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Biomedical subjects

R H Asch

Publications and source records attributed to R H Asch.

At least 91 records · Page 5Linked to original sources
PubMed1989

Regulation of gonadotropin-stimulable adenylyl cyclase of the primate corpus luteum.

In an effort to understand the molecular mechanisms that control luteal function in the human and nonhuman primates, we have investigated the experimental conditions for expression of gonadotropin-induced adenylyl cyclase (AC) in membrane particles from primate corpus luteum (CL) and some of the factors modulating the enzyme activity. We also examined the usefulness of the cell-free model for studying the role of AC in the regulation of CL functions in human and nonhuman primates. Enzyme activity was dependent on guanine nucleotide and Mg ion. Dose-response curves showed that the AC activation constants for hCG was about 0.1 microgram/ml. This value did not shift after the addition of guanine nucleotide. Enzyme responsiveness to prostaglandin E2 was small and, in contrast to a number of other nonprimate species, AC from the human CL was not stimulated by catecholamines. Calcium directly inhibited responsiveness of hCG-sensitive AC; inhibition was significant at 0.5 mM CaCl2 (in the presence of 1 mM EDTA and 2 mM ATP), being 90% at 2.5 mM CaCl2. These results support the concept that Ca2+ might play a role in the regulation of gonadotropin action and life span of human CL. Changes in AC activities during luteal phase and pregnancy were similar in the CL of monkeys and humans. Thus, in both cases, maximal gonadotropin responsiveness was observed during the midluteal phase. Also, during pregnancy (term and early pregnancies), responsiveness to exogenous hCG in vitro was very low, but the enzyme was readily responsive to NaF (10 mM) and forskolin (100 microM). These activities suggest that the tissue remains functionally active during pregnancy. It is concluded that the cell-free AC system is an effective model to study the cellular mechanisms that regulate luteal function in human and nonhuman primates.

Adenylyl Cyclases↗
PubMed1989

Low incidence of sperm antibodies in men with congenital absence of the vas deferens.

The incidence of antisperm antibodies in serum and seminal fluid of 27 azoospermic men with congenital absence of the vas deferens is evaluated. The presence of antisperm antibodies was assessed using the immunobead test, the agglutination test, and immobilization test. Five patients with vasovasostomy or vasoepididymostomy attempts were included in the study and tested for the presence of antisperm antibodies. Contrary to a previous report, a low incidence (11%) of antisperm antibodies has been found in patients with congenital absence of the vas. In agreement with previous studies, in five patients who had failed vasoepididymostomy or vasovasostomy, a high incidence (71%) of antisperm antibodies was found.

Autoantibodies↗
PubMed1989

The importance of egg and sperm factors in predicting the likelihood of pregnancy from gamete intrafallopian transfer.

The relative contribution of factors affecting the probability of pregnancy from gamete intrafallopian transfer was estimated using data from 218 cycles performed in San Antonio, Texas, and Orange, California. Mature eggs, all of which contained an expanded cumulus, were subclassified according to the corona radiata; those with a starburst corona were considered the most fully mature. Sixty-two clinical pregnancies were established, representing a pregnancy rate of 28.4%. Excluding 49 cases of male factor infertility, the pregnancy rate was 34.9%. Pregnancy rates were not significantly different according to age, cause of female factor infertility, parity, duration of infertility, stimulation protocol, or estradiol level. The only variables having a strong association with pregnancy were sperm and egg parameters. Sperm motility and morphology were statistically more important than sperm density. Based on odds ratios calculated from multiple logistic analysis, pregnancy was 3.80 times more likely if three or more fully mature eggs were transferred, 0.34 times as likely if motility were less than or equal to 30%, and 0.22 times as likely if normal morphology was less than or equal to 50%, controlling for other egg and sperm factors. If all egg and sperm factors in a given cycle were unfavorable, the probability of pregnancy estimated by the logistic model was 4%, whereas if all were favorable the probability of pregnancy in that cycle was 59%.

Adult↗
PubMed1989

Immunoreactive insulin-like growth factor I in human follicular fluid.

