GnRH Agonist Protocol Research Articles

Reference values in ovarian response to controlled ovarian stimulation throughout the reproductive period

The age-related decline in ovarian response to gonadotropins has been well known since the beginning of ovarian stimulation in IVF cycles and has been considered secondary to the age-related decline in ovarian reserve. The objective of this study was to establish reference values and to construct nomograms of ovarian response for any specific age to gonadotropins in IVF/ICSI cycles. We analyzed our database containing information on IVF cycles. According to inclusion and exclusion criteria, a total of 703 patients were selected. Among inclusion criteria, there were regular menstrual cycle, treatment with a long GnRH agonist protocol and starting follicle-stimulating hormone (FSH) dose of at least 200 IU per day. To estimate the reference values of ovarian response, the CG-LMS method was used. A linear decline in the parameters of ovarian response with age was observed: the median number of oocytes decreases approximately by one every three years, and the median number of follicles >16 mm by one every eight years. The number of oocytes and growing follicles corresponding to the 5th, 25th, 50th, 75th and 95th centiles has been calculated. This study confirmed the well known negative relationship between ovarian response to FSH and female ageing and permitted the construction of nomograms of ovarian response.

Intrafollicular Endocrine Milieu After Addition of hCG to Recombinant FSH During Controlled Ovarian Stimulation for In Vitro Fertilization

The role of human chorionic gonadotropin (hCG) supplementation on the intrafollicular steroid milieu has been studied. The objective of the study was to assess the impact on steroid levels in follicular fluids (FFs) after different doses of hCG supplementation to recombinant FSH for controlled ovarian stimulation. This was a prospective randomized dose-response study conducted at Copenhagen University Hospital, Rigshospitalet, Denmark. From 62 in vitro fertilization patients, 334 FFs were selected for analyses. Patients were treated using a GnRH agonist protocol with recombinant FSH 150 IU/d and randomized from stimulation day 1 to supplementation with hCG: D0, 0 IU/d; D50, 50 IU/d; D100, 100 IU/d; and D150, 150 IU/d. Intrafollicular hormone concentrations in relation to treatment groups, follicular sizes, and embryo quality were measured. In large follicles, hCG supplementation induced a nearly 3-fold increase of estradiol (nanomoles per liter) [D0: 1496; D50: 3138; D100: 4338; D150: 4009 (P < .001)], a significant 3-fold increase of androstenedione, and a 5-fold increase of T (nanomoles per liter) [D0: 15; D50: 38; D100: 72; D150: 56 (P < .001)]. The estradiol to T ratio decreased significantly, with the lowest ratio in D100 and the highest in D0. Large follicles giving rise to good-quality embryos had significantly higher estradiol and progesterone levels and estradiol to T, estradiol to androstenedione, and progesterone to estradiol ratios, compared with small follicles, leading to poor-quality embryos. Increasing doses of hCG supplementation markedly stimulated the intrafollicular concentration of both estradiol and androgens, with a shift toward a more androgenic milieu. In large follicles with oocytes giving rise to good-quality embryos, the FFs were significantly more estrogenic than in small follicles with oocytes developing into poor quality embryos.

Serum estradiol as a predictor of success of in vitro fertilization.

