Clomiphene is commonly first-line treatment for ovulation induction in women with PCOS. Clomiphene results in a rise in serum FSH concentration; its effect upon FSH glycosylation is less clear. Glycosyl components of serum gonadotrophins are important determinants of their bioactivity.
We compared serum FSH glycosylation in blood samples taken from healthy women with regular ovulatory cycles (group A; n=8) and anovulatory women before (group B; n=7) and during treatment with clomiphene (group C; n=7).
Serum was chromatographed on Superdex-75 pg and fractions containing FSH-immunoactivity were further chromatographed on immobilised lectins, ConA and WGA.
Chromatography fractions were assayed for FSH content using a commercially available platform from Roche.
Eluted FSH was divided into 1 unbound, (batch 1), and 7 bound batches (weakly bound; batch 2 through to strongly bound; batch 8). Elution profiles for groups B and C were compared to group A by Mann Whitney U test, from which z values were derived, a z value >1.96 is significant at the 95% (P=<0.05) level.
When compared with women in group A, FSH from group B showed significantly different ConA binding in batches 1, 3, 6, 7 & 8 (z=3.06, 2.17, 2.32, 3.33 and 4.26 respectively) and WGA binding in batches 2, 3, 4, 5, 7 & 8 (z=2.09, 3.17, 2.66, 3.02, 4.04 and 3.29).
When compared with women in group A, FSH from group C showed significantly different ConA binding in batches 6, 7 & 8 (z=2.3, 3.09 and 2.67) and WGA binding in batches 1, 4 & 7 (z=2.9, 4.5 and 3.2).
Failure of clomiphene to induce physiological patterns of FSH glycosylation may explain clomiphene-resistance in some women.
Declaration of interest: There is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.
Funding: No specific grant from any funding agency in the public, commercial or not-for-profit sector.