Triggering final oocyte maturation using different doses of human chorionic gonadotropin: a randomized pilot study in patients with polycystic ovary syndrome treated with gonadotropin-releasing hormone antagonists and recombinant follicle-stimulating hormone.

OBJECTIVE: To evaluate the effect of different human chorionic gonadotropin (hCG) doses on the ongoing pregnancy rates in patients with polycystic ovary syndrome (PCOS). DESIGN: Prospective, randomized, controlled trial. SETTING: Tertiary university referral center. PATIENT(S): Eighty PCOS patients. INTERVENTION(S): Patients were randomized to receive 10,000 IU (n = 28), 5000 IU (n = 26), or 2500 IU (n = 26) of hCG for triggering final oocyte maturation as soon as >or=3 or more follicles of 17 mm or larger were present at ultrasound. Patients were stimulated with recombinant follicle stimulating hormone (FSH) and daily gonadotropin-releasing hormone (GnRH) antagonist, starting on day 6 of stimulation. MAIN OUTCOME MEASURE(S): Ongoing pregnancy, fertilization rates. RESULT(S): The median fertilization rates were 52.8%, 65.4%, and 55.6% after administration of 10,000 IU, 5000 IU and 2500 IU, respectively. The ongoing pregnancy rates per PCOS patient receiving hCG were 26.9% (7 of 26), 30.8% (8 of 26) and 34.8% (8 of 23), respectively. CONCLUSION(S): A decrease in the dose of hCG used to trigger final oocyte maturation does not appear to affect adversely the probability of pregnancy in PCOS patients treated by IVF using GnRH antagonists and recombinant FSH, and further testing in future larger-scale trials is recommended.

Effect of oral contraceptive pill pretreatment on ongoing pregnancy rates in patients stimulated with GnRH antagonists and recombinant FSH for IVF. A randomized controlled trial.

BACKGROUND: The objective of this randomized controlled trial was to assess the effect of oral contraceptive pill (OCP) pretreatment on the probability of ongoing pregnancy in patients treated with a GnRH antagonist for IVF. METHODS: A fixed dose of 200 IU recombinant FSH (rFSH) was started in 425 patients either on day 2 of the menstrual cycle (non-OCP group: n = 211) or 5 days after discontinuing the OCP (OCP group: n = 214). GnRH-antagonist was initiated on day 6 of stimulation, and triggering of final oocyte maturation was performed with 10,000 IU of HCG. RESULTS: Ongoing pregnancy rates per started cycle in the non-OCP and OCP group were 27.5% and 22.9%, respectively [95% confidence interval (CI) of the difference: -3.7 to +12.8]. Pregnancy loss was significantly increased in the OCP (36.4%) compared with the non-OCP group (21.6%) (95% CI of the difference: -28.4 to -2.3). CONCLUSION: Pretreatment with OCP, as compared with initiation of stimulation on day 2 of the cycle in patients treated with GnRH antagonist and recombinant FSH, appears to be associated with a not significant difference in ongoing pregnancy rates per started cycle and results in a significantly higher early pregnancy loss.

Menstruation-free interval and ongoing pregnancy in IVF using GnRH antagonists.

BACKGROUND: The purpose of this study was to evaluate prospectively the association between the achievement of ongoing pregnancy and the time interval from the end of menstruation until the administration of HCG (menstruation-free interval) in patients treated by IVF. METHODS: A fixed dose of 200 IU of recombinant FSH (rFSH) was started in 90 patients on day 2 of the menstrual cycle and daily GnRH antagonist was initiated on day 6 of stimulation. Triggering of final oocyte maturation was performed with 10,000 IU of HCG as soon as three follicles of > or =17 mm were present at ultrasound. RESULTS: Single embryo transfer was performed in 64.6% of the patients who reached embryo transfer (53/82). Ongoing pregnancy rate per embryo transfer was 18.3% (95% CI 11.4-28.0%). The menstruation-free interval significantly predicted the probability of ongoing pregnancy in a logistic regression analysis, controlling for female age and LH on day 1 of stimulation (odds ratio for the menstruation-free interval: 0.70; 95% CI: 0.54-0.92). CONCLUSION: The longer the interval from the end of menstruation until the administration of HCG, the lower the probability of ongoing pregnancy in patients stimulated with recombinant FSH and GnRH antagonist for IVF.

Prolongation of follicular phase by delaying hCG administration results in a higher incidence of endometrial advancement on the day of oocyte retrieval in GnRH antagonist cycles.

