Dataset Information

Comparisons of GnRH antagonist versus GnRH agonist protocol in supposed normal ovarian responders undergoing IVF: a systematic review and meta-analysis.

ABSTRACT:

Objective

To evaluate the effectiveness and safety of GnRH antagonist and GnRH agonist in supposed normal ovarian responders undergoing IVF.

Methods

Data from 6 databases were retrieved for this study. The RCTs of GnRH agonist and GnRH antagonist use during IVF-EF therapy for patients with supposed normal ovarian response were included. A meta-analysis was performed with Revman 5.1software.

Results

Twenty-three RCTs met the inclusion criteria. The number of stimulation days (mean difference (MD): -0.66, 95% confidence interval (CI): -1.04?-0.27), Gn amount (MD: -2.92, 95% CI: -5.0?-0.85), E2 values on the day of HCG (MD: -330.39, 95% CI: -510.51?-150.26), Number of oocytes retrieved (MD: -1.33, 95% CI: -2.02?-0.64), clinical pregnancy rate (odds ratio (OR): 0.87, 95% CI: 0.75-1.0), and ovarian hyperstimulation syndrome (OHSS) incidence (OR: 0.59, 95% CI: 0.42?0.82) were significantly lower in GnRH antagonist protocol than GnRH agonist protocol. However, the endometrial thickness on the day of HCG (MD: -0.04, 95% CI: -0.23?0.14), the ongoing pregnancy rate (OR: 0.87, 95% CI: 0.74?1.03), live birth rate (OR: 0.89, 95% CI: 0.64?1.24), miscarriage rate (OR: 1.17, 95% CI: 0.85?1.61), and cycle cancellation rate (OR: 1.11, 95% CI: 0.90?1.37) did not significantly differ between the 2 groups.

Conclusions

During IVF treatment for patients with supposed normal responses, the incidence of OHSS were significantly lower, whereas the ongoing pregnancy and live birth rates were similar in the GnRH antagonist compared with the standard long GnRH agonist protocols.

SUBMITTER: Xiao JS

PROVIDER: S-EPMC4162565 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Publications

Comparisons of GnRH antagonist versus GnRH agonist protocol in supposed normal ovarian responders undergoing IVF: a systematic review and meta-analysis.

Xiao Jin-song JS Su Cun-mei CM Zeng Xian-tao XT

PloS one 20140912 9

<h4>Objective</h4>To evaluate the effectiveness and safety of GnRH antagonist and GnRH agonist in supposed normal ovarian responders undergoing IVF.<h4>Methods</h4>Data from 6 databases were retrieved for this study. The RCTs of GnRH agonist and GnRH antagonist use during IVF-EF therapy for patients with supposed normal ovarian response were included. A meta-analysis was performed with Revman 5.1software.<h4>Results</h4>Twenty-three RCTs met the inclusion criteria. The number of stimulation days ...[more]

