GnRH antagonist versus long agonist protocols in IVF: a systematic review and meta-analysis accounting for patient type.
Topic: Hormone Therapy

Most reviews of IVF ovarian stimulation protocols have insufficiently accounted for various patient populations, such as ovulatory women, women with polycystic ovary syndrome (PCOS) or women with poor ovarian response, and have included studies in which the agonist or antagonist was not the only variable between the compared study arms.

PICO
Population: Women undergoing IVF treatment, including ovulatory women, women with polycystic ovary syndrome (PCOS), and women with poor ovarian response
Intervention: GnRH antagonist protocol for ovarian stimulation in IVF
Comparison: Long agonist protocol for ovarian stimulation in IVF
Outcomes: Comparison of treatment outcomes, including clinical pregnancy rates, live birth rates, and ovarian response, in different patient populations

Included studies:
title: Effect of antagonists vs agonists on in vitro fertilization outcome.
abstract: To compare outcome following in vitro fertilization-embryo transfer (IVF-ET) using controlled ovarian hyperstimulation (COH) regimens using either the gonadotropin-releasing hormone (GnRH) agonist leuprolide acetate vs the GnRH antagonist ganirelix.
title: GnRH antagonist versus long GnRH agonist protocol in poor IVF responders: a randomized clinical trial.
abstract: To compare the efficacy of the long GnRH agonist and the fixed GnRH antagonist protocols in IVF poor responders.
title: IVF/ICSI outcomes between cycles with luteal estradiol (E2) pre-treatment before GnRH antagonist protocol and standard long GnRH agonist protocol: a prospective and randomized study.
abstract: To study if luteal E(2) pre-treatment before GnRH antagonist protocol improves IVF/ICSI outcomes compared with standard long GnRH agonist protocol.
title: Fixed versus flexible gonadotropin-releasing hormone antagonist administration in in vitro fertilization: a randomized controlled trial.
abstract: To evaluate whether the incidence of luteinizing hormone (LH) rise is reduced by using a flexible compared with a fixed day-6 protocol of GnRH antagonist administration.
title: Comparison of GnRH agonists and antagonists in normoresponder IVF/ICSI in Turkish female patients.
abstract: To evaluate the results of gonadotropin-releasing hormone agonist (GnRHa) and gonadotropin-releasing hormone antagonist (GnRHant) use in two demographically matched groups of normoresponder in-vitro fertilisation or intracytoplasmic sperm injection (IVF/ICSI) patients in a prospective study.
title: GnRH agonist versus GnRH antagonist in oocyte donation cycles: a prospective randomized study.
abstract: The specific role of LH in folliculogenesis and oocyte maturation is unclear. GnRH antagonists, when administered in the late follicular phase, induce a sharp decrease in serum LH which may be detrimental for IVF outcome. This study was performed to evaluate whether the replacement of GnRH agonist (triptorelin) by a GnRH antagonist (ganirelix; NV Organon) in oocyte donation cycles has any impact on pregnancy and implantation rates.
title: AIDS-related Kaposi's sarcoma displays differential expression of endothelial surface antigens.
abstract: The authors studied 11 cases of Kaposi's sarcoma (KS) in patients with the acquired immunodeficiency syndrome (AIDS) for their reactivity with two monoclonal antibodies (B721 and E431) that recognize endothelial cell surface antigens. Reactivity of these antibodies with KS was compared with the reactivity of other known endothelial markers (F8rAg, Ia, HCL-1). Staining was done with avidin-biotin-alkaline phosphatase immunohistochemistry on acetone-fixed frozen sections. In all samples of tumor both the spindle cell component and the vascular lining cells stained with both B721 and E431. In general, the spindle cells stained less intensely than did the vascular lining cells. There was both intratumor and intertumor variability. B721 and E431 are proposed as two additional markers for KS, and it is suggested that their reactivity with the tumor supports the hypothesis that KS is derived from vascular endothelium. The possibility is also raised that the variability of staining for vascular markers could have diagnostic possibilities, and further studies for investigation of this hypothesis are suggested.
title: A randomized prospective trial comparing gonadotropin-releasing hormone (GnRH) antagonist/recombinant follicle-stimulating hormone (rFSH) versus GnRH-agonist/rFSH in women pretreated with oral contraceptives before in vitro fertilization.
abstract: To compare the effects of oral contraceptive (OC) pill pretreatment in recombinant FSH/GnRH-antagonist versus recombinant FSH/GnRH-agonist stimulation in in vitro fertilization (IVF) patients, and to evaluate optimization of retrieval day.
title: [A rare complication of bacterial endocarditis].
title: "Mild" vs. "long" protocol for controlled ovarian hyperstimulation in patients with expected poor ovarian responsiveness undergoing in vitro fertilization (IVF): a large prospective randomized trial.
abstract: This large prospective, randomized study was designed to compare the "mild" protocol with clomiphene citrate, low-dose gonadotropins and a GnRH-antagonist (CC/Gn/GnRH-ant protocol) with the "long" protocol with a GnRH-agonist and high-dose Gn for the controlled ovarian hyperstimulation (COH) of patients with expected poor ovarian responsiveness undergoing IVF.
title: Ovarian stimulation by concomitant administration of cetrorelix acetate and HMG following Diane-35 pre-treatment for patients with polycystic ovary syndrome: a prospective randomized study.