BACKGROUND: Prolongation of follicular phase by delaying hCG administration has been reported to result in a significantly lower ongoing pregnancy rate that did not seem to be due to an embryonic factor. The aim of this prospective randomized study was to assess the effect of delaying hCG administration on endometrial histology. METHODS: Ten oocyte donors underwent endometrial biopsy on the day of oocyte retrieval and endometrial histology was assessed by Noyes' criteria. Ovarian stimulation was performed with recombinant (r)FSH and daily GnRH antagonist starting on day 6 of stimulation. Patients were randomized by a computer-generated list to receive 10 000 IU of hCG either as soon as > or =3 follicles > or =17 mm were present on ultrasound (early-hCG group, n = 5) or 2 days after this criterion was met (late-hCG group, n = 5). RESULTS: When hCG was delayed, endometrial advancement was present in all samples examined (median advancement 3 days, range 2-3 days). On the contrary, no secretory changes were observed when the follicular phase was not prolonged (difference in the proportion of patients with advancement between the early-hCG and the late-hCG group: 100%, 95% CI: 38-100). CONCLUSIONS: Prolongation of follicular phase by delaying hCG administration results in a higher incidence of endometrial advancement on the day of oocyte retrieval in GnRH antagonist cycles.

Prolongation of the follicular phase in in vitro fertilization results in a lower ongoing pregnancy rate in cycles stimulated with recombinant follicle-stimulating hormone and gonadotropin-releasing hormone antagonists.

OBJECTIVE: To assess the effect of altering the timing of hCG administration on ongoing pregnancy rates in patients stimulated with recombinant FSH (rec-FSH) and GnRH antagonists for IVF. DESIGN: Prospective, randomized, controlled trial. SETTING: Tertiary referral center. PATIENT(S): Four hundred thirteen patients undergoing IVF. INTERVENTION(S): Rec-FSH stimulation starting on day 2 of the cycle combined with daily GnRH antagonist starting on day 6 of stimulation. Patients were randomized to receive 10000 IU of hCG either as soon as at least three follicles were >or=17 mm on ultrasound (early-hCG group, 208 patients) or 2 days later after this criterion was met (late-hCG group, 205 patients). MAIN OUTCOME MEASURE(S): Ongoing pregnancy rate. RESULT(S): Fertilization rates and number and quality of embryos transferred did not differ between the two groups. However, a significantly lower ongoing pregnancy rate was present in the late-hCG as compared with the early-hCG group (25.0% vs. 35.6%, respectively). CONCLUSION(S): Prolongation of the follicular phase in patients stimulated with rec-FSH and GnRH antagonists for IVF does not affect oocyte or embryo quality but is associated with a significantly lower ongoing pregnancy rate.

Administration of gonadotropin-releasing hormone antagonist from day 1 of stimulation in in vitro fertilization.

After administration of GnRH antagonist from day 1 of stimulation for IVF, 12.1 cumulus oocyte complexes were retrieved (95% confidence interval [CI], 10.6-13.6), 1.9 embryos were transferred (95% CI, 1.7-2.0), and 2.4 embryos were cryopreserved (95% CI, 1.7-3.1). Stimulation for 8.8 days (95% CI, 8.4-9.2) with recombinant FSH resulted in an ongoing implantation rate of 26.5% (95% CI, 17.1-35.9) and an ongoing pregnancy rate of 39.7% per started cycle (95% CI, 30.1-50.8) and of 42.4% per ET (95% CI, 32.3-53.1).

Initiation of gonadotropin-releasing hormone antagonist on day 1 as compared to day 6 of stimulation: effect on hormonal levels and follicular development in in vitro fertilization cycles.

The objective of the present study was to assess the effect of altering the timing of GnRH antagonist initiation on the hormonal environment and follicular development in in vitro fertilization cycles. Sixty women undergoing in vitro fertilization participated in a prospective randomized controlled trial. Patients were stimulated with a fixed dose of 200 IU recombinant FSH, starting on d 2 of the cycle, and with GnRH-antagonist, starting either on d 1 (n = 30) or on d 6 of stimulation (n = 30). A significantly lower exposure to LH (P < 0.001) and estradiol (P < 0.001) during the follicular phase was observed in the d-1 group, compared with the d-6 group of antagonist administration. No differences in follicular development were seen between the two groups on either d 6 of stimulation or on the day of human chorionic gonadotropin administration. Similar fertilization rates, implantation rates, and ongoing pregnancy rates per transfer were, in addition, present between the two groups compared. In conclusion, administration of GnRH antagonist on d 1 (compared with d 6) of stimulation is associated with a lower exposure to LH and estradiol, which does not seem to affect follicular development.