PMID: 25216031

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Project description:ObjectiveTo evaluate the effectiveness and safety of gonadotropin-releasing hormone antagonist (GnRH-ant) protocol and gonadotropin-releasing hormone agonist (GnRH-a) long protocol in patients with normal ovarian reserve.MethodsWe searched the PubMed (1992-2016), Cochrane Library (1999-2016), Web of Science (1950-2016), Chinese Biomedical Database (CBM, 1979-2016), and China National Knowledge Infrastructure (CNKI, 1994-2016). Any randomized controlled trials (RCTs) that compared GnRH-ant protocol and GnRH-a long protocol in patients with normal ovarian reserve were included, and data were extracted independently by two reviewers. The meta-analysis was performed by Revman 5.3 software.ResultsTwenty-nine RCTs (6399 patients) were included in this meta-analysis. Stimulation days (mean difference (MD) [95% confidence interval (CI)] = -0.8 [-1.36, -0.23], P = 0.006), gonadotrophin (Gn) dosage (MD [95% CI] = -3.52 [-5.56, -1.48], P = 0.0007), estradiol (E2) level on the day of human chorionic gonadotrophin (HCG) administration (MD [95% CI] = -365.49 [-532.93, -198.05], P<0.0001), the number of oocytes retrieved (MD [95% CI] = -1.41 [-1.84, -0.99], P<0.00001), the embryos obtained (MD [95% CI] = -0.99 [-1.38, -0.59], P<0.00001), incidence of ovarian hyperstimulation syndrome (OHSS) (OR [95% CI] = 0.69 [0.57, 0.83], P<0.0001) were statistically significantly lower in GnRH-ant protocol than GnRH-a long protocol. However, the clinical pregnancy rate (OR [95% CI] = 0.90 [0.80, 1.01], P = 0.08), ongoing pregnancy rate (OR [95% CI] = 0.88 [0.77, 1.00], P = 0.05), live birth rate (OR [95% CI] = 0.95 [0.74, 1.09], P = 0.27), miscarriage rate (OR [95% CI] = 0.98 [0.69, 1.40], P = 0.93), and cycle cancellation rate (OR [95% CI] = 0.86 [0.52, 1.44], P = 0.57) showed no significant differences between the two groups.ConclusionGnRH-ant protocol substantially decreased the incidence of OHSS without influencing the pregnancy rate and live birth rate compared to GnRH-a long protocol among patients with normal ovarian reserve.

Project description:A suggested explanation for the pituitary-suppressive effects of progestin-primed ovarian stimulation cycles (PPOS) is pituitary luteinizing hormone (LH) depletion with progestin exposure during the follicular phase. The GnRH agonist (GnRHa) trigger releases endogenous LH from the pituitary, and if the LH depletion theory is correct, the response to the agonist trigger would be dampened in PPOS cycles. In this study, we compared the performance of the GnRHa trigger after PPOS and GnRH antagonist ovarian stimulation cycles. All women who underwent ovarian stimulation with the GnRH antagonist or flexible PPOS (fPPOS) and received a GnRH agonist trigger were eligible for inclusion. Outcomes included number of metaphase-II (MII) oocytes retrieved per cycle, rates of empty follicle syndrome, maturation, fertilization, blastulation, and cumulative clinical pregnancy per stimulation cycle. During the screening period, there were 166 antagonists and 58 fPPOS cycles triggered with a GnRH agonist. Groups were matched for potential confounders using propensity score matching. Progestin-downregulated cycles had 19% high mature oocyte yield (median: 14 vs. 19 MII oocytes, P = 0.03). Cumulative ongoing pregnancy or live birth rates were estimated after matching for transferred embryo count, and rates were similar between GnRH antagonist and fPPOS group (57.0% vs. 62.1%, P = 0.68). However, the number of remaining blastocysts was higher in the fPPOS group (median: 5.0 vs. 6.0, P < 0.001). LH levels were higher in fPPOS cycles compared to GnRH antagonist cycles up to the trigger day (P < 0.001). After the GnRHa trigger, fPPOS cycles were associated with a steeper LH surge compared with antagonist cycles (P = 0.02). Higher endogenous gonadotropin levels through the stimulation period and an LH surge of higher magnitude following a GnRHa trigger suggest a milder pituitary suppression by fPPOS, which needs to be confirmed in larger samples. It appears that progestins do not deplete pituitary LH reserves and a GnRHa trigger is usable after PPOS in women with high ovarian reserve.

