GnRH agonist and antagonist protocols for stage I-II endometriosis and endometrioma in in vitro fertilization/intracytoplasmic sperm injection cycles. Comparison of GnRH agonists and antagonists in normoresponder IVF/ICSI in Turkish female patients. GnRH agonist protocol administration in the luteal phase in ICSI-ET cycles stimulated with the long GnRH agonist protocol: a randomized, controlled double blind study. Effect of prolonged gonadotropin-releasing hormone agonist therapy on the outcome of in vitro fertilization-embryo transfer in patients with endometriosis. Beneficial effect of luteal-phase GnRH agonist administration on embryo implantation after ICSI in both GnRH agonist- and antagonist-treated ovarian stimulation cycles. Increased pregnancy rates after ultralong postoperative therapy with gonadotropin-releasing hormone analogs in patients with endometriosis. 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. A randomised study of GnRH antagonist (cetrorelix) versus agonist (busereline) for controlled ovarian stimulation: effect on safety and efficacy. Single-dose GnRH agonist administration in the luteal phase of GnRH antagonist cycles: a prospective randomized study.
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.
                Prospective randomize trial.
                A private IVF center.
                A total of 246 ICSI cycles in 246 patients were divided into three groups: women with mild-to-moderate endometriosis (n = 98); women who had ovarian surgery for endometrioma (n = 81); women with endometrioma and no history of previous surgery (n = 67).
                Patients in each group were randomized to COH with either triptrolein or cetrorelix.
                Clinical parameters, characteristics of COH, and ICSI results were analyzed.
                Outcomes of COH with both GnRH antagonist and GnRH-a were similar in patients with mild-to-moderate endometriosis. Implantation rates were 15.9% vs. 22.6% and clinical pregnancy rates were 27.5% vs. 39% with GnRH antagonist and GnRH-a protocols, respectively, in patients who had ovarian surgery for endometrioma. Implantation rates were 12.5% vs. 14.8% and clinical pregnancy rates were 20.5% vs. 24.2% with GnRH antagonist and GnRH-a protocols, respectively, in patients with endometrioma and no history of ovarian surgery.
                Considering the implantation and clinical pregnancy rates, COH with both GnRH antagonist and GnRH-a protocols may be equally effective in patients with mild-to-moderate endometriosis and endometrioma who did and did not undergo ovarian surgery. 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.
                We randomised 93 patients undergoing IVF/ICSI between May 2005 and August 2006. Patients with IVF indications were included except for those with polycystic ovary syndrome or azoospermia, women older than 38 years and those with follicle-stimulating hormone (FSH) > or =10 IU/ml. Patients were stimulated with standard 225 IU recombinant FSH. In Group I (n=45) a daily dose of GnRHant cetrorelix acetate 0.25 mg was administered when follicles reached a diameter of > or =14 mm. Group II (n=48) patients were desensitised with the GnRHa, leuprolide acetate, in a long protocol. Human chorionic gonadotropin (hCG) was administered when at least three follicles of 18 mm in diameter were observed. Oocyte retrieval was scheduled 36 hours following hCG administration and embryos were transferred on day 3 after oocyte retrieval.
                The two groups were homogenous for age, infertility duration, basal FSH and serum oestradiol (E2) (P=0.537, P=0.911, P=0.103 and P=0.733, respectively). In Group II (the GnRHa group) more antral follicles (P<0.001), a longer induction duration (P=0.017) and higher peak E2 levels (P<0.001) were observed. No differences were observed in the number of oocytes retrieved (P=0.749), embryos achieved and transferred (P=0.677), or fertilisation rates (P=0.839) between the two groups. There was no statistically significant difference between groups in clinical pregnancy rates, cycle cancellation and ovarian hyperstimulation (P=0.437, P=0.109 and P=0.415, respectively).
                GnRHant and GnRHa provide comparable results in normoresponder patients, while GnRHant allows a greater flexibility in their treatment. GnRH agonist administration in the luteal phase was reported to beneficially affect the clinical outcome of intracytoplasmic sperm injection (ICSI) and embryo transfer (ET) cycles. This double blind, randomized, placebo controlled trial evaluates whether a single dose GnRH agonist administered 6 days after ICSI increases ongoing pregnancy rates following ET in cycles stimulated with the long GnRH agonist protocol.
