Revisiting criteria for hCG administration in mild-stimulation intrauterine insemination cycles: a multicentric, prospective, randomized study

Abstract

OBJECTIVE: Contrasting with the multiple achievements in drugs reliability and flexibility for control final follicle maturation and the advancements in ovarian follicle imaging obtained during the last years, clinical criteria to determine follicle readiness for ovulation triggering in assisted reproductive technologies (ART) still remain surprisingly fuzzy. Indeed, scant data associating follicle diameters on the day of hCG administration and ART outcome is available. The objective of the present investigation was to compare pregnancy rates of early (smaller follicles) versus late (larger follicles) hCG administration to trigger ovulation in stimulated IUI cycles.DESIGN: Randomized, open label, multi centric, clinical trial.MATERIALS AND METHODS: Per-protocol analysis included 347 women undergoing mild ovarian stimulation + IUI. All of them were 20-40 years of age, had regular menstrual cycles, documented normal uterine cavity, tubes, basal hormonal screening, and partner's sperm parameters. Ovarian stimulation was obtained with HP-hMG, 75 IU/day SC, from cycle days 4-8 and then as per ovarian response. hCG (5,000 IU, IM) was administrated randomly when the leading follicle diameter ranged either 16.0-17.0 mm (Early hCG group, n=187) or 18.0-19.0 mm (Late hCG group, n=160) and IUI was performed approximately 36 hours later. Non-inferiority analysis has been powered to detect >2.7% differences in clinical pregnancy rates.RESULTS: Population characteristics in the Early and Late hCG groups were comparable. The incidence of premature LH peak tended to be lower in the Early hCG group, but not significantly (13.6% vs.16.5%). On the day of hCG administration, the number (mean; 95% CIs) of follicles ≥14 mm (1.6; 1.3-1.9 vs. 1.7; 1.5-1.9, P< 0.04) and the leading follicle size (16.4; 16.3-16.5 mm vs. 18.3; 18.2-18.4 mm; P< 0.001) were smaller in the Early hCG group. Despite these differences, non-inferiority of early versus late hCG administration regarding clinical (10.7% vs. 12.5%, respectively) and ongoing (10.7% vs. 11.3%, respectively) pregnancy rates was demonstrated. No case of moderate or severe ovarian hyperstimulation syndrome was observed.CONCLUSIONS: The present data indicate that lengthening of ovarian stimulation to reach follicle sizes >18 mm in diameter does not offer a significant improvement in IUI outcome as compared to hCG administration at smaller follicle sizes. Therefore, early hCG administration strategy (16-17 mm) may be more cost-effective and simple to patients. OBJECTIVE: Contrasting with the multiple achievements in drugs reliability and flexibility for control final follicle maturation and the advancements in ovarian follicle imaging obtained during the last years, clinical criteria to determine follicle readiness for ovulation triggering in assisted reproductive technologies (ART) still remain surprisingly fuzzy. Indeed, scant data associating follicle diameters on the day of hCG administration and ART outcome is available. The objective of the present investigation was to compare pregnancy rates of early (smaller follicles) versus late (larger follicles) hCG administration to trigger ovulation in stimulated IUI cycles. DESIGN: Randomized, open label, multi centric, clinical trial. MATERIALS AND METHODS: Per-protocol analysis included 347 women undergoing mild ovarian stimulation + IUI. All of them were 20-40 years of age, had regular menstrual cycles, documented normal uterine cavity, tubes, basal hormonal screening, and partner's sperm parameters. Ovarian stimulation was obtained with HP-hMG, 75 IU/day SC, from cycle days 4-8 and then as per ovarian response. hCG (5,000 IU, IM) was administrated randomly when the leading follicle diameter ranged either 16.0-17.0 mm (Early hCG group, n=187) or 18.0-19.0 mm (Late hCG group, n=160) and IUI was performed approximately 36 hours later. Non-inferiority analysis has been powered to detect >2.7% differences in clinical pregnancy rates. RESULTS: Population characteristics in the Early and Late hCG groups were comparable. The incidence of premature LH peak tended to be lower in the Early hCG group, but not significantly (13.6% vs.16.5%). On the day of hCG administration, the number (mean; 95% CIs) of follicles ≥14 mm (1.6; 1.3-1.9 vs. 1.7; 1.5-1.9, P< 0.04) and the leading follicle size (16.4; 16.3-16.5 mm vs. 18.3; 18.2-18.4 mm; P< 0.001) were smaller in the Early hCG group. Despite these differences, non-inferiority of early versus late hCG administration regarding clinical (10.7% vs. 12.5%, respectively) and ongoing (10.7% vs. 11.3%, respectively) pregnancy rates was demonstrated. No case of moderate or severe ovarian hyperstimulation syndrome was observed. CONCLUSIONS: The present data indicate that lengthening of ovarian stimulation to reach follicle sizes >18 mm in diameter does not offer a significant improvement in IUI outcome as compared to hCG administration at smaller follicle sizes. Therefore, early hCG administration strategy (16-17 mm) may be more cost-effective and simple to patients.