nafarelin and Infertility--Female

Effects of exogenous LH on ovarian androgen secretion during ovulation induction have not been clearly characterized in polycystic ovarian syndrome (PCOS). The purpose of this study was to compare androgen secretion in PCOS women during ovarian stimulation with either recombinant FSH (rFSH) alone or combined with recombinant LH (rLH).. Clomiphene-resistant women with PCOS were allocated, in a factorial study design, to receive either daily injections of rFSH (n = 24) or rFSH + rLH (n = 24) in a 1:1 ratio starting: (i) on day 2-3 of progestogen-induced menses (n = 8); (ii) after 6 weeks of GnRH agonist treatment (nafarelin, 400 micro g twice daily; n = 8); or (iii) after nafarelin treatment as in (ii) plus dexamethasone (n = 8). The effects of rFSH with rFSH + rLH under these three hormone conditions on serum LH, 17alpha-hydroxyprogesterone (17-OHP), androstenedione (DeltaDelta(4)) and testosterone were contrasted by analysis of variance with specific treatment days as a repeated measures factor.. Pre-study hormone levels were similar for all groupings. Nafarelin significantly suppressed LH levels, which remained at the lower limit of assay sensitivity (0.5 IU/l) during stimulation with rFSH but increased significantly to >1 but <2 IU/l when rLH was added. As expected, 17-OHP, DeltaDelta(4) and testosterone levels fell following nafarelin treatment. Dexamethasone further suppressed 17-OHP, DeltaDelta(4) and testosterone levels and unmasked a small but significant rise in these ovarian steroids 24 h following the first dose of rFSH + rLH, a rise that was absent with rFSH alone. Secretion of these steroids then appeared to 'catch-up' after 5 days of rFSH stimulation.. Despite profound LH, 17-OHP, DeltaDelta(4) and testosterone suppression, comparable E(2) response, follicle development and successful pregnancies in PCOS subjects receiving rFSH alone to those receiving rFSH + rLH would argue that circulating LH at levels as low as 0.5 IU/l are sufficient to sustain adequate follicle development and function when FSH is present in abundance. Whether the observed dichotomy between rFSH and rFSH + rLH treatment in temporal secretion patterns reflects a greater reliance on evolving paracrine mechanisms as the follicles mature under profound LH suppression remains to be explored but may influence the optimal LH threshold for ovulation induction in PCOS.

Topics: 17-alpha-Hydroxyprogesterone; Adult; Androgens; Dexamethasone; Female; Follicle Stimulating Hormone; Glucocorticoids; Humans; Infertility, Female; Kinetics; Luteinizing Hormone; Nafarelin; Ovary; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Prospective Studies; Recombinant Proteins; Testosterone

Nafarelin acetate is a new gonadotropin releasing (GnRH) agonist analogue with unique potency, intranasal administration, and convenient storage. Hence, nafarelin was considered as an alternative for temporary pituitary suppression in patients undergoing ovulation induction in IVF. A crossover treatment in a prospective study was performed including 40 women with bilateral obstructed tubes and normal ovarian function, treated in 80 ovulation induction cycles using the long protocol. Twenty patients used nafarelin acetate 600 micrograms/daily in their first cycle and received D-Trp6-LHRH, 0.5 mg/daily, in their following cycle. The other 20 women used decapeptyl in their cycle and received nafarelin in the second.. Estradiol suppression was achieved by both D-Trp6-LHRH and nafarelin at equal time intervals. The average total number of ampoules (P = 0.0005) and the length of administration of hMG required for ovarian stimulation (P = 0.0002) and the time interval between GnRHa initiation to oocyte retrieval (P = 0.04) was significantly lower in nafarelin cycles. The number and the distribution between large and small follicles as well as the average number of oocytes retrieved did not differ between the two GnRH analogues.. Our results demonstrate that nafarelin acetate is comparable to D-Trp6-LHRH for temporary pituitary suppression used for controlled ovarian stimulation in IVF patients. However, using nafarelin ovarian stimulation was achieved with few ampoules of hMG, administered for a shorter period of time, thus with a lesser cost.

