LHRH analogues for ovulation induction, with particular reference to polycystic ovary syndrome. Ovarian suppression induced with Buserelin or danazol in the management of endometriosis: a randomized, comparative study. Reversible pituitary ovarian suppression induced by an LHRH agonist in the treatment of endometriosis--comparison of two dose regimens. A prospective randomized trial comparing the clinical and endocrinological outcome with rosiglitazone versus laparoscopic ovarian drilling in patients with polycystic ovarian disease resistant to ovulation induction with clomiphene citrate. Effect of prolonged gonadotropin-releasing hormone agonist therapy on the outcome of in vitro fertilization-embryo transfer in patients with endometriosis. Combined luteinizing hormone releasing hormone analogue and exogenous gonadotrophins for the treatment of infertility associated with polycystic ovaries. Ablation of lesions or no treatment in minimal-mild endometriosis in infertile women: a randomized trial. Gruppo Italiano per lo Studio dell'Endometriosi. Adjunctive leuprolide therapy does not improve cycle fecundity in controlled ovarian hyperstimulation and intrauterine insemination of subfertile women. A randomized clinical trial of treatment of clomiphene citrate-resistant anovulation with the use of oral contraceptive pill suppression and repeat clomiphene citrate treatment.
Infertile women with PCO have been treated with exogenous gonadotrophins (hMG/hCG) for ovulation induction either with or without LHRH-agonist treatment. Those treated without LHRH-agonist-induced LH suppression showed PL in greater than 30% of the cycles and this problem was eliminated by LHRH-agonist therapy. The pregnancy rate (approximately 80% of patients) during the combined therapy was approximately twice that of the group treated with hMG/hCG alone. The suppression of endogenous LH by the LHRH-agonist appeared to have no effect upon the profiles of follicular development in response to hMG, and a high rate of follicle recruitment characterized all PCO treatment cycles irrespective of circulating LH concentrations. These results suggest that LH suppression improves the efficacy of ovulation induction but has no influence on the primary metabolic disturbance in the PCO syndrome. The effectiveness of Buserelin (Hoechst-Roussel Pharmaceuticals, Inc., Somerville, NJ) (0.2 mg subcutaneously [SC] or 1.2 mg intranasally [IN] per day) and danazol (800 mg per day) in inducing ovarian suppression for the management of endometriosis was compared in a prospective randomized study. During 6 months of treatment, peripheral follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol concentrations were suppressed to a similar degree in both groups. Symptomatic improvement and laparoscopically assessed regression of endometriotic lesions also were comparable. After treatment, 8 of 18 infertile women treated with Buserelin and 5 of 8 treated with danazol conceived. General and hypoestrogenic side effects were similar in both groups, while androgenic and anabolic were more frequent with danazol. High density lipoprotein (HDL)-cholesterol increased in the Buserelin and decreased in the danazol group. The study indicates that at the dose tested, buserelin and danazol induce a similar degree of ovarian suppression resulting in a comparable clinical improvement and regression of endometriotic lesions. Buserelin [D-Ser(TBU)6-des Gly NH2(10) LHRH ethylamide], an LHRH agonist, was administered intranasally at two dose levels, 200 micrograms t.d.s or 300 micrograms t.d.s., to 20 women with proven endometriosis, many with recurrent disease. Both dose schedules achieved significant suppression of circulating 17 beta-oestradiol levels often to within the postmenopausal range, the larger dose inducing significantly greater suppression (P less than 0.05). Serum FSH values were suppressed below baseline but serum LH remained at pretreatment levels or above, whilst on treatment. Complete resolution of endometriotic deposits was achieved in 68% of cases following 6 months treatment with dramatic and long-standing relief of symptoms with no apparent dose difference. In all other subjects there was significant reduction in the extent of endometriotic deposits and improvement in American Fertility Society classification of disease stage. The most commonly occurring side effect was hot flushes; their intensity and frequency related to the degree of suppression of serum oestradiol and the dose of Buserelin administered. Rosiglitazone, an insulin sensitizing agent is used currently in women with clomiphene citrate (CC) resistant polycystic ovarian syndrome (PCOS). Our study proposed to compare the efficacy of rosiglitazone and CC with laparoscopic ovarian drilling (LOD) and CC in terms of biochemical effects, ovulation rate and pregnancy rate in patients of PCOS resistant to CC.
