Preconception steroid treatment in infertile women with antithyroid autoimmunity undergoing ovarian stimulation and intrauterine insemination: a double-blind, randomized, prospective cohort study.

OBJECTIVE: This study investigated the role of a steroid pretreatment on the pregnancy rate and pregnancy outcomes in patients positive for antithyroid antibodies who were undergoing induction of ovulation and intrauterine insemination (IUI). METHODS: A double-blind, randomized, prospective cohort study was conducted on infertile women who met the following criteria: infertility for ≥ 1 year, age 20-38 years, no more than 2 previous assisted reproduction treatment cycles, regular spontaneous menstrual cycles, no treatments 1 month before recruitment, normal uterine cavity, and bilateral tubal patency. The patients were divided into 2 groups: a study group of infertile women with antithyroid autoimmunity (radioimmunoassay positive with titer >100 U/mL) and a control group of infertile women without antithyroid autoimmunity. The patients with antithyroid autoimmunity were randomly assigned in a blinded manner to an intervention group treated with prednisone (administered orally for 4 weeks before IUI) or a group given matching placebo. The primary objective was to compare the pregnancy and miscarriage rates among all 3 the groups. RESULTS: The study included 98 infertile women: 48 with antithyroid autoimmunity (antibody positive) and 50 without antithyroid autoimmunity (antibody negative). The study groups were comparable for baseline characteristics (age, race, body mass index, hormonal pattern, number of smokers, previous miscarriage). In the antithyroid antibody-positive group, the pregnancy rate was 33.3% (8/24) among women treated with prednisone compared with 8.4% (2/24) among women who received placebo (odds ratio [OR] = 5.5; 95% CI, 1.13-25.76; P = 0.03). In the antibody-negative group, the pregnancy rate was 8.0% (4/50). Among the pregnancies, the miscarriage rate was 70% (7/10) versus 75% (3/4) for women with or without antithyroid antibodies, respectively (P = NS); the miscarriage rate was 75% (6/8) for women treated with prednisone versus 50% (1/2) for women taking placebo (P = 0.49). No adverse effects were reported. CONCLUSIONS: In this small cohort study of infertile women with antithyroid antibodies undergoing induction of ovulation and IUI, prophylactic therapy with prednisone was associated with a significantly higher rate of pregnancy compared with placebo. The miscarriage rate was not significantly different among the 3 groups.

Follicular fluid nitric oxide (NO) concentrations in stimulated cycles: the relationship to embryo grading.

OBJECTIVE: The microenvironment of the ovarian follicle is vital for normal oocyte development, folliculogenesis, and timely ovulation. We investigated the concentration of nitric oxide (NO) in follicular fluid, collected during oocyte retrieval after in-vitro fertilization and embryo transfer (IVF-ET) and its relationship to oocyte and embryo grading. METHODS: A total of 53 follicular fluid samples were obtained from 15 patients undergoing IVF-ET program, oocyte retrieval by transvaginal guidance was per formed approximately 34-35 h after the hCG administration in stimulated cycles. Using a modified grading system the samples were divided in Group 1 with very few fragments in the cytoplasm with equal size blastomeres (best embryos) and Group 2 with significant or severe fragmentation or blastomeres of distinctively unequal size. Follicular NO was measured as nitrite/nitrate. RESULTS: The mean concentration of NO follicular fluid is significantly higher in Group 2 than in Group 1 (57.54 +/- 12.67 nmol/mg vs. 42.43 +/- 16.32 nmol/mg). Using the correlation analysis, we observed a direct correlation between follicular NO and embryo grading (r = 0.61; P < 0.001) and an inverse correlation between follicular NO and serum 17beta-estradiol (r = -0.28; P < 0.05). CONCLUSIONS: High levels of NO in human follicles may be detrimental. The inverse correlation found between NO and serum concentrations of 17beta-estradiol may be explained as a regulation of estradiol on maturation process of the oocytes and embryos in stimulated cycles through NO mediation.