                Five hundred and seventy women undergoing ET following controlled ovarian stimulation with a long GnRH agonist protocol were included. In addition to routine luteal phase support with progesterone, women were randomized to receive a single 0.1 mg dose of triptorelin or placebo 6 days after ICSI. Randomization was done on the day of ET according to a computer generated randomization table. Ongoing pregnancy rate beyond 20th week of gestation was the primary outcome measure. The trial was powered to detect a 12% absolute increase from an assumed 38% ongoing pregnancy rate in the placebo group, with an alpha error level of 0.05 and a beta error level of 0.2.
                There were 89 (31.2%) ongoing pregnancies in the GnRH agonist group, and 84 (29.5%) in the control group (absolute difference +1.7%, 95% confidence interval -5.8% to +9.2%). Implantation, clinical pregnancy and multiple pregnancy rates were likewise similar in the GnRH agonist and placebo groups.
                Single 0.1 mg triptorelin administration 6 days after ICSI following ovarian stimulation with the long GnRH agonist protocol does not seem to result in an increase >or=12% in ongoing pregnancy rates. To evaluate the effect of a 3-month course of GnRH agonist administered immediately before IVF-ET in infertile patients with endometriosis.
                Prospective, randomized trial.
                Three tertiary care assisted reproductive technology programs.
                IVF-ET candidates with surgically confirmed endometriosis.
                Twenty-five patients received three courses of a long-acting GnRH agonist, 3.75 mg i.m. every 28 days, followed by standard controlled ovarian hyperstimulation. Twenty-six patients received standard controlled ovarian hyperstimulation with mid-luteal phase GnRH agonist down-regulation or microdose flare regimens.
                Response to controlled ovarian hyperstimulation, ongoing pregnancy rates per cycle, group implantation rates, and implantation rate per embryo transfer procedure.
                The extent of surgically confirmed endometriosis was greater in patients who received the long-acting GnRH regimen for 3 months before IVF-ET. The groups did not differ significantly in terms of dose or duration of gonadotropin stimulation, number of oocytes retrieved, fertilization rate, or number of embryos transferred. Patients who received the long-acting GnRH regimen had significantly higher ongoing pregnancy rates (80% vs. 53.85%) and a trend toward higher implantation rates (42.68% vs. 30.38%).
                Prolonged use of GnRH agonist before IVF-ET in patients with endometriosis resulted in significantly higher ongoing pregnancy rates than did standard controlled ovarian hyperstimulation regimens. No deleterious effect on ovarian response was observed. GnRH agonist was recently suggested as a novel luteal-phase support that may act at different levels, including the pituitary gonadotrophs, the endometrium and the embryo itself. This prospective randomized study evaluates the effect of GnRH agonist administered in the luteal phase on ICSI outcomes in both GnRH agonist- and GnRH antagonist-treated ovarian stimulation protocols.
                Six hundred women about to undergo ovarian stimulation for ICSI (300 using a long GnRH agonist protocol and 300 using a GnRH antagonist protocol) were enrolled in this study. Patients treated with each of these two protocols were randomly assigned to receive a single injection of GnRH agonist or placebo 6 days after ICSI. Implantation and live birth rates were the primary outcomes.
                Administration of 0.1 mg of GnRH agonist triptorelin on day 6 after ICSI led to a significant improvement of implantation and live birth rates after ICSI as compared with placebo. In GnRH antagonist-treated ovarian stimulation cycles, luteal-phase GnRH agonist also increased ongoing pregnancy rate. Moreover, luteal-phase GnRH agonist administration increased luteal-phase serum HCG, estradiol and progesterone concentrations in both ovarian stimulation regimens.
                Luteal-phase GnRH agonist administration enhances ICSI clinical outcomes after GnRH agonist- and GnRH antagonist-treated ovarian stimulation cycles, possibly by a combination of effects on the embryo and the corpus luteum. To examine whether ultralong GnRH analog (GnRH-a) therapy after surgical treatment of endometriosis and before ART influences the pregnancy rate.
                Prospective, randomized, controlled study.
                University clinic for reproductive medicine and gynecologic endocrinology.
                One hundred ten patients with stage II to IV endometriosis according to ASRM criteria.
                Fifty-five patients received GnRH-a for 6 months after surgery and subsequently underwent up to 3 cycles of ART, and 55 patients received 3 cycles of ART alone immediately after surgery.
                Clinical pregnancy rates.
                The pregnancy rate per patient was higher among patients who received follow-up treatment with GnRH-a. The same results were found in patients with stage III or IV endometriosis who were undergoing IUI or IVF/ICSI.