                This prospective randomised trial included 43 patients of PCOS resistant to CC. Twenty-two women were assigned to the rosiglitazone (4 mg twice daily) and CC group and other 21 patients underwent unilateral LOD and then received CC and multivitamins. The treatment continued for six cycles in both the groups. The biochemical response, ovulation rate and pregnancy rate over a follow up period of 6 months were compared.
                Treatment with rosiglitazone and CC or LOD and CC resulted in increased ovulation (80.8 vs. 81.5%) and pregnancy (50 vs. 42.8%), respectively. There was no statistical difference between the two groups in terms of biochemical response, ovulation rate and pregnancy rate.
                To avoid the risk of adverse effects of LOD preference may be given to the use of rosiglitazone and CC therapy in patients of PCOS resistant to CC. To evaluate the effect of a 3-month course of GnRH agonist administered immediately before IVF-ET in infertile patients with endometriosis.
                Prospective, randomized trial.
                Three tertiary care assisted reproductive technology programs.
                IVF-ET candidates with surgically confirmed endometriosis.
                Twenty-five patients received three courses of a long-acting GnRH agonist, 3.75 mg i.m. every 28 days, followed by standard controlled ovarian hyperstimulation. Twenty-six patients received standard controlled ovarian hyperstimulation with mid-luteal phase GnRH agonist down-regulation or microdose flare regimens.
                Response to controlled ovarian hyperstimulation, ongoing pregnancy rates per cycle, group implantation rates, and implantation rate per embryo transfer procedure.
                The extent of surgically confirmed endometriosis was greater in patients who received the long-acting GnRH regimen for 3 months before IVF-ET. The groups did not differ significantly in terms of dose or duration of gonadotropin stimulation, number of oocytes retrieved, fertilization rate, or number of embryos transferred. Patients who received the long-acting GnRH regimen had significantly higher ongoing pregnancy rates (80% vs. 53.85%) and a trend toward higher implantation rates (42.68% vs. 30.38%).
                Prolonged use of GnRH agonist before IVF-ET in patients with endometriosis resulted in significantly higher ongoing pregnancy rates than did standard controlled ovarian hyperstimulation regimens. No deleterious effect on ovarian response was observed. This study was designed to compare the results of treatment with, firstly, exogenous gonadotrophins, with (57 cycles) and without (65 cycles) pretreatment with a superactive analogue of luteinizing hormone releasing hormone (LHRH) and, secondly, pure follicle stimulating hormone (FSH) (50 cycles) with those of human menopausal gonadotrophin (HMG) (72 cycles) in 46 women with clomiphene-citrate-resistant anovulation associated with polycystic ovaries. Patients randomly allocated to the analogue group received buserelin (Suprefact, Hoechst, UK, Ltd, Hounslow, Middlesex), 800 micrograms/day by nasal insufflation and when hypogonadism was achieved, patients were again randomly allocated for ovarian stimulation with either FSH or HMG. Controls received FSH or HMG alone. Patients pretreated with the analogue had similar pregnancy and ovulation rates, needed larger doses and more days of gonadotrophin therapy and had more ovarian overstimulation than those receiving no pretreatment. The role of superactive LHRH analogues for induction of a single ovulation for in-vivo fertilization is thus uncertain. Pure FSH had no advantages over HMG, the LH content of HMG having no deleterious effect on the ovary. In order to analyse the efficacy of resection/ablation of minimal/mild endometriotic lesions for improving fertility, we conducted a randomized clinical trial. Eligible patients were women aged </=36 years who were trying to conceive and had a laparoscopically confirmed diagnosis of minimal/mild endometriosis (stage I or II of the revised American Fertility Society classification) and otherwise unexplained infertility for >/=2 years. Eligible women were randomly assigned to resection or ablation of visible endometriosis (54 