PubMed Health⌕ Search

Biomedical subjects

J Itskovitz

Publications and source records attributed to J Itskovitz.

At least 37 records · Page 2Linked to original sources

Hemodynamic evaluation of the female pelvic vessels using a high-frequency transvaginal image-directed Doppler system.

Perfusion characteristics of the female pelvic vessels were studied by a high-frequency transvaginal image-directed Doppler system. A 5-MHz Doppler transducer was coupled to a 6.5-MHz probe especially designed for intravaginal use. Distinct patterns of flow velocity waveforms were obtained from the ascending branch of the uterine artery, before and during pregnancy. A gradual increase in diastolic flow throughout gestation was observed, consistent with a decrease in vessel resistance. Flow velocity profiles in the ovarian artery were sampled from the infundibulo-pelvic ligament. Only limited diastolic flow could be detected in either ovary during the follicular phase of the cycle. In the luteal phase there was a marked increase in this flow but only in the ovary containing the corpus luteum. In early pregnancy the high diastolic flow was maintained or even increased, consistent with a low arterial resistance. High image resolution and a higher frequency Doppler transducer increase the usefulness of this technique in the hemodynamic evaluation of the female pelvic vessels.

Blood Flow Velocity↗

Changes in uterine blood flow during human pregnancy.

A transvaginal duplex Doppler ultrasonography system was used to measure blood flow characteristics in the ascending uterine artery before and during pregnancy. The system uses a 5 MHz Doppler transducer coupled to a 6.5 MHz imaging probe. There was a steady increase in volume flow rate in the left ascending uterine artery from a mean of 94.5 ml/min before pregnancy to a mean of 342 ml/min in late gestation (reflecting a 3.5-fold increase). With the assumption of equal flow on both uterine arteries, the fraction of the cardiac output that is distributed to these vessels was calculated to be 3.5% in early pregnancy and to reach 12% near term. The mean diameter of this vessel in the nonpregnant state was 1.6 mm, increasing to 3.7 mm toward term. The resistance to flow, expressed as the peak systolic to end-diastolic flow velocity ratio, declined from a mean of 5.3 in the nonpregnant state to a mean of 2.3 near term. These changes reflect the perpetual growth and development of the uteroplacental circulation, which provides the metabolic demands of the growing fetus throughout gestation.

Arteries↗

Human sperm and hamster oocyte interaction: a model system to assess sperm entry into the oocyte after partial zona dissection.

A model system of hamster oocyte and human sperm interaction was used to assess sperm entry into the perivitelline space after partial zona dissection. The procedure of zona dissection was standardized by creating slits which included one fourth, one eighth, one eighth X 2, or one sixteenth of the zonal circumference. Manipulated eggs were allowed to interact with 1 X 10(6) sperm/mL for 3 hours. A single large or medium slit was equally effective in permitting sperm entry into 46% and 47% of the manipulated eggs, respectively. However, the longer slit doubled the average number of sperm detected in the perivitelline space. A second medium-sized slit increased the rate of sperm entry into the perivitelline space to 76%, but the incidence of damaged oocytes also increased. A small slit did not permit sperm entry into any of the manipulated oocytes. This heterologous system of gamete interaction provides a model to evaluate requirements for successful partial zona dissection or other related procedures for assisted fertilization in the human.

Animals↗

The physical and mental development of co-sibs surviving selective reduction of multifetal pregnancies.

Fetal reduction in humans is still controversial and considered exploratory. The medical, legal and ethical issues involved have been widely discussed, yet, the long term effects on the surviving co-sibs have not been documented. We report on the psychomotor and physical development of seven children born following fetal reduction in three women, initially bearing 13 fetuses altogether. To these children we matched controls for birth weight, gestational age, sex, mode of delivery, parity, age at examination and mother's age and education. The children's age at evaluation varied between 12.5 and 38 months. It was found that the mental and physical indices of these children did not differ from their matched controls. It is our belief that reduction of pregnancies of high fetal order into pregnancies of low fetal order is medically acceptable.

Abortion, Incomplete↗

Serum follicle-stimulating hormone inhibition is a marker for preovulatory oocytes in in-vitro fertilization and embryo transfer.