The aim of this study was to assess the role of total serum estradiol on the day of injection HCG, estradiol per mature follicle, and estradiol per oocytes retrieved (OR) on clinical pregnancy rate (CPR) and oocyte/embryo quality in assisted reproduction. A retrospective review of 342 in vitro fertilization cycles with normal ovarian reserve in women who underwent long GnRH agonist protocol was included. The outcomes assessed are number of OR, number of mature oocytes (MO), number of oocytes fertilized (FO), fertilization rate, number of embryos cleaved (EC), cleavage rate (CR), number of Grade I embryos (E), number of cryopreserved embryos (CPE), and CPR. The Estradiol/follicle ratio (E2/fol) was defined as estradiol level per mature follicle>14 mm in diameter. Estradiol/oocyte (E2/O) ratio was defined as estradiol level per OR. These two ratios were categorized by the 25th percentile into four groups. A positive correlation was seen between E2/fol and OR (r=.334, p value=.0001), MO (r=.335, p value=.0001), FO (r=.222, p value=.002), and CPE (r=.289, p value=.0001). Increased CPR was seen in Group C (E2/fol=200-299.99) compared to Group A, B, and D (p value=.033). With E2/O ratio, negative correlation was seen between E2/O and OR (r=-.281, p value=.002), MO (r=-.296, p value=.008), FO (r=-.220, p value=.003), EC (r=-.211, p value=.004), Grade 1 embryo (r=-.216, p value=.001), and CPE (r=-.206, p value=.005). No difference in FR, CR, or CPR was seen. No difference was seen in CPR with total serum estradiol. In conclusion, serum estradiol is an important determinant of IVF success. While total serum estradiol does not exert any positive or negative influence on IVF outcome, estradiol per mature follicle and retrieved oocytes do have an impact. Pregnancy rate is better when E2/fol is between 200 and 299.99pg/ml. Also, increasing serum E2/fol positively correlates with better oocytes and embryo quality. In contrast, E2/O negatively correlates with oocytes and embryo quality parameters.

Impact of antimüllerian hormone assays on the outcomes of in vitro fertilization: a prospective controlled study

To assess the value of routine antimüllerian hormone (AMH) assays in patients considered high risk for cancellation. Prospective controlled study. A private IVF center, Cairo, Egypt. In total 4,917 patients received counseling before starting IVF/intracytoplasmic sperm injection (ICSI). They were comprised of group A1 (n = 1,335), who were considered to be at risk for cancellation after ovarian stimulation, and group A2 (n = 3,582), who were considered low risk for cancellation. A control group, B (n = 4,639), included group B1 (n = 1,248) and group B2 (n = 3,391) based on the same criteria as groups A1 and A2. An AMH assessment was performed for group A1. All of the patients were stimulated using the long GnRH agonist protocol. Patients with low AMH levels received the flare-up protocol. The cancellation of IVF/ICSI cycles before or after stimulation, as well as the pregnancy rates (PR) in relation to AMH levels. The group A1 patients (6.4%) did not start IVF due to low AMH, and some (6.6%) had their cycles canceled due to poor responses, compared with 2.6% in group A2 and 13.2% in group B1. The clinical PR was 42% in patients with normal AMH and 20% in patients with low AMH. The differences among these three groups were highly significant. The AMH assays reduced the cancellations, cost, and stress experienced by couples.

Comparison of the Effects and Safety of Mild Ovarian Stimulation and Conventional Ovarian Stimulation with A Long GnRH Agonist Protocol on IVF Outcomes

Objective To conduct a Meta-analysis of studies that compared the efficacies of mild ovarian stimulation and conventional long GnRH agonist protocol in patients undergoing IVF or intracytoplasmic sperm injection (ICSI). Methods Meta-analysis was performed. All studies were published by July 2012 with data related to outcomes following mild ovarian stimulation compared with the conventional protocol. Odds ratios (ORs) and weighted / standardized mean difference (WMD/SMD) from individual study were pooled in fixed and random effect models. Main outcome measure was the efficacy of mild ovarian stimulation. Results Six articles were included in this Meta-analysis. The number of oocytes retrieved was lower, the cycle cancellation rate was higher and the incidence of ovarian hyperstimulation syndrome (OHSS) was lower in the mild stimulation group than in conventional ovarian stimulation group. Clinical pregnancy rates were similar in both mild and conventional stimulation groups. Conclusions The level of evidence supporting the use of mild stimulation protocols in IVF is low, considering the fewer oocytes retrieved and the higher rates of cycle cancellation.

