Features of follicle-stimulating hormone-stimulated follicles in a sheep model: keys to elucidate embryo failure in assisted reproductive technique cycles.

OBJECTIVE: To evaluate the individual functionality of gonadotropin-stimulated preovulatory follicles, for understanding embryo failure in assisted reproductive technique cycles, in a sheep model. DESIGN: Observational, model study. SETTING: Public research unit. ANIMAL(S): Fifteen adult Manchega ewes. INTERVENTION(S): Synchronization of the estrous cycle with intravaginal progestagens and ovarian stimulation with FSH; evaluation of reproductive activity, plasma sampling, ovarian ultrasonography, and ovariectomies. MAIN OUTCOME MEASURE(S): Determination of estrus behavior, plasma and intrafollicular concentrations of E(2) and inhibin A, number and size of ovarian follicles, and developmental competence of oocytes. RESULT(S): These results support the usefulness of serial measurements of plasma inhibin A for assessment of follicular growth during the FSH treatment, rather than of E(2) assays commonly used. Functionality of FSH-stimulated preovulatory follicles is clearly disturbed, as confirmed by a negative correlation between follicular size and intrafollicular concentrations of inhibin A and E(2) in preovulatory follicles after individual dissection; moreover, the ability of their oocytes to resume meiosis was diminished. CONCLUSION(S): Functionality of follicles in controlled ovarian stimulation (COS), and developmental competence of their oocytes, is disturbed by the high doses of gonadotropin supplied and finally determined by follicular sizes at starting FSH treatment.

Long-term suppression of reproductive function by a single dose of gonadotropin-releasing hormone antagonists in a sheep model.

OBJECTIVE: To determine the effect of single long-acting doses of GnRH antagonists on reproductive function in a sheep model. DESIGN: Observational, model study. SETTING: University-affiliated research unit. ANIMAL(S): Nine intact mature Merino sheep in experiment 1 and 12 mature Merino-crossed ewes with the ovary autotransplanted to the neck in experiment 2. INTERVENTION(S): Synchronization of estrous cycle either with intravaginal progestins or prostaglandin F2alpha analogues and treatment with a single dose of GnRH antagonist; evaluation of reproductive activity, plasma sampling, and ovarian ultrasonography. MAIN OUTCOME MEASURE(S): Determination of estrus behavior; plasma concentrations of P, FSH, LH, and inhibin A; and number and size of ovarian follicles. RESULT(S): In both experiments, the concentrations of FSH and LH were suppressed when compared with those in control ewes. In experiment 1, the ovulatory cycles were suppressed for > or = 55 days in treated sheep. In experiment 2, there were no follicles sized > or = 5 mm in treated ewes for 50 days. CONCLUSION(S): The suppression of the development of large follicles for > or = 30 days after a single injection of a long-acting GnRH antagonist provides a novel convenient method of pretreatment before COS.

Effect of ageing on hormone secretion and follicular dynamics in sheep with and without the Booroola gene.

It has been suggested that ewes carrying the Booroola gene (Fec(B)) consistently ovulate more follicles because they recruit more primordial follicles and/or have a lower rate of atresia. If the former is correct, the pool of follicles would be depleted sooner in Fec(B) animals. We have studied follicular dynamics and endocrine function during follicular and early luteal phases of the estrous cycle of older ewes with or without the fecundity gene and compared this data with data obtained 6 yr previously in the same animals. Older sheep carrying the Booroola gene maintained a significantly higher ovulation rate than noncarrier ewes [4.2 +/- 0.8 vs. 2.2 +/- 0.6 corpora lutea (CL), respectively; P < 0.05], and in keeping with data from young animals, both ovulatory follicles and CL (4.7 +/- 0.3 vs. 6.9 +/- 0.7 mm and 12.8 +/- 0.5 vs. 16.7 +/- 0.8 mm, respectively) were smaller than those of noncarrier ewes (P < 0.05). The interval from luteolysis to the onset of the LH surge increased with age in all the animals (from 52.0 +/- 8.0 to 67.0 +/- 7.5 h in gene carrier sheep and from 56.0 +/- 2.0 to 79.5 +/- 9.6 h in noncarrier sheep, P < 0.05). The concentration of estradiol and inhibin A in the early luteal phase was lower in older noncarrier ewes (P = 0.08 and P < 0.05, respectively), and the level of inhibin A was inversely related to the level of FSH in aged sheep of both genotypes (P < 0.0001). In contrast, the number of developing follicles in older ewes of both genotypes was similar to the number found in younger ewes, suggesting that increased ovulation rate in sheep carrying the Fec(B) mutation is related to a reduced rate of atresia.