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Biomedical subjects

D Navot

Publications and source records attributed to D Navot.

At least 91 records · Page 5Linked to original sources

Advanced secretory changes in the proliferative human endometrial epithelium following clomiphene citrate treatment.

In an effort to characterize the effect of clomiphene citrate (CC) on the human endometrium, we took biopsy specimens of the endometrium 24 to 48 hours after CC treatment (100 to 250 mg/day for 5 consecutive days). Nineteen biopsy specimens were taken from 19 patients. Fifteen of the patients suffered from anovulatory infertility associated with oligomenorrhea or normal cycle length. The other four patients were amenorrheic, two in association with hypogonadotropic hypogonadism and two with hypergonadotropic hypogonadism. The histopathology of all samples was evaluated with the use of light microscopy, including periodic acid-Schiff (PAS) and PAS-diastase staining for glycogen demonstration. All samples were also examined with the use of scanning electron microscopy (SEM). Serum levels of estradiol (E2), progesterone (P), luteinizing hormone, and follicle-stimulating hormone were determined on the day of biopsy. In 10 of the 19 biopsy specimens, local or diffuse signs of early secretory events were demonstrated by the presence of subnuclear vacuolization and glycogen in the glandular epithelial cells. SEM corroborated these findings of advanced secretory changes by demonstrating apical protrusions at luminal epithelial cells and secretory products within the glands' openings. The E2 levels ranged between 110 and 1500 pg/ml (mean, 371 pg/ml) and P levels were either undetectable or less than 1.1 ng/ml. The two patients with hypogonadotropic hypogonadism both exhibited the same phenomena; those with primary ovarian failure had atrophic endometrium even after high-dose CC treatment. This observation, together with the low P levels detected, indicating the lack of luteinization, suggests a possible direct effect of CC on the endometrium.(ABSTRACT TRUNCATED AT 250 WORDS)

Anovulation↗

Fetal heart rate accelerations and fetal movements in twin pregnancies.

The rate of fetal heart rate accelerations associated with fetal movements to total fetal movements of twin pregnancies was found to be significantly lower than that of pregnancies with singleton infants. The number of fetal heart rate accelerations was similar. As fetal heart rate accelerations are reflective of fetal movements, the results indicate increased fetal activity in twins that is related to an additive effect of two normally active fetuses.

Female↗

Combined 21- and 11 beta-hydroxylase deficiency in familial congenital adrenal hyperplasia.

Studies in three families (A, B, and C) revealed five patients with congenital adrenal hyperplasia (CAH) due to partial and combined 21- and 11 beta-hydroxylase deficiency. One patient (A-11 1), a 23-yr-old severely virilized chromosomal female, was reared as a male, and two females (B-11 2 and C-1) complained only of hirsutism, acne, and menstrual abnormalities. Patients A-11 2 and B-11 8 (17 1/2 and 10 yr old) were asymptomatic and detected by finding an HLA genotype identical to that of their respectively affected brother and sister. Three patients (A-11 1, A-11 2, and C-1) had moderate hypertension. In spite of the wide range of clinical manifestations, all individuals had elevated androgen levels, while cortisol secretion was severely impaired only in A-11 2. 21-Hydroxylase deficiency was diagnosed on the basis of markedly increased plasma and urinary levels of 17-hydroxyprogesterone (17-OHP) and 21-deoxycortisol and their respective urinary metabolites pregnanetriol and pregnanetriolone. PRA was elevated in three patients, while urinary aldosterone was normal or increased. 11 beta-Hydroxylase deficiency was diagnosed on the basis of increased 11-deoxycortisol and deoxycorticosterone in plasma and tetrahydro-11-deoxycortisol and deoxycorticosterone in urine, particularly after ACTH administration. In contrast to classical 11 beta-hydroxylase deficiency CAH, urinary 18-hydroxycorticosterone and 18-hydroxy-11-deoxycorticosterone were normal or elevated. The nature and mechanism of a combined enzymatic defect are unknown. The coincidental presence in a single individual of the mutant genes for both 21- and 11 beta-hydroxylase deficiency CAH is very unlikely to occur. Two alternative hypotheses may explain our findings. One is the existence of a genetically inherited abnormal (or aberrant) 11 beta-hydroxylase, whose affinity for its normal substrate is changed for an abnormal one (17-OHP). As a result, 11 beta-hydroxylation of 11-deoxycortisol is deficient while 17-OHP 11 beta-hydroxylation is markedly enhanced. Thus, both 11-deoxycortisol and 21-deoxycortisol as well as their urinary metabolites accumulate. The ability for 18-hydroxylation, however, remains normal. In this case, 21-hydroxylase is not deficient, yet 21-deoxycortisol cannot be further hydroxylated to cortisol, since this steroid is not a suitable substrate for the enzyme. Such a disorder may represent a new allelic variant of 11 beta-hydroxylase deficiency CAH, which, similar to 21-hydroxylase deficiency, is completely linked to the HLA complex.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenal Hyperplasia, Congenital↗

Effect of caffeine on human sperm penetration into zona-free hamster ova.