The effectiveness of gonadotropin-releasing hormone antagonist in poor ovarian responders undergoing in vitro fertilization: a systematic review and meta-analysis

To evaluate the effectiveness of gonadotropin-releasing hormone (GnRH) antagonist in poor ovarian responders undergoing in vitro fertilization (IVF). Systematic review and meta-analysis. Affiliated hospital with a medical university. None. Electronic search. Clinical pregnancy rate, number of oocytes retrieved, cycle cancellation rate. A total of 12 published studies (1,332 cases) were included. Both the stimulation period (mean difference [MD], -0.43; 95% confidence interval [CI], -0.68 to -0.17) and the gonadotropin dosage (MD, -5.41; 95% CI, -7.51 to -3.31) were statistically significantly lower in the GnRH antagonist protocol than in the long GnRH agonist protocol. Both the endometrial thickness (MD -0.45; 95% CI, -0.76 to -0.13) and estrogen (E2) level on the day of hCG administration (MD, -1,299.15; 95% CI, -1,716.34 to -881.95) were statistically significantly lower in the GnRH antagonist protocol than the GnRH agonist protocol. Fewer oocytes were retrieved for the GnRH antagonist protocol than the long GnRH agonist protocol (MD, -0.34; 95% CI, -0.54 to -0.13) or the short GnRH agonist protocol (MD, -0.54; 95% CI, -0.9, 8 to -0.10). The cycle cancellation and clinical pregnancy rates were not statistically significantly different between the two groups. Compared with GnRH agonist protocols, the GnRH antagonist protocol is associated with fewer oocytes retrieved, lower E2 levels, and thinner endometrium whereas the clinical pregnancy and cycle cancellation rates are similar.

Effect of Pioglitazone on Production of Regulated upon Activation Normal T-cell Expressed and Secreted (RANTES) and IVF Outcomes in Infertile Women with Endometriosis.

This study was performed to investigate the effect of peroxisome proliferators activated receptor-γ (PPAR-γ) ligand, pioglitazone, on production of regulated upon activation normal T-cell expressed and secreted (RANTES) and in vitro fertilization (IVF) outcome in infertile patients with endometriosis. Sixty-four infertile patients with stage III or IV endometriosis undergoing IVF were randomly allocated to the study or the control group. The long protocol of GnRH agonist (GnRH-a) was used for controlled ovarian stimulation (COS) in all patients. Patients in the study group were treated with pioglitazone at a dose of 15 mg/day orally from the starting day of GnRH-a treatment to the day of hCG injection. Blood samples were drawn for serologic assay of RANTES on the first day of GnRH-a treatment and the day of hCG injection. There were no differences between the study and control groups in patient characteristics. There were also no differences between the two groups in COS duration, and the numbers of retrieved oocytes, fertilized oocytes and embryos transferred. The clinical pregnancy rate per cycle was higher in the study group, but this difference was not statistically significant. However, embryo implantation rate was significantly higher in the study group of 12.5% compared with 8.6% in the control group (P<0.05). The serum RANTES levels after pioglitazone treatment were significantly lower than those before pioglitazone treatmen in the study group (P<0.05). Our data suggest that pioglitazone treatment can suppress RANTES production and improve the embryo implantation rate in patients with endometriosis undergoing IVF.

Transient intrauterine (IU) or intracervical (IC) fluid accumulation (FA) not due to hydrosalpinx or any identifiable pelvic pathology is not detrimental to IVF outcome

Transient intrauterine (IU) or intracervical (IC) fluid accumulation (FA) not due to hydrosalpinx or any identifiable pelvic pathology is not detrimental to IVF outcome

Effect of GnRH-antagonist versus agonist on embryo quality by comparing the outcomes of fets

Effect of GnRH-antagonist versus agonist on embryo quality by comparing the outcomes of fets

Comparing stimulation requirements and final outcome between early follicular and mid luteal starting of pituitary suppression in the long gonadotropin releasing hormone agonist protocol

To compare the stimulation requirements and the outcome of the intracytoplasmic sperm injection (ICSI) when treatment with the agonist is started in the early follicular phase as compared to the mid luteal phase of the cycle.

