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Biomedical subjects

N Laufer

Publications and source records attributed to N Laufer.

At least 181 records · Page 10Linked to original sources

Treatment of oligoasthenospermia with human chorionic gonadotropin: hormonal profiles and results.

Forty-seven oligoasthenospermic patients were treated with human chorionic gonadotropin, 5000 IU twice weekly for 12 to 15 weeks. Only three patients impregnated their wives following treatment. Sperm concentration subsequent to treatment decreased in 26 patients, increasing in only 8 cases. Sperm motility improved in 36% of the patients and deteriorated in 30%. During treatment, mean testosterone levels rose by 72%, mean estradiol levels rose by 140%, and mean follicle-stimulating hormone levels decreased by 80%. Mean prolactin levels remained unaltered. The disappointing results with human chorionic gonadotropin treatment fail to make it a recommendable therapy for patients with idiopathic oligoasthenospermia.

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↗

Zona-free hamster ovum penetration assay as a screening procedure for in vitro fertilization.

Twenty couples with primary sterility due to mechanical factors entered our program of IVF. In addition to routine sperm evaluation, an SPA was performed in all cases. Whenever the SPA was pathologic, none of the human ova were fertilized in vitro, while 77% of the patients with a normal SPA had IVF of at least one human ovum. The good correlation between pathologic SPA and failure of IVF stresses the clinical value of this assay. The use of the SPA for patient selection for IVF is suggested.

Animals↗

The use of high-dose human menopausal gonadotropin in an in vitro fertilization program.

Sixty-three normal ovulatory women suffering from obstructive tubal disease not corrected by previous surgery were enrolled in an in vitro fertilization (IVF) program. To achieve a large number of mature follicles, a relatively high dose of human menopausal gonadotropin (hMG) was administered (19 +/- 4 ampules/cycle). Monitoring consisted of daily follicular ultrasonography and serum estradiol measurements. Human chorionic gonadotropin (10,000 IU) was administered when more than two large follicles (1.6 to 1.8 cm in diameter) were visualized. Fifty-five laparoscopies for oocyte retrieval were performed. A mean of 4.3 follicles per woman were aspirated, and 3.2 oocytes per woman were recovered. The oocytes were preincubated for 8 or 24 hours according to the morphologic degree of mucification and dispersal of the oocyte-corona-cumulus complex. Seventy-seven percent of the oocytes were fertilized and were transferred into the uterus 38 to 40 hours after insemination. Fifty-two women received one to eight embryos (mean, 3.5 +/- 1.9), and 9 (17%) conceived. This regimen of high-dose hMG precludes the need for serum or urine luteinizing hormone monitoring, because the occurrence of spontaneous ovulation is low. It is valuable in increasing the number of fertilizable oocytes, the percentage of women undergoing embryo transfer, and compensates with multiple oocyte transfer for the high embryonic loss involved in IVF.

Adult↗

Reduced fertilization ability of zona-free hamster ova by spermatozoa from male partners of normal infertile couples.

Zona-free hamster ova were used as a penetration test system for human semen obtained from male members of infertile couples. Forty semen samples from normal infertile couples were tested and compared with penetration rates obtained with control semen samples from fertile donors. Normal penetration rates ranged between 20-100%. Out of the 40 tested males, 11 were found to have penetration rates below 10%, two had between 11 and 19%, and in the remaining 27, the rate was above 20%. Three women, whose husbands were found to be in the first group (penetration rate below 10%), conceived after artificial donor insemination within three months of treatment. Thus, the use of the human-hamster ova penetration test should be used as an additional tool in diagnosis of infertility.

Adult↗

Timing of ovulation for AIH with freeze-thawed, subfertile sperm: two case studies.

