Oestradiol and immunoreactive inhibin-like secretory patterns following controlled ovarian hyperstimulation with urinary (Metrodin) or recombinant follicle stimulating hormone (Puregon).
Inhibin (and its alpha-subunit) may be of particular value as a marker for follicular development in in-vitro fertilization (IVF) in comparison with the classic follicle stimulating hormone (FSH)-dependent marker oestradiol in patients following pituitary desensitization and treatment with recombinant FSH (rFSH). This preparation lacks luteinizing hormone (LH), which is essential for thecal cell androgen secretion and thus oestradiol production. Our study has assessed oestradiol and immunoreactive inhibin-like secretion following ovarian stimulation with rFSH or a purified urinary FSH preparation (Metrodin) (uFSH). A randomized, assessor-blind study was initiated using patients receiving a single treatment cycle of IVF (using fresh embryos) following pituitary desensitization with intranasal buserelin (500 microg daily) and the i.m. injection of either rFSH (n = 38) or uFSH (n = 17). Ovarian ultrasound examinations were performed and bloods (10 ml) collected prior to FSH treatment and every 1-2 days until ovulation induction with human chorionic gonadotrophin. LH and FSH concentrations were measured by an immunoradiometric assay, and inhibin-like immunoreactivity by a radioimmunoassay and an enzyme-linked immunosorbent assay, both with alpha-subunit specificity. Oestradiol concentration was measured with a coated tube radioimmunoassay. Following desensitization, basal LH, FSH and oestradiol concentrations were measured, as was that of immunoreactive inhibin. Following treatment with either rFSH or uFSH, LH concentrations remained low while FSH concentrations rose to a plateau of 5.6-6.7 IU/l in both groups. In contrast, the concentration of oestradiol was higher (P < 0.05) with rFSH than with uFSH in the last four days of treatment, a pattern that was repeated for inhibin-like immunoreactivity. The change in oestradiol and inhibin concentrations during treatment was approximately 2-fold higher with rFSH. The total number of follicles obtained with rFSH was similar to that with uFSH. However, the number of follicles with a diameter of >/= 15 mm was higher the rFSH group, and there was a concomitant increase in the number of oocytes recovered. Oestradiol concentration and inhibin-like immunoreactivity (determined by either method) were associated with total follicle number and number of follicles >/= 15 mm in diameter, as well as with each other (P < 0.001). When ovarian hormone output was normalized per follicle produced, oestradiol output was higher for rFSH than for uFSH P = 0.04). Inhibin output was clearly higher using rFSH than uFSH. There were seven pregnancies (one miscarriage) with rFSH and two with uFSH. Despite similar concentrations od FSH in patients, rFSH (Puregon) appears to be more potent in vitro in terms of follicular number, ovarian hormone secretion (both concentration and output/follicle) and oocyte recovery. In both groups, LH concentrations of approximately 1.3 IU/l were sufficient to support oestradiol secretion similar to that normally found in IVF programmes using human menopausal gonadotrophin preparations containing large amounts of LH. Despite known problems of specificity with the assays od inhibin, its measurement was of similar value to oestradiol as a marker of follicular development.
Mitchell
R
R
University of Manchester Department of Medicine, Hope Hospital, Eccles Old Road, Salford M6 8HD, UK.
Buckler
H M
HM
Matson
P
P
Lieberman
B
B
Burger
H G
HG
Hilton
B
B
Horne
G
G
Dyson
M
M
Robertson
W R
WR
D000328:Adult; D006063:Chorionic Gonadotropin / Q000627:therapeutic use; D004958:Estradiol / Q000378:metabolism*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood / Q000627:therapeutic use*; D006801:Humans; D007247:Infertility, Female / Q000628:therapy; D007265:Inhibins / Q000378:metabolism*; D007986:Luteinizing Hormone / Q000097:blood; D006080:Ovarian Follicle / Q000502:physiology; D010053:Ovary / Q000000981:diagnostic imaging; D010062:Ovulation Induction; D011994:Recombinant Proteins / Q000627:therapeutic use; D014463:Ultrasonography
D006063:Chorionic Gonadotropin; D011994:Recombinant Proteins; D004958:Estradiol; D007265:Inhibins; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone