Impact of Mid-Luteal Phase GnRH Agonist Administration on Reproductive Outcomes in GnRH Agonist-Triggered Cycles: A Randomized Controlled Trial (original) (raw)
Related papers
Human Reproduction Update, 2011
background: The aim of this systematic review and meta-analysis was to evaluate whether the addition of GnRH agonist for luteal support in ICSI/IVF cycles enhances the probability of live birth. methods: Systematic literature search (MEDLINE, EMBASE, CENTRAL and RCT registries) was conducted to identify relevant randomized controlled trials published as full manuscripts. Meta-analysis of data yielded pooled risk differences (RDs) and 95% confidence intervals (CIs). A random effects model was applied for pooling the studies. results: Six relevant RCTs were identified including a total of 2012 patients. The probability of live birth rate (RD: +16%, 95% CI: +10 to +22%) was significantly higher in patients who received GnRH agonist support compared with those who did not. The subgroup analysis according to the type of GnRH analogue used for LH suppression did not change the effect observed (studies in which GnRH agonist was used during ovarian stimulation, RD: +15%, 95% CI: +5 to +23%); (studies in which GnRH antagonist was used during ovarian stimulation, RD: +19%, 95% CI: +11 to +27%).
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.
JBRA Assisted Reproduction
Objective: This study aimed to evaluate the effects of three different luteal phase support protocols with estrogen on the pregnancy rates and luteal phase hormone profiles of patients undergoing in vitro fertilization-embryo transfer (IVF-ET) cycles. A secondary objective was to evaluate which ovarian reserve markers correlated with pregnancy rates. Methods: This retrospective observational study was carried out at a private tertiary reproductive medicine teaching and research center. The study enrolled 104 patients undergoing intracytoplasmic sperm injection (ICSI) on an antagonist protocol for controlled ovarian hyperstimulation (COH). The women were divided into three groups based on the route of administration of estrogen (E2) for luteal phase support: oral (Primogyna); transdermal patches (Estradott); or transdermal gel (Oestrogel Pump). The administration of estrogen provided the equivalent to 4 mg of estradiol daily. All women received 600mg of vaginal progesterone (P) per day (Utrogestan) for luteal phase support. Blood samples were drawn on the day of hCG administration and on the day of beta hCG testing to measure E2 and P levels. Clinical pregnancy rate (PR) was the main endpoint. Results: The patients included in the three groups were comparable. No significant differences were found in implantation rates, clinical PR, miscarriage rates, multiple-pregnancy rates, E2 or P levels on the day of beta hCG measurement. Concerning ovarian reserve markers, significant correlations between testing positive for clinical pregnancy and AMH (r = 0.66, p<0.0001) and E2 levels on beta hCG measurement day (r = 0.77; p<.0001) were observed. Conclusions: No significant differences were seen in the pregnancy rates of patients submitted to IVF-ET cycles with GnRH antagonists given oral, transdermal patches, or transdermal gel E2 during the luteal phase. A correlation was found between clinical pregnancy rate and AMH and E2 levels on beta hCG testing day.
Frontiers in Endocrinology
Objective: To examine the correlation between serum luteinizing hormone (LH) levels on the day of GnRH agonist (GnRH-a) trigger and reproductive outcomes following in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment and fresh embryo transfer, and to identify a pre-trigger serum LH threshold which would be compatible with the most optimal cycle outcome. Design: This study is based on data from a previously published randomized controlled trial conducted from 2014 to 2016. Patients: A total of 322 participants were enrolled. Setting: Private IVF center. Intervention(s): GnRH-antagonist-based IVF cycles triggered with GnRH-a. For the purpose of the study, patients were stratified according to preovulatory LH quartiles (Q1-Q4). Main Outcome Measure(s): Ongoing pregnancy rates (OP), live birth rates (LB) and early pregnancy loss (EPL) rates. Results: The results of the present study showed increasing OP as well as LB rates and decreasing EPL rates with increasing pre-trigger serum LH levels (P for trend < 0.06, 0.07, and 0.02), respectively. The absolute difference between the highest LH(Q4) and the lowest LH (Q1) group was 13.4%, 12.1%, and 12% in OP, LB, and EPL rates, respectively. In multivariate regression analysis, a pre-trigger serum LH level of 1.60 mIU/ml was identified as a threshold below which reproductive outcomes decreased. The ROC curve values were statistically significant for OP, LB, and EPL; the AUC (95% CI) = [0.57 (0.50-0.63) P < 0.04; 0.57 (0.50-0.63) P < 0.05, and 0.60 (0.51-0.70) P < 0.04], respectively. A significant positive correlation was found on the day of GnRH-a trigger between serum LH, the number of follicles, serum P4, and serum E2, p < 0.03; P < 0.03; and P < 0.001, respectively. Benmachiche et al. Pre-ovulatory LH Levels and IVF Outcomes Conclusion: Low serum LH levels on the day of GnRH-a trigger is associated with reduced ongoing pregnancy and live birth rates and increased early miscarriage rates. Our findings suggest a lower threshold of serum LH values on the day of GnRH-a trigger necessary to optimize reproductive outcomes in fresh embryo transfer cycles.
