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PubMed1978

Characteristics of an antiluteinizing hormone isoantibody produced during gonadotropin induction of ovulation.

Production of an antihuman LH antibody was suspected in a woman with isolated LH deficiency who received human pituitary gonadotropin (hPG) to induce ovulation and who developed secondary drug failure associated with very high "serum LH' values. Binding of [125I]LH to various dilutions of the patient's serum was demonstrated by precipitation with polyethylene glycol or sheep antihuman immunoglobulin G (anti-IgG) but not by precipitation with sheep antihuman immunoglobulin M (anti-IgM). Unlabeled LH competitively displaced [125I]LH from a 1:200 final dilution of the patient's serum, and indicated a single class of binding sites with a binding affinity of 1.5 X 1011 M-1 and a binding capacity of 84 ng LH/ml serum. The isoantibody was reactive against antigenic determinants in hPG, LH, and hCG but not against human FSH. Further examination showed binding to the beta, but not the alpha, subunit of two LH preparations and to beta hCG. It is concluded that repeated administration of hPG to this patient with isolated LH deficiency evoked IgG isoantibody formation against the beta subunit of LH.

Adult↗
PubMed1981

Induction of ovulation in a true hermaphrodite with male phenotype.

Ovulation was induced in a 16-yr-old 46 XX/47 XXY true hermaphrodite with a male phenotype. The presence of testicular tissue was assessed by a normal androgen response to hCG. Administration of FSH and LH for 8 consecutive days, followed by a single dose of hCG, induced a biphasic serum profile of 17 beta-estradiol and progesterone similar to that observed in normal menstrual cycles. In addition, a significant rise in serum testosterone was noticed during the luteal phase. Laparotomy revealed the presence of a uterus, with evidence of endometrial bleeding and absence of a vagina. These results demonstrated that gonadotropins were able to induce follicular maturation, ovulation, and endometrial bleeding in a true hermaphrodite resembling a normal ovulatory cycle. Gonadotropin administration can be used as a diagnostic tool for establishing the presence of ovarian tissue in this gonadal development abnormality.

Adolescent↗
PubMed2000

Free androgen index and leptin are the most prominent endocrine predictors of ovarian response during clomiphene citrate induction of ovulation in normogonadotropic oligoamenorrheic infertility.

We have previously demonstrated that obese hyperandrogenic amenorrheic women are less likely to ovulate after clomiphene citrate (CC) medication. The present study was designed to identify whether additional endocrine screening characteristics, all potentially involved in ovarian dysfunction in 182 normogonadotropic oligoamenorrheic infertile women, are associated with ovarian response, which may improve overall prediction of CC-resistant anovulation. Standardized endocrine screening took place before initiation of CC medication (50 mg/day; increasing doses up to 150 mg/day if required) from cycle days 3-7. Screening included serum assays for fasting insulin and glucose, insulin-like growth factor I (IGF-I), IGF-binding protein-1 (IGFBP-1), IGFBP-3, free IGF-I, inhibin B, leptin, and vascular endothelial growth factor. Forty-two women (22% of the total group) did not ovulate at the end of follow-up (a total number of 325 cycles were analyzed). Fasting serum insulin, insulin/glucose ratio, IGFBP-1, and leptin were all significantly different in univariate analyses (P < or = 0.02), comparing CC responders vs. nonresponders. Forward stepwise multivariate analyses in combination with factors reported earlier for prediction of patients remaining anovulatory after CC revealed a prediction model including 1) free androgen index (FAI = testosterone/sex hormone-binding globulin ratio), 2) cycle history (oligomenorrhea or amenorrhea), 3) leptin level, and 4) mean ovarian volume. These data suggest that decreased insulin sensitivity, hyperandrogenemia, and obesity, all associated with polycystic ovary syndrome, are prominent factors involved in ovarian dysfunction, preventing these ovaries from responding to stimulation by raised endogenous FSH levels due to CC medication. By using leptin instead of body mass index or waist to hip ratio, the previous model for prediction of patients remaining anovulatory after CC medication could be slightly improved (area under the curve from 0.82-0.85). This may indicate that leptin is more directly involved in ovarian dysfunction in these patients. The capability of insulin and IGFBP-1 to predict patients who remain anovulatory after CC disappears when FAI enters into the model due to a significant correlation between FAI and these endocrine parameters. This suggests that markers for insulin sensitivity (e.g. IGFBP-1 and insulin) are associated with abnormal ovarian function through its correlation with androgens, whereas leptin is directly involved in ovarian dysfunction.