abstract: Patients with polycystic ovary syndrome (PCOS) may need a longer period of pituitary downregulation to suppress the elevated serum LH and androgen levels effectively during IVF treatment using the GnRH agonist long protocol. We proposed a stimulation protocol incorporating Diane-35 and GnRH antagonist (Diane/cetrorelix protocol) and compared it with the GnRH agonist long protocol for PCOS patients.
title: Prospective, randomized, comparative study of leuprorelin + human menopausal gonadotropins versus ganirelix + recombinant follicle-stimulating hormone in oocyte donors and pregnancy rates among the corresponding recipients.
abstract: To compare the clinical pregnancy rate in recipients of oocytes from donors treated with leuprorelin + human menopausal gonadotropins (hMG) with that obtained when the donors were treated with ganirelix + recombinant follicle-stimulating hormone (rFSH). The secondary aim was to compare the donors' response to the two treatments.
title: Risk of severe ovarian hyperstimulation syndrome in GnRH antagonist versus GnRH agonist protocol: RCT including 1050 first IVF/ICSI cycles.
abstract: Is the risk of severe ovarian hyperstimulation syndrome (OHSS) similar in a short GnRH antagonist and long GnRH agonist protocol in first cycle IVF/ICSI patients less than 40 years of age?.
title: A randomized trial of microdose leuprolide acetate protocol versus luteal phase ganirelix protocol in predicted poor responders.
abstract: We performed a randomized trial to compare IVF outcomes in 54 poor responder patients undergoing a microdose leuprolide acetate (LA) protocol or a GnRH antagonist protocol incorporating a luteal phase E(2) patch and GnRH antagonist in the preceding menstrual cycle. Cancellation rates, number of oocytes retrieved, clinical pregnancy rates (PR), and ongoing PRs were similar between the two groups.
title: Comparison of outcome of clomiphene citrate/human menopausal gonadotropin/cetrorelix protocol and buserelin long protocol--a randomized study.
abstract: 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.
title: Cetrorelix in an oral contraceptive-pretreated stimulation cycle compared with buserelin in IVF/ICSI patients treated with r-hFSH: a randomized, multicentre, phase IIIb study.
abstract: The aim of this study was to assess the non-inferiority of an oral contraceptive (OC)-pretreated cetrorelix regimen and a buserelin regimen in IVF/ICSI patients treated with r-hFSH in terms of total number of oocytes retrieved.
title: Comparison of GnRH antagonist with long GnRH agonist protocol after OCP pretreatment in PCOs patients.
abstract: To evaluate the efficacy of GnRH antagonist in comparison with the GnRH agonist protocol in OCP pretreated polycystic ovary syndrome (PCOs) patients undergoing their first ART cycle.
title: [25 years of social medicine in Brno].
title: Cetrorelix protocol versus gonadotropin-releasing hormone analog suppression long protocol for superovulation in intracytoplasmic sperm injection patients older than 40.
abstract: To determine which protocols work better between cetrorelix and long protocols in older patients in a randomized controlled study.
title: Follicular growth and oocyte maturation in GnRH agonist and antagonist protocols for in vitro fertilisation and embryo transfer.
abstract: The aim of this study was to evaluate the response to treatment in a group of patients undergoing IVF and randomised to receive GnRH-antagonist or the GnRH-agonist. The endpoints were the pattern of follicular growth, the maturity of the oocytes collected, the embryo quality and the pregnancy outcome.
title: Cycle scheduling with oral contraceptive pills in the GnRH antagonist protocol vs the long protocol: a randomized, controlled trial.
abstract: To compare cycle outcomes after scheduling with the standard long protocol versus the use of oral contraceptive pills (OCPs) in patients undergoing GnRH antagonist cycles.
title: Flexible GnRH antagonist protocol versus GnRH agonist long protocol in patients with polycystic ovary syndrome treated for IVF: a prospective randomised controlled trial (RCT).
abstract: Women with polycystic ovary syndrome (PCOS) are at risk of developing ovarian hyperstimulation syndrome (OHSS) during ovarian stimulation. Use of GnRH antagonist in the general subfertile population is associated with lower incidence of OHSS than agonists and similar probability of live birth but it is unclear if this is true for patients with PCOS. Our aim was to compare the flexible GnRH antagonist and GnRH agonist long protocols in patients with PCOS undergoing IVF (primary end-point: ongoing pregnancy rate per patient randomized).
title: Efficacy of low-dose human chorionic gonadotropin (hCG) in a GnRH antagonist protocol.
abstract: To examine the efficacy of low-dose hCG using a GnRH antagonist protocol.
title: [90 years of the Düsseldorf dermatology clinic].
title: Milder ovarian stimulation for in-vitro fertilization reduces aneuploidy in the human preimplantation embryo: a randomized controlled trial.
abstract: To test whether ovarian stimulation for in-vitro fertilization (IVF) affects oocyte quality and thus chromosome segregation behaviour during meiosis and early embryo development, preimplantation genetic screening of embryos was employed in a prospective, randomized controlled trial, comparing two ovarian stimulation regimens.
title: The use of gonadotropin-releasing hormone (GnRH) agonist to induce oocyte maturation after cotreatment with GnRH antagonist in high-risk patients undergoing in vitro fertilization prevents the risk of ovarian hyperstimulation syndrome: a prospective randomized controlled study.