Recent studies in laboratory animals suggest that insulin-like growth factor I (IGF-I) plays an important role in the regulation of granulosa cell function. The purpose of the present study was to investigate the presence of immunoreactive IGF-I in human follicular fluid (FF) and compare the levels of follicular IGF-I (64 follicles) with those detectable in serum (n = 19) in hyperstimulated cycles from 25 infertile patients. Also, the FF IGF-I levels were correlated to corresponding follicular volume (n = 62) and oocyte maturation (n = 37). Levels of IGF-I were determined using a specific radioimmunoassay after acidification and extraction by reversed phase chromatography. Levels of IGF-I in serum were significantly higher than those in FF (37.1 +/- 10.1 versus 24.0 +/- 9.3 nmol/l, n = 19, P less than 0.001). A positive correlation was found between follicular and serum IGF-I concentrations (r = 0.73). No significant differences were found in FF IGF-I levels derived from follicles of different size or from follicles having oocytes with different grades of maturation. These data indicate that immunoreactive IGF-I is present in human FF in nanomolar concentrations and that FF IGF-I levels correlate with those detectable in serum. The source of FF IGF-I and its regulatory role in humans remains to be elucidated.

Female↗
PubMed1989

Studies on chorionic gonadotrophin hormone in rhesus monkeys--disappearance rates.

The disappearance rate of macaque chorionic gonadotrophin (MCG) was investigated in six pregnant monkeys. The animals were hysterectomized with a rapid initial ligature of the uterine and ovarian vessels with minimal uterine manipulation. The entire procedure lasted less than 2 min. Blood samples were drawn before and after the hysterectomy (5, 20, 30, 45, 60, 90, 120 min), and MCG was measured in serum by radioimmunoassay. For all animals, a progressive decrease (rate of disappearance) of MCG values in serum was found, which appeared to follow a double exponential curve. Averaged curves produced disappearance rates of T1/2(1) = 17.2 h for the first compartment (72 h), and T1/2(2) = 87.1 h for the second compartment (156 h). The results suggest that the disappearance of MCG after interruption of pregnancy in rhesus monkey is very similar to that occurring in humans. These data demonstrate that the rhesus monkey is an excellent animal model to study the dynamics of placental hormone secretion in humans.

Abortion, Induced↗
PubMed1989

A program of oocyte donation and gamete intra-fallopian transfer.

The outcome of a series of 19 patients with premature ovarian failure (POF) undergoing gamete intra-Fallopian transfer (GIFT), utilizing donated oocytes, is described. The steroid replacement protocol consisted of the administration of increasing dosages of 17 beta-oestradiol (E2) and progesterone (P4). Hormonal replacement was maintained until day 100 of gestation. All patients underwent an evaluation cycle in which serum levels of E2 and P4 were monitored and an endometrial biopsy was performed either 7 or 11 days after initiation of progesterone administration. All cases of GIFT were performed between days 12 and 15 of the induced menstrual cycle. Of the 19 patients treated, 11 became pregnant, giving a clinical pregnancy rate of 58% (visualization of gestational sac by ultrasound). Two patients aborted between the 4th and 5th weeks of gestation. No ectopic pregnancies occurred. Three of the seven deliveries involved multiple births. Details of the circulating hormone levels and endometrial response are discussed.

Adult↗
PubMed1989

Delayed occurrence of an LH surge after HCG administration during ovarian stimulation with gonadotrophins: effect of LHRH treatment.

Previous studies have shown the appearance of a spontaneous luteinizing hormone (LH) surge after human chorionic gonadotrophin (HCG) administration in human menopausal gonadotrophin (HMG)/HCG-stimulated menstrual cycles. In this report we investigated the effect of leuprolide acetate, a long-acting luteinizing hormone releasing hormone (LHRH) agonist, on the occurrence of these post-HCG rises in serum LH. Two groups of patients were included. Group 1: 10 patients receiving HCG as a part of an HMG/HCG protocol for induction of follicular development in an IVF/GIFT program and Group II: 10 patients treated as Group I, but receiving the LHRH agonist leuprolide acetate to inhibit gonadotrophin secretion prior to and during ovarian stimulation. In Group I, none of the patients showed a surge prior to HCG administration. However, an LH surge following HCG treatment was apparent in four patients (40%). Pregnant patients (2/10) had low mean levels (less than or equal to 2.5 mIU/ml LH) in the follicular phase and showed no LH surge after HCG. In Group II, baseline levels of serum LH were reduced significantly (mean, 1.4 +/- 0.1 mIU/ml; P less than 0.001) compared to Group I. No patient showed an LH surge either before or after HCG administration and the occurrence of pregnancy was higher (6/9 transfers) than in Group I. In spite of the differences in pregnancy rates, the combined therapy versus HMG therapy showed no significant difference in number of oocytes collected or serum oestradiol levels. This suggests that high levels of serum LH, whether prior to or after HCG administration, may have a detrimental effect on the establishment of pregnancy despite adequate follicular growth.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Programming of ovarian stimulation with norethindrone acetate in IVF/GIFT cycles.

