Efficacy of native and hyperglycosylated follicle-stimulating hormone analogs for promoting fertility in female mice.
OBJECTIVE
To compare the efficacy of recombinant human FSH (rhFSH) with rhFSH with four additional O-linked carbohydrates (rhFSH-CTP), rhFSH with four additional N-linked carbohydrates (rhFSH-N4), and the current gold standard for rodent ovarian stimulation, pregnant mare serum gonadotropin (PMSG), on fertility parameters in mice.


METHODS
Animal study.


METHODS
Academic research center.


METHODS
Adult C57Bl/6J female mice.


METHODS
Ovarian stimulation with 5 IU of rhFSH, rhFSH-CTP, rhFSH-N4, or PMSG. Forty-six hours later, 5 IU of hCG was injected to promote ovulation and females were mated overnight.


METHODS
Eggs retrieved after ovulation, in vitro embryo development, delivery rate, and litter size.


RESULTS
The hyperglycosylated FSH analogs, rhFSH-CTP and rhFSH-N4, enhanced ovulation and embryo maturation significantly better than rhFSH. RhFSH-N4 produced more eggs (28.5 +/- 1.9 per mouse) and embryos (17.8 +/- 1.6) compared with rhFSH-CTP (18.3 +/- 1.2 and 9.0 +/- 1.0, respectively). Treatment with rhFSH, rhFSH-N4, and PMSG produced statistically equivalent delivery rates and litter sizes. The delivery rate was surprisingly lower with rhFSH-CTP (14%) compared with PMSG (33%).


CONCLUSIONS
Compared with rhFSH, treatment with hyperglycosylated rhFSH-CTP and rhFSH-N4 led to superior rates of ovulated eggs and subsequent in vitro embryo development. RhFSH-N4 was equivalent to PMSG, while all of the fertility parameters studied were lower with rhFSH-CTP than with PMSG therapy.
Trousdale
Rhonda K
RK
Department of Obstetrics and Gynecology, Columbia University, College of Physicians and Surgeons, New York, New York 10032, USA.
Yu
Bo
B
Pollak
Susan V
SV
Husami
Nabil
N
Vidali
Andrea
A
Lustbader
Joyce W
JW
D000818:Animals; D047108:Embryonic Development / Q000187:drug effects / Q000502:physiology; D005260:Female; D005298:Fertility / Q000187:drug effects / Q000502:physiology*; D005640:Follicle Stimulating Hormone / Q000031:analogs & derivatives* / Q000235:genetics / Q000494:pharmacology*; D006031:Glycosylation; D006801:Humans; D008098:Litter Size / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010060:Ovulation / Q000187:drug effects / Q000502:physiology; D010062:Ovulation Induction / Q000379:methods; D011994:Recombinant Proteins / Q000494:pharmacology*
D011994:Recombinant Proteins; D005640:Follicle Stimulating Hormone