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Impairment of dopaminergic and opioidergic activity in patients with polycystic ovarian disease is restored by treatment for the induction of ovulation.

The luteinizing hormone (LH) response to metoclopramide (MCP), a dopamine receptor antagonist, and naloxone (NAL), an opioid receptor antagonist, was evaluated in 7 patients with polycystic ovarian disease (PCOD) before and during treatment with purified human urinary follicle-stimulating hormone (hFSH), and in 6 control women during spontaneously ovulating cycles. Before treatment, in all patients both MCP and NAL administration did not increase plasma LH levels. In the 6 subjects ovulating following hFSH treatment the LH response to MCP and NAL at preovulatory and midluteal phases was restored, as it occurred in control women. Our results suggest that in PCOD the dopamine and opioid activity in the hypothalamus are decreased. The reversal of peripheral ovarian response induced by treatment for the induction of ovulation may restore these impaired neuroendocrine activities.

Adult↗

[Induction of ovulation and pregnancy resulting from chronic and pulsatile administration of gonadotropin-releasing-hormone (Gn-RH)].

Amenorrhoea of high origin, namely hypothalamic, reflects inhibition or a drop in endogenous secretion of Gn-RH. Two patients with this trouble were treated with synthetic Gn-RH in a pulsatile way and by a continuous method. We have been using a portable reprogrammable mini-pump (Zyklomat-Ferring) connected up to an intravenous catheter which has delivered 15 to 20 micrograms of Gn-RH for one minute every 90 minutes. This treatment brought about progressive rises in serum concentrations of oestradiol and of LH. The ovulation was obtained in both women, and checked by the demonstration by ultra-sound of rupture of the dominant follicle and by estimation of plasma and progesterone levels. One of them became pregnant following this treatment. This kind of therapy seems to us to be an attractive physiological alternative for induction of ovulation.

Adult↗

Sclerotherapy--an adjuvant therapy to endometriosis.

OBJECTIVE: Recurrent endometriomas after medical or surgical treatment is a difficult clinical problem for those patients who wish to perform ovulation induction. Therefore we tried to investigate the efficacy of sclerotherapy as an adjuvant management before ovulation induction to preserve more ovarian tissue for folliculogenesis in ART program. METHODS: Thirty-two patients with persistent or recurrent endometrioma after surgical or medical treatment were included in this study. Transvaginal ultrasound needle guided aspiration of the cyst followed by tetracycline instillation was performed before ovulation induction. RESULTS: There is an encouraging clinical pregnancy rate of 34.37%. Also, there is a disappointing recurrent rate of 46.87% in 12 months follow-up course. CONCLUSION: The increased interest in cost-effective outpatient therapy and the expected difficulty in surgical treatment of recurrent endometriomas made aspiration and sclerotherapy of endometrioma an attractive option before ovulation induction.

Adult↗

Plasma beta-endorphin levels in anovulatory states: changes after treatments for the induction of ovulation.

The goal of this study was to evaluate the effects of menstrual cyclicity on plasma beta-endorphin (beta-EP) levels. For this purpose, beta-EP and cortisol plasma concentrations were measured during the menstrual cycle in healthy control subjects (n = 12), in patients affected by anovulatory syndrome (n = 6), and in amenorrheic patients (n = 8). In the same patients, beta-EP and cortisol were also measured under treatment for the induction of ovulation with pulsatile luteinizing hormone-releasing hormone or human menopausal gonadotropin plus human chorionic gonadotropin administration. In spontaneous and pharmacologically induced ovulatory cycles, a significant preovulatory rise of plasma beta-EP levels was always evident. Constant levels were found in the other periods of ovulatory cycles and in the patients affected by anovulatory syndrome and primary amenorrhea. Cortisol levels did not show any significant change throughout the cycle, either in controls or in patients before or after treatment. This result suggests that when ovulation occurs, plasma beta-EP levels show a relevant rise, the physiologic significance of which remains to be elucidated.

Adult↗

Induction of ovulation in normo-androgenic women, affected by primary hypothalamic amenorrhea, with chronic pulsatile administration of GnRH, using an automatic portable pump (Zyklomat).