A retrospective analysis was performed on 64 cycles stimulated with human menopausal gonadotrophin and/or pure follicle-stimulating hormone (FSH) and oestrogen (E2) levels. The increase in serum E2 on the day of HCG administration did not correlate (r = 0.05) with the number of preovulatory oocytes (preovs) or with an increase or decrease in serum FSH (r = 0.31). However, the change in serum FSH showed a significant correlation with the number of preovs (r = -0.95, P = 0.013). The probability of obtaining two or more preovs was relatively greater (1.47x) than that of other IVF patients, when there was a drop in FSH of 5% on the day of human chorionic gonadotrophin administration.

Chorionic Gonadotropin↗

Spontaneous luteinizing hormone (LH) surges are associated with more rapidly increasing estradiol (E2) and follicle stimulating hormone (FSH) in in vitro fertilization and embryo transfer.

In a retrospective analysis of 64 patients stimulated with human menopausal gonadotropin (hMG) and/or pure follicle stimulating hormone (FSH); 35 cycles with spontaneous luteinizing hormone (LH) surges were compared with 29 control cycles with respect to serum FSH and estradiol (E2) levels drawn on the day prior to and the day of human chorionic gonadotropin (hCG), approximately 16 hr after gonadotropin stimulation. FSH decreased significantly (P less than 0.05) in control cycles where two or more preovulatory oocytes (preovs) were obtained, in contrast to cycles with a spontaneous LH surge, where FSH increased irrespective of the number of preovs. The E2 increase in the LH surge cycles was significantly higher (P less than 0.05) than in the control cycles. However, the increase in E2 did not correlate with the change in FSH levels or with the number of preovs.

Chorionic Gonadotropin↗

Transplacental passage of a progesterone antagonist in monkeys.

The progesterone antagonist RU 486 dramatically increases myometrial contractility of the pregnant uterus, making it a potential adjunctive therapy for labor induction or therapeutic pregnancy termination. Sixteen female cynomolgus monkeys were studied during the second or third trimester of pregnancy. Hysterotomies were performed with the animals under anesthesia, providing access to the intact placental vasculature. RU 486 (25 mg) was injected intravenously into the mothers. Serial blood samples were drawn from the maternal and fetal-placental compartments for a period of 2 hours. RU 486 achieved a gradient equilibrium between the maternal and fetal-placental circulation within 5 minutes, suggesting free passage by simple diffusion. The clearance kinetics of immunoreactive RU 486 are consistent with an open three-compartment system in mother and fetus. The fetal-placental index decreased from 31.2% to 17.8% between the second and the third trimester of pregnancy. There was no acute toxicity of the RU 486 noticed during the experimental course.

Animals↗

Endocrine basis for the initiation, maintenance and termination of pregnancy in humans.

Channels of hormonal communication between the embryo and the mother are established early in the conceptual process. The preimplantation embryo exerts local uterine and systemic effects on the maternal organism to provide a suitable environment for embryonic development, to enable the development of a receptive endometrium for implantation, and to maintain corpus luteum function. In primates, implantation can be induced with progesterone alone if the proliferative effects of estrogens on the endometrium have already been achieved; estrogens may have a priming effect for progesterone on the endometrium, but it is not obligatory for implantation. Progesterone secretion from the corpus luteum is essential for the maintenance of early pregnancy until the placenta takes over the major role of steroidogenesis. This luteo-placental shift is completed at about the 50th day of human gestation. Withdrawal of progesterone effects by the administration of the competitive progesterone antagonist, RU 486, within 24 days after conception will terminate 85% of human pregnancies. Other nonsteroidal functions of the corpus luteum have been recently suggested. Relaxin and prorenin are peptides secreted by corpus luteum of pregnancy but their role remains putative at the present time.

Abortion, Spontaneous↗

The ovarian prorenin-angiotensin system. Lessons from IVF.

Recent evidence suggests that prorenin and other active components of the renin-angiotensin system may be linked to ovarian physiology. Prorenin, the inactive form of the enzymatically active renin, is present in the fluid of mature human ovarian follicles in concentrations more than 10 times higher than that found in the plasma of women undergoing ovarian stimulation. Only 1% of the renin in follicular fluid is in active form. Concentrations of prorenin in fluid of immature follicles are lower than levels detected in concomitantly aspirated mature follicles. Study of prorenin levels disclosed a positive correlation to testosterone and E2 in fluids of mature follicles. Plasma prorenin increases about twofold at midcycle at the time of the LH surge; the peak of prorenin is sustained for about 40 hours. In patients undergoing ovarian stimulation for IVF, hCG administration results in much higher plasma prorenin levels and the height of prorenin response is directly related to the number of mature follicles. It peaked 4 to 6 days after hCG injection and then fell, close to baseline, by about 12 days after hCG administration. Examination of the time course of hormonal changes in response to hCG revealed a temporal relationship between prorenin and both plasma E2 and progesterone. In women who conceived, prorenin began to rise again on days 8 to 12 after embryo transfer when endogenous hCG was detected in the blood. No such changes in prorenin occurred in women with ovarian failure who conceived after transfer of a donor egg. These findings indicate that prorenin is produced by the mature follicle and the corpus luteum in response to LH/hCG. Since angiotensin II affects intracellular calcium and phospholipase activity, there are many potential roles for prorenin via angiotensin II action. Putative actions of the ovarian renin system may include control of oocyte maturation, ovulation, ovarian blood flow, and ovarian steroid biosynthesis. Future work to elucidate the function of this new renin system may have relevance to many basic and clinical aspects of human reproduction.