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.
Human Reproduction, 2006
BACKGROUND: Our prospective randomized controlled trial was designed to assess whether the use of GnRH antagonists can improve the success rate of controlled ovarian stimulation (COS)/intrauterine insemination (IUI) treatments, via inhibition of the premature LH rise. METHODS: A total of 104 patients were randomly divided, using a randomization list, into two groups: in group A (n = 52), recombinant FSH (rFSH) was given with GnRH antagonist Cetrorelix, and in group B (n = 52), the patients received rFSH alone in a manner similar to that of group A. The primary outcome measure was clinical pregnancy rate per couple. RESULTS: The pregnancy rate per patient was 53.8% in group A and 30.8% in group B (P = 0.017). The rate of premature LH surge was 7% in group A and 35% in group B (P < 0.0001). A premature luteinization was observed in two cycles of 144 in group A (1.4%) and in 16 cycles of 154 in group B (10.4%) (P = 0.001). The mean values of LH and progesterone were significantly lower in patients receiving GnRH antagonist than in those who did not (3.3 ± 3.3 mIU/ml in group A versus 9.9 ± 7.9 mIU/ml in group B, P < 0.0001, for LH; 1.3 ± 1.1ng/ml versus 2.1 ± 1.9ng/ml for group A and B, respectively, P < 0.0001, for progesterone). CONCLUSION: The use of GnRH antagonist in COS/IUI cycles improves pregnancy rate, preventing the premature LH rise and luteinization.
Human Reproduction, 2005
BACKGROUND: This study was designed to assess whether the use of ganirelix in women undergoing stimulated IUI could prevent the occurrence of premature LH rises and luteinization (LH + progesterone rises). METHODS: Women of infertile couples, diagnosed with unexplained or male factor infertility, were randomized to receive either ganirelix (n = 103) or placebo (n = 100) in a double-blind design. All women were treated with an individualized, lowdose rFSH regimen started on day 2-3 of cycle. Ganirelix (0.25 mg/day) was started if one or more follicles Ն14 mm were visualized. Ovulation was triggered by HCG injection when at least one follicle Ն18 mm was observed and a single IUI was performed 34-42 h later. The primary efficacy outcome was the incidence of premature LH rises (± progesterone rise). RESULTS: In the ganirelix group, four subjects had a premature LH rise (value Ն10 IU/l), one LH rise prior to the start of ganirelix and three LH rises during ganirelix treatment, whereas in the placebo group 28 subjects had a premature LH rise, six subjects prior to the start of placebo and 22 subjects during placebo treatment. The incidence of LH rises was significantly lower in ganirelix cycles compared to placebo cycles (3.9 versus 28.0%; P = 0.003 for ITT analysis). When excluding subjects with an LH value Ն10 IU/l before the start of ganirelix/placebo the incidence of LH rises was also significantly lower in ganirelix cycles compared to placebo cycles (2.9 versus 23.4%; P = 0.003 for ITT analysis). Premature luteinization (LH rise with concomitant progesterone rise Ն1 ng/ml) was observed in one subject in the ganirelix group and in 17 subjects in the placebo group of which three subjects had a premature spontaneous ovulation. Ongoing pregnancy rates per attempt were 12.6 and 12.0% for the ganirelix and placebo groups respectively. CONCLUSIONS: Treatment with ganirelix effectively prevents premature LH rises, luteinization in subjects undergoing stimulated IUI. Low-dose rFSH regimen combined with a GnRH antagonist may be an alternative treatment option for subjects with previous proven luteinization or in subjects who would otherwise require insemination when staff are not working.
The addition of GnRH antagonists in intrauterine insemination cycles: a pilot study
PubMed, 2013
Aim: 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.