abstract: To determine whether there are any differences in the incidence of ovarian hyperstimulation syndrome (OHSS) and implantation rates in high-risk patients undergoing IVF using a protocol consisting of GnRH agonist trigger after cotreatment with GnRH antagonist or hCG trigger after dual pituitary suppression protocol.
title: Media for all seasons.
title: GnRH-agonist versus GnRH-antagonist IVF cycles: is the reproductive outcome affected by the incidence of progesterone elevation on the day of HCG triggering? A randomized prospective study.
abstract: In view of the current debate concerning possible differences in efficacy between the two GnRH analogues used in IVF stimulated cycles, the current study aimed to explore whether progesterone control in the late follicular phase differs when GnRH antagonist is used as compared with GnRH agonist, and if so, to what extent the progesterone rise affects the probability of pregnancy.
title: Dose-finding study of triptorelin acetate for prevention of a premature LH surge in IVF: a prospective, randomized, double-blind, placebo-controlled study.
abstract: Gonadotrophin-releasing hormone agonists (GnRHa) are routinely used in IVF programmes to prevent an unwanted LH surge and consequent ovulation. Despite its widespread use in IVF, a convincing dose recommendation for GnRHa in IVF does not exist. In our opinion, the lowest possible dose of GnRHa should be used. Thus, we performed a prospective, randomized, double-blind, placebo-controlled study to determine the minimal daily dose of triptorelin acetate needed to suppress a premature LH surge during IVF treatment in a long protocol. A total of 240 women (60 in each group) was randomized to either placebo or to one of three doses of triptorelin, i.e. 15, 50 or 100 microg daily. Ovarian stimulation was performed with two or three ampoules of FSH daily. A premature LH surge occurred in 23% of placebo-treated patients, but in none of the triptorelin acetate-treated patients. There were significantly more oocytes and embryos in the 50 and 100 microg triptorelin groups. There was no dose relationship in rates of either implantation, pregnancy, ongoing pregnancy, live birth or baby take-home. In this study we showed that daily administration of 15 microg triptorelin is sufficient to prevent a premature LH surge, and that 50 microg is equivalent to 100 microg in terms of IVF results.
title: IVF/ICSI outcomes of the OCP plus GnRH agonist protocol versus the OCP plus GnRH antagonist fixed protocol in women with PCOS: a randomized trial.
abstract: To compare the IVF/ICSI outcomes of the long GnRH agonist and the fixed GnRH antagonist protocol in women with PCOS.
title: A comparative randomized trial to assess the impact of oral contraceptive pretreatment on follicular growth and hormone profiles in GnRH antagonist-treated patients.
abstract: This randomized controlled trial was designed to assess the impact of oral contraceptive (OC) scheduling with a GnRH antagonist (ganirelix) regimen on the ovarian response of women undergoing recombinant FSH (rFSH) stimulation for IVF, compared with a non-scheduled ganirelix regimen and a long GnRH agonist (nafarelin) protocol.
title: Periodontics for the general practitioner.
title: Dose-finding study of daily gonadotropin-releasing hormone (GnRH) antagonist for the prevention of premature luteinizing hormone surges in IVF/ICSI patients: antide and hormone levels.
abstract: The aim of this study was to define the minimal effective dose of antide (Iturelix) to prevent premature luteinizing hormone (LH) surges in in vitro fertilization (IVF) patients.
title: Treatment with the gonadotrophin-releasing hormone antagonist ganirelix in women undergoing ovarian stimulation with recombinant follicle stimulating hormone is effective, safe and convenient: results of a controlled, randomized, multicentre trial. The European Orgalutran Study Group.
abstract: A multicentre, open-label, randomized study of the gonadotrophin-releasing hormone (GnRH) antagonist ganirelix (Orgalutran((R))/Antagon((TM))) was performed in women undergoing ovarian stimulation with recombinant FSH (rFSH: Puregon((R))). The study was designed as a non-inferiority study using a long protocol of buserelin (intranasal) and rFSH as a reference treatment. A total of 730 subjects was randomized in a treatment ratio of 2:1 (ganirelix:buserelin) using an interactive voice response system which stratified for age, type of infertility and planned fertilization procedure [IVF or intracytoplasmic sperm injection (ICSI)]. The median duration of GnRH analogue treatment was 5 days in the ganirelix group and 26 days in the buserelin group, whereas the median total rFSH dose was 1500 IU and 1800 IU respectively. In addition, in the ganirelix group the mean duration of stimulation was 1 day shorter. During ganirelix treatment the incidence of LH rises (LH >/=10 IU/l) was 2.8% versus 1.3% during rFSH stimulation in the buserelin group. On the day of triggering ovulation by human chorionic gonadotrophin (HCG), the mean number of follicles >/=11 mm diameter was 10.7 and 11.8, and the median serum oestradiol concentrations were 1190 pg/ml and 1700 pg/ml in the ganirelix and buserelin groups respectively. The mean number of oocytes per retrieval was 9.1 and 10.4 respectively, whereas the mean number of good quality embryos was 3.3 and 3.5 respectively. The fertilization rate was equal in both groups (62.1%), and the same mean number of embryos (2.2) was replaced. The mean implantation rates were 15.7% and 21.8%, and the ongoing pregnancy rates per attempt were 20.3% and 25.7% in the ganirelix and buserelin groups respectively. Evaluation of all safety data indicated that the ganirelix regimen was safe and well tolerated. The overall incidence of ovarian hyperstimulation syndrome was 2.4% in the ganirelix group and 5.9% in the reference group. The results of this study support a safe, short and convenient treatment regimen of ganirelix, resulting in a good clinical outcome for patients undergoing ovarian stimulation for IVF or ICSI.
