Oocyte Maturity and Fertilization Outcomes Using IVF/ICSI

Abstract

To determine if the percentage of mature oocytes at retrieval impacts embryo quality or In Vitro Fertilization (IVF)/ Intracytoplasmic Sperm Injection (ICSI) outcomes. A retrospective data analysis using a coded database of 1349 patients undergoing their first attempted cycles of IVF/ICSI at an academic infertility center. All patients received luteal suppression with a gonadotropin releasing hormone agonist (GnRH-a) and controlled ovarian hyperstimulation with follicle stimulating hormone (FSH) +/- human menopausal gonadotropin, hMG(75-300IU). A standard step-down protocol was utilized for all cycles. Doses were individualized based on age and serum estradiol response. When ultrasound confirmed 2-3 lead follicles with a diameter of 17mm, hCG was administered and oocytes were harvested 35 hours later. ICSI was performed on all metaphase II oocytes. The best embryos available were transferred to patients on days 3-5 per our protocols. Luteal support was given. Cycles were analyzed in subgroups by age (<33, 34-36, 37-39 and >40 years). Outcomes measured included the total number of oocytes, % mature oocytes, % fertilized, embryos transferred, clinical pregnancies, implantation rate (sacs and fetal heart/ per transfer) and deliveries per cycle. The Student’s t-test and Chi-square test were used where appropriate. Pearson correlation coefficients were also calculated. SAS Version 9.1 was used. The groups of patients, stratified by age, were comparable with respect to the number of oocytes produced and the percentage of mature oocytes per cycle. A positive trend in the percentage of mature oocytes and percent fertilized was seen in all age groups with the strongest correlations seen for the extremes of ages; r=0.15. p=0.002 (<33yo) and r=0.16, p=0.009 (>40yo), compared to r=0.10, p=0.07 (34-36yo) and r=0.01, p=0.83 (37-39yo). For the number of embryos transferred, the strongest correlation with percent mature oocytes was seen for ages 34-36yo (r=0.20, p=0.0002) and >40yo (r=0.14, p=0.02). The relationship between percent mature oocytes and implantation rate was only statistically significant with respect to patients >40yrs (r=0.13, p=0.03) and <33yrs of age (r=0.10, p=0.04). Overall, patients with >80% mature oocytes had more fertilized oocytes (mean=8.1 vs. 6.0, respectively, p<0.0001), percent fertilized oocytes per cycle (mean=76.9% vs. 71.3%, respectively, p<0.0001), number of embryos transferred (mean=3.0 vs. 2.8, respectively, p=0.003), and delivery rate (31.9% vs 23.4%, respectively, p=0.001). Similarly, patients with <30% mature oocytes, had fewer fertilized oocytes (mean=1.8 vs. 7.1, respectively, p<0.0001) and number of embryos transferred (mean=1.3 vs. 2.9, respectively, p<0.0001). Minimal stimulation protocols should be utilized to achieve an adequate number of mature oocytes at retrieval. Outcomes of IVF/ICSI at our center appear to be directly correlated to the number of mature oocytes retrieved. Since stimulation protocols and criteria for hCG administration are standard, the effects of prolonging stimulation past the point where most of the retrieved oocytes are mature is unknown. What we can say from our data is that administration of hCG at the earliest point when most oocytes recovered are mature offers the greatest chance for pregnancy insofar as it will provide for the greatest number of fertilized oocytes and embryos to select for transfer.