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Biomedical subjects

K S Moghissi

Publications and source records attributed to K S Moghissi.

At least 19 recordsLinked to original sources

Effects of oocyte exposure to local anesthetics on in vitro fertilization and embryo development in the mouse.

The effect on fertilization and development of local anesthetics routinely used during ultrasound-guided oocyte retrieval in women undergoing in vitro fertilization was examined in a mouse in vitro fertilization system. Mouse oocytes were exposed in vitro to lidocaine, chloroprocaine, and bupivacaine at concentrations of 0 (control), 0.01, 0.1, 1.0, 10.0, 100.0 micrograms/mL for 30 min, washed, and then inseminated. In vitro oocyte fertilization at 24 and 48 h and embryo development at 72 h were determined. Bupivacaine adversely affected mouse in vitro fertilization and embryo development only at the highest exposure concentration, 100 micrograms/mL, while lidocaine and chloroprocaine produced adverse effects at concentrations as low as 1.0 and 0.1 microgram/mL, respectively. Furthermore, an adverse dose-related effect on fertilization and embryo development was shown for lidocaine and chloroprocaine, but not for bupivacaine. These data demonstrate that the local anesthetics, lidocaine (L), chloroprocaine (C), and bupivacaine (B), adversely affect mouse in vitro fertilization and embryo development in the order of C greater than L greater than B.

Anesthetics, Local

Clinical versus subclinical varicocele: improvement in fertility after varicocelectomy.

OBJECTIVE: To assess the fertility after varicocelectomy in men with subclinical varicocele. DESIGN: We define subclinical varicocele as the varicocele detected by Doppler examination of the scrotum, in which no varicocele was found on clinical examination. Varicocelectomy was performed on subclinical varicocele, and fertility was assessed. SETTING: We reviewed the records of 54 men who underwent unilateral varicocelectomy at the Department of Urology, Wayne State University, between 1986 and 1987. PATIENTS: Records of 54 men were analyzed. Thirty-eight (70%) of the varicocele were diagnosed clinically (confirmed by Doppler examination) in group 1. In 16 (30%) men, the varicocele was diagnosed by Doppler examination only, with no varicocele detectable clinically, subclinical varicocele (group 2). RESULTS: Spermiograms improved in 76% of the patients in group 1 and in 81% of the patients in group 2. Fertility was assessed after 2 years of varicocelectomy. Eighteen (47%) of 38 patients in group 1 and 8 (50%) of 16 men in group 2 managed to impregnate their partners. Statistical analysis by chi 2 shows similar improvement in fertility potential between the two groups (P = 0.86). Multivariate repeated measure analysis showed significant improvement in sperm density (P = 0.0006) and sperm morphology (P = 0.0016) after varicocelectomy. CONCLUSIONS: These data suggest that varicocelectomy, in infertile men with subclinical varicocele, leads to fertility in 50% of the patient population as compared with 47% in clinical varicocele group. We suggest that the use of sophisticated, noninvasive techniques such as Doppler may have a place in the management of male infertility to detect subclinical varicocele.

Adult

Cocaine inhibits mating-induced, but not human chorionic gonadotropin-stimulated, ovulation in the rabbit.

The effects of cocaine on ovulation and corpus luteum function were investigated in New Zealand White rabbits. Forty females were randomly assigned to control and cocaine-treated groups. Controls were given vehicle s.c. daily for 5 days and cocaine-treated rabbits received 40 mg/kg cocaine hydrochloride s.c. daily for 5 days. One hour after the last cocaine dose, half the control and half of the cocaine-treated groups were mated with fertile males and the other half of each group received hCG i.v. Serial blood samples were obtained over 4 h on the day of mating or hCG treatment (Day 0), and then at intervals from Days 1-18. No mated, cocaine-treated rabbits ovulated, vs. 6 of 10 controls (chi-square: p = 0.01). In contrast, all animals given hCG had comparable numbers of corpora lutea (control: 7.1 +/- 0.8; cocaine: 5.7 +/- 0.8). Peak levels of benzoylecgonine (the major cocaine metabolite) occurred between 180 and 240 min after cocaine administration. In cocaine-treated animals that were mated, Day 0 serum LH (repeated measures MANOVA, p less than 0.01) and FSH (p less than 0.03) concentrations were lower than those in pregnant controls. Serum LH and FSH levels for all hCG recipients (cocaine-treated and control) did not differ. Serum prolactin concentrations in mated, pregnant rabbits were higher than in all other groups; cocaine treatment did not affect this hormone.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Histology of ovaries of female rabbits immunized with deglycosylated zona pellucida macromolecules of pigs.