Pulsatile administration of GnRH appears to be the most rational and physiological treatment of infertility in patients affected by hypothalamic amenorrhea. The authors conclude that the results obtained with this method of treatment in patients with severe hypothalamic amenorrhea suggest that the choice of pulsatile GnRH therapy is an effective and practical method for induction of ovulation.

Adult↗

Induction of ovulation in rabbits with pure urinary luteinizing hormone and human chorionic gonadotrophin: comparison of oocyte and embryo quality.

Thirty-six 18-week-old nulliparous does were stimulated with a single dose of 25 IU pregnant mare serum gonadotrophin (PMSG). Ovulation was induced 48 h later with 50 IU luteinizing hormone (LH) (18 does) or 50 IU human chorionic gonadotrophin (HCG) (18 does) in order to determine the effects of pure urinary LH and HCG on the quality of oocytes and embryos. Nine does were mated in each group. The does were slaughtered 24 h after induction of ovulation to recover oocytes and 48 h after mating to recover embryos. The number of haemorrhagic, preovulatory and luteinizing follicles per ovary were recorded. The quality of oocytes and embryos recovered were evaluated. No significant differences in the number of haemorrhagic follicles (blood follicles without stigma), preovulatory and luteinizing follicles were observed between LH and HCG groups. LH has a selective action, which could permit the acquisition of better quality oocytes. Although the fertilization rate was similar in both groups (LH versus HCG), the percentage of degenerate embryos (grade 5) was lower for the LH (3%) than the HCG (13%) groups.

Animals↗

Evaluation of a new surgical approach for the treatment of clomiphene citrate-resistant infertility in polycystic ovary syndrome: laparoscopic ovarian multi-needle intervention.

Laparoscopic ovarian drilling (LOD) is the accepted second-line treatment for clomiphene citrate-resistant anovulatory infertility in polycystic ovary syndrome (PCOS). Although multiple pregnancy rates are reduced with ovarian drilling procedures, postoperative adhesion formation is a potential complication in up to 85% of the women subjected to laparoscopic destructive ovarian procedures. Our objective was to determine the effectiveness of a new, specially designed laparoscopic device and technique that might enable treatment for patients with anovulatory PCOS with less trauma and fewer postoperative adhesions. Thirty-five infertile clomiphene citrate-resistant women with PCOS were included. Seventeen women underwent laparoscopic ovarian multi-needle intervention (LOMNI), and 18 women received step-up ovulation induction treatment with recombinant follicle-stimulating hormone followed by intrauterine insemination for three cycles. Patients were followed for a period of 6 months after either laparoscopic surgery or the initiation of ovulation induction therapy. Outcome measures were cycle regularity, pregnancy rate, safety, postoperative adhesion formation, and cost effectiveness. There were no significant differences between the two groups in terms of age, body-mass index, duration of infertility, and basal cycle-day 2 hormone levels. Significant improvement in cycle regularity (p <.01) was found after LOMNI. Cumulative pregnancy rates (35.3% in the LOMNI group vs 33.3% in the ovulation induction group) did not differ between the groups. No adverse events following surgery were noted. Moderate ovarian hyperstimulation syndrome and multiple pregnancies occurred in four and two patients, respectively, in the ovulation induction group. Eight nonpregnant women in the LOMNI group underwent repeat laparoscopy at the end of the follow-up period. No adhesion formation attributable to LOMNI was observed in any of those eight women. The cost of LOMNI was significantly (p <.001) lower than the ovulation induction treatment. In conclusion, LOMNI may be a safe, inexpensive, and effective procedure for the treatment of CC-resistant infertility in patients with PCOS. It seems to preserve the beneficial effects and probably omits unwanted effects (such as adhesion formation) of LOD.

Adult↗

Estrone-3-glucuronide chemiluminescence immunoassay: an alternative method for monitoring induction of ovulation with human menopausal gonadotropin in an in vitro fertilization program.