Adult↗
PubMed1999

Induction of ovulation by Sairei-to for polycystic ovary syndrome patients.

In anovulatory patients ovulation is usually induced by clomiphene citrate (CC) or gonadotropin therapy, but in the case of polycystic ovary syndrome (PCOS), diagnosed by the presence of several micropolycysts in the ovaries and a high LH/FSH ratio in the serum, CC is only minimally effective, and side effects are often a problem with gonadotropin therapy. In the present study we administered a Chinese herbal medicine Sairei-to which appears to have a steroidal effect in anovulatory PCOS patients. As a result of the treatment, serum LH and the LH/FSH ratio significantly decreased (P<0.01) and the ovulatory rate was 70.6%. Serum testosterone levels were within normal limits before the treatment, and did not significantly change during the treatment. Sairei-to may therefore be useful for the treatment of anovulation in PCOS patients.

Anovulation↗
PubMed2002

A modified hMG-GnRH method for the induction of ovulation in infertile women with severe hypogonadotropic amenorrhea.

The objective of this study was to compare, in infertile women suffering from severe hypogonadotropic amenorrhea, the therapeutic utility and the incidence of complications arising from fertility treatment by the conventional human menopausal gonadotropin/human chorionic gonadotropin (hMG-hCG) method, the hMG step-down method, the sequential hMG/gonadotropin-releasing hormone (GnRH) method and a new, modified hMG-GnRH method that has been developed by us. In the step-down method, the daily dose of hMG was decreased from 150 IU to 75 IU when the follicle diameter reached 11-13 mm. In the sequential hMG-GnRH, hMG injection was switched to pulsatile GnRH administration (20 microg/120 min SC), when the follicle diameter reached 11-13 mm. In our new modified hMG-GnRH, pulsatile GnRH was injected together with hMG. Daily hMG was stopped and the GnRH dosage was changed from 10 microg to 20 microg when the follicle diameter reached 11-13 mm. Initially, the three established methods were applied randomly to treat 34 cycles in 20 women; and subsequently, five patients who failed to conceive following treatment by sequential hMG-GnRH were then treated by the modified hMG-GnRH method. More than eight growing follicles and multiple pregnancies were observed during treatment by the conventional method. The incidence of ovarian hyperstimulation syndrome (OHSS) was 25.7% with the conventional method, 20.0% with the step-down method and 0% with the sequential hMG-GnRH method; however, the rate of ovulation was only 50% with the sequential hMG-GnRH method. By contrast, with the modified hMG-GnRH method, less than three growing follicles occurred in 81.8% of patients, there was a 100% rate of ovulation, and neither OHSS nor multiple pregnancies were observed. Moreover, the modified hMG-GnRH method induced pregnancy in 3 out of 5 patients. These data indicate that this new method is favorable for the treatment of severe hypogonadotropic amenorrhea.

Adult↗
PubMed1982

Induction of ovulation in immature female rats by a single injection of 4-hydroxyoestradiol-dibenzoate.

This study was designed to test the ability of 2- and 4-hydroxyoestrogens to induce ovulations and the formation of corpora lutea in immature female rats. To this end 25 day old animals received a single injection of different doses of either 4-hydroxyoestradiol-dibenzoate (10, 25, 50 micrograms) or 2-hydroxyoestradiol-dibenzoate (25, 250 micrograms) or oestradiol-benzoate (10, 25, 60 micrograms). On day 31 the ovaries were checked for corpora lutea. 4-Hydroxyoestradiol-dibenzoate and oestradiol-benzoate in doses of 50 or 25 micrograms significantly increased the number of animals with corpora lutea whereas animals treated with 10 micrograms of either steroid did not differ significantly fron the respective vehicle groups. 2-Hydroxyoestradiol-dibenzoate, even at the high dose of 250 micrograms did not show a significant effect. This is the first demonstration that a catecholoestrogen - 4-hydroxyoestradiol - can induce ovulation. As its potency in doing so is similar to that of oestradiol and as 4-hydroxyoestradiol can be formed in neuroendocrine tissues from primary oestrogens, we conclude that this catecholoestrogen might play a role in the regulation of ovulation.