Project description:Gonadotropin-releasing hormone antagonist (GnRH-ant) has been shown to negatively influence endometrial receptivity. Reducing the GnRH-ant dose during controlled ovarian stimulation (COS) when using a GnRH-ant protocol may be beneficial to embryo implantation. However, whether or not the minimum daily GnRH-ant dose should be individualized remains uncertain. In this retrospective study, we aimed to elucidate the feasibility and effectiveness of moderately reducing the daily GnRH-ant dose to 0.125 mg, and then adjusting the dose to 0.25 mg based on subsequent luteinizing hormone (LH) levels. Of the 434 patients analyzed in this study, 209 received our new flexible low-dose GnRH-ant protocol (Group 1) and 225 received a conventional GnRH-ant protocol with a fixed daily dose of 0.25 mg (Group 2). Furthermore, 105 and 114 cycles from groups 1 and 2 received fresh embryo transfer. In Group 1, 30 patients whose dose of 0.125 mg GnRH-ant was adjusted according to their LH levels and 179 patients who received consistently low doses were further divided into subgroups 1 and 2, respectively. Neither the number of retrieved oocytes and available embryos nor the implantation rate, clinical pregnancy rate, and ongoing pregnancy rate significantly differed between the two groups. However, GnRH-ant dose and stimulation duration were much lower and shorter in Group 1 than in Group 2 (p < 0.05). Subgroup 1 exhibited higher basal follicle-stimulating hormone (FSH) and lower antral follicle count (AFC) than subgroup 2 significantly. The number of retrieved oocytes and available embryos were lower in subgroup 1 than in subgroup 2 (6.83 ± 3.28 vs. 11.83 ± 4.82, 2.93 ± 1.86 vs. 4.99 ± 3.46, respectively, p < 0.05), while more canceled cycles for pre-ovulation occurred in subgroup 1 than in subgroup 2 (3/30 vs. 1/179, p < 0.05). The results showed that the flexible low-dose GnRH-ant protocol was as effective as the conventional fixed-dose GnRH-ant protocol with 0.25 mg per day for most patients with normal ovarian reserve. This retrospective analysis and the small sample size are the main limitations of this study, and a large sample RCT will be carried out in the future.

Project description:BackgroundCurrently, there is no universal criteria for the trigger time of controlled ovarian hyperstimulation (COH), especially with the emerging depot GnRH agonist protocol. It is challenging to explore an indicator that is representative of target follicle cohort development as an alternative to the conventional approach of determining the trigger time based on a few leading follicles.MethodsThis was a large-sample retrospective analysis. Between January 2016 and January 2020, 1,925 young normal ovarian responders who underwent their first in vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) cycle using the depot GnRH agonist protocol were included. They were divided into three groups based on the dominant follicular proportion (DFP, defined as the ratio of ≥ 18 mm dominant follicles/ ≥ 14 mm large follicles on the human chorionic gonadotropin (HCG) day; Group A: < 30%; Group B: 30%-60%; and Group C: ≥ 60%). The binary logistic regression and multivariate linear regression were used to assess whether the DFP was associated with clinical pregnancy, the number of frozen blastocysts, the blastocyst formation rate, and the low number of frozen blastocysts.ResultsThe logistic regression analysis showed that compared with Group A, the odds ratio (OR) for clinical pregnancy was 1.345 in Group B (P = 0.023), and there was no statistical difference between Group C and Group A (P = 0.216). The multivariate linear regression analysis showed that DFP was negatively associated with the number of frozen blastocysts (β ± SE: Group B vs. Group A = - 0.319 ± 0.115, P = 0.006; Group C vs. Group A = - 0.432 ± 0.154, P = 0.005) as well as the blastocyst formation rate (β ± SE: Group B vs. Group A = - 0.035 ± 0.016, P = 0.031; Group C vs. Group A = - 0.039 ± 0.021, P = 0.067). Furthermore, the OR for the low number of frozen blastocysts was 1.312 in Group B (P = 0.039) and 1.417 in Group C (P = 0.041) compared to Group A.ConclusionsFor young normal ovarian responders using the depot GnRH agonist protocol, increasing DFP might reduce the developmental potential of oocytes and reduce the number of available blastocysts, and this might result in a lower cumulative pregnancy rate. However, further confirmation using strict prospective randomised controlled studies is required.

Dataset Information

Comparisons of GnRH antagonist versus GnRH agonist protocol in supposed normal ovarian responders undergoing IVF: a systematic review and meta-analysis.

Objective

Methods

Results

Conclusions

Publications

Comparisons of GnRH antagonist versus GnRH agonist protocol in supposed normal ovarian responders undergoing IVF: a systematic review and meta-analysis.

Similar Datasets

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