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PubMed1980

Estrogen radioimmunoassay suitable for the monitoring of ovulation induction.

A rapid radioimmunoassay for estrogen in serum was characterized and validated. Analytical recoveries of estrone and estradiol were essentially 100%; estriol was not measured because it was eliminated by sample-handling procedures. Nonspecific interference from serum extracts, which was initially reflected by positive blanks, was eliminated by a sodium hydroxide wash of the extract. Validation of the procedure included determination of a reference interval for estrogen that agreed with the sum of estradiol and estrone concentrations reported in the literature for eugonadal women. Clinical applicability of the assay was demonstrated by monitoring estrogen concentrations during the menstrual cycle and during urogonadotropin (Pergonal)-induced follicular maturation. Because of its rapid turnaround time, the assay is ideally suited for monitoring the frequency with which urogonadotropin should be administered to the infertile patient, and the dosage, thus decreasing the likelihood of multiple pregnancies or ovarian hyperstimulation.

Estradiol↗
PubMed1993

The relationship between follicle-stimulating hormone dose and level and its relevance for ovulation induction with adjuvant gonadotropin-releasing hormone-agonist treatment.

OBJECTIVE: To investigate the effect of a GnRH agonist (GnRH-a) on the FSH threshold level and the relationship between the FSH dose and the FSH level of patients suffering from polycystic ovarian syndrome (PCOS). DESIGN: The stimulation with low-dose FSH in PCOS (group 1) was compared with the subsequently performed stimulation with low-dose FSH combined with GnRH-a in another group of patients suffering from the same syndrome (group 2). SETTING: Specialist Reproductive Endocrine Unit. PATIENTS: Suffering from clomiphene citrate-resistant PCOS. MAIN OUTCOME MEASURES: The FSH threshold level for ongoing follicular growth and the relationship between dose and level of FSH. RESULTS: In 15 patients in group 1 and in 13 patients in group 2, respectively, 39 and 32 stimulation cycles were performed. Below and above threshold values of FSH of group 1 and 2 did not differ significantly. For the equation stable level of FSH (Y mIU/mL) = A X infusion rate of FSH (X IU/24 h) + basal level of FSH (B mIU/mL), the median A of group 1 was 0.027 and A of group 2 was 0.055 (significant difference). CONCLUSIONS: In PCOS, a change of the FSH threshold level for ongoing follicular growth induced by the GnRH-a could neither be proven nor ruled out. The use of a GnRH-a resulted in larger FSH level increases per IU/24 h of FSH administered and might therefore interfere with the effect of low-dose FSH treatment.

Adjuvants, Pharmaceutic↗
PubMed2003

Leukocyte behaviour and permeability in the rat mesenteric microcirculation following induction of ovulation.

BACKGROUND: Ovarian hyperstimulation syndrome (OHSS), a highly dangerous and incompletely understood complication of ovulation induction with exogenous gonadotrophins, can include haemoconcentration, hypovolaemia, hypotension, acute renal insufficiency, thromboembolism and ultimately death. Using intravital microscopy, we examined microvascular permeability and leukocyte-endothelial cell interactions in the rat mesenteric microcirculation associated with induction of ovulation. METHODS: In female rats treated with hMG and hCG, mesenteric venules were observed by intravital microscopy assisted by a video imager. Erythrocyte velocity was monitored, and rolling and adhesion of leukocytes were studied by transmission video images. Transvascular leakage of fluorescein isothiocyanate-labelled albumin was assessed by epi-illumination. RESULTS: Administration of hMG and hCG significantly increased vascular protein leakage within a few hours, and also reduced rolling velocities of leukocytes in venules and increased numbers of leukocytes adherent to endothelium at 16 h following hCG injection. The administration of antibodies against intracellular adhesion molecule (ICAM)-1 inhibited these reactions. CONCLUSION: By induction of ovulation, vascular permeability is increased not only at the surface of the ovary but also in the mesentery. Alteration of leukocyte behaviour in the microcirculation through mechanisms involving ICAM-1 is one likely cause of the protein leakage.

Animals↗
PubMed1991

Relationship between blood radioimmunoreactive beta-endorphin and hand skin temperature during the electro-acupuncture induction of ovulation.

Thirteen cycles of anovulation menstruation in 11 cases were treated with Electro-Acupuncture (EA) ovulation induction. In 6 of these cycles which showed ovulation, the hand skin temperature (HST) of these patients was increased after EA treatment. In the other 7 cycles ovulation was not induced. There were no regular changes in HST of 5 normal subjects. The level of radioimmunoreactive beta-endorphin (r beta-E) fluctuated, and returned to the preacupunctural level in 30 min. after withdrawal of needles in normal subjects. After EA, the level of blood r beta-E in cycles with ovulation declined or maintained the range of normal subjects. But the level of blood r beta-E in cycles in which the induction failed to cause ovulation was kept higher that that of normal. (P less than 0.05). There was a negative correlation in the decrease of blood r beta-E and increase of HST after EA (r = 0.677, P less than 0.01). EA is able to regulate the function of the hypothalamic-pituitary-ovarian axis. Since a good response is usually accompanied with the increase of HST, monitoring HST may provide a rough but simple method for predicting the curative effect of EA. The role of r beta-E in the mechanism of EA ovulation induction was discussed.