Relationship between LH and oestradiol in IVF cycles before GnRH antagonist initiation.

The objective of this prospective study was to assess the relationship of LH and oestradiol on day 7 of the cycle in patients stimulated with recombinant FSH (rec-FSH) for IVF before initiation of gonadotrophin-releasing hormone (GnRH) antagonist. One hundred and forty-six women treated for IVF using GnRH antagonists for premature LH rise suppression were stimulated with 150 IU of rec-FSH from day 2 to day 6 of the cycle. On cycle day 7, LH concentrations (median 1.8, range 0.1-7.51) were positively associated with oestradiol concentrations on the same day by multiple regression analysis controlling for patient's age, concentrations of FSH and LH on cycle day 2, FSH concentrations on cycle day 7 and follicular index on cycle day 7. In conclusion, the higher the endogenous unsuppressed LH concentrations on day 7 of the cycle after 5 days of stimulation with rec-FSH for IVF, the higher the serum oestradiol concentrations on the same day.

Exposure to high levels of luteinizing hormone and estradiol in the early follicular phase of gonadotropin-releasing hormone antagonist cycles is associated with a reduced chance of pregnancy.

OBJECTIVE: To compare ongoing implantation rates under two different GnRH antagonist protocols. DESIGN: Randomized controlled trial. SETTING: Tertiary referral center. PATIENT(S): One hundred eleven women undergoing ovarian stimulation for in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). INTERVENTION(S): Ovarian stimulation with 150 IU recombinant-FSH (rec-FSH) starting on day 2 of the cycle and GnRH antagonist starting either on day 6 of stimulation (fixed group) or when a follicle of > or = 15 mm was present after at least 5 days of stimulation (flexible group). In the flexible group, the rec-FSH dose was increased to 250 IU when the antagonist was initiated. MAIN OUTCOME MEASURE(S): Ongoing implantation and pregnancy rate. RESULT(S): In patients with no follicle of > or = 15 mm present on day 6 of stimulation, a significantly lower ongoing implantation rate was observed if the flexible scheme was applied as compared with the fixed scheme of administration (8.8% vs. 23.9%, respectively). Exposure of the genital tract to LH or E2 from initiation of stimulation to antagonist administration was able to distinguish between pregnant and nonpregnant patients in the population studied. CONCLUSION(S): High exposure of the genital tract to LH and E2 in the early follicular phase is associated with a reduced chance of pregnancy in cycles stimulated with recombinant FSH and GnRH antagonist for IVF/ICSI.

Endometrial hormone receptors and proliferation index in the periovulatory phase of stimulated embryo transfer cycles in comparison with natural cycles and relation to clinical pregnancy outcome.

OBJECTIVE: To investigate the endometrial steroid receptors and proliferation index in GnRH analogue/hMG-stimulated cycles in comparison with natural cycles and their relation to clinical pregnancy outcome. DESIGN: Prospective observational study. SETTING: Tertiary referral center. PATIENT(S): Twenty-seven stimulated patients with GnRH agonist and hMG. Twenty normo-ovulatory patients were the natural cycle controls. INTERVENTION(S): Endometrial aspiration biopsies: in stimulated cycles on the day of oocyte retrieval within the ET cycle (Day OPU) (n = 20) or 2 days later (Day OPU + 2) (n = 7); in natural cycles on the natural day of ovulation (Day NO) (n = 10) or on the day of ovulation + 2 (Day NO + 2) (n = 10). MAIN OUTCOME MEASURE(S): Comparison of endometrial maturation, estrogen (ER) and P receptor (PR), and proliferation index by immunohistochemistry in natural and stimulated cycles, correlation with pregnancy outcome in stimulated cycles. RESULT(S): Stimulated cycles Day OPU showed significantly advanced endometrial maturation compared to natural cycles Day NO; stromal ER and glandular and stromal PR staining was lower in stimulated than in natural cycles, but higher on Day OPU than on Day NO + 2; proliferation index was lower in all stimulated cycles. Steroid receptors and proliferation index in stimulated cycles were unrelated to clinical pregnancy occurrence. CONCLUSION(S): Compared to natural cycles, ovarian stimulation induced an imbalance in endometrial ER and PR and led to a profound antimitotic effect in the peri-ovulatory phase. These parameters were, however, not predictive of clinical pregnancy in cycles with ET.