title: [The properties of urinary sulfosalicylic acid soluble mucoproteins].
title: Prospective, randomized, controlled study of in vitro fertilization-embryo transfer with a single dose of a luteinizing hormone-releasing hormone (LH-RH) antagonist (cetrorelix) or a depot formula of an LH-RH agonist (triptorelin).
abstract: To confirm the value of a single dose of 3 mg of cetrorelix in preventing the occurrence of premature LH surges.
title: Initiation of GnRH antagonist on Day 1 of stimulation as compared to the long agonist protocol in PCOS patients. A randomized controlled trial: effect on hormonal levels and follicular development.
abstract: BACKGROUND The optimal time for GnRH antagonist initiation is still debatable. The purpose of the current randomized controlled trial is to provide endocrine and follicular data during ovarian stimulation for IVF in patients with polycystic ovarian syndrome (PCOS) treated either with a long GnRH agonist scheme or a fixed day-1 GnRH antagonist protocol. METHODS Randomized patients in both groups (antagonist: n = 26; long agonist: n = 52) received oral contraceptive pill treatment for three weeks and a starting dose of 150 IU of follitropin beta. The primary outcome was E(2) level on Day 5 of stimulation, while secondary outcomes were follicular development, LH during ovarian stimulation and progesterone levels. RESULTS Significantly more follicles on days 5, 7 and 8 of stimulation, significantly higher estradiol (E(2)) levels on days 1, 3, 5, 7 and 8 and significantly higher progesterone levels on days 1, 5 and 8 of stimulation were observed in the antagonist when compared with the agonist group. E(2) was approximately twice as high in the antagonist when compared with the agonist group on day 5 of stimulation (432 versus 204 pg ml(-1), P lt; 0.001). These differences were accompanied by significantly lower LH levels on days 3 and 5 and significantly higher LH levels on days 1, 7 and 8 of stimulation in the antagonist when compared with the agonist group. CONCLUSIONS In PCOS patients undergoing IVF, initiation of GnRH antagonist concomitantly with recombinant FSH is associated with an earlier follicular growth and a different hormonal environment during the follicular phase when compared with the long agonist protocol.
title: Ovarian response and follicular development for single-dose and multiple-dose protocols for gonadotropin-releasing hormone antagonist administration.
abstract: To determine the efficiency of a single-dose and a multiple-dose protocol for GnRH antagonist administration.
title: GnRH antagonist in IVF poor-responder patients: results of a randomized trial.
abstract: The aim of this prospective study was to evaluate the efficacy of gonadotrophin-releasing hormone antagonist (GnRH) in comparison with the standard long protocol in poor-responder patients. Sixty patients with poor ovarian response in previous treatment cycles were randomized into two groups: group A (n = 30) was stimulated with a standard long protocol, and group B (n = 30) received GnRH antagonist. Vaginal ultrasound was performed to evaluate ovarian response. There was a significantly reduced duration of ovarian stimulation (9.8 +/- 0.8 versus 14.6 +/- 1.2, P = 0.001) in group B in comparison with group A, and a reduced number of ampoules was used in group B (49.3 +/- 4.3 versus 72.6 +/- 6.8, P = 0.0001). In group B, the number of oocytes retrieved was significantly higher than in group A (5.6 +/- 1.6 versus 4.3 +/- 2.2, P = 0.02) and there was an increased number of follicles with a diameter >15 mm at human chorionic gonadotrophin administration in group B (P = 0.0001). Fewer cycles were cancelled with the use of an antagonist protocol. Five pregnancies (17% for embryo transfer) were obtained with GnRH antagonist protocol and two (7% for embryo transfer) with GnRH agonist protocol.
title: Comparable effectiveness using flexible single-dose GnRH antagonist (cetrorelix) and single-dose long GnRH agonist (goserelin) protocol for IVF cycles--a prospective, randomized study.
abstract: This prospective randomized study compared the effectiveness of a flexible single-dose gonadotrophin-releasing hormone (GnRH) antagonist (cetrorelix) and a single-dose long GnRH agonist (goserelin) protocol for ovarian stimulation in IVF/intracytoplasmic sperm injection (ICSI) cycles. All patients from the waiting list were successively included in the study, pre-programmed with an oral contraceptive, and randomized into goserelin and cetrorelix groups. Depending on the date on which their menstrual period started, patients took oral contraceptives for one or two cycles. Ultimately, 236 patients in the first group received a single dose of depot preparation of goserelin and 224 patients received a single 3 mg dose of cetrorelix in the late follicular phase, when the mean follicle diameter exceeded 12 mm. The mean number of ampoules of FSH and the duration of stimulation was statistically significantly lower in the cetrorelix group than in the goserelin group (25.9 versus 34.5, and 9.6 versus 12.2 days, P < 0.01). The mean number of oocytes retrieved was similar (6.7 +/- 4.5 versus 7.2 +/- 4.6, NS). Similar results were observed in fertilization rates, blastulation rates and blastocyst transfer rates in both groups. Clinical pregnancy and delivery rates per cycle were higher in the goserelin group (34.3 and 30.1%) than in the cetrorelix group (31.9 and 28.3%), but the differences were not statistically significant. The flexible single-dose GnRH antagonist protocol is an advantageous alternative to the long GnRH agonist protocol, with similar efficacy, shorter duration, a significant reduction in the number of FSH ampoules used and without the menopause-like effects of the GnRH antagonist.
