GnRH antagonist-induced inhibition of the premature LH surge increases pregnancy rates in IUI-stimulated cycles. A prospective randomized trial (original) (raw)
Related papers
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.
Human Reproduction, 2004
BACKGROUND: An optimal range of LH concentrations for achieving pregnancy has not been established. The aim of this study was to investigate the effect of various LH levels induced by different GnRH antagonist doses on IVF outcome. METHODS: This was a prospective, single centre study including 144 IVF patients, stimulated with recombinant FSH from cycle day 2, and co-treated with daily GnRH antagonist (antide/Iturelix) (2 mg/2 ml, 1 mg/ml, 0.5 mg/ml, 0.5 mg/0.5 ml or 0.25 mg/ml) from cycle day 7 onwards. Serum samples were taken three times daily. RESULTS: Clinical pregnancies were only observed within a particular range of change in LH levels. The upper and lower thresholds for the mean LH area under the curve (AUC), adjusted for the baseline LH level before the antagonist was started (LH AUC 2S6 ; S6 5 stimulation day 6) were 22.2 and 12.4 (IU/l) respectively (a negative value 5 below baseline levels). There were no clinical pregnancies outside these threshold values. Similar results were found for progesterone, the threshold levels of progesterone AUC 2S6 were 3.98 and 21.21 ng/ml. Moreover, there were no pregnancies with progesterone levels > 0.26 ng/ml/follicle on the day of hCG. CONCLUSIONS: Excessive or insufficient suppression of LH and progesterone levels during GnRH antagonist administration and high progesterone/follicle on hCG day seems to be associated with impaired clinical pregnancy rates.
Background: To assess the usefulness of premature luteinization hormone (LH) surge prevention in an intrauterine insemination (IUI) cycle by GnRH antagonist administration. Materials and Methods: Sixty patients with unexplained or mild male infertility or minimal to mild endometriosis were enrolled in this prospective randomized controlled trial. There were twenty patients in group A (with GnRH antagonist) and 40 patients in group B (without GnRH antagonist). In all of the participants, clomiphene citrate and human menopausal gonadotropin (CC+HMG) were used for ovarian stimulation. When at least one follicle with ≥ 16 mm diameter was seen, LH surge was checked by a urinary LH kit. In patients with negative results, human chorionic gonadotropin was continued in both groups, but in group A 0.25 mg Ganirelix SQ was administered for two days, ,then in both groups human chorionic gonadotropin (HCG) was injected on the third day and IUI was done 36-40 hours later. Ongoing pregnancy was the primary outcome. Results: Baseline characters and clinical parameters were similar in both groups with the exception of ≥14 mm follicles which were higher in group A (p value= 0.003). The pregnancy rate in both groups was not significantly different, although it was higher in group B (10% in group A and 15% in group B). Conclusion: At least in CC+HMG stimulated cycles for IUI, the occurrence of premature LH surge could have a useful rule and GnRH antagonist administration could be an inappropriate intervention.
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.
Frontiers in Endocrinology
Objective: To explore whether the addition of a mid-luteal bolus of GnRH agonist (GnRHa) improves the implantation rate (IR) in in vitro fertilization (IVF) cycles. Design: A randomized controlled trial. Setting: Private IVF center. Patients: 328 IVF/intracytoplasmic sperm injection patients were triggered with GnRHa and received 1,500 IU HCG on the day of oocyte pickup (OPU) in addition to a standard luteal phase support (LPS). intervention(s): In addition, the study group received a bolus of GnRHa 6 days after OPU, whereas the control group did not. Main outcome measure: Implantation rate. Secondary outcome measure(s): Ongoing pregnancy (OP) and live birth (LB) rates. results: Although serum concentrations of FSH, LH, E2, and P on day OPU + 7 were significantly higher in the study group compared to the control group, the IR was not statistically different between the treatment group (27%) and the control group (23%) [odds ratio (OR) 1.2 (95% CI 0.9-1.7), P < 0.27]. Similarly, the OP rate was 37% in the treatment group and 31% in the control group [OR 1.3 (95% CI 0.8-2.0), P < 0.23]. The LB rate was 36% in the treatment group and 31% in the control group [OR: 1.3 (95% CI 0.8-2.0), P < 0.27]. Conclusion: Although a trend toward a higher IR and pregnancy rate was observed in the treatment group, this difference was not statistically significant. However, the absolute risk difference of 5% found for LB is clinically relevant, warranting further investigation. nCT: 02053779.
Human Reproduction, 2004
BACKGROUND: The significance of suppressed LH levels in GnRH antagonist cycles for IVF outcome is currently unknown. The purpose of this study was to evaluate prospectively the association between LH levels and ongoing pregnancy achievement after GnRH antagonist initiation in IVF cycles. METHODS: Ovarian stimulation with a fixed dose of 200 IU recombinant FSH and daily GnRH antagonist (ganirelix) 0.25 mg from day 6 of stimulation was initiated in 116 women. Patients were not pretreated with an oral contraceptive. Induction of final oocyte maturation was performed with HCG 10 000 IU as soon as three follicles of $17 mm were present in ultrasound, and was followed by oocyte pick-up, conventional IVF or ICSI, and embryo transfer. The luteal phase was supplemented with vaginal progesterone. RESULTS: A significant decrease of both ongoing pregnancy rate and implantation rate was present across groups of patients with increasing LH levels. The highest implantation rate and ongoing pregnancy rate was present in those patients with LH levels on day 8 of stimulation #0.5 IU/l. CONCLUSIONS: Profound suppression of LH on day 8 of stimulation is associated with a significantly higher chance of achieving an ongoing pregnancy. More studies are necessary to evaluate this phenomenon further.