Female rabbits (n = 36, 6 per group) were immunized with: (i) solubilized isolated porcine zona pellucida (SIZP), which contains ZP1, 82 kDa; ZP3 alpha, 55 kDa; and ZP3 beta, 55 kDa; (ii) a purified preparation of ZP3 alpha and ZP3 beta (ZP3); (iii) purified endo-beta-galactosidase digested glycoproteins ZP3 alpha-(EBGD) and (iv) ZP3 beta-(EBGD) (each about 30% deglycosylated); (v) chemically deglycosylated core proteins ZP3 alpha-(DG) and (vi) ZP3 beta-DG (each greater than 92% deglycosylated). Rabbits injected with saline (n = 6) or Freund's adjuvant (n = 6) served as controls. Rabbits were bled weekly to monitor titres. Every six weeks two animals from each group (n = 16) were selected for unilateral oophorectomy followed by histological examination. Sections were scored for numbers of primary, secondary and tertiary follicles. Anti-ZP3 titres developed in all treatment groups and correlated with carbohydrate content (peak per cent [125I]-labelled ZP3 binding by radioimmunoassay: SIZP 71.9 +/- 1.2, ZP3 70.0 +/- 2.5, ZP3 alpha-EBGD 60.9 +/- 5.3, ZP3 beta-EBGD 56.4 +/- 5.0, ZP3 alpha-DG 56.4 +/- 4.0, ZP3 beta-DG 53.5 +/- 4.3) (means +/- SEM). Animals immunized with SIZP, ZP3 and ZP3 beta-EBGD showed a statistically significant reduction in the number of primary, secondary and tertiary follicles compared with controls (P less than 0.01, MANOVA), whereas animals immunized with ZP3 alpha-EBGD, ZP3 alpha-DG and ZP3 beta-DG did not (P greater than 0.05, MANOVA). These results demonstrate that immunization with purified ZP3 alpha macromolecules (ZP3 alpha-EBGD, ZP3 alpha-DG) or ZP3 beta-DG does not produce histopathological changes in ovaries. Such deglycosylated ZP macromolecules represent potential target antigens for immunocontraceptive development.

Animals

Future directions in reproductive medicine.

Major advances in assisted reproductive technology and fertility enhancement in the last decade are discussed in this article. Sustained research efforts have led to refinement in in vitro fertilization and related technologies. Other therapeutic innovations such as the use of newer pharmacologic agents and surgical procedures to preserve reproduction function are highlighted. Future directions and anticipated developments are briefly reviewed.

Fertilization in Vitro

Clinical applications of gonadotropin-releasing hormones in reproductive disorders.

Gonadotropin-releasing hormone (GnRH) agonists show promise as new therapeutic agents with considerable potential for clinical applications in endocrinology, gynecology, pediatrics, and oncology. GnRH agonists are derived from GnRH. This article reviews the physiology and neuroendocrine effects of GnRH and discusses clinical applications of the native substance and its analogs.

Endocrine System Diseases

Ovulation detection.

Despite major achievements in elucidating many details of the physiologic processes of human reproduction during the past 2 decades, a simple, reliable, and inexpensive method for the prediction and detection of the time of ovulation is still not available. For clinical purposes, studies of BBT and biophysical and biochemical constituents of cervical mucus appear to be the most practical methods of ovulation detection. The development of rapid and easy-to-use urinary LH assays and steroid assay kits for measurement of urinary and salivary estrogen and progesterone or their metabolites may further improve the precision of ovulation timing.