                Ultralong GnRH-a therapy increases the pregnancy rate of ART in patients with severe endometriosis. To study if luteal E(2) pre-treatment before GnRH antagonist protocol improves IVF/ICSI outcomes compared with standard long GnRH agonist protocol.
                A prospective, randomized and controlled study.
                ART center of a state public hospital
                Two hundred twenty infertile women underwent IVF/ICSI treatments.
                Participants received oral Estradiol Valerate 4 mg/day preceding the IVF cycle from day 21 until day 2 of next cycle before GnRH antagonist protocol (E(2) pre-treatment group n=109) or received standard long GnRH agonist protocol as control group (n=111).
                Number of oocytes collected, MII oocytes, fertilization, implantation, live birth and early pregnancy rate, and hormone profiles.
                E(2) pre-treatment exerted a significant suppressive effect on FSH but not LH secretion compared with basal FSH and LH levels. In E(2) pre-treatment group serum LH level was significantly higher during COH and serum P was also significantly higher on the day of HCG injection compared with control group. Five patients from E(2) pre-treatment group had elevated LH at all time (>or= 10 IU/L) and also a concomitantly high P (>1 ng/mL). Two of the five women achieved pregnancy but had early pregnancy loss. Overall, IVF/ICSI outcomes such as implantation, clinical pregnancy and live birth rates were similar between E(2) pre-treatment and control groups.
                Luteal E(2) pre-treatment before GnRH antagonist protocol significantly increases serum LH level and incidence rate of premature LH but no significant effect is observed on implantation, clinical pregnancy, live birth and early pregnancy loss rates compared with long GnRH agonist protocol. However, more studies in large numbers of cycles are needed to confirm that increased serum LH level by E(2) pre-treatment during COH has no negative effect on the IVF/ICSI outcomes. To assess safety and efficacy of cetrorelix utilisation in controlled ovarian stimulation (COS).
                Phase III, randomized, single center study of 131 patients undergoing COS and IVF with or without ICSI, in a University affiliated Hospital. Sixty-six patients were allocated to the protocol with antagonist and 65 to the agonist protocol arm. The Student's t-test, the Mann-Whitney test and the chi-square test were applied as required, using SPSS for Windows with a two-sided 5% significance level.
                The mean (+/-S.D.) duration of stimulation was 9.5+/-1.7 days in the antagonist group and 10.6+/-2.1 days in the agonist group (P=0.02). The mean (+/-S.D.) duration of suppression was 4.6+/-1.3 days in the antagonist group and 27.3+/-5.2 days in the agonist group (P<0.0001). No significant differences were noted in other outcome measures: amount of rFSH required, estradiol level on hCG day, number of follicles>or=15 mm and endometrial thickness on oocyte retrieval day, number of oocytes retrieved, fertilization rate and number of OHS cases. Clinical pregnancy rates per-attempt and per-transfer were 15.1% and 17.0% in the antagonist group and 16.9% and 20.0% in the agonist group (P=0.79 and 0.71, respectively).
                GnRH antagonists are an effective, safe and well tolerated alternative to agonists for COS. This study was designed to evaluate the effect of luteal-phase administration of single-dose gonadotrophin-releasing hormone (GnRH) agonist on pregnancy, implantation and live birth rates in patients who received GnRH antagonist for pituitary suppression. The study population consisted of 164 patients who underwent intracytoplasmic sperm injection (ICSI) after ovulation induction by gonadotrophins and GnRH antagonist for the prevention of a premature LH surge. For luteal-phase support, all the cases received intravaginal 600 mg micronized progesterone. In this prospective study, patients were randomly assigned to two groups. In one group, patients received an additional single dose of GnRH agonist (0.5 mg leuprolide acetate) subcutaneously on day 6 after ICSI, whereas the patients in the other group did not. Although the number of embryos transferred and the grade of the embryos were similar in the two groups, the patients in the luteal-phase agonist group had significantly higher rates of implantation and clinical pregnancy rates ( P < 0.05). When the two groups were compared, there were also statistically significant differences in multiple pregnancy and live birth rates ( P < 0.05). Administration of single-dose GnRH agonist as a luteal-phase support in ovarian stimulation-GnRH antagonist cycles in addition to standard luteal support seems to be effective in all cycle outcome parameters.
The administration of GnRH agonists for a period of three to six months prior to IVF or ICSI in women with endometriosis increases the odds of clinical pregnancy by fourfold. Data regarding adverse effects of this therapy on the mother or fetus are not available at present.