patients) or diagnostic laparoscopy only (47 patients). After laparoscopy women tried to conceive spontaneously for 1 year (follow-up period). A total of five women withdrew from the study: three for personal reasons, and two were lost to follow-up. Considering 51 women in the resection/ablation and 45 in the no-treatment group who ended the follow-up period, 12 (24%) in the resection/ablation group and 13 (29%) in the no treatment group conceived; the difference was not significant. Two spontaneous abortions were observed in the resection/ablation group and three in the no-treatment one. Thus the 1 year birth rate was 10 out of 51 women (19.6%) in the resection/ablation group and 10 out of 45 women (22.2%) in the no-treatment group. In conclusion, the results of this study do not support the hypothesis that ablation of endometriotic lesions markedly improves fertility rates. Problems arising from controlled ovarian hyperstimulation for intrauterine insemination, such as premature luteinization and asynchronous ovarian follicular development, are identical to those encountered with controlled ovarian hyperstimulation for in vitro fertilization (IVF) and gamete intrafallopian transfer (GIFT). It has been suggested that the adjunctive use of GnRH agonists for controlled ovarian hyperstimulation improves the efficiency of GIFT and IVF cycles. We hypothesized that adjunctive use of leuprolide acetate, a GnRH agonist, would have a similarly beneficial effect on cycle quality and cycle fecundity in subfertile women treated with controlled ovarian hyperstimulation and intrauterine insemination. We randomly assigned the first cycle of controlled ovarian hyperstimulation and intrauterine insemination for each of 97 subfertile women to include either human menopausal gonadotropins (hMGs) alone or hMGs following midluteal pre-treatment with leuprolide. If a pregnancy did not occur in the first cycle, the woman was given the other treatment in the second cycle. Although the cycles that included leuprolide required a larger amount of hMGs and more days of stimulation per cycle, the mean estradiol concentrations and numbers of follicles were not different. Despite prevention of premature luteinization with leuprolide, the cycle fecundity was not different between groups (0.11 with adjunctive leuprolide treatment and 0.22 with hMGs alone). We conclude that in unselected subfertile patients, the adjunctive use of leuprolide for controlled ovarian hyperstimulation and intrauterine insemination does not improve cycle fecundity compared with treatment cycles that do not include adjunctive leuprolide therapy. The purpose of this study was to evaluate the effectiveness and endocrine response of oral contraceptive ovarian suppression followed by clomiphene citrate in patients who previously were clomiphene citrate resistant.
                Forty-eight patients from a private tertiary infertility clinic were assigned randomly prospectively to either group 1 (oral contraceptive/clomiphene citrate), which received continuous oral contraceptives followed by clomiphene citrate, or to group 2 (control) received no treatment in the cycle before clomiphene citrate treatment. On day 3, 17 beta-estradiol, follicle-stimulating hormone, luteinizing hormone, and androgens were assayed before and after treatment. Follicle growth, ovulation, and pregnancy were evaluated. The Student t test and analysis of variance were used for statistical significance.
                The oral contraceptive/clomiphene citrate group had a significantly higher percentage of patients who ovulated and of ovulatory cycles and pregnancies. Significantly lower levels of 17 beta-estradiol, luteinizing hormone, and androgen levels were seen in the oral contraceptive/clomiphene citrate group, with no significant changes in group 2.
                Suppression of the ovary with oral contraceptives results in excellent rates of ovulation and pregnancy in patients who previously were resistant to clomiphene citrate. The decreases in ovarian androgens, luteinizing hormone, and 17 beta-estradiol may be responsible for the improved response.
There is no evidence of benefit in the use of ovulation suppression in subfertile women with endometriosis who wish to conceive.