title: Ovarian stimulation with HMG: results of a prospective randomized phase III European study comparing the luteinizing hormone-releasing hormone (LHRH)-antagonist cetrorelix and the LHRH-agonist buserelin. European Cetrorelix Study Group.
abstract: In this prospective and randomized study, 188 patients received the luteinizing hormone-releasing hormone (LHRH) antagonist cetrorelix, and 85 patients the LHRH agonist buserelin to prevent endogenous luteinizing hormone (LH) surges during ovarian stimulation in in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles. Ultimately, 181 patients (96.3%) in the cetrorelix group, and 77 (90.6%) in the buserelin group, reached the day of the human chorionic gonadotrophin (HCG) injection. The mean number of human menopausal gonadotrophin (HMG) ampoules administered and the mean number of stimulation days with HMG were significantly less in the cetrorelix group than in the buserelin group (P < 0.01). A rise in LH and progesterone concentrations was observed in three of the 188 patients (1.6%) who received cetrorelix. On the day of the HCG administration, more follicles of a small diameter (11-14 mm) were observed in the buserelin group than in the cetrorelix group (P = 0. 02) and the mean serum oestradiol concentration was significantly higher in patients who received buserelin than in those who received cetrorelix (P < 0.01). Similar results were observed in fertilization, cleavage and pregnancy rates in the two groups. In conclusion, the use of the LHRH antagonists might be considered more advantageous because of the short-term application needed to inhibit gonadotrophin secretion, so allowing a reduction in the treatment time in a clinically significant manner.
title: Long gonadotropin-releasing hormone agonist versus short agonist versus antagonist regimens in poor responders undergoing in vitro fertilization: a randomized controlled trial.
abstract: To compare the efficacy of the long GnRH agonist vs. the short GnRH agonist vs. the GnRH antagonist regimens in poor responders undergoing IVF.
title: Ovarian stimulation with daily late follicular phase administration of low-dose human chorionic gonadotropin for in vitro fertilization: a prospective, randomized trial.
abstract: Evaluate the effectiveness of a new ovarian stimulation (OS) protocol before IVF.
title: Comparative efficacy and safety of cetrorelix with or without mid-cycle recombinant LH and leuprolide acetate for inhibition of premature LH surges in assisted reproduction.
abstract: An open label, randomized, multi-centre study was performed to compare cetrorelix and leuprolide acetate for prevention of premature LH surge and to assess whether patients treated with cetrorelix benefit from addition of recombinant human (r-h)LH. Normo-ovulatory women (n = 74) undergoing ovarian stimulation prior to intracytoplasmic sperm injection were treated with leuprolide acetate (n = 25) before ovarian stimulation with recombinant human FSH (r-hFSH) or with cetrorelix 3 mg on stimulation day 7 (with (n = 25) or without (n = 24) r-hLH 150 IU on days 7-10). The main outcome measures were the number of metaphase II (MII) oocytes retrieved; secondary efficacy end-points; adverse events (AE) and other safety measures. There were no significant differences between groups for MII oocytes retrieved, duration of stimulation, total r-hFSH dose and pregnancy rates. The group treated with cetrorelix alone had a significantly lower concentration of oestradiol per follicle compared with the other groups. The majority of AE were mild to moderate in severity. Cetrorelix and leuprolide acetate appear to have comparable efficacy and safety, although cetrorelix has the advantage of typically requiring only one injection.
title: Comparing GnRH agonist long protocol and GnRH antagonist protocol in outcome the first cycle of ART.
abstract: This prospective study evaluated the efficacy of gonadotropin-releasing hormone (GnRH) antagonist protocol in comparison with the GnRH agonist protocol in the first cycle of assisted reproductive technique (ART).
title: A mild treatment strategy for in-vitro fertilisation: a randomised non-inferiority trial.
abstract: Mild in-vitro fertilisation (IVF) treatment might lessen both patients' discomfort and multiple births, with their associated risks. We aimed to test the hypothesis that mild IVF treatment can achieve the same chance of a pregnancy resulting in term livebirth within 1 year compared with standard treatment, and can also reduce patients' discomfort, multiple pregnancies, and costs.
title: Comparison of embryological and clinical outcome in GnRH antagonist vs. GnRH agonist protocols for in vitro fertilization in PCOS non-obese patients. A prospective randomized study.
abstract: Embryological and clinical efficacy of gonadotropin-releasing hormone (GnRH) antagonist and agonist stimulation protocols in non-obese women with polycystic ovarian syndrome (PCOS) were compared.
title: GnRH agonist and antagonist protocols for stage I-II endometriosis and endometrioma in in vitro fertilization/intracytoplasmic sperm injection cycles.
abstract: To investigate the outcomes of intracytoplasmic sperm injection (ICSI) cycles after controlled ovarian hyperstimulation (COH) with GnRH antagonist or GnRH agonist (GnRH-a) in mild-to-moderate endometriosis and endometrioma.