Fertility and Sterility, 2013
Aims and Objective To evaluate the role of GnRH antagonist in prevention of premature LH surge and increasing pregnancy rates in IUI cycle with mild ovarian hyperstimulation (MOH). Study Design Prospective parallel, randomised controlled study. Material and Methods Couples diagnosed with unexplained, male factor subfertility and with one or both tubes patent were randomised to receive either a GnRH antagonist (study group) or no intervention (control group). All Presentation at a meeting: Presented paper on Evaluation of role of GnRH antagonist in Intrauterine insemination (IUI) cycles with mild ovarian hyperstimulation (MOH) at IFFS/ASRM, Boston, USA 12-17 October 2013.
Reproductive BioMedicine Online, 2011
KJ Doody). Kevin Doody, MD, received his medical degree and served a residency in obstetrics and gynaecology at Baylor College of Medicine in Houston. After completing his residency, Dr Doody received subspecialty training at UT Southwestern Medical Center. He completed his fellowship in reproductive endocrinology/infertility in 1989. He is board certified in obstetrics and gynaecology and subspecialty board certified in reproductive endocrinology/ infertility. Dr Doody has been repeatedly honoured as one of Fort Worth's Top Docs, one of Texas's Super Doctors and one of the Best Doctors in America. Dr Doody was also recognized as Microsoft Physician of the Year 2004.
Human Reproduction, 2012
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. methods: Overall 190 patients were randomized: 94 in the GnRH-agonist group and 96 in the GnRH-antagonist group. The GnRHagonist long protocol started on Day 21 of the preceding cycle with intranasal buserelin (600 mg per day). The GnRH-antagonist protocol started on Day 6 of the stimulation with ganirelix or cetrorelix (each 0.25 mg). All blood samples were analysed with the Elecsys analyzer. An intention-to-treat analysis was applied. results: A progesterone rise .1.5 ng/ml was noticed in 23.0% of the antagonist group, comparable with 24.1% incidence within the agonist group. Per patient randomized, delivery rates were also comparable: 28.1% in the antagonist group and 24.5% in the agonist group (odds ratio ¼ 1.21, 95% confidence interval: 0.63-2.31, P ¼ 0.56). However, there was a reduction in delivery rates when progesterone exceeded the threshold of 1.5 ng/ml, both in the agonist group (9.5 versus 31.8%, P ¼ 0.03) and in the antagonist group (14.3 versus 34.3%, P ¼ 0.07). conclusions: Although the incidence of a progesterone rise was similar between the two analogues, our findings reconfirm previous observations that insufficient progesterone control (.1.5 ng/ml) on the day of ovulation triggering is related to poor delivery rates in both protocols. The current study has shown that the reproductive outcomes with the two GnRH analogues are comparable. Possible modes of action to circumvent late follicular progesterone rise should be explored.
Human Reproduction, 2005
BACKGROUND: The purpose of the study was to assess ongoing pregnancy rates across groups of patients treated by IVF, which were defined according to criteria aimed at the prevention of premature LH surge and used for initiating GnRH antagonist. METHODS: This is a prospective observational cohort study. During the last 3 years, in IVF-ICSI patients undergoing controlled ovarian stimulation (COS) with the antagonist protocol, the antagonist administration was initiated according to at least one of the following patient-specific criteria: (i) at least one follicle measuring > 14 mm; (ii) estradiol levels > 600 pg/ml; and (iii) LH levels >10 IU/l. Based upon these criteria, 208 cases of normal responders were analysed and categorized into three groups according to the starting day of the regimen: group D4 (n 5 40) for day 4, group D5 (n 5 98) for day 5 and group D6 (n 5 70) for day 6. The main outcome measure was the ongoing pregnancy rate per started cycle. RESULTS: The total number of patients in the D4 and D5 groups (138 out of 208), who received the antagonist earlier, was considerably larger compared with that of D6 (70 out of 208). Ongoing pregnancy rates were 37.5, 34.7 and 18.6% for groups D4, D5 and D6, respectively. Patients who initiated the GnRH antagonist on days 4 and 5 had statistically significant higher pregnancy rates compared with day 6. Rapid response, causing earlier antagonist administration initiation, according to the proposed criteria for the prevention of premature LH surges, and the absence of premature luteinization, as evidenced by normal progesterone levels on HCG day, were found to be independent positive predictive factors for favourable IVF outcome. CONCLUSIONS: The employment of an algorithm of criteria, aimed at the prevention of premature LH surges in a flexible antagonist protocol, resulted in antagonist initiation earlier than on stimulation day 6 in a significant proportion of patients. In those patients, a higher pregnancy rate was observed.