Animals↗
PubMed1981

Inadequate corpus luteum function after the induction of ovulation in anoestrous ewes by LH-RH or an LH-RH agonist.

Scottish Blackface ewes were given LH-RH (3 x 30 micrograms i.v., at 90 min intervals) or D-Ser-(But)6-des Gly10 LH-Rh ethylamide (LH-RH agonist) as a single injection (8 or 40 micrograms) during anoestrus. Ovulation as judged by laparoscopy occurred in 8 of the 27 animals. Despite the fact that the LH-RH agonist induced a greater release of LH and FSH the different treatments had no effect on the number of ewes ovulating and within each treatment group there was no apparent difference in the amounts of gonadotrophins released between the ewes that did or did not ovulate. All ovulations resulted in the formation of CL associated with plasma progesterone concentrations of less than 1 ng/ml (1--5 ng/ml in the normal luteal phase). In comparison with CL of the normal cycle the induced CL were of lower weight and had reduced progesterone content and ability to secrete progesterone in vitro. However, the binding of hCG was equivalent to that of normal CL. These results suggest that the inadequate CL formed in anoestrous ewes after a single LH-RH injection have not developed the ability to synthesize and secrete progesterone in spite of the presence of normal amounts of LH receptors.

Animals↗
PubMed1981

Observations on the induction of ovulation and expulsion of uterine eggs in the mink, Mustela vison.

In 8 of 12 mink paired for the first time, pairing alone induced ovulation and a short (5 min) interrupted mating led to 8/8 ovulating with normal numbers of corpora lutea. However, in already mated mink, a short mating (Day 7) failed completely or partly (reduced number of ovulations) to induce ovulation. In mink which refused to mate, hCG consistently induced ovulation. In already mated mink (Day 0) a later mating (Day 7), even if interrupted after 5 min, led to expulsion of the first set of eggs, approximately 50% of which were 'lost' by Day 4 and virtually 100% by Day 6. This effect was not produced by pairing without intromission or by treatment with hCG to induce ovulation. It is concluded that copulation is primarily responsible for the loss of eggs from the uterus, although the exact mechanism remains obscure.

Animals↗
PubMed1983

Induction of ovulation in seasonally anoestrous ewes by continuous infusion of low doses of Gn-RH.

Two groups of 12 seasonally anoestrous ewes were infused with Gn-RH at the rate of 125 or 250 ng/h for 48 h. Four control ewes were infused with the saline vehicle alone. Mean LH concentrations increased significantly in response to Gn-RH infusion and were significantly higher (P less than 0.05) in ewes receiving 250 ng Gn-RH/h. LH concentrations remained unchanged in the control ewes. Oestrus was detected in 22/24 Gn-RH-treated ewes and occurred at a mean time of 37.0 +/- 1.2 h after the start of infusion. Ovulation occurred in all but one of the 24 Gn-RH-treated ewes with mean ovulation rates of 1.27 +/- 0.14 (125 ng-Gn-RH/h) and 1.75 +/- 0.22 (250 ng Gn-RH/h). These results demonstrate that a sustained elevation in mean circulating concentrations of LH induced by continuous administration of Gn-RH is sufficient to invoke the final phases of follicular development, and thereby ovulation, in the seasonally anoestrous ewe.

Anestrus↗
PubMed1983

Induction of ovulation with chronic intermittent (pulsatile) administration of Gn-RH in women with hypothalamic amenorrhoea.

The physiological and pathophysiological basis of hypothalamic amenorrhoea are reviewed as well as the clinical results of chronic intermittent (pulsatile) administration of Gn-RH in the treatment of infertility. Hypothalamic amenorrhoea is considered to be the result of a deficient hypothalamic secretion of Gn-RH. By pulsatile administration of Gn-RH, which is a pre-requisite of normal pituitary gonadotrophic function, deficient endogenous Gn-RH is replaced. If an adequate dose of Gn-RH is provided, which takes into account the degree of impairment of hypothalamic function in the individual case, follicular maturation, ovulation and corpus luteum formation are achieved in nearly every treatment cycle. Although dependent also on factors other than the treated dysfunction, a high conception rate is achieved.