In low AMH level, which protocol is best on IVF?

Anti-müllerian hormone (AMH) is now considered one of the best predictive markers of ovarian response for ART and many clinical applications of AMH measurement has been proposed. Low AMH levels have been associated with poor ovarian response and may correlated to unsuccessful IVF outcomes. But, there is little result which protocol shows better outcomes in poor responder. The aim of this study was to find better IVF protocol for low AMH patients. Retrospective analysis. The study included 1413 IVF cycles from June 2010 to December 2012, controlled ovarian hyperstimulations were performed with GnRH agonist protocol (n=886) or GnRH antagonist protocol (n=527). The patients were divided into two groups according to serum AMH level (AMH<2.0 or >2.0 ng/ml). In each group, we analysed pregnancy rates in GnRH agonist and antagonist cycles. Patients’ age was higher in low AMH group than normo-high AMH group (38.0 vs. 34.5) and other demographics (infertility causes, period, etc.) had no differences. A total pregnancy rate was 48.5% (685/1413). In analysis of pregnancy rates between protocol groups, agonist group was 48.4% (429/886) and antagonist group was 48.5% (256/527), there was no significant difference (P=0.45). As we expected, low AMH group (AMH<2.0) showed significantly lower pregnancy rate than normo-high AMH group (33.0% [146/442] vs. 55.5% [539/971], p<0.001) regardless of protocol. In low AMH group (AMH<2.0), antagonist protocol group showed higher pregnancy rate than agonist group (38.5% [57/148] vs. 30.2% [89/294], P<0.0001). In normo-high AMH group (AMH>2.0), opposite result was shown (52.5% [199/379] vs. 57.4% [340/592], P<0.005). Our results showed that low AMH level could be considered as a predictor of poor outcome in IVF cycles. But, using GnRH antagonist protocol showed enhancing pregnancy rate in low AMH patients. In conclusion, if you encounter patients with low AMH, we recommend using GnRH antagonist protocol as good counterplan.

A prospective randomised controlled study comparing a low-cost antagonist protocol using oral ovulation inducing agents in IVF-ICSI cycles with a standard agonist long protocol

The objective of this prospective randomised controlled study was to compare the cost-effectiveness of a low cost antagonist protocol using oral ovulation inducing agents (Clomiphine Citrate or Aromatase Inhibitors) with a standard long GnRH agonist protocol in IVF-ICSI cycles. IVF-ICSI cycles at our centre from 2006 to 2012 were prospectivly studied for gonadotropin usage and cost effectiveness. The patients in the study underwent a long GnRH-Agonist or an Antagonist protocol after randomisation using a computer generated list. The antagonist protocol patients were given only oral ovulogens (Clomiphine Citrate or Aromatase Inhibitors) for the first five days of cycle, followed by gonadotropins. A total of 346 IVF-ICSI cycles were prospectivly studied in patients less than 40 years of age. All patients received low-dose oral contraceptive pills in the preceding cycle. They were randomised into two groups using a computer generated list. The agonist group underwent the standard long GnRH analogue protocol. The antagonist group received oral ovulation inducing agents (Clomiphene Citrate / Aromatase Inhibitor) for the first five days of cycle followed by gonadotropins and 0.25mg antagonist (Cetrorelix) injection daily till the day of hCG, using a flexible antagonist start approach. There was a significant difference in the gonadotropin usage between the two groups. As a result, the cost of the oral ovulation inducing agents (Clomiphene Citrate / Aromatase Inhibitor) - gonadotropin - antagonist cycle was significantly lower than the long GnRH agonist - gonadotropin protocol. Though the mean number of oocytes retrieved was higher in the long protocol group, yet the clinical pregnancy rate per transfer was similar in both the groups. Use of GnRH antagonist in combination with oral ovulation inducing agents offers the advantage of an economical method of stimulation in IVF-ICSI cycles, as compared to the agonist protocol, with a similar pregnancy rate.