Two couples were studied in whom the male partner had become sterile due to irradiation therapy given for advanced Hodgkin's disease. Both couples achieved conception during the first and second treatment cycle, respectively, despite obviously subfertile freeze-thawed sperm. The success is attributed to optimal timing of a single homo-insemination (AIH), which was made possible because we could detect ovulation by using currently available sophisticated methods. The importance of precise timing of ovulation for insemination and the ability to retain fertilizing capacity of young males with compromised sperm, who underwent sterilizing treatment, is discussed.

Adult↗

In vitro fertilization and embryo transfer--legal and religious aspects in Israel, patient selection, and a modified technique for oocyte collection.

In vitro fertilization (IVF) and embryo transfer (ET) have recently become an accepted treatment modality for patients with mechanically caused infertility. The first series admitted to our program comprised 42 patients with confirmed mechanical infertility. The method of patient selection and the techniques of laparoscopy, follicular aspiration and oocyte recovery are described. From 26 laparoscopies, a total of 39 oocytes was recovered. Normal cleavage of 10 oocytes was obtained; they were transferred into the uterus at the 4- to 16-cell stage. One pregnancy was obtained. An IVF and ET program involves certain ethical, legal and religious questions, which have special implications in Israel: foster mothers and the use of donor sperm are forbidden. Only married couples may enter the program. Indications, methods, success rates and method failure are discussed.

Embryo Transfer↗

The pattern of luteal phase plasma progesterone and estradiol in fertile cycles.

Serum levels of progesterone and estradiol at early, middle, and late luteal phases were compared in nonfertile cycles in which only ovulation occurred to those in cycles in which ovulation was verified by conception. Two groups of patients were studied: 33 normal ovulatory women (12 of whom conceived) and 28 women who underwent induction of ovulation (8 of whom conceived). In each group, mean midluteal levels of progesterone and estradiol were essentially similar in nonfertile and fertile cycles. In fertile cycles, the late luteal levels of both steroids were higher than their respective midluteal values, whereas the late luteal values dropped in the nonfertile cycles. The late luteal rise in estradiol was found to be a more sensitive indicator of pregnancy than that of progesterone. The progesterone/estradiol ratio was stable during the luteal phase of fertile and nonfertile cycles. The ratio in spontaneous cycles was 34.4 +/- 4.7 and only 17.9 +/- 4.3 in induced cycles. This marked decrease suggests an impairment of steroid metabolism in women who require induction of ovulation.

Adult↗

In vitro effects of cannabinoids on follicular function in the rat.

delta 1-Tetrahydrocannabinol (delta 1-TCH), the major psychoactive constituent of marihuana, was found to suppress the preovulatory surge of gonadotropins and thereby to prevent ovulation in rats, rabbits and rhesus monkeys. These studies suggested that the drug acts primarily on the hypothalamus to suppress luteinizing hormone releasing hormone (LHRH) secretion. The aim of the present study was to examine the direct effect of delta 1-THC, the psychoactive constituent of marihuana and cannabidiol (CBD), one of its nonpsychoactive constituents, on preovulatory rat follicles in vitro. Both cannabinoids inhibited follicular steroidogenesis in a dose-dependent manner. Basal accumulation of progesterone (P), testosterone (T) and estradiol-17 beta (E2) was reduced up to 60% by the highest doses examined (100-200 microM). The luteinizing hormone (LH)-stimulated increase in P and T was inhibited by 75-88% by the highest doses of both cannabinoids (50-200 microM), while E2, accumulation was inhibited by only 40%. It appears that the inhibitory action of cannabinoids is exerted beyond LH binding and activation of adenylate cyclase and prior to pregnenolone formation in the gonadal steroidogenic pathway. In addition to this anti-steroidogenic effect, both cannabinoids induced resumption of meiosis in follicle-enclosed oocytes cultured in hormone-free medium; 200 microM delta 1-THC resulted in 80% maturation and CBD in 75%. It seems that the action of cannabinoids on rat follicles in vitro is unrelated to their psychotropic activity.

Adenylyl Cyclases↗

Effect of clomiphene citrate on preovulatory rat follicles in culture.