Twenty patients were given norethindrone acetate (NET) to program the initiation of controlled ovarian hyperstimulation and to coordinate follicular aspiration with surgery to obtain spermatozoa from the husband. Patients received NET, 10 mg/day orally, starting between days 2 and 4 of the cycle. The duration of NET therapy varied from 9 to 37 days. The mean time of onset of vaginal bleeding, after cessation of NET, was 2.9 +/- 0.7 days. Ovarian stimulation was carried out with a combination of a luteinizing hormone releasing hormone analog, follicle-stimulating hormone and human menopausal gonadotrophin. The day of human chorionic gonadotrophin (HCG) administration ranged from day 8 to day 15 of the cycle (10.1 +/- 1.7). On the day of HCG injection, the mean E2 level was 2188 +/- 1126. The mean number of follicles aspirated was 18.4 +/- 9.9 per cycle. The mean number of oocytes collected per cycle was 15.5 +/- 8.5. There was no correlation between duration of NET suppression and the number of days of gonadotrophin therapy needed to reach HCG administration. The large number of oocytes retrieved is probably related more with the fact that the patients represented a group with a purely male factor of infertility, than by the specific drug protocol utilized. Our results demonstrate that the ovarian response to gonadotrophin stimulation was not affected by NET administration. The main advantages of the use of this drug for cycle control are that its administration is oral, simple and inexpensive.

Adult↗
PubMed1989

Expression of insulin-like growth factor-II (IGF-II) messenger ribonucleic acid (mRNA), but not IGF-I mRNA, in human preovulatory granulosa cells.

Increasing evidence suggests that insulin-like growth factors (IGFs) play an important role as intra-ovarian regulators in several mammalian species. Recently, we and others have reported the presence of both IGF-I and IGF-II in human follicular fluid. The source of these follicular IGFs, however, has not been determined. In this study, we have evaluated the possibility that human ovarian granulosa cells are a production site of IGFs in vivo. We used cDNA probes to analyse directly IGF-I and IGF-II gene expression at the level of mRNA content in granulosa cells from preovulatory follicles of women undergoing either gamete intra-Fallopian transfer or in-vitro fertilization. Samples of granulosa cell RNA enriched for polyadenylated RNA [poly(A)+RNA] were hybridized with probes for human IGF-I, human IGF-II and human actin (as a control). Transfer blot analysis revealed that the enriched poly(A)+RNA of human granulosa cells from preovulatory follicles contained no detectable IGF-I mRNA. In contrast, three species of IGF-II mRNA of approximately 6.1, 4.9 and 2.1 kb were detected. These data suggest that IGF-II mRNA, but not IGF-I mRNA, is expressed in human granulosa cells collected immediately before ovulation. Our results support the concept that human ovarian IGF-II is produced locally and may function in an autocrine or paracrine fashion in the human ovary in vivo.

Animals↗
PubMed1989

Intrauterine insemination and controlled ovarian hyperstimulation in cycles before GIFT.

We have combined intrauterine insemination (IUI) and controlled ovarian hyperstimulation (COH), for the treatment of infertility due to different aetiologies, prior to performing GIFT. To date, we have treated 186 patients over a total of 489 cycles. The mean age of the patients was 34.1 +/- 4 years and the mean duration of infertility was 4.8 +/- 2.8 years. Follicular development was induced with human menopausal gonatrophin (HMG). Patients were monitored using serum oestradiol determinations and ovarian ultrasound. Two intrauterine inseminations were performed 12 and 36 h after HCG injection. Semen samples were prepared utilizing one of two techniques, swim-up or Percoll gradient. A total of 33 pregnancies have occurred, the gross pregnancy rate being 17.7% per patient and 6.7% per cycle. The cumulative pregnancy rate was 30%. Thirty-one pregnancies (94%) occurred within the first four cycles of treatment. During the same period of time, the pregnancy rate per cycle in patients treated with gamete intra-Fallopian transfer (GIFT) was 32.9%. Our data suggest that IUI combined with COH can result in pregnancy in a significant proportion of patients, but that the efficiency per cycle of the technique is significantly lower than GIFT.

Adult↗
PubMed1989

Changes in adenylyl cyclase activity of the human and nonhuman primate corpus luteum during the menstrual cycle and pregnancy.

