The Number of Small Antral Follicles (2-5 Mm) Determines the Ovarian Reserve

Abstract

Age and antral follicle count (AFC) are widely used as markers of ovarian reserve in subfertile women. Ovarian reserve tests (FSH, Inhibin B, Clomiphene Citrate Challenge Test (CCCT), Exogenous FSH Ovarian Reserve Test (EFORT)) have been introduced to predict spontaneous pregnancy chances and ovarian response in IVF. The relation between the size of the antral follicles and the results of ovarian reserve tests is not extensively studied. We studied which size of antral follicles determines the response of the various ovarian reserve tests in a general subfertile population. Prospective cohort study, 1999-2003. Setting: outpatient fertility clinic of UMC Groningen and Martini Hospital, the Netherlands. Patients: subfertile women. Inclusion criteria: regular ovulatory cycles, subfertility for more than twelve months, at least one ovary and at least one patent tube. Exclusion criteria: severe male subfertility (a total motile sperm count < 1 x106) and endometriosis AFS III/IV. The number of antral follicles (sized 2-10 mm) and ovarian volume were measured by transvaginal ultrasound on cycle day three to five. Serum basal FSH and Inhibin B were measured, the CCCT was performed and a subgroup underwent the EFORT. CCCT: 100 mg clomiphenecitrate was applied from cycle day three till seven. The sum of serum FSH on day three and day ten is the outcome of the CCCT. EFORT: 300 IU subcutaneous injection of Puregon® was applied on day two of the consecutive cycle. Serum Estradiol (E2) was measured on cycle day two and 24 hours later. Delta-E2 is the result of E2 day three minus day two. Statistical analysis was performed by SPSS 11.0 for Windows. Non-parametric tests were used to determine Spearman’s correlations. A total of 490 subfertile women participated in this study. Mean age was 32.7 years (19.9-44.7), mean duration of subfertility was 26.4 months (12-153), mean cycle length was 28 days (21-42), 70% of the women had a primairy infertility. AFC was significantly correlated with ovarian volume (r=0.49; p<0.01), Inhibin B (r = 0.16; p<0.01), basal FSH (r=-0.31; p<0.01) and CCCT (r=-0.31; p<0.01). In the subgroup (n=62) the correlation of AFC with the EFORT was strong (r=0.54; p<0.01). The correlations after dividing the AFC in two groups (2-5 and 6-10mm) are shown in the table: Tabled 1Spearman’s coefficient * P-waarde<0,05 ** P-waarde<0,01 Spearman’s coefficient * P-waarde<0,05 ** P-waarde<0,01 The correlations of the number of small antral follicles (2-5mm) with basal FSH, CCCT and EFORT were statistically significant in contrary to the correlations of the larger follicles (6-10mm). Moreover the EFORT showed a strong correlation with AFC and can easily be used in clinical practice as a marker of ovarian reserve. The CCCT has no additional value to basal FSH. We conclude that the number of small follicles is responsible for the endocrine response and can be seen as a marker for the functional ovarian reserve.