion: Contraceptive pre-treatment facilitates cycle scheduling for IVF and does not affect ovarian response. Moreover, though the number and quality of oocytes and embryos have no significant difference, in good responder patients oral contraceptive pretreatment seems to have a beneficial effect in clinical pregnancy rate. To conclude, the present study suggests that oral contraceptive pretreatment achieves better pregnancy rates in IVF antagonists GNRH flexible protocols.
Session 58: Fertility Preservation 2
Human Reproduction, 2010
GnRH antagonists have emerged as a major breakthrough in the field of controlled ovarian hyperstimulation. They induce immediate pituitary desensitization, thus preventing and interrupting unscheduled LH surges. Till date, a trend of lower pregnancy rates has been observed in GnRH antagonist cycles, both in fixed and flexible protocols. The clinical outcome may be improved by developing more flexible antagonist regimens, taking into account individual patient characteristics. The aim of the present study is to evaluate one such improvised protocol to augment pregnancy rates. We compared the outcome of ICSI cycles by administering GnRH antagonist at lead follicle diameter of 14mm vs 18mm.Antagonist administration was planned at 18mm follicle size, since it is known that prolonged exposure of GnRH antagonist could be detrimental for implantation and pregnancy. material and methods: This randomized controlled study was conducted during the period June 2008 to December 2009 at the Institute of Reproductive Medicine, Kolkata, India. A total of 84 women between 25-35 years of age were selected. All were normogonadotropic, euthyroid and normoprolactinaemic. Male factor infertility and endometriosis subjects were excluded from the study. Patients were randomized on alternate basis into two groups, Group-A and Group-B. Controlled ovarian hyperstimulation was initiated from D 2 of index cycle with recombinant FSH 150IU daily. Folliculometry was started from D 6 , and dose of rFSH was adjusted accordingly. In Group-A (n = 42), serum estradiol, LH and progesterone were estimated when lead follicle diameter reached 14mm. GnRH antagonist Cetrorelix 0.25 mg was administered subcutaneously daily and continued till the day of hCG at lead follicle diameter of 18mm. In Group-B (n = 42), the same investigations were carried out when lead follicle diameter was 14mm and continued daily till lead follicle reached 18mm. Cetrorelix 0.25 mg was administered when at least one follicle was 18mm in size. In both the groups recombinant hCG 250μg was given and oocyte retrieval was carried out 35 hours later. Evaluation of oocyte quality was done by routine morphological grading and polarized microscopy. Routine culture techniques were adopted and ICSI was performed in all cases, as all oocytes were denuded for polscopic examination. All women were subjected to D 2 cleavage stage transfer with 2 embryos. Luteal support was given with micronized progesterone pessaries 600mg daily. Serum bhCG was estimated at 13 days post-embryo transfer. Transvaginal USG for evidence of fetal cardiac activity was performed 4 weeks after ET. Statistical analysis was done by Chi square test and 't' test. results: The results were compared between Group-A and Group-B. The primary outcome measures were LH (3.309 ± 1.963 vs 4.043 ± 2.136;NS) and P 4 levels (0.973 ± 0.287 vs 1.120 ± 0.573;NS) on the day of initiation of GnRH antagonist and pregnancy rates (21.42% vs 45.23%; P < 0.05) per cycle. The secondary outcome measures were terminal E 2 (1643.67