Anovulation↗
PubMed1990

Induction of ovulation: historical aspects.

The cornerstone of the conquest of infertility was laid in the beginning of this century. It took, however, nearly 80 years of work of many scientists from all over the globe to slowly unravel the puzzle of nature's most guarded secret, the control of the reproductive processes. The estimated population size of women between the ages 19 and 34 years in the developed world in 1990 will be about 130 million. If we assume that at least 8% will be infertile, then the pool of the infertile population will be above 10 million, with about 700,000 new patients entering this pool every year between the years 1990 and 1995. In the past only about 40% of infertile patients benefited from ovulation induction regimens. With the advent of assisted reproduction this population increased to about 80%. With the use of gonadotrophins for induction of superovulation in normally ovulating women conceptual changes in treatment regimens and monitoring schemes had to be introduced. It is obvious that the primary task of infertility clinics is to diagnose the main cause (or causes) of infertility in each couple in order to be able to institute appropriate therapy within a reasonable time. We have attempted to review briefly the regulation of follicular development, particularly with regard to new findings demonstrating the potentiating effect of growth hormone and/or various growth factors on ovarian sensitivity to FSH. This new knowledge, as well as availability of potent GnRH analogues, will evidently refine our clinical approach to treatment of functional infertility. Continuous advances in the understanding of mechanisms regulating reproductive processes and the better recognition of underlying causes of infertility will lead to the optimal choice of first-, second- and third-line routine therapies which will apply to the majority of patients. Furthermore, it will become possible to design tailor-made ovulation-inducing protocols for specific patients who do not respond properly to the routine treatment.

Adult↗
PubMed1983

Induction of ovulation with human urinary follicle-stimulating hormone: endocrine pattern and ultrasound monitoring.

Nine infertile patients, suffering from polycystic ovaries, were treated with human urinary FSH and hCG (eight cases) to induce ovulation. Oestrone, oestradiol, 17 alpha-hydroxyprogesterone, testosterone and androstenedione serum levels increased during the treatment. A decrease in luteinizing hormone serum levels was noticed, and in five cases a spontaneous peak was observed. No changes were noted in 5 alpha-dihydrotestosterone serum levels. Ultrasound scanning of the ovaries often revealed multiple follicles at different speeds and stages of growth and their marked turnover was observed. The beginning of the LH spontaneous surge was precocious compared to the normal ovulating follicular sizes: it does not appear that an optimum size exists but when the LH peak occurred too prematurely, ovulation did not take place. Administration of hCG seems to be necessary as spontaneous peaks of LH are not always followed by rupture of the follicle. Ultrasound scanning plays an important role in monitoring ovulation induction, while oestradiol and 17 alpha-hydroxyprogesterone serum levels are not good indicators of follicular maturity in multifollicular growth. Ovulation occurred in eight patients; four conceptions were obtained, one of which resulted in abortion. No ovarian hyperstimulations were observed.

Adolescent↗
PubMed2000

Induction of ovulation by clomiphene citrate in the Indian vespertilionid bat, Scotophilus heathi.

The ovulation induction property of clomiphene citrate (CC) and human chorionic gonadotropin (hCG) was studied in Scotophilius heathi, an Indian tropical vespertilionid bat, during the period of delayed ovulation between December to early January. The results of the study showed that 10 microg of CC alone was ineffective to induce ovulation, whereas 100 microg CC and 10 IU hCG alone induced ovulation. A significant (P < 0.01) increase in the ovulation rate was observed when 10 microg CC followed by 10 IU hCG, compared to 10 IU hCG and 100 microg CC alone groups. Finally, CC at a 100 microg dose, followed by 10 IU hCG, produced superovulation (14.00 +/- 0. 70), which is significantly different in comparison to all other groups. This is the first report of ovulation induced by CC in the Indian tropical bat as well as in any animal model that exhibits temporary anovulation similar to polycystic ovary syndrome (PCOD) during the normal physiology of reproduction.

Animals↗
PubMed1986

Further demonstration of induction of ovulation with a hybrid human chorionic gonadotropin compound (AB1ER-CR-2XY).

Further demonstration of the ability of the hybrid human chorionic gonadotropin (hCG) compound, AB1ER-CR-2XY, to induce ovulation is presented. Nineteen patients previously treated with human menopausal gonadotropin (hMG) and commercial hCG were selected for the study. The patients received 37 courses of treatment with dosages of hMG ranging from 1200 IU (16 ampules) to 8400 IU (112 ampules), followed by the administration of 5000 or 10,000 IU of the hybrid hCG. Of the total number of courses given, 75.5% were ovulatory; serum progesterone levels at midluteal phase of the cycle were within normal range, and the cycle length was about 12 days. Seven patients became pregnant, three with twins, one with triplets, and three with aborted single fetuses. Before the hybrid hCG was administered the serum estrogen levels were less than 1200 pg/ml in 12 cycles (32.4%), and the estrogen levels ranged from 1400 to 7400 pg/ml in 25 (67.6%). However, in spite of high estrogen levels, clinical hyperstimulation, which occurred in 22.4% of previous treatments with conventional hMG-commercial hCG, did not develop when the hybrid hCG was administered, an effect which could be attributed to its short circulatory half-life. Studies are in progress to confirm whether the hybrid hCG may provide a better margin of safety than commercial hCG for ovulation induction in patients pretreated with hMG.