A simple, rapid, and sensitive solid-phase immunoassay procedure for the determination of estrone-3-glucuronide (E1-3-G), which uses chemiluminescence as the end point in unextracted morning urine, is described. Thirty-one patients undergoing induction of ovulation in an in vitro fertilization (IVF) unit participated in the study. From day 3 of the menstrual cycle until the day of hCG administration, morning blood samples and morning urine specimens were collected for the determination of serum 17 beta-estradiol (E2) and urine E1-3-G, respectively. A good correlation was noted between E2 measured by radioimmunoassay (RIA) and the E1-3-G measured by chemiluminescence immunoassay (CIA), from day 5 up to the day of hCG administration (0.6 less than r less than 0.85, P less than 0.001). It is evident from this study that the CIA measurement of E1-3-G in morning urine is an accurate and rapid (2.5 hours) method and is convenient for monitoring induction of ovulation with human menopausal gonadotropins.

Adult↗

Pulsatile GnRH therapy--an alternative successful therapy for induction of ovulation in infertile normo- and hyperprolactinaemic amenorrhoeic women with pituitary tumours.

Pulsatile treatment with gonadotrophin-releasing hormone (GnRH) was given to induce ovulation in 3 infertile, amenorrhoeic women with pituitary tumours not suitable for conventional therapy with human gonadotrophins or dopamine agonists. Two of the women had prolactinomas and the third a non-secreting adenoma. The GnRH therapy resulted in ovulations in all the 3 women, in 2 of them despite marked hyperprolactinaemia. Two women conceived and had term pregnancies. One pregnancy was uneventful while the woman with the non-secreting tumour developed symptoms of raised intracranial pressure. These symptoms rapidly disappeared when bromocriptine therapy was instituted. Chronic pulsatile GnRH administration is an effective alternative treatment for induction of ovulation in some amenorrhoeic women with pituitary tumours.

Adenoma↗

Induction of ovulation and spermatogenesis by hMG/hCG in hypogonadotropic GH-deficient patients.

Nine female and 20 male hypogonadotropic GH-deficient patients were studied for sexual development by hCG/hMG. In the female patients, gonadotropin therapy was started at the mean age of 22.7 +/- 2.1 years. The administration of progesterone induced withdrawal bleeding at an average of 2.77 +/- 1.94 years after the initiation of hMG/hCG therapy in 8 of the 9 patients studied. Of 6 patients who had been confirmed as positive in a gestagen test, induction of ovulation by hMG/hCG was observed in 5 patients at an average of 5.58 +/- 1.23 years after the onset of therapy, but not in the remaining patient who had been given estrogen and progesterone 4 years 9 months prior to the initiation of the gonadotropin therapy. In male patients, gonadotropin therapy was started at the mean age of 23.6 +/- 5.7 years. Seminal fluid was obtained by masturbation and brought to our clinic in the morning. Of the 20 patients, 19 patients could be observed once a month regularly. Of the 19 patients, spermatozoa could be detected at a mean period of 2.19 +/- 0.87 years after initiation of hCG/hMG therapy in 18, but not in the remaining patient, after 5 years of therapy, who did not receive hCG/hMG regularly. The sperm count exceeded 20 x 10(6)/ml and more in 12 and was lower than that in 8 patients after 3 years of the therapy. No side effects were observed in female patients, but gynecomastia developed in 2 of the 20 male patients. These data suggest that gonadotropin therapy for hypogonadotropic GH-deficient patients is effective in promoting ovulation and spermatogenesis despite the initial replacement therapy with sex hormones.

Adolescent↗

Hormonal induction of ovulation and artificial insemination in suckled beef cows under nutritional stress.

