Evidence for different aetiologies of low estradiol response to FSH: age-related accelerated luteinization of follicles or presence of ovarian autoantibodies.
BACKGROUND
We found granulosa cells of low responders (LR) expressed more LH receptors, suggesting that follicles were more luteinized than normal responders (NR). The objectives were to test the hypothesis that follicles of LR were more luteinized than follicles of NR, and to determine if LR with (LR+) and without (LR-) ovarian antibodies differed.


METHODS
Hormone levels and ovarian autoantibodies (OVAB) were measured in follicular fluid from mature follicles (>17 mm), and in serum obtained on the day of oocyte retrieval during controlled ovarian stimulation. The gonadotrophin response was defined as a ratio of peak estradiol/number of FSH ampoules.


RESULTS
NR (32.5 +/- 4.6 years; n = 11) were similar in age to LR+ (33.4 +/- 4.2 years; n = 9) and were younger than LR- (37.1 +/- 3.8 years; n = 12) (P = 0.03). Likewise, dehydroepiandrosterone sulphate was lower in LR- compared with LR+ or NR (P < 0.01). FSH, progesterone, inhibin-A and vascular endothelial growth factor levels were higher in follicular fluid of LR than NR. LR- and LR+ differed. For example, the follicular fluid progesterone/estradiol ratio was similar in NR (11.1 +/- 8.9) and LR+ (9.8 +/- 6.6) but was lower than LR- (22.9 +/- 19.6) (P = 0.05). Serum hormone levels did not reflect follicular fluid hormone profiles.


CONCLUSIONS
In the absence of ovarian antibodies, low responses are associated with higher age and accelerated luteinization of mature follicles, rather than diminished responsiveness. Ovarian antibody may be an additional tool to predict and individualize treatment regimens in poor responders.
D000328:Adult; D000375:Aging; D000735:Androstenedione / Q000032:analysis / Q000097:blood; D001323:Autoantibodies / Q000032:analysis* / Q000097:blood; D003338:Corpus Luteum / Q000502:physiology*; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood; D004351:Drug Resistance; D016228:Endothelial Growth Factors / Q000032:analysis / Q000097:blood; D004958:Estradiol / Q000032:analysis / Q000097:blood*; D005260:Female; D005307:Fertilization in Vitro; D005640:Follicle Stimulating Hormone / Q000008:administration & dosage* / Q000032:analysis / Q000097:blood; D015571:Follicular Fluid / Q000737:chemistry; D006801:Humans; D007265:Inhibins / Q000032:analysis / Q000097:blood; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis / Q000097:blood; D008222:Lymphokines / Q000032:analysis / Q000097:blood; D006080:Ovarian Follicle / Q000502:physiology*; D010053:Ovary / Q000276:immunology*; D010062:Ovulation Induction; D011374:Progesterone / Q000032:analysis / Q000097:blood; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D001323:Autoantibodies; D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; C422362:inhibin A; C422364:inhibin B; D000735:Androstenedione; D011374:Progesterone; D004958:Estradiol; D007265:Inhibins; D019314:Dehydroepiandrosterone Sulfate; D005640:Follicle Stimulating Hormone