title: Comparison of multiple dose GnRH antagonist and minidose long agonist protocols in poor responders undergoing in vitro fertilization: a randomized controlled trial.
abstract: To investigate the efficacy of gonadotropin releasing hormone antagonist (GnRH) in poor responders undergoing in vitro fertilization.
title: A randomized comparison of two ovarian stimulation protocols with gonadotropin-releasing hormone (GnRH) antagonist cotreatment for in vitro fertilization commencing recombinant follicle-stimulating hormone on cycle day 2 or 5 with the standard long GnRH agonist protocol.
abstract: Extending the FSH window for multifollicular development by administering FSH from the midfollicular phase onward constitutes a novel mild protocol for ovarian stimulation for in vitro fertilization (IVF) based on the physiology of single dominant follicle selection in normo-ovulatory women. We compared outcomes from this protocol with two other stimulation protocols. One hundred and forty-two normo-ovulatory patients with an indication for IVF (or IVF/ICSI) were randomized to a GnRH agonist long protocol (group A; n = 45) or one of two GnRH antagonist protocols commencing recombinant FSH on cycle d 2 (group B; n = 48) or cycle d 5 (group C; n = 49). A fixed dose (150 IU/d) of rFSH was used for ovarian stimulation, and GnRH antagonist cotreatment was initiated on the day when the leading follicle reached 14 mm diameter. Group C showed a shorter duration of stimulation (median duration, 11, 9, and 8 d for groups A, B, and C, respectively; P < 0.001), reflected in a significantly lower total dose of rFSH used (median amount of rFSH, 1650, 1350, and 1200 IU for groups A, B, and C, respectively; P < 0.001). In group C more cycles were cancelled during the stimulation phase due to insufficient response, resulting in a lower percentage of oocyte retrievals (84%, 73%, and 63% for groups A, B, and C; P = 0.02). However, women in group C obtained better quality embryos (percentage of embryo score of 1 for best embryo, 29%, 37%, and 61% for groups A, B, and C, respectively; P = 0.008), resulting in more transfers per oocyte retrieval (68%, 71%, and 90% for groups A, B, and C, respectively; P = 0.04). After profound ovarian stimulation (groups A and B) only 7% of the patients who retrieved four oocytes or less conceived, whereas after mild stimulation (group C) 67% of these patients conceived (P < 0.01). Overall, no differences were found among the three groups comparing pregnancy rate per started IVF cycle. In conclusion, application of the described mild ovarian stimulation protocol resulted in pregnancy rates per started IVF cycle similar to those observed after profound stimulation with GnRH agonist cotreatment despite shorter stimulation and a 27% reduction in exogenous FSH. A higher cancellation rate before oocyte retrieval was compensated by improved embryo quality concomitant with a higher chance of undergoing embryo transfer. A relatively low number of oocytes retrieved after mild ovarian stimulation distinctly differs from the pathological reduction in the number of oocytes retrieved after profound ovarian stimulation (poor response) associated with poor IVF outcome. The relatively small number of oocytes obtained after mild ovarian stimulation may represent the best of the cohort in a given cycle.
title: Efficacy and safety of ganirelix acetate versus leuprolide acetate in women undergoing controlled ovarian hyperstimulation.
abstract: To assess the efficacy, safety, and local tolerance of ganirelix acetate for the inhibition of premature luteinizing hormone (LH) surges in women undergoing controlled ovarian hyperstimulation (COH).
title: Follicular oestradiol and VEGF after GnRH antagonists or GnRH agonists in women with PCOS.
abstract: The aim of this study was to determine whether follicular oestradiol and vascular endothelial growth factor (VEGF) concentrations in women with polycystic ovarian syndrome (PCOS) differ according to the use of gonadotrophin-releasing hormone (GnRH) antagonists or GnRH agonists. Furthermore, the effect of follicular oestradiol and VEGF concentrations on oocyte and embryo quality was investigated. In this prospective clinical study, 20 women with PCOS undergoing intracytoplasmic sperm injection for male factor infertility were included using a GnRH antagonist or a GnRH agonist protocol. In each follicle, oestradiol and VEGF concentrations were determined. In the GnRH antagonist group 254 follicles and in the GnRH agonist group 245 follicles, were aspirated. Fewer metaphase II (MII) and more immature and degenerative oocytes were registered in the GnRH antagonist group. Follicular oestradiol and VEGF were lower in the GnRH antagonist group (P = 0.014 and P < 0.001, respectively). Moreover, higher oestradiol concentrations were related to embryos of higher quality (P = 0.037). It is concluded that GnRH antagonists decrease follicular oestradiol and VEGF concentrations and the number of retrieved MII oocytes in women with PCOS.
title: GnRH-antagonist programming versus GnRH agonist protocol: a randomized trial.
abstract: Testing the ability to program IVF GnRH-antagonist cycles to avoid weekend oocyte retrieval.
title: The effect of luteal phase vaginal estradiol supplementation on the success of in vitro fertilization treatment: a prospective randomized study.
abstract: To determine whether the use of luteal phase vaginal E(2) supplementation improves clinical pregnancy rates in patients undergoing IVF treatment.
title: A comparative study of luteal estradiol pre-treatment in GnRH antagonist protocols and in micro dose flare protocols for poor-responding patients.
