Metformin treatment of patients with polycystic ovary syndrome undergoing in vitro fertilization improves outcomes and is associated with modulation of the insulin-like growth factors.
OBJECTIVE
To determine if metformin therapy improves in vitro fertilization (IVF) outcomes in patients with clomiphene-resistant polycystic ovarian syndrome (PCOS).


METHODS
Retrospective data analysis of selective groups of patients.


METHODS
A private IVF unit.


METHODS
Forty-six women with clomiphene citrate-resistant PCOS underwent 60 cycles of IVF embryo transfer with intracytoplasmic sperm injection.


METHODS
In half of the cycles, patients received metformin (1000 to 1500 mg) daily, starting the cycle prior to gonadotropin treatment.


METHODS
Total number of follicles; serum estradiol (E2) on the day of hCG administration and the cycle's E2 maximum; total number of oocytes, mature oocytes, embryos, fertilization, and pregnancy rates; and follicular fluid levels of insulin-like growth factors (IGF-I, IGF-II) and IGF-binding proteins (IGFBP-1, IGFBP-3).


RESULTS
In patients treated with metformin, the total number of follicles on the day of hCG treatment was decreased (23 +/- 1.2 vs. 33 +/- 2.6) with no change in follicles > or = 14 mm in diameter (21 +/- 1.2 vs. 25 +/- 1.7). Metformin treatment did not affect the mean number of oocytes retrieved (22 +/- 1.9 vs. 20.3 +/- 1.5). However, the mean number of mature oocytes (18.4 +/- 1.5 vs. 13 +/- 1.5) and embryos cleaved (12.5 +/- 1.5 vs. 5.9 +/- 0.9) were increased after metformin treatment. Fertilization rates (64% vs. 43%) and clinical pregnancy rates (70% vs.30%) were also increased. Metformin led to modulation of preovulatory of follicular fluid IGF levels with increases of IGF-I (140 +/- 8 vs. 109 +/- 7ng/mL) and decreased of IGFBP-1 (133 +/- 8 vs.153 +/- 9ng/mL).


CONCLUSIONS
Metformin use appears to improve IVF outcomes in patients with clomiphene citrate-resistant PCOS.
North Carolina Center for Reproductive Medicine, Cary, USA. drls78@aol.com
L A
LA
Stadtmauer
S K
SK
Toma
R M
RM
Riehl
L M
LM
Talbert
D000328:Adult; D006063:Chorionic Gonadotropin / Q000008:administration & dosage; D002996:Clomiphene; D004351:Drug Resistance; D004624:Embryo Transfer; D004622:Embryo, Mammalian / Q000502:physiology; D004958:Estradiol / Q000097:blood; D005260:Female; D015571:Follicular Fluid / Q000737:chemistry*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000032:analysis; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000032:analysis; D007334:Insulin-Like Growth Factor I / Q000032:analysis*; D007335:Insulin-Like Growth Factor II / Q000032:analysis*; D008687:Metformin / Q000627:therapeutic use*; D009865:Oocytes; D006080:Ovarian Follicle / Q000000981:diagnostic imaging; D011085:Polycystic Ovary Syndrome / Q000188:drug therapy*; D011247:Pregnancy; D012189:Retrospective Studies; D020554:Sperm Injections, Intracytoplasmic; D014463:Ultrasonography
D006063:Chorionic Gonadotropin; D007004:Hypoglycemic Agents; D018970:Insulin-Like Growth Factor Binding Protein 1; D018972:Insulin-Like Growth Factor Binding Protein 3; D002996:Clomiphene; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D008687:Metformin