Progress in the investigation and treatment of anovulation.
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This study was designed to compare the effects of [N-Ac-D-Trp1,3, D-p-Cl-Phe2, D-Phe6, D-Ala10] (A-LH-RH), an inhibitory analogue, and D-Trp6-LH-RH, an agonist of LH-RH, administered to normally cycling cynomologous monkeys. Animals were divided into three groups (n = 5 each), each group receiving one of the following daily during the first 25 days of the menstrual cycle: 1) 20 micrograms of D-Trp6-LH-RH daily, 2) 1 mg of A-LH-RH, and 3) vehicle. Ovulation was established by serial laparoscopies and serum estradiol measurement. Controls presented normal cycles, as evidenced by ovulation day, luteal phase length and hormone levels. Ovulation was completely inhibited during drug administration in all animals of groups 1 and 2. Luteal phase length of all monkeys that ovulated was normal. The present data, therefore, not only show evidence for a consistent anovulatory effect of agonistic and antagonistic analogues of LH-RH in non-human primates, but also open a new approach for non-steroidal contraception.
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We performed a prospective study to assess the effects of a starting dose of 50 units of recombinant follicle stimulating hormone (Puregon) during gonadotrophin-releasing hormone agonist therapy (Suprecur) on follicular development in patients with clomiphene citrate-resistant polycystic ovary syndrome (PCOS). In a prospective clinical trial, 25 women with clomiphene citrate-resistant PCOS who wanted to become pregnant were treated by a low-dose step-up protocol of SC recombinant follicle stimulating hormone administration during gonadotrophin-releasing hormone agonist therapy, monitored by transvaginal ultrasonography and retrospectively by serum endocrine assays taken at each monitoring visit. Cancellation of cycles, ovulation, rate and size of follicles growth, serum E2 concentration and pregnancy were recorded. All patients exhibited a response: 22 patients ovulated, of whom 10 conceived. Using the low-dose protocol during gonadotrophin-releasing hormone agonist therapy permitted induction of ovulation safely and successfully in patients with clomiphene citrate-resistant PCOS who were patients previously difficult to treat with the conventional ovulation induction protocol.
The present study compared ovarian performance and hormone concentrations, after ovulation induction, in polycystic ovarian syndrome (PCOS) patients, using recombinant human FSH (rhFSH) in low-dose step-up and modified step-down regimens. Twenty-six women with clomiphene citrate-resistant chronic anovulatory infertility were treated with rhFSH in two consecutive cycles according to two different low-dose regimens: (i) the classic chronic low-dose step-up protocol, the starting dose being 75 IU; (ii) a modified step-down protocol where the starting dose was 300 IU followed by 3 days free of treatment, then rhFSH 75 IU daily was given and stepwise dose increments were performed exactly the same as in the step-up method. Each woman received both treatment approaches, in a randomized order, with an interval of > or = 1 month between treatments. The total number of follicles that were > 10, > 14 and > 17 mm in diameter on the day of human chorionic gonadotrophin (HCG) administration, and thus cycles with HCG cancelled, were significantly increased with the step-up approach. The total number of rhFSH ampoules tended to be higher with the step-down schedule despite the fact that both the mean duration of treatment and the threshold dose were similar with the two low-dose approaches. A physiological step-down approach for ovulation induction in PCOS patients may be more appropriate in order to avoid multifollicular cycles than the step-up approach.
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Administration of antiprogesterone RU486 to female cyclic rats results in blockade of ovulation associated with both a decreased ovulatory release of LH and an increased rate of follicular atresia. These rats also exhibit increased LH:FSH and testosterone:oestradiol ratios in serum during the period of follicular development as well as an increase in serum concentrations of prolactin that can be suppressed by a dopamine agonist. The increase in either prolactin or testosterone concentrations as well as the relative deficiency in FSH might be responsible for the increase in follicular atresia. The present work evaluated the involvement of LH, FSH, prolactin and testosterone in follicular atresia and in blockade of ovulation induced by RU486 in the cyclic rat. Although bromocriptine treatment did not modify the blockade of ovulation induced by RU486, unilateral ovariectomy at metoestrus and anti-androgen flutamide treatment reversed, in part, the effects of RU486 on both follicular development and ovulation. The combined increase in FSH serum concentration during dioestrus induced by unilateral ovariectomy and the treatment with flutamide had no additive effects. Furthermore, treatment with a superovulatory amount of hFSH did not reverse the effects of RU486. Moreover, unilateral ovariectomy halved testosterone serum concentrations and flutamide treatment had no effect on LH and FSH concentrations in RU486-treated rats. It was therefore concluded that androgens play a role, at least in part, in the process of follicular atresia induced by RU486.