Enzyme Precursors↗

Reduction of the number of embryos in a multiple pregnancy: quintuplet to triplet.

The technique for reduction of the number of embryos was applied in a patient who conceived following IVF and transfer of six embryos. On the 10th week of gestation, the number of embryos was reduced from five to three by an U/S-guided intra-uterine procedure. Two healthy girls and a boy were delivered in the 36th week by cesarean section. No trace of the other two fetuses was found. The moral and technical aspects of partial preventive termination of multiple pregnancy are discussed.

Abortion, Induced↗

Characterizing pituitary response to a gonadotropin-releasing hormone (GnRH) antagonist in monkeys: tonic follicle-stimulating hormone/luteinizing hormone secretion versus acute GnRH challenge tests before, during, and after treatment.

Pituitary sensitivity to a gonadotropin-releasing hormone (GnRH) challenge test before, during, and after GnRH antagonist administration was compared in four ovariectomized female monkeys receiving GnRH antagonist intramuscularly (IM) at increasing doses of 0.3, 1.0, and 3.0 mg/kg/day over 9 days. Three days before and 3 days after treatment, monkeys received vehicle alone. On experiment days 4, 7, 10, 13, and 16, 100 micrograms of GnRH was administered intravenously (IV) and blood drawn at 0 and 30 minutes. Before treatment, tonic follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were 248 +/- 105 and 178 +/- 31 ng/ml, respectively; after 0.3 mg/kg/day of GnRH antagonist, FSH and LH decreased to 30 +/- 6 and 41 +/- 4 ng/ml, respectively. After treatment with either 1 mg/kg/day or 3 mg/kg/day of GnRH antagonist, both gonadotropins were undetectable in serum. Monkeys with lower initial levels of gonadotropins were suppressed by 48 hours after GnRH antagonist, while those with higher tonic gonadotropins were suppressed 6 days later (FSH: r = 0.992; LH: r = 0.833). The data show that initial physiologic status is predictive of the rapidity of the suppression response induced by a GnRH antagonist and that, after achieving pituitary suppression, responsivity to an IV GnRH challenge test may be restored before normal tonic FSH/LH secretion is regained.

Animals↗

Plasma prorenin response to human chorionic gonadotropin in ovarian-hyperstimulated women: correlation with the number of ovarian follicles and steroid hormone concentrations.

Plasma prorenin and active renin were measured before and after human chorionic gonadotropin (hCG) administration in two groups of patients undergoing ovarian stimulation for 4-6 days with follicle-stimulating hormone alone or in combination with luteinizing hormone, for in vitro fertilization. Baseline total plasma renin (prorenin plus active renin; n = 12) averaged 25 +/- 8 ng/ml per hr (mean +/- SD). Total renin did not change during ovarian stimulation but it increased to 46 +/- 16 ng/ml per hr (P less than 0.05) 1 or 2 days later, just before hCG administration. Thirty-six hours after hCG administration, just before laparoscopy and egg retrieval, total renin was 123 +/- 97 ng/ml per hr; a peak of 182 +/- 143 ng/ml per hr occurred 2-6 days later--i.e., during the luteal phase of the menstrual cycle. In eight of the patients who did not conceive, total renin returned to baseline 14 days after hCG administration. In four who conceived, a nadir was reached (57 +/- 13 ng/ml per hr) 8-12 days after hCG administration and then total renin increased again as the plasma beta hCG measurement began to rise. By day 16 it averaged 225 +/- 157 ng/ml per hr. In a second group of five patients active renin and prorenin were measured separately. Active renin comprised less than 20% of the total renin at all times. It was unchanged until day 4 after hCG administration and then increased significantly only when plasma progesterone was high. Thus, the initial response to hCG was entirely due to an increase in prorenin. A highly significant correlation was observed between the number of follicles and the total renin increases on the day of aspiration (r = 0.93, P less than 0.001) and at the peak (r = 0.89, P less than 0.001). After hCG administration, a temporal relationship was observed between the rise in total renin and plasma estradiol and progesterone levels. These results demonstrate that plasma prorenin increases markedly after administration of hCG and that the rise is directly related to the number of ovarian follicles and to plasma estrogen and progesterone levels. The findings suggest that prorenin is produced by the mature ovarian follicle and by the corpus luteum in response to gonadotropin stimulation.