Topics: Adult; Cross-Over Studies; Estradiol; Female; Fertilization in Vitro; Hormones; Humans; Infertility, Female; Nafarelin; Oocytes; Ovary; Pituitary Gland; Prospective Studies; Triptorelin Pamoate

To use a GnRH agonist (GnRH-a) to induce ovulation after priming with exogenous hMG.. Prospective, randomized double-blind protocol using one or two doses of intranasal nafarelin.. Office-based ovulation induction program. PATIENTS, INTERVENTIONS: Infertile women not conceiving after use of clomiphene citrate for at least 6 months who were given hMG and nafarelin. No luteal support was given.. Serum concentrations of FSH, LH, E2, and P acutely and at 6 days after GnRH-a administration. Duration of the luteal phase was assessed.. Ovulation with elevation of both FSH and LH was achieved. The two-dose regimen was more effective than one dose for sustained LH release. Luteal phase P values and luteal phase duration were both less than usually seen with gonadotropin hCG therapy in the absence of luteal phase support.. Ovulation induction with GnRH-a after hMG priming produces unacceptable luteal phase cycles in the absence of hormonal support.

Topics: Adult; Chorionic Gonadotropin; Dose-Response Relationship, Drug; Estradiol; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Luteal Phase; Luteinizing Hormone; Nafarelin; Ovulation Induction; Progesterone; Triptorelin Pamoate

In this double-blind study of changes in plasma lipid and lipoprotein concentrations during 6-month medical treatment of endometriosis, 53 patients were randomly assigned to one of four treatment schedules: danazol, 800 mg/day (n = 10); danazol, 600 mg/day (n = 8); intranasal nafarelin acetate, 800 micrograms/day (n = 10); or intranasal nafarelin acetate, 400 micrograms/day (n = 25). Plasma levels of triglycerides, cholesterol, and low-density lipoprotein, very low-density lipoprotein, and high-density lipoprotein cholesterol fractions were obtained before, during, and 1 month after treatment. High-density lipoprotein2 and high-density lipoprotein3 cholesterol concentrations were measured in selected patients. Body weight was also followed. The drugs were equally effective in achieving symptomatic relief and laparoscopically demonstrated resolution of endometriosis but differed significantly in their effects on lipid concentrations. Nafarelin acetate had no adverse effects on serum lipoprotein concentrations, whereas danazol significantly decreased high-density lipoprotein cholesterol (p less than 0.01), as well as the high-density lipoprotein2 subfraction (p less than 0.05), and increased low-density lipoprotein cholesterol (p less than 0.01). Danazol significantly increased body weight (p less than 0.01), whereas nafarelin did not.

Topics: Administration, Intranasal; Adult; Cholesterol; Clinical Trials as Topic; Danazol; Double-Blind Method; Endometriosis; Female; Genital Neoplasms, Female; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Lipids; Lipoproteins, HDL; Lipoproteins, LDL; Nafarelin; Pregnadienes; Pregnancy; Random Allocation; Time Factors

To determine the effect of dose of GnRH agonist on the follicular environment in controlled ovarian hyperstimulation (COH) cycles.. Twenty-eight IVF patients with normal ovarian function were divided into three groups: group I received GnRHa (nafarelin acetate/Synarel) intranasally at 200 microg daily, group II received 400 microg daily until hCG injection, and group III was given 400 microg daily before the initiation of ovarian stimulation, then 200 microg daily before the day of hCG injection. Serum estradiol, progesterone, and leptin levels were measured on the day of hCG injection. After aspiration, expression of pregnancy-associated alpha-plasma protein (PAPP)-A in the follicular fluid of dominant follicles (>20 mm) was determined by Western blot analysis.. No significant difference was noted in serum estradiol, progesterone, and leptin levels. But intrafollicular PAPP-A expression was significantly higher in group II compared to other groups (P<0.05).. The dose of GnRHa may have an impact on the intrafollicular environment of dominant follicles in COH cycles.

Topics: Administration, Intranasal; Adult; Blotting, Western; Dose-Response Relationship, Drug; Drug Administration Schedule; Estradiol; Female; Follow-Up Studies; Humans; Infertility, Female; Leptin; Menstrual Cycle; Nafarelin; Ovulation Induction; Pregnancy-Associated Plasma Protein-A; Probability; Progesterone; Prospective Studies; Radioimmunoassay; Risk Assessment; Statistics, Nonparametric