The objective was to develop a program for inducing estrus (followed by insemination) of suckled beef cows under nutritional stress (poor body condition). A total of 123 cows, from 60 to 75 days postpartum, were classified according to their body condition score (BCS; range from 1 to 5, in increments of 0.5) and allocated into two groups. On Day 0 (without regard to stage of the estrous cycle), cows (n = 59) in the hormone induction (HI) treatment group were given an intravaginal device (IVD) containing 250 mg of medroxiprogesterone acetate (MAP) and an i.m. injection of 2.5 mg estradiol benzoate (EB). On Day 6, these cows were given 500 IU eCG i.m. and calves were weaned for 96 h. The IVD were removed on Day 7. Cows detected in estrus by 45 h after IVD removal were inseminated 12 h after standing estrus; cows not in estrus by 45 h after IVD removal received an i.m. injection of 100 microg gonadorelin (GnRH) and were inseminated 16-18 h later. In the control group (C), cows (n = 64) only had their calves weaned at Day 6 (for 96 h), with estrus detection and AI from Days 6 to 11. Overall, the BCS ranged from 2.0 to 3.0. In the treatment group, estrus and pregnancy rates in cows with BCS 2.0 (20 and 30%, respectively) was lower (P < 0.05) than those with BCS 3.0 (50 and 66.6%, respectively), but did not differ (P > 0.05) from BCS 2.5 (23.3 and 47.6%). In C group, only 2 of 66 cows were detected in estrus and bred (neither was pregnant). In conclusion, the program for induction of ovulation using MAP, EB, eCG and GnRH increased the pregnancy rate in beef cows in poor body condition, enabling AI to be done in a 63-h interval.

Administration, Intravaginal↗

Induction of ovulation by the chronic administration of naltrexone in hypothalamic amenorrhea.

Ovulatory menstrual cycles were induced by the administration of the specific opiate antagonist naltrexone at a dose of 50 mg/day for 28 days in 3 women suffering from secondary hypothalamic amenorrhea. The occurrence of ovulation was based on demonstration of follicular growth and corpus luteum formation by ultrasonography and a LH midcycle surge and rise of progesterone. After discontinuation of treatment, the women became amenorrheic again and serum gonadotropins as well as estradiol declined to the low levels found before naltrexone administration. Naltrexone or other specific opiate antagonists may be useful agents for the induction of ovulation in patients with hypothalamic amenorrhea.

Adult↗

Induction of ovulation with combined human gonadotropins and dexamethasone in women with polycystic ovarian disease.

A combined treatment of human menopausal gonadotropin (hMG), human chorionic gonadotropin (hCG), and dexamethasone was administered to 27 infertile patients with polycystic ovarian disease who failed to conceive with clomiphene citrate and hMG-hCG alone. Twenty-two (81%) of the patients ovulated according to basal body temperature and progesterone values, and 20 (74%) conceived during one to four treatment cycles. Fifteen (74%) pregnancies terminated in live full-term deliveries (14 singletons and 1 set of twins), and 5 (25%) have terminated in first-trimester abortions. Only one of the treatment cycles was complicated by moderate ovarian hyperstimulation. The average hMG dose required for the induction of ovulation was significantly reduced from 25 ampules with hMG-hCG alone to 18 ampules under the combined treatment (P less than 0.01). The combination of hMG-hCG and dexamethasone is an additional, safe, and effective nonsurgical treatment for women with polycystic ovarian disease who have failed to respond to an hMG-hCG regimen alone.

Adult↗

Induction of ovulation--past, present and future.

Attempts to induce ovulation have been made since the early 1920s, but the major breakthrough came in the early 1960s with the introduction of clomiphene citrate and the gonadotropins. Additional progress was made in the early 1970s with the introduction of bromocriptine and in the early 1980s with the introduction of pulsatile GnRH. At the present, 'pure' FSH and GnRH agonists are being evaluated as adjuncts to HMG for induction of ovulation. As more insight is gained in the neuroendocrine control of the ovulating cycle, we may soon be able to induce ovulation by direct manipulation of the central nervous system.

Chorionic Gonadotropin↗

Induction of ovulation by endothelin-3 in rats.