The effect of clomiphene citrate was tested on rat preovulatory follicles in culture. Clomiphene inhibited both basal and luteinizing hormone (LH)-stimulated steroid accumulation. The dose-dependent effect of clomiphene was much more pronounced on follicles cultured with LH; while 0.01 mM had no effect, 2 mM clomiphene decreased progesterone accumulation by 97%, estradiol-17 beta by 90% and testosterone by 65% (P less than 0.001). The inhibitory action of the drug was not prevented by addition of 8-Br-cAMP (1 mM) or pregnenolone (1 microgram/ml) to the culture medium. clomiphene (0.01 - 0.5 mM) induced the resumption of meiotic maturation even in LH-free medium in approximately 60% of follicle-enclosed oocytes. At the higher concentrations tested (0.1 - 0.5 mM) degenerative changes were noted in a high proportion of oocytes (30-40%). Follicles incubated for 24 h with clomiphene exhibited dose-dependent atretic-like changes. These effects of clomiphene on preovulatory follicles may account for the discrepancy between ovulation and pregnancy rates observed in women treated with clomiphene.

Animals↗

Clomiphene citrate does not modify the exaggerated thyrotrophin response to thyrotrophin-releasing hormone occurring in primary testicular failure.

Patients with primary testicular failure have increased basal TSH levels and an exaggerated TSH response to TRH in the presence of normal circulating levels of thyroid hormones. In order to evaluate it this TSH profile is an oestrogen-related phenomenon, sixteen patients with primary testicular failure were challenged with 200 micrograms TRH prior to and after the administration of clomiphene citrate. The latter was given in a dose of 100 mg/day for 4 weeks to ten patients; 200 mg/day for 4 weeks to three patients and 100 mg/day for 2 months to the final three patients. The patients demonstrated increased mean basal TSH levels with an exaggerated TSH response to TRH. Following the administration of clomiphene citrate, there were no changes in T4, T3 sephadex or total T3 levels and in basal or stimulated TSH levels. Clomiphene did produce an increase in oestradiol, testosterone, basal gonadotrophins and LH response to LHRH. Since the oestrogen antagonist, clomiphene citrate, had no effect on TSH secretion, it is unlikely that the exaggerated TSH response to TRH is mediated by oestrogens.

Adult↗

Norepinephrine in Graafian follicles is depleted by follicle-stimulating hormone.

The purpose of the present study was to measure norepinephrine (NE) in Graafian follicles and correlate changes in its concentration with circulating gonadotropins secreted endogenously or administered exogenously. Graafian follicles were removed from the ovaries of adult cycling rats. The follicles were pooled in groups of 10-13, and NE was determined by high performance liquid chromatography. Follicular NE(picograms per micrograms protein) did not change between 0900 h (3.61 +/- 0.34) and 1300 h (3.12 +/- 0.25) on proestrus, but was reduced significantly to 1.45 +/- 0.16 at 2100 h, which is 4 h after the peak of the gonadotropin surge. There was a further reduction to 0.83 +/- 0.08 in fresh corpora lutea taken on estrus at 0900 h. The decrease in follicular NE was prevented in estrous rats which were either hypophysectomized 24 h previously or treated with sodium pentobarbital at 1330 h on proestrus. To determine which pituitary hormone was responsible for follicular NE depletion, rats were injected at 0900 h on proestrus with LH (5 micrograms), FSH (20 micrograms), LH plus FSH (5 and 20 micrograms, respectively), or PRL (20 micrograms), and follicular NE was determined 4 h later. FSH reduced follicular NE significantly to 1.86 +/- 0.16 compared to both the control (3.12 +/- 0.25) and the PRL-injected group (2.92 +/- 0.32), whereas LH caused a small but nonsignificant decrease (2.49 +/- 0.2). Both LH and FSH doses used resulted in ovulation, as determined by counting tubal ova 12 h after hormonal treatment. We conclude that 1) NE in Graafian follicles is markedly reduced within 4 h after the preovulatory gonadotropin surge in the normal cycling rat; this reduction is prevented when the surge is abolished; 2) the hormone responsible for follicular NE depletion is FSH rather than LH or PRL; and 3) finally, it is suggested that follicular NE may be involved with the formation and/or functioning of the corpus luteum.