Amenorrhea↗
PubMed1988

Induction of ovulation in chronically hypophysectomized Booroola ewes.

Booroola Merino ewes, with (F+; N = 17) and without (++; N = 13) a copy of the fecundity gene were hypophysectomized and 6 weeks later were given an i.m. injection of PMSG (high, medium or low dose) followed by hCG. The induced ovulation rates were observed laparoscopically. Ovulation rates were significantly higher (P less than 0.01) in Booroola F+ ewes than in ++ ewes (8.00 +/- 1.66 s.e.m. vs 3.62 +/- 1.10 respectively). This suggests that the high fecundity of the Booroola ewe may be due primarily to ovarian rather than pituitary factors.

Animals↗
PubMed1992

Insulin and insulin-like growth factor I in follicular fluid after induction of ovulation in women undergoing in vitro fertilization.

This study was undertaken to evaluate the relationship between concentrations of insulin and insulin-like growth factor I (IGF-I) in follicular fluid and fertilization and cleavage of human oocytes fertilized in vitro. The concentration of oestradiol, progesterone, luteinizing hormone, follicle-stimulating hormone, testosterone, insulin and IGF-I was determined in 36 follicular fluids, free of visible blood contamination and containing mature oocyte-corona-cumulus complexes, obtained from 12 women undergoing in vitro fertilization. Follicular development was induced by clomiphene citrate and human menopausal gonadotrophin, and follicular aspiration was performed 35 h after an ovulatory dose of human chorionic gonadotrophin. Concentrations of IGF-I were significantly higher in follicular fluids associated with mature oocytes that fertilized and cleaved, than in follicular fluid associated with mature oocytes that did not fertilize (P < 0.001). There was no difference in the concentration of insulin between follicular fluids from which fertilized oocytes were obtained and those with oocytes that remained unfertilized. No significant correlations were found between rates of embryo cleavage, concentrations of insulin and IGF-I. Multiple linear regression analysis demonstrated that the concentrations of IGF-I in follicular fluid were predicted statistically by a negative regression coefficient for the concentration of testosterone, and by a positive regression coefficient for the concentration of progesterone in follicular fluid. No candidate variable was included in the model to predict concentrations of insulin. These data suggest an important role for IGF-I in the mature follicle.

Adult↗
PubMed1993

Induction of ovulation and superovulation in mares using equine LH and FSH separated by hydrophobic interaction chromatography.

Pharmacological control of reproduction in mares requires the use of equine gonadotrophins to avoid induced immunological resistance. Crude equine gonadotrophins (CEG) have been used but the presence of equine luteinizing hormone (eLH) and follicle-stimulating hormone (eFSH) in CEG has led to disappointing results in superovulation studies. Separation of eLH and eFSH activities from CEG is necessary to overcome this problem. The hydrophobic properties of the two hormones were sufficiently different to permit their separation by hydrophobic interaction chromatography (HIC) on a phenyl Sepharose matrix. Good yields of separate FSH and LH fractions were readily obtained by stepwise elution and the method was adapted for large scale preparations of enriched fractions of eLH and eFSH. Two experiments were performed in vivo to evaluate the biological activity of the HIC fractions. Experiment 1 showed that biological activity of the LH fraction in inducing ovulation of preovulatory follicles was similar to that obtained with CEG, indicating that LH bioactivity was not altered by HIC. Experiment 2 demonstrated that biological activity of the FSH fraction was identical (as far as rate of ovulation was concerned) to that of CEG in superovulating mares, indicating that FSH activity was also not altered by HIC. Although we have not obtained better results with the separate equine gonadotrophins than with CEG, it is potentially advantageous to use preparations with single activity to obtain a controlled balance of FSH and LH activity. The HIC technique was chosen because it could easily be scaled up to provide the large amounts of the separate hormones needed for the treatment of a large number of mares.

Animals↗