In-vitro fertilization (IVF) is an effective infertility treatment for women with endometriosis, but most women need to undergo several cycles of treatment to become pregnant. This case-control study was designed to assess how consistently women with ovarian endometriosis respond to ovarian stimulation in consecutive treatment cycles compared to women with tubal infertility. We compared outcome measures in 40 women with a history of surgically confirmed ovarian endometriosis and 80 women with tubal infertility, all of whom had at least three IVF treatment cycles. The groups were matched for age and early follicular follicle stimulating hormone (FSH) concentration at their first IVF cycle. Outcome measures included number of follicles, number of oocytes, peak oestradiol concentration and number of FSH ampoules required per follicle. Cumulative pregnancy and live birth rates were calculated in both groups. The ovarian endometriosis group had a significantly poorer ovarian response and required significantly more ampoules of FSH per cycle, a difference that became greater with each subsequent cycle. However, cumulative pregnancy (63.3 versus 62.6% by fifth cycle) and live birth (46.8 versus 50.9% by fifth cycle) rates were similar in both groups. In conclusion, despite decreased ovarian response to FSH, ovarian endometriosis does not decrease the chances of successful IVF treatment.

Topics: Adult; Case-Control Studies; Cell Count; Chorionic Gonadotropin; Embryo Transfer; Endometriosis; Estradiol; Fallopian Tube Diseases; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Humans; Infertility, Female; Menotropins; Nafarelin; Oocytes; Ovarian Diseases; Ovarian Follicle; Ovulation Induction; Pregnancy; Prospective Studies

The aim of this study was to obtain data about the pregnancy rate in patients with uterine leiomyomata after treatment with gonadotropin-releasing hormone (GnRH) agonists followed by myomectomy. Between 1987 and 1993, 61 patients with uterine leiomyomata and sterility underwent 6 months' GnRH agonist treatment, in part with a surgical intervention. Sixty-two per cent of the patients suffered from concomitant endometriosis. After hormonal therapy 41 patients underwent a myomectomy. According to sonographic and clinical criteria, there was no indication for the enucleation of the leiomyomata for the remaining 20 patients. Owing to the combined therapy, consisting of primary treatment of uterine leiomyomata with GnRH agonists, followed by surgical intervention, 25 patients (41%) suffering from long-term sterility (average 4 years) became pregnant. An early abortion occurred in only three cases (12%). No patient who underwent a myomectomy developed new myomata during the following pregnancy. Four patients suffering from a single leiomyoma became pregnant within the first 3 months after myomectomy, all of them conceiving spontaneously. Considering the high rate of spontaneous conceptions and the low abortion and complication rates during pregnancy, the combined therapy of GnRH agonists followed by myomectomy represents a major step forwards in the effective treatment of sterility in patients with uterine leiomyomata.

Topics: Administration, Intranasal; Adult; Antineoplastic Agents, Hormonal; Buserelin; Chemotherapy, Adjuvant; Female; Gonadotropin-Releasing Hormone; Goserelin; Hormones; Humans; Infertility, Female; Injections, Intramuscular; Leiomyoma; Leuprolide; Nafarelin; Pregnancy; Pregnancy Rate; Retrospective Studies; Time Factors; Triptorelin Pamoate; Uterine Neoplasms

An enzyme-linked immunosorbent assay (ELISA) was developed to measure anti-endometrial antibody concentrations in the serum of women with endometriosis. Pooled cytosolic protein extracts from the endometrial gland cells of 10 women were used as an antigen source. Serum samples were obtained from women with endometriosis before (n = 51) and after 6 months treatment with danazol or nafarelin (n = 30). Control sera came from women with a normal pelvis at laparoscopy, performed for sterilization (n = 23) or the investigation of pain and/or infertility (n = 22), 13 women with Rokitansky syndrome, and 10 umbilical cord bloods and adult males. There were no significant differences in serum anti-endometrial antibody concentrations before and after treatment, or between women with endometriosis and without endometriosis. Concentrations were lower in male and cord blood serum than in female's serum (P < 0.0001). We conclude that the ELISA is not a useful diagnostic tool for endometriosis unless more specific antigens can be isolated.

Topics: Adult; Autoantibodies; Danazol; Endometriosis; Endometrium; Enzyme-Linked Immunosorbent Assay; Female; Fetal Blood; Humans; Infertility, Female; Male; Nafarelin; Uterus; Vagina

Twenty-five women with regular menstruation and laparoscopically confirmed endometriosis received 100 mcg nafarelin intranasally twice daily for six months in an open study. American Fertility Society (AFS) laparoscopic scores pre- and post-treatment, symptom severity, hormonal status, bone density and biochemical indices of bone turnover were studied. Five patients were still menstruating at three months and nafarelin was increased to 400 mcg daily. At the end of treatment, the median serum estradiol was 57 pmol/l and all patients were amenorrhoeic. AFS scores for endometriosis improved significantly in 19/23 (82.6%) patients (p = 0.001). Adhesions were not affected. Symptom severity scores were markedly decreased (p < 0.0001) and remained so six months after the end of treatment. Biochemical indices of bone activation were increased but bone loss was insignificant. During treatment, 23/25 patients reported hot flushes. Nafarelin 200 mcg daily significantly reduced signs and symptoms of endometriosis, although five patients needed a dosage increase before menses stopped. The study suggests that lower doses of nafarelin may be efficacious, although symptomatic changes should be treated with caution due to the open and non-comparative nature of the study.

