Comparisons of GnRH antagonist protocol versus GnRH agonist long protocol in patients with normal ovarian reserve: A systematic review and meta-analysis

Abstract

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.

Use of progestins to inhibit spontaneous ovulation during ovarian stimulation: the beginning of a new era?

“…However, the effectiveness of antagonists is still under debate. According to multiple studies comparing a GnRH agonist protocol and GnRH antagonist protocol, effectiveness, the number of oocytes retrieved and the number of embryos obtained are significantly lower when the antagonist is used (Wang et al, 2017). Furthermore, the cycle cancellation rate seems higher in women who received GnRH antagonist protocols compared with GnRH agonist protocols (Kahyaoğlu et al, 2017).…”

The Frequency of Ovarian Hyperstimulation Syndrome and Thromboembolism with Originator Recombinant Human Follitropin Alfa (GONAL-f) for Medically Assisted Reproduction: A Systematic Review

“…There is also a risk for thromboembolic events, which is increased in the presence of pregnancy and OHSS. Recent reports of the occurrence of OHSS and thromboembolism in different populations have reported rates of less than 0.5% [4], meaning these adverse events (AEs), although important, occur rarely during ovarian stimulation with r-hFSH [4,17,18].…”

Live Birth Rate of Fresh Embryo Transfer with GnRH Agonist Long Protocol is Higher Than Frozen Embryo Transfer

“…It is still controversial about the e cacy of GnRH-a and GnRH-ant protocols with fresh ET. Several studies suggested that the pregnancy rate, ongoing pregnancy rate and live birth rate of fresh transfer cycles were lower in the GnRH-ant protocol than in the GnRH-a protocol (3,18), whereas other studies showed no signi cant difference (2,19). Furthermore, implantation is one of the most important steps to achieve live birth, therefore it is considered as an important indicator to the e cacy of the treatment.…”

“…Gonadotropin-releasing hormone agonist (GnRH-a) has been used since the early 1980s and plays an important role in controlled ovarian stimulation (COS) (1). Currently, GnRH antagonist (GnRH-ant) protocol is widely used due to its shorter treatment time, fewer injections and lower ovarian hyperstimulation syndrome (OHSS) rate than GnRH-a protocol (2). However, the standard GnRH-a long protocol is still one of the key down regulation protocol in China, due to its steady and higher clinical pregnancy rate in fresh embryo transfer (ET) in vitro fertilization (IVF) patients (3).…”