Adult↗
PubMedDate not supplied

Induction of ovulation for gamete intrafallopian transfer (GIFT) using a gonadotropin-releasing hormone agonist and "pure" FSH: results obtained in 30 normally menstruating women.

About 30% of the ovulation induction cycles in GIFT and FIVET programmes are cancelled due to an inadequate response of patients to gonadotropins and/or clomiphene citrate. GnRH agonist-gonadotropins and/or "pure" FSH combination has been successful in inducing ovulation in patients with a previous history of cycle cancellation and/or alterations in the menstrual cycles. In order to reduce the number of cycle cancellations and obtain more homogeneous oocytes, GnRH agonist-gonadotropins and/or "pure" FSH combination in all candidates for GIFT and FIVET has been recently hypothesised. The Authors report results obtained from GnRH agonist-"pure" FSH combination in 30 normally menstruating patients of the GIFT programme: in 93% of cases the harvested oocytes were preovulatory, in 27.6% of cycles and in 28.6% of the GIFTs respectively an ongoing pregnancy was obtained. While the results obtained must be considered preliminary, they nevertheless suggest that the use of a combination of GnRH-agonist "pure" FSH in all patients in the GIFT programme may be of real clinical validity.

Adult↗
PubMed1981

Induction of ovulation and pregnancy with pulsatile luteinizing hormone releasing factor: dosage and mode of delivery.

The efficacy of intravenous and subcutaneous routes for pulsatile delivery of differing dosages of synthetic luteinizing hormone releasing factor (LRF) for ovulation induction were evaluated sequentially in two patients with presumed deficiency of endogenous LRF: isolated gonadotropin deficiency and pituitary stalk transection with hyperprolactinemia. Observations were made of the amplitude and duration of the induced LH-FSH pulses, of follicular growth and ovulation (via ultrasound), and of ovarian steroids. Remarkable differences in each of these parameters were found between the two modes of LRF delivery. LRF pulses administered subcutaneously resulted in inappropriate gonadotropin secretion, arrest of follicular development, elevated ratios of E1/E2 and androgens/estrogens, and the appearance of acne - features of polycystic ovary syndrome. In contrast, the first intravenous course of pulsatile LRF induced orderly follicular maturation and ovulation with subsequent pregnancy in both subjects. From these findings we conclude that, in these patients, the intravenous mode of delivery of LRF pulses was superior to the subcutaneous route at all doses tested.

Adult↗
PubMed1984

Successful induction of ovulation and conception with pulsatile intravenous administration of human menopausal gonadotropins in anovulatory infertile women resistant to clomiphene and pulsatile gonadotropin-releasing hormone therapy.

Gonadotropins are released in a pulsatile fashion at a frequency of between 1 and 2 hours in the follicular phase of the menstrual cycle. Human menopausal gonadotropins are usually administered intramuscularly. We evaluated the gonadal response to intravenous human menopausal gonadotropins administered in a pulsatile fashion over nine treatment cycles in three anovulatory infertile women. Human menopausal gonadotropin pulses in doses up to 12 IU follicle-stimulating hormone at frequencies between 2 to 3 hours over 3 to 17 days resulted in ovulation in five cycles with one pregnancy being conceived. In the ovulatory cycles (5,000 to 10,000 IU of human chorionic gonadotropin was used to induce ovulation), the 17 beta-plasma estradiol level was 961 +/- 128 versus 326 +/- 95 pg/ml (mean +/- SEM) in the anovulatory cycles (p = 0.015). The dose of human menopausal gonadotropins (in ampules of Pergonal, 75 IU of follicle-stimulating hormone and 75 IU of luteinizing hormone) in the intravenous cycles needed to induce ovulation was 12.3 +/- 1.4 versus 20.4 +/- 0.9 for intramuscular cycles (n = 80 in 23 women, p = 0.008). Treatment was well tolerated and without complications. We are continuing to explore the use of this apparently more efficient mode of administering human menopausal gonadotropins to anovulatory patients resistant to other techniques of ovulation induction therapy.

Adult↗
PubMedDate not supplied

Induction of ovulation with pulsatile GnRH: comparison between subcutaneous and intravenous administration in the same patients.

In this study we compared the results obtained during GnRH pulsatile therapy for ovulation induction in the same patients receiving successively GnRH by subcutaneous (10 mcg/90') and intravenous route (2.5 or 5 mcg/90'). Our data suggest that intravenous administration is the most effective procedure for restoring fertility, either in terms of hormonal levels (oestradiol and gonadotropin peaks) or ovulation rate (100% of ovulatory cycles on GnRH treatment versus 25% on subcutaneous administration). With regard to intravenous GnRH therapy, the dose of 2.5 mcg/90' may be more advisable and safe from ovarian overstimulation.

Adult↗