The effect of caffeine on spermatozoal ability to penetrate zona-free hamster ova was examined on fresh and frozen-thawed semen samples. The mean motility of 10 fresh semen samples incubated with caffeine significantly increased from 29% to 35%. Sperm penetration into zona-free hamster ova did not differ between the control group and the specimens to which caffeine was added. The same effect of caffeine on sperm motility and hamster ova penetration was noted in the frozen-thawed sperm samples. Motility was enhanced by 21%, but hamster ova penetration did not significantly change. The increase in sperm motility caused by caffeine does not change the fertilizing ability of fresh and frozen-thawed human sperm.

Animals↗

Reduced penetration of zona-free hamster ova by cryopreserved human spermatozoa.

The effect of cryopreservation on human sperm fertilizing potential was assessed by using the human sperm penetration into zona-free hamster ovum test. Semen samples from 12 fertile men were compared before and after cryopreservation for motility, sperm penetration rate, and number of sperm cells incorporated per oocyte. In fresh samples sperm concentration was 102 +/- 51 X 10(6) cells/ml, motility 66 +/- 14%, penetration rate 77.8 +/- 19%, and sperm incorporation 4.3 +/- 3.9 sperm per ovum. Frozen-thawed sperm cells showed a marked reduction of 61 +/- 21% (p less than 0.001) in motility. Penetration rate was reduced by 53 +/- 34% (p less than 0.01), and sperm incorporation dropped by 50 +/- 28% (p less than 0.05). Despite this substantial reduction in all three parameters, 75% of the samples maintained a penetration rate exceeding 14%, which is the lower limit for fertile semen. For the individual subject the decrease in sperm motility did not reflect actual fertility potential as expressed by its ability to penetrate zona-free hamster ova. These findings are related to morphological and biochemical changes in frozen-thawed semen and apparently are correlated with the decrease in pregnancy rates after cryopreservation. This test may be a valuable supplement to routine microscopic semen analysis for semen cryopreservation candidates.

Animals↗

Antepartum fetal heart rate pattern associated with major congenital malformations.

Antenatal fetal heart rate monitoring of 20 fetuses with major congenital malformations revealed loss of long-term variability in 11 (55%) and an isolated, abrupt-onset fetal heart rate deceleration in 13 (65%). In ten (50%), loss of variability coexisted with periodic fetal heart rate decelerations. These fetal heart rate changes were significantly more prevalent in the malformed group than in a control population. There was also a significantly increased incidence of fetal distress in labor and in the requirement for primary cesarean section delivery. Perinatal mortality was 75%, reflecting the lethal nature of the malformations. Loss of long-term fetal heart rate variability associated with isolated, abrupt occurrence of fetal heart rate deceleration should raise the possibility of congenital malformations in an apparently normal pregnancy.

Abnormalities, Multiple↗

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↗

Diagnosis of fetal jeopardy by assessment of fetal movement and heart rate accelerations.

Assessment of fetal movements by the pregnant woman is a useful screening test in high and low risk pregnancies. Decreased fetal movements to less than 10 during 12 hours is an expression of fetal distress, and may be the first alert of impending fetal death. Pregnancies with decreased fetal activity comprise a very high risk group, however some normal pregnancies are still included. With the object of excluding false positive observations, fetal heart rate monitoring was added as a secondary screening procedure. There were seventy patients with diminished fetal movements, 28 had two or more fetal heart rate accelerations in twenty minutes, while 42 had one or no accelerations in twenty minutes. In the former group there was no perinatal mortality, while in the latter, 18 (42.8%) succumbed either pre- (16.6%) or post-natally (26.2%). It is suggested that daily fetal movement recording should be the primary screening test for pregnant women. Whenever reduced fetal activity to less than 10 in 12 hours is perceived, fetal heart rate should be monitored. The existence of at least two accelerations in 20 minutes excludes all the fetuses prone to disaster. One or no accelerations in 20 minutes when coexisting with decreased fetal movements, have a very grave prognosis, and interruption of pregnancy should be considered.

Female↗