Topics: Abdominal Pain; Administration, Intranasal; Adult; Bone Density; Dose-Response Relationship, Drug; Dysmenorrhea; Endometriosis; Estradiol; Estrone; Female; Follow-Up Studies; Humans; Infertility, Female; Laparoscopy; Menstruation; Nafarelin; Pregnancy; Severity of Illness Index

A patient with long-standing secondary infertility was explored for myomectomy, at which time severe adenomyosis was found. A 6-month course of nafarelin acetate resulted in resolution of dysmenorrhea and uterine enlargement. The patient conceived quickly. Although the patient spontaneously aborted, this report presents the first in which medical therapy of adenomyosis is associated with successful treatment of infertility.

Topics: Administration, Inhalation; Adult; Biopsy; Endometriosis; Female; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Nafarelin; Pregnancy; Triptorelin Pamoate; Ultrasonography

We investigated the mechanisms of desensitization induced by gonadotropin-releasing hormone agonist in the pituitary.. Effects of gonadotropin-releasing hormone agonist on the pituitary were studied in vitro and in vivo in the rat. In the clinical study serum luteinizing hormone was measured by radioimmunoassay with a polyclonal luteinizing hormone antibody (luteinizing hormone-radioimmunoassay) and by immunoradiometric assay with monoclonal luteinizing hormone antibodies (luteinizing hormone-immunoradiometric assay) during gonadotropin-releasing hormone agonist treatment.. In the in vitro study bead-attached pituitary cells that were desensitized with a continuous infusion of 10(-7)mol/L gonadotropin-releasing hormone responded to 50 mmol/L K+. In the in vivo study gonadotropin-releasing hormone binding sites and rat luteinizing hormone beta-messenger ribonucleic acid in the pituitary decreased during gonadotropin-releasing hormone agonist treatment, but serum levels of rat luteinizing hormone did not decrease. In addition, a disparity between luteinizing hormone-radioimmunoassay and luteinizing hormone-immunoradiometric assay was demonstrated during gonadotropin-releasing hormone agonist treatment.. Pituitary desensitization in response to gonadotropin-releasing hormone agonist may not be wholly receptor mediated and a nonreceptor process may be involved.

Topics: Animals; Buserelin; Cells, Cultured; Endometriosis; Female; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Leuprolide; Luteinizing Hormone; Male; Nafarelin; Pituitary Gland; Polycystic Ovary Syndrome; Rats; Rats, Sprague-Dawley; Rats, Wistar; Receptors, LHRH; RNA, Messenger

Topics: Adult; Face; Female; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Menstruation Disturbances; Nafarelin; Neck; Paresthesia

Gonadotropin-releasing hormone (GnRH), a decapeptide synthesized and released by the hypothalamus, regulates production and release of the gonadotropins luteinizing hormone (LH) and follicle-stimulating hormone (FSH) by the adenohypophysis. Parenterally administered GnRH was initially used diagnostically as a test of adenohypophyseal reserve of LH and FSH. Subsequently, native GnRH was used therapeutically to treat hypothalamic hypogonadal and infertility states in both men and women. Because of the low potency and short half-life of native GnRH, long-acting, potent analogs have been developed that suppress secretion of native pituitary gonadotropins, resulting in medical gonadectomy. When administered parenterally and, more recently, intranasally, these compounds are useful in the management of prostate and breast carcinoma, endometriosis and uterine leiomyomata, precocious puberty and nontumorous ovarian hyperandrogenic syndromes.

Topics: Endometriosis; Female; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Leuprolide; Male; Nafarelin; Prostatic Neoplasms

Patients with infertility caused by endometriosis may be managed by expectant strategies, surgery, or pharmacologic intervention. The relative benefits conferred by each of these approaches remain to be confirmed. Data gathered thus far suggest, however, that nafarelin, a gonadotropin-releasing hormone agonist, may be associated with fecundity rates as low as those seen after surgical intervention.

Topics: Danazol; Endometriosis; Female; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Nafarelin; Pregnancy