Animals↗

Dissociation between sleep-related and TRH-induced prolactin secretion in seminiferous tubule failure.

Prolactin (PRL) secretion has been measured during sleep and following TRH administration in 8 patients aged 24-39 yr with seminiferous tubule failure and 36 controls. Basal LH levels were 25.7 +/- 14.7 mIU/ml in the patients compared to 11.5 +/- 4.2 mIU/ml in the controls (p less than 0.01) Corresponding FSH levels were 26.2 +/- 10.7 mIU/ml and 5.9 +/- 2.1 mIU/ml (p less than 0.001) Mean estradiol 17B and testosterone levels were similar in the 2 groups. The mean PRL secretion during sleep was 16.5 +/- 11.7 ng/ml in the patients and not different in 11 of the controls (12.4 +/- 3.2 ng/ml). One patient had a mean nocturnal PRL concentration of 44.1 ng/ml. In both groups, the mean sleep related PRL concentration was greater than that during waking hours. The average number of peaks in the 2 groups was similar. In the same patients, the peak PRL response to TRH (200 ug IV) was 81.9 +/- 18.8 ng/ml as compared to 32.1 +/- 10.7 ng/ml in the controls (p less than 0.001). It is concluded that PRL concentrations following pharmacological stimulation are increased in seminiferous tubule failure, whereas levels are normal in relation to the physiological stimulus of sleep.

Adult↗

Prolactin response to metoclopramide and chlorpromazine in primary testicular failure and isolated gonadotrophin deficiency.

The aim of the present study was to measure the PRL response to metoclopramide (MET) and chlorpromazine (CPZ) in seventeen patients with primary testicular failure and eight patients with isolated gonadotrophin deficiency (IGD). The responses were compared with those to TRH. Basal gonadotrophins and peak responses to LHRH were increased in testicular failure and reduced in IGD. Basal PRL levels were normal in both groups of patients. However, when compared with controls, the PRL response to both MET and CPZ as well as to TRH was exaggerated in primary testicular failure, whereas the responses wee decreased in IGD. In both patient groups, as well as in the controls, the PRL response to MET exceeded that to TRH and CPZ. It is suggested that alterations in the steroid milieu are responsible for the exaggerated PRL response to MET, CPZ and TRH in primary testicular failure and the reduced response observed in IGD.

Adolescent↗

The TSH response to TRH is exaggerated in primary testicular failure and normal in the male castrate.

Basal TSH levels and the TSH response to TRH have been evaluated in 26 males aged 20-48 years with primary testicular failure, and 6 males aged 58-69 years who had been orchidectomised for prostatic carcinoma. The patients with testicular failure were sequentially challenged at 30 min intervals with iv LRH (100 microgram), TRH (200 microgram) and the dopaminergic antagonist, metoclopramide (10 mg). The castrates received a bolus of LRH and TRH given together. The responses in the 2 patient groups were compared to a group of 28 healthy male controls aged 20-40 years, who received the sequential protocol and 8 elderly controls aged 65-79 years, who were given the LRH, TRH bolus. Mean +/- SD basal TSH levels were 3.0 +/- 1.2 muU/ml in primary testicular failure and significantly greater than both control and castrate groups. The peak TSH response to TRH was 18.4 +/- 7.4 muU/ml in testicular failure and significantly greater than in the young controls, where it was 11.5 +/- 5.0 muU/ml. The peak levels in the castrates and in the elderly controls were similar to the young male controls. Total T4 and T3, as well as FTI, primary testicular failure had a reduction in their T3 resin uptake. The normal TSH profile in the castrates indicates that a testicular factor produces the exaggerated responses in primary testicular failure.

Adult↗