Chorionic Gonadotropin↗

Ovarian prorenin-renin-angiotensin system.

Renin is classically considered to be an enzyme that is synthesized by the kidneys and secreted into the circulation where it affects angiotensin production. We review here recent evidence that suggests the existence of an extra-renal renin system, the ovarian prorenin-renin-angiotensin system, which may be linked to reproductive function. Prorenin, the inactive form of the enzyme renin, is present in the fluid of mature human ovarian follicles in extremely high concentrations; however, only 1 per cent of the renin in follicular fluid is in the active form. Plasma prorenin increases about 2-fold at midmenstrual cycle at the time of the LH surge, and the peak of prorenin is sustained for about 2 days. No change in plasma active renin levels occurs at this time. Administration of hCG to women whose ovaries have been stimulated with gonadotropins results in much higher plasma prorenin levels and the height of prorenin response is directly related to the number of mature follicles. Plasma prorenin also increases 10-fold during the early stages of pregnancy. It begins to rise on days 8 to 12 after embryo transfer, in parallel with the rise in endogenous hCG. The ovaries are the apparent source of the increase in plasma prorenin in early pregnancy since no such increase in prorenin occurred in a woman with ovarian failure who conceived after receiving a donor egg. These results suggest that prorenin is synthesized and secreted by the mature ovarian follicle and by the corpus luteum in response to LH/hCG. They also suggest that an ovarian renin system exists that is regulated by changes in prorenin.(ABSTRACT TRUNCATED AT 250 WORDS)

Chorionic Gonadotropin↗

Effects of cord compression on fetal blood flow distribution and O2 delivery.

We used the radionuclide microsphere technique in nine fetal lambs to examine the effect of partial cord compression on distribution of cardiac output and O2 delivery to fetal organs and venous flow patterns. With a 50% reduction in umbilical blood flow the fraction of fetal cardiac output distributed to the brain, heart, carcass, kidneys, and gastrointestinal tract increased. Pulmonary blood flow fell. O2 delivery to the brain and myocardium was maintained but was reduced to peripheral, renal, and gastrointestinal circulations. Hepatic blood flow decreased and O2 delivery fell by 75%. The proportion of umbilical venous blood passing through the ductus venosus increased from 43.9 to 71.8%. The preferential distribution of ductus venosus blood flow through the foramen ovale was enhanced (29.4 vs. 47.2%) and the proportion of O2 delivery to upper body organs derived from the ductus venosus increased (33.2 vs. 49.4%). Abdominal inferior vena caval blood flow increased, and it was also preferentially distributed through the foramen ovale (21.9 vs. 44.2%) and constituted the major fraction of the arterial blood supply to the upper body organs (16.5 vs. 36.4%). Thus cord compression modified the distribution of cardiac output and the patterns of venous returns in the fetus. This pattern of circulatory response differs from that observed with other causes of reduced O2 delivery.

Animals↗

Cardiorespiratory response to cyanide of arterial chemoreceptors in fetal lambs.

Cardiorespiratory response to the stimulation of the carotid and aortic receptors by sodium cyanide was examined in fetal lambs in utero at 0.8 (120 days) gestation. Injections of 50-400 micrograms cyanide into the inferior vena cava or the carotid artery of intact fetuses elicited bradycardia and respiratory responses that varied from a single gasp to rhythmic respiratory movements but no significant change in arterial blood pressure. Carotid sinus denervation eliminated the cardiorespiratory response to intracarotid injection of cyanide and sinoaortic denervation abolished the response to inferior vena caval injection. It is concluded that in fetal lamb in utero the aortic and carotid bodies are active, and hypoxic stimulation of these chemoreceptors results in cardiorespiratory response characterized by slowing of fetal heart rate, respiratory effort, and no consistent change in arterial blood pressure.

Animals↗