abstract: This study aims to verify if luteal estradiol pre-treatment improves IVF/ICSI outcomes in a GnRH antagonist protocol as compared with a micro dose GnRH agonist protocol in poor-responding patients.
title: A randomized controlled trial of the GnRH antagonist ganirelix in Chinese normal responders: high efficacy and pregnancy rates.
abstract: Gonadotropin-releasing hormone (GnRH) antagonists for controlled ovarian stimulation (COS) were only recently introduced into China. The efficacy and safety of the GnRH antagonist ganirelix was assessed in a multicenter, controlled, open-label study, in which Chinese women were randomized to either ganirelix (n = 113) or a long GnRH agonist protocol of triptorelin (n = 120). The primary end point was the amount of recombinant follicle-stimulating hormone (rFSH) required to meet the human chorionic gonadotropin criterion (three follicles ≥17 mm). The amount of rFSH needed was significantly lower for ganirelix (1272 IU) vs. triptorelin (1416 IU; P< 0.001). Ongoing pregnancy rates per started cycle were 39.8% (ganirelix) and 39.2% (triptorelin). Although both treatments were well tolerated, cancellation due to risk of ovarian hyperstimulation syndrome (OHSS) was less frequent with ganirelix (1.8%) than triptorelin (7.5%) (P = 0.06). Less rFSH was needed in the ganirelix protocol than the long GnRH agonist protocol, with fewer reported cases of OHSS and similar pregnancy rates.
title: A modified gonadotropin-releasing hormone (GnRH) antagonist protocol failed to increase clinical pregnancy rates in comparison with the long GnRH protocol.
abstract: The purpose of this prospective randomized study was to compare stimulation characteristics and IVF outcomes of the standard long GnRH agonist protocol for ovarian stimulation with a modified GnRH antagonist protocol. Starting GnRH antagonist in a flexible protocol according to the size of the leading follicle, with simultaneous augmentation of 75 IU recombinant FSH, failed to increase clinical pregnancy rates.
title: Comparable clinical outcome using the GnRH antagonist ganirelix or a long protocol of the GnRH agonist triptorelin for the prevention of premature LH surges in women undergoing ovarian stimulation.
abstract: This multicentre, randomized study was performed to assess the efficacy and safety of 0.25 mg ganirelix (Orgalutran, Antagon) treatment, using triptorelin (Decapeptyl) in a long protocol as a reference treatment. In total, 236 subjects were randomized to treatment with ganirelix (0.25 mg, s.c.) and 119 to triptorelin (0.1 mg, s.c.) treatment (treatment ratio 2:1). Treatment with ganirelix started on day 6 of stimulation, whereas treatment with triptorelin started on menstrual cycle day 21 to 24 of the previous cycle (i.e. the midluteal phase). The ganirelix regimen was on average 17 days shorter (9 versus 26 days) compared to the triptorelin regimen. The median total dose of recombinant FSH (Puregon) used was 450 IU less (1350 versus 1800 IU) in the ganirelix protocol. The initial follicular growth was faster and, consequently, oestradiol concentrations were higher in the ganirelix group. On the day of human chorionic gonadotrophin (HCG), the mean number of follicles > or = 11 mm was 10.1 and 10.7 and the median serum oestradiol concentration was 1090 and 1370 pg/ml in the ganirelix and triptorelin groups respectively. Per attempt, 7.9 and 9.6 oocytes (mean) were retrieved in the ganirelix and triptorelin groups respectively. The fertilization rates (64.0% ganirelix and 64.9% triptorelin) and the mean number of good quality embryos (2.7 and 2.9) were comparable in both treatment groups. The implantation rate was identical (22.9%). The ongoing pregnancy rate per attempt was 31.0 and 33.9% in the ganirelix and triptorelin groups respectively. The ganirelix regimen showed an improved local tolerance in that the percentage of subjects with at least one local skin reaction was 2-fold lower than in the triptorelin group (11.9 versus 24.1%). Taking all data together, it may be concluded that ganirelix offers a new treatment regimen in ovarian stimulation that is short, safe and well-tolerated, optimizing convenience for the patient.
title: Follicular fluid vascular endothelial growth factor concentrations are increased during GnRH antagonist/FSH ovarian stimulation cycles.
abstract: The aim of this study was to investigate the effect of GnRH antagonists (GnRH-ant) on follicular fluid vascular endothelial growth factor (FF VEGF).
title: Induction of multiple follicular development by a single dose of long-acting recombinant follicle-Stimulating hormone (FSH-CTP, corifollitropin alfa) for controlled ovarian stimulation before in vitro fertilization.