Biopsy

Luteal phase support with hCG does not improve fecundity rate in human menopausal gonadotropin-stimulated cycles.

The luteal phase of cycles stimulated with human menopausal gonadotropins (hMG) may be characterized by aberrant hormone levels, altered endometrial development, and shortened length. Luteal phase support with supplemental progesterone or hCG has been recommended to help correct these problems and thus improve pregnancy rates, but the efficacy of such regimens is controversial. Therefore, a randomized cross-over study was performed to evaluate the effects of luteal phase hCG administration on pregnancy rates during ovulation induction with hMG. Sixty-seven infertile women were randomly assigned to either group A (N = 33) or group B (N = 34). Non-treatment cycles (no luteal phase support) were alternated with treatment cycles, in which patients received 2500 IU hCG on the third, sixth, and ninth days after the ovulatory dose of 10,000 IU hCG. Patients in group A received supplemental hCG in odd-numbered cycles, whereas group B was given luteal support in even-numbered cycles. The mean number of cycles per patient was 2.2 and 2.3 for groups A and B, respectively. Analysis of 151 cycles revealed a cycle fecundity of 0.15 for 72 hCG-supported cycles, versus 0.13 for 79 nonsupported cycles (P = not significant). Midluteal progesterone levels were significantly higher in supported (45.6 ng/mL) versus unsupported cycles (31.9 ng/mL) (P less than .001). There were no significant differences in the mean peak estradiol levels in hCG-supported versus -unsupported cycles. We conclude that hCG support of the luteal phase is not routinely warranted in hMG-stimulated cycles.

Adult

Natural family planning: looking ahead.

Natural family planning is used by a relatively small number of people worldwide. The Institute's goal is to increase the knowledge, availability, effectiveness, and acceptability of natural family planning. To do so, the Institute is conducting biomedical research in several areas including: (1) the development of a home test kit for ovulation prediction, (2) sperm-mucus interaction, (3) the mechanisms and fertility impact of lactational amenorrhea, and (4) outcome of pregnancies in natural family planning users.

Amenorrhea

Endocrine response in rabbits immunized with native versus deglycosylated porcine zona pellucida antigens.

Previous studies evaluating porcine zona pellucida antigens for immunocontraceptive purposes have in some cases revealed altered ovarian function in association with antibody response. This study was undertaken in an attempt to identify zona immunogens that do not cause adverse endocrine effects. To this end, we investigated the effects of highly purified preparations of native and deglycosylated pig zona pellucida antigens on ovarian function and immune response in the rabbit. Thirty female rabbits were immunized, 5 per group, with 100 micrograms each of either 1) SIZP, solubilized isolated zonae pellucidae; 2) ZP3, a purified porcine zona preparation containing the two principle glycoproteins, ZP3 alpha and ZP3 beta, endo-beta-galactosidase-digested ZP3 glycoproteins (approximately 30% deglycosylated) termed 3) ZP3 alpha/EBGD and 4) ZP3 beta/EBGD; and chemically deglycosylated ZP3 alpha and ZP3 beta (greater than or equal to 92% deglycosylated), termed 5) ZP3 alpha/DG and 6) ZP3 beta/DG. Rabbits injected with saline (n = 2) or Freund's adjuvant alone (n = 3) served as controls. Serum LH, FSH, estradiol, and progesterone were measured at 5-day intervals during seven 20-day cycles of hCG-induced pseudopregnancy over 42 wk. Anti-ZP3 titers, determined by RIA, developed in all treatment groups and correlated directly with carbohydrate content. Animals immunized with SIZP, ZP3, and ZP3 beta/EBGD showed a significant elevation of LH and FSH and a significant decline of peak progesterone levels by the fourth pseudopregnancy cycle. In contrast, animals immunized with ZP3 alpha/EBGD, ZP3 alpha/DG, and ZP3 beta/DG showed no significant elevations of gonadotropins and continued to display cyclic progesterone secretion in response to hCG.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Hormonal therapy before surgical treatment for uterine leiomyomas.