Treatment of poor responders with corifollitropin alfa followed by hpHMG in GnRH agonist protocols. Two prospective feasibility studies

To examine the feasibility and safety of 2 novel treatment protocols with 150μg corifollitropin alfa followed by 300IU hMG in a short GnRH agonist or long GnRH agonist protocol for the treatment of poor ovarian responders.

IVM rescue in high responders patients at risk of OHSS

In this pilot study, we tested the hypothesis that, after a few days of FSH administration conventional COH cycles (either daily long GnRH agonist protocols or GnRH antagonist regimens) can be converted into IVM cycles before hCG administration, when follicle count and estradiol levels are high and follicle sizes are small, preventing OHSS risk and cycle cancellation.

Gonadotropin-releasing hormone (GnRH) agonist versus antagonist protocols in patients ≥40 years old undergoing intracytoplasmic sperm injection

Gonadotropin-releasing hormone (GnRH) agonist versus antagonist protocols in patients ≥40 years old undergoing intracytoplasmic sperm injection

Gonadotropin-releasing hormone (GnRH) agonist versus antagonist protocols in patients≥ 43 years old undergoing intracytoplasmic sperm injection

Gonadotropin-releasing hormone (GnRH) agonist versus antagonist protocols in patients≥ 43 years old undergoing intracytoplasmic sperm injection

Evaluation of the oocyte morphology in the patients undergoing IVF-ICSI cycles receiving GnRH agonists and antagonists protocols: a retrospective study

Maternal age, genetic defects and controlled ovarian stimulation protocols may cause extra and/or intracytoplasmic morphological alterations in the oocytes which in turn may result in fertilization failure or developmental impairments. The data in the literature concerning the impact of GnRH agonist and antagonist protocols on oocyte morphology still remains controversial. Our aim is to investigate the effect of agonist and antagonist protocols on oocyte dysmorphism.

Microdose GnRH agonist flare-up versus flexible GnRH antagonist protocol in poor responders undergoing in-vitro-fertilization (IVF) cycles: a randomized controlled trial

Optimal stimulation protocol for poor responders remains undefined. The aim of this study was to compare the efficacy of microdose flare-up GnRH agonist (GnRH-a) and multiple dose flexible GnRHantagonist protocols in poor responders.

A prospective randomised controlled study of serum anti-mullerian hormone (AMH) as a predictive marker of ovarian hyperstimulation syndrome (OHSS) in IVF-ICSI cycles

A prospective randomised controlled study of serum anti-mullerian hormone (AMH) as a predictive marker of ovarian hyperstimulation syndrome (OHSS) in IVF-ICSI cycles

Prevention of ovarian hyperstimulation syndrome in GnRH agonist IVF cycles in moderate risk patients: randomized study comparing hydroxyethyl starch versus cabergoline and hydroxyethyl starch

ObjectiveTo assess whether, in GnRH agonist IVF cycles where there is a risk of ovarian hyperstimulation syndrome (OHSS), the addition of cabergoline to the hydroxyethyl starch (HES) infusion could decrease OHSS incidence and severity. Materials and methodsProspective randomized study. The population under study consisted of women undergoing IVF cycles with GnRH agonist protocols, at risk of OHSS (more than 20 follicles observed larger than 12mm in diameter and/or estradiol levels of 3000–5000pg/mL). Women received a slow infusion of 500mL of 6% HES during follicular aspiration alone or combined with 0.5mg cabergoline administration for 8 days, starting on the day of hCG administration. ResultsThe rates of OHSS (both early and late) were very similar in the HES alone group (3.19% (3/94)) and in the HES plus cabergoline group (5.68% (5/88)), as were the rates of severe cases of OHSS (1.06% and 2.27%). Pregnancy rates (PR) were also similar in the two groups (ongoing PR per transfer, 47.56% and 47.50%). CommentsThe co-administration of cabergoline in patients receiving HES due to OHSS risk did not reduce the rate or severity of OHSS in GnRH agonist IVF cycles.