abstract: In a first feasibility study, the efficacy and safety of a single dose of recombinant long-acting FSH (FSH-CTP) were investigated in in vitro fertilization (IVF) patients undergoing controlled ovarian stimulation with a flexible GnRH antagonist protocol. Eligible subjects were randomized to receive a single dose of 120 micro g (n = 25), 180 microg (n = 24), or 240 microg (n = 25) corifollitropin alfa (FSH-CTP) or to start daily fixed doses of 150 IU recombinant FSH (rFSH) (n = 24, reference). Subjects who received a single dose of FSH-CTP continued 1 wk after injection (treatment d 8) with fixed daily doses of 150 IU rFSH (Puregon/Follistim) until the day of triggering final oocyte maturation. The terminal half-life of FSH-CTP was, on average, 65 h and dose independent. Cycle cancellation before human chorionic gonadotropin (hCG) administration occurred in only three subjects treated with FSH-CTP. The median duration of stimulation was 10.0 d in each FSH-CTP group and 9.0 d in the daily rFSH group. The total number of follicles at least 11 mm at stimulation d 8 and at the day of hCG administration tended to increase with dose of FSH-CTP, although a significant dose-response relationship was revealed only for the number of follicles at least 15 mm on the day of hCG (P = 0.03). Serum estradiol levels and inhibin-B levels were not significantly different between the four groups on d 8 and on the day of hCG. In total, 12 subjects (17.6%) in the FSH-CTP groups and two subjects (8.3%) in the rFSH group experienced a premature LH rise (defined as LH >or= 10 IU/liter) before the start of the GnRH antagonist (P value not significant between groups). This relatively high incidence of women demonstrating an early LH rise in the FSH-CTP groups may be related to the higher initial rises of serum estradiol and the use of a flexible GnRH antagonist protocol. The mean number of oocytes recovered per started cycle was higher in FSH-CTP-treated subjects compared with rFSH-treated subjects (significant at P = 0.03 for the 240- microg FSH-CTP group), but no difference could be noted between the number of good quality embryos (range of means, 3.8-4.8 per attempt), and equal numbers of embryos were available for embryo transfer. In summary, FSH-CTP appeared to be a potent inducer of multiple follicular growth; additional research will be needed to select the optimal FSH-CTP dose and treatment time interval.
title: Comparison of GnRH antagonist protocol with or without oral contraceptive pill pretreatment and GnRH agonist low-dose long protocol in low responders undergoing IVF/intracytoplasmic sperm injection.
abstract: This prospective randomized study was performed to compare the efficacy of GnRH antagonist multiple-dose protocol (MDP) with or without oral contraceptive pill (OCP) pretreatment and GnRH agonist low-dose long protocol (LP) in 82 patients undergoing IVF/intracytoplasmic sperm injection (ICSI). GnRH antagonist MDP with OCP pretreatment was at least as effective as GnRH agonist low-dose LP in low responders, and can benefit the low responders by reducing the amount of FSH and the number of days of stimulation required for follicular maturation.
title: Use of a GnRH antagonist in controlled ovarian hyperstimulation for assisted conception in women with polycystic ovary disease: a randomized, prospective, pilot study.
abstract: To compare the outcome of using gonadotropin-releasing hormone (GnRH) antagonists versus agonists in women with polycystic ovary disease (PCOD) who underwent controlled ovarian hyperstimulation (COH) for assisted reproductive techniques (ART).
title: Luteal phase characteristics following GnRH antagonist or agonist treatment - a comparative study.
abstract: Due to inherent differences between gonadotrophin-releasing hormone (GnRH) antagonists and agonists, their late effect on ovarian steroidal production during the luteal phase of IVF cycles may differ. The aim of this study was to characterize and compare the luteal phase hormonal profile after the use of GnRH antagonists or agonists in ovarian stimulation protocols for IVF, in non-conception cycles, to avoid the effect of human chorionic gonadotrophin (HCG) during the luteal phase in conception cycles. Seventy-eight normo-ovulatory patients <35 years old, undergoing IVF due to male or tubal infertility were randomly allocated either to a GnRH antagonist (study group) or GnRH agonist treatment (control group). Similar standard luteal support was given to all patients, using vaginal micronized progesterone. In non-conception cycles, no statistically significant differences were found comparing luteal phase. oestradiol or progesterone levels in the study and control groups. No statistically significant differences were found comparing the hormonal profile dynamics, the mid-luteal (HCG day +8) oestradiol/progesterone ratio and the percentage of mid-luteal oestradiol decline between the study and control groups. In conclusion, similar characteristics and dynamics of luteal phase oestradiol and progesterone were demonstrated comparing ovarian stimulation for IVF using GnRH agonist or antagonists, under similar luteal support.
title: A randomised study of GnRH antagonist (cetrorelix) versus agonist (busereline) for controlled ovarian stimulation: effect on safety and efficacy.
abstract: To assess safety and efficacy of cetrorelix utilisation in controlled ovarian stimulation (COS).
title: GnRH antagonist versus long GnRH agonist protocol in poor responders undergoing IVF: a randomized controlled trial.
abstract: This is the first published report of a prospective, randomized, controlled trial comparing a fixed, multi-dose GnRH antagonist protocol with a long GnRH agonist protocol in poor responders undergoing IVF.
title: [Efficiency of antagonist IVF cycle programming by estrogens].
abstract: Assess the efficiency of estradiol programming in In Vitro Fertilization (IVF) with antagonists by comparing with classical long luteal agonist protocol.
title: Comparison of gonadotropin-releasing hormone agonists and antagonists in assisted reproduction cycles of polycystic ovarian syndrome patients.
abstract: Gonadotropin-releasing hormone (GnRH) antagonists have reduced the incidence of severe ovarian hyper stimulation syndrome (OHSS) and rate of hospitalization due to severe OHSS, especially in polycystic ovarian syndrome (PCOS) patients. The present study aimed to compare the outcomes of patients with PCOS undergoing controlled ovarian hyperstimulation (COH) with GnRH agonist versus GnRH antagonist protocols for assisted reproduction cycles.