Endothelins vary in their biological activity. We therefore examined the effects of endothelin-3 (ET-3) on ovulation and secretion of LH, FSH and prolactin in rats in which naturally occurring ovulation was blocked by the administration of sodium pentobarbital (40 mg/kg, i.p.) prior to the critical period (1330 h) on the day of pro-oestrus. ET-3 (10 nmol/kg) was given via the jugular vein under pentobarbital anaesthesia from 1600 to 1800 h on the day of pro-oestrous and induced ovulation in all rats whether given by venous injection or by infusion but the number of ova in rats injected with ET-3 was less than that in normally cycling control rats. Infusion of ET-3 stimulated the secretion of LH but caused a lower than expected rate of secretion of FSH. It would therefore appear that ET-3 causes release of the total amount of LH that is required for induction of ovulation. Our findings strongly suggest that ET-3 has a physiologically significant role in the regulation of anterior pituitary hormone secretion.

Animals↗

Can growth hormone increase, after clonidine administration, predict the dose of human menopausal hormone needed for induction of ovulation?

Recent observations claimed that growth hormone (GH) administration increased the sensitivity of the ovary to gonadotropin stimulation. These findings prompted us to assess whether ovarian response to human menopausal gonadotropin (hMG) is correlated to GH reserve. Before hMG administration, 25 patients were tested for GH reserve by administration of clonidine. Of the 25 patients, 8 showed a significant increase in GH (9.2 +/- 4.5 ng/mL) and needed a significantly lower dose of hMG/human chorionic gonadotropin to elicit a good ovarian response than the 17 patients who did not respond to clonidine administration may help to estimate the initial dose range of hMG necessary for induction of ovulation.

Administration, Oral↗

Alternative solutions to hCG induction of ovulation in the mare.

Injection of hCG (2000-2500 i.u., i.v.) to mares when a follicle reaches 35 mm induces ovulation between 24 and 48 h. However, repeated injections induce antibodies against hCG. We report attempts to induce ovulation without this inconvenience. We called 'response' an ovulation between 24 and 48 h after treatment. The typical response to hCG was obtained in 73% (N = 145) of treated mares. After immunization against hCG, the response (0%, N = 10) was less than in nonimmunized controls (100%, N = 9). Simultaneous injection of dexamethasone and hCG resulted in induction of ovulation (71%, N = 14). However, simultaneous hCG + dexamethasone resulted in antibody formation similar to that induced by hCG alone, when injected repeatedly every 21 days. Neither GnRH (2 mg i.m.) nor partly purified pig LH (26 mg i.v. or s.c.) induced ovulation consistently (40%, N = 30 and 31%, N = 16). Crude horse gonadotrophin (60 mg i.v. or s.c.) induced ovulation (86%, N = 14). Fertility was not different from control (61%, N = 13 vs 40%, N = 10). Crude horse gonadotrophin also induced ovulation in mares previously immunized against hCG (78%, N = 9): 50 or 25 mg gave satisfactory response (86%, N = 29 and 57%, N = 40). We conclude that crude horse gonadotrophin is a good alternative to hCG for the induction of ovulation in mares.

Animals↗

Ovarian stimulation and in vitro fertilization in women with mature cystic teratomas.

OBJECTIVE: To report the results of ovulation induction and in vitro fertilization-embryo transfer (IVF-ET) in patients with ovarian cystic teratomas. METHODS: Six women with ultrasonographically diagnosed ovarian cystic teratomas (mean diameter 2.4 cm) who presented with infertility underwent IVF-ET (n = 4) or ovulation induction (n = 2). Serial ultrasound examinations were used to determine the size of the cystic teratomas during therapy and throughout pregnancy. RESULTS: Ovarian stimulation was successful, as evidenced by the serum estradiol concentration on the day of hCG administration (mean in IVF-ET patients, 3558+/-1319 pg/mL) and the number of oocytes retrieved (10+/-4.24). Three patients having IVF-ET and both patients having ovulation induction conceived, and six healthy infants were born. Cyst sizes remained unchanged throughout treatment and pregnancy. There were no cyst-related complications during ovulation induction or IVF-ET, or during the entire course of pregnancy, labor, and delivery. CONCLUSION: The presence of ovarian cystic teratoma should not be considered a contraindication for therapy in women undergoing ovulation induction and IVF-ET.

Adult↗