Adenylyl cyclase (AC) activity in membrane particles of corpora lutea (CL) from humans and cynomolgus monkeys was examined at various stages of the menstrual cycle and pregnancy. AC activity was monitored by the conversion of [alpha-32P]ATP into [32P]cAMP under basal conditions and in the presence of several activators: NaF (10 mmol/L) plus forskolin (100 mumol/L); hCG (10 micrograms/mL); guanyl 5'-yl-imidodiphosphate [GMP-P(NH)P; 100 mumol/L]; and hCG (10 micrograms/ml) plus GMP-P(NH)P (100 mumol/L). The groups of human CL were midluteal (n = 10), late luteal (n = 4), following cycle (old CL; n = 5), and early pregnancy (6-11 weeks; n = 10). The groups of monkey CL were early luteal (n = 4), midluteal (n = 5), and pregnancy at term (n = 3). Luteal AC activity changed significantly during the menstrual cycle. In newly (less than 48 h after ovulation) formed CL, the enzyme was unresponsive to hCG, and total AC activity, as determined by NaF plus forskolin, averaged 86.5 +/- 28.9 (+/- SE) pmol cAMP/min.mg protein. As the CL developed, AC activity increased. Thus, in the midluteal phase, maximal hCG responsiveness in the presence of guanine nucleotide was 125 +/- 27 and 232 +/- 15 pmol/min.mg in human and monkey CL, respectively. No hCG responsiveness was detected in the late luteal phase or in the old CL. Maximal AC activity was also high in the midluteal phase (382 +/- 56 and 256 +/- 28 pmol/min.mg in human and monkey CL, respectively); the activity remained fairly high during the late luteal phase and then declined to less than 100 pmol/min.mg in the follicular phase of the next cycle. During early pregnancy, luteal AC was unresponsive to hCG stimulation, yet basal levels, maximal activity, and the characteristics of stimulation by nonhormonal activators were similar, if not identical, to those at the midluteal phase of the menstrual cycle. At term pregnancy, the enzyme remained unresponsive to hCG. However, basal activity and stimulation by NaF and forskolin were remarkably elevated, being between 2- and 7-fold higher than corresponding stimulations in the midluteal phase. We conclude that 1) AC activity in human luteal membranes is highly dependent on hormonal changes and functional state of the ovary, 2) the activity of luteal AC is similar in the CL of humans and cynomolgus monkeys, and 3) the AC system in the primate CL is functionally active during and at the end of pregnancy.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Triphosphate↗
PubMed1989

Micromanipulation of sperm by a laser generated optical trap.

The force generated by the radiation pressure of a low power laser beam induces an optical trap which may be used to manipulate sperm. We studied the effect of the optical trap on sperm motility. A Nd:YAG laser beam was coupled to a conventional microscope and focused into the viewing plane by the objective lens. Sperm were caught in the trap and manipulated by a joy stick controlled motorized stage. After different exposure periods, the velocity and patterns were analysed by a computerized image processor. There were minor changes in sperm velocity when exposed to the trap for 30 seconds or less. A gradual decrease in the mean linear velocity was observed after 45 seconds of exposure. This optical micromanipulator may also be useful for studying the force generated by a single spermatozoa and evaluating the influence of drugs on motility.

Humans↗
PubMed1988

Successful gamete intrafallopian transfer following failed artificial insemination by donor: evidence for a defect in gamete transport?

Gamete intrafallopian transfer (GIFT) was offered as an alternative treatment to 48 women who failed to conceive after artificial insemination with donor semen (AID) in numerous attempts (9 to 24 cycles). The evaluation of these women showed no major cause of infertility as evidenced by normal endocrine, cervical, uterine, and tubal factor studies. Their partners were either azoospermic or severely oligoasthenospermic. During the GIFT cycle, follicular development was induced with (1) clomiphene citrate (days 3 to 7) plus human menopausal gonadotropins (hMG) from day 6 on or (2) human follicle-stimulating hormone (days 3 to 4) plus hMG (day 5 on), until ultrasound revealed 2 follicles 16 mm and serum estradiol (E2) was greater than 700 pg/ml. Human chorionic gonadotropin (hCG) 10,000 IU was administered, and 36 hours later follicular aspiration was performed. One to three oocytes and 100,000 motile sperm were transferred to each fallopian tube through the fimbria via laparoscopy or minilaparotomy. Twenty-seven clinical pregnancies were achieved (56%) per GIFT cycle. Eight miscarriages occurred during the first trimester (29% of all pregnancies), whereas no ectopic pregnancies were observed. These data conclusively show the value of the GIFT procedure in the treatment of cases with failed AID.

Adult↗
PubMed1988

Tubal embryo transfer as a treatment for infertility due to male factor.