Use of GnRH-A offers a promising medical approach to treating uterine leiomyomas. This therapy can be useful in selected patients, preserving fertility by delaying the need for imminent surgical treatment. In selected perimenopausal women, agonist therapy may, in fact, be an alternative to surgical intervention. Shrinking the size of myomas and reducing uterine volume with these agents have been reported to control symptoms of myoma, making myomectomy or vaginal hysterectomy a safer procedure. Used preoperatively, GnRH-A therapy can also reduce the risk of surgical complications and excessive blood loss.

Antineoplastic Agents

Sequential invasive assessment of fetal renal function and the intrauterine treatment of fetal obstructive uropathies.

Persistent fetal lower urinary tract obstruction carries a very poor prognosis secondary to damaged renal capacity and oligohydramnios, with its related pulmonary hypoplasia. Several attempts in the past several years to divert urinary flow via an intrauterine shunt have generally been disappointing, primarily because of poor patient selection. In this study we report our experiences with aggressive decompression of megacystis in 11 patients, the value in selected cases of sequential evaluations of fetal urine biochemistry, and the success of intrauterine bladder shunting procedures in appropriately chosen patients. Our data suggest that a single fetal urine determination may be insufficient to declare irreversible damage. Following decompression, improvement in urine biochemistry or its lack may be more likely representative of ultimate outcome. Decompression by either needle aspiration or intrauterine shunting is warranted in carefully selected cases and can save fetuses that are otherwise very likely doomed.

Female

Determinants of parental decisions to abort for chromosome abnormalities.

Parental decisions concerning the continuation of pregnancy following prenatal detection of abnormal chromosomes were evaluated for 80 patients whose diagnosis and prenatal counselling were performed in our centre. Twenty-two anomalies were diagnosed by chorionic villus sampling (CVS) and 58 by amniocentesis. The severity of the chromosome anomaly and associated ultrasound findings in the first vs. second trimester were correlated with patients' decisions. No difference was found in the likelihood of parental decisions to interrupt or continue a pregnancy between CVS and amniocentesis for either the 'severe' or the 'questionable' group of chromosome anomalies. Ninety-three per cent of patients with severe prognosis and 27 per cent with questionable prognosis opted for pregnancy termination (p less than 0.0001). The association of ultrasound anomalies and termination was highly significant (p less than 0.001). The severity of the chromosome anomaly, and, to a lesser extent, the visualization of anomalies on ultrasound were the major determinants of parental decisions to terminate the pregnancy. The diagnosis of an anomaly in the first trimester was no more likely ito lead to a termination of pregnancy than in the second trimester.

Abortion, Therapeutic

Variation of movement characteristics with washing and capacitation of spermatozoa. II. Multivariate statistical analysis and prediction of sperm penetrating ability.

Fifty semen samples were studied by computer-assisted semen analysis before testing in the sperm penetration assay (SPA). Twenty-one concentration and movement measurements were obtained from each sample on sperm in semen, after washing and swim-up, and again after an 18-hour capacitation period. Discriminant analysis was then used to define a function from these measurements that would classify the SPA results as above or below a 10% penetration rate. A significant function was identified using the following variables: sperm concentration and motility in semen, and mean curvilinear velocity, linearity, and amplitude of lateral head displacement of washed sperm. Movement measurements of capacitated spermatozoa were not useful predictors in this analysis. The overall accuracy of this function for predicting SPA results was 72%. These findings demonstrate that computer-derived measurements of sperm movement provide biologically useful information regarding sperm function, and, in addition, emphasize the importance of multivariate techniques in the analysis and description of human sperm motion.

Analysis of Variance