Transvaginal follicular aspiration (TVA) with ultrasonically guided needles allows the transfer of in vitro generated embryos to the fallopian tubes (TET), performing only one surgical procedure in the process. Up to now, this approach has been used to treat 16 couples with infertility due to severe male factor. Follicular development was induced with a combination of clomiphene citrate and human menopausal gonadotropin (hMG) or follicle-stimulating hormone and hMG. Follicles were aspirated by TVA 36 hours after an injection of human chorionic gonadotropin 10,000 IU intramuscularly. A total of 169 oocytes were recovered (10.5 +/- 6.9 X +/- SD) from the 16 patients. There was failure of fertilization in 6 cases. In the remaining 10, a TET was performed 44 to 50 hours after TVA, utilizing embryos at the pronuclear stage. Six pregnancies resulted from the 10 transfers. This technique combines the advantages of proof of fertilization with a more adequate tubal embryo development and entrance to the uterine cavity that may determine and increase chance of implantation.

Adult↗
PubMed1988

Assessment of serum luteinizing hormone during ovarian stimulation with gonadotrophins.

An immunoradiometric assay (IRMA), using monoclonal antibodies with high affinity for human luteinizing hormone (HLH), was evaluated for quantitative measurement of serum LH after human chorionic gonadotrophin (HCG) administration in patients undergoing stimulation of multiple follicular development. Compared to a radioimmunoassay (RIA) commonly used to monitor serum LH, LH IRMA was more effective by several orders of magnitude in discriminating between HLH and HCG and showed no cross-reactivity at HCG concentrations normally found in serum after hormone treatment. Assays of serum samples obtained from 10 patients receiving HCG as part of an HMG/HCG protocol to induce ovulation for IVF/GIFT also demonstrated that RIA values were greatly affected by exogenous HCG. It was estimated that 17-32% of serum HCG was measured as serum LH in RIA. In contrast, determinations of serum LH by IRMA was not biased by exogenous HCG. Data from IRMA indicated that eight of the 10 patients showed a significant rise in LH secretion, relative to mean baselines, at either 12 or 36 h after administration. In one patient the rise had already occurred before HCG administration. When an LH rise occurred, either before or after HCG injection, mean values were 2- to 9-fold higher than those of baseline levels. Assuming that LH rises greater than 12 mIU/ml may relate to an endogenous surge of LH, none of the patients showed a surge prior to HCG administration. On the contrary, the occurrence of an 'LH surge' after HCG was apparent in four patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
PubMed1988

The GIFT experience: an evaluation of the outcome of 115 cases.

The outcome of a series of 115 patients undergoing GIFT by minilaparotomy is described, their duration of infertility ranging between 3 and 19 years. Ovarian stimulation was carried out using clomiphene from day 3 and HMG from day 6, and HCG was used to induce follicular maturation. A maximum of four oocytes, two per oviduct with 100,000 spermatozoa, were replaced. Thirty-six pregnancies were established. The highest incidence of pregnancy was obtained in cases of unexplained infertility (42%) and endometriosis (28%), and the lowest with male factors (13%). The most mature oocytes gave the best results. There were eleven miscarriages (30.5%) and two ectopic pregnancies (5.5%). Eleven of the 23 deliveries involved multiple births.

Adult↗
PubMed1988

The role of pre-ovulatory progesterone in the midcycle gonadotrophin surge, ovulation and subsequent luteal phase: studies with RU486 in rhesus monkeys.

Conflicting evidence exists on the possible physiological role of progesterone in the regulation of the midcycle surge of gonadotrophins during the normal primate menstrual cycle. We designed the present study based on the availability of a potent antiprogesterone, RU486, that acts by binding to the progesterone receptor without inducing progestational activity. Regularly cycling rhesus monkeys received daily administration of RU486, 10 mg orally (n = 8) or vehicle (n = 5) from the day of the menstrual cycle in which serum oestradiol was 130 pg/ml or more, and a laparoscopy revealed the presence of a dominant follicle. While vehicle administration did not affect the normal ovulatory pattern nor the hormonal milieu of the menstrual cycles, RU486 induced marked aberrations during the treated cycles. Delay of ovulation with a normal subsequent luteal phase was observed in three animals. Three animals remained anovulatory until the following cycle and two animals that ovulated on days 14 and 16 of the treated cycles had short luteal phases. Analysis of daily FSH, LH, oestradiol and progesterone revealed that the administration of RU486 disrupted the midcycle pattern of gonadotrophins by disrupting them after the surge was initiated. Oestradiol surges were not different from controls and in all animals the ascendant levels of progesterone were interrupted by the administration of the antiprogesterone. This study clearly shows that the pre-ovulatory administration of RU486, a potent antiprogesterone, alters pre-ovulatory gonadotrophin secretion, inducing different degrees of menstrual irregularities such as anovulation, delayed ovulations and short luteal phases.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