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Biomedical subjects

J Dor

Publications and source records attributed to J Dor.

At least 19 recordsLinked to original sources
PubMed1995

Sperm capacitation in humans is transient and correlates with chemotactic responsiveness to follicular factors.

In humans, only a small fraction (2-12%) of a sperm population can respond by chemoattraction to follicular factors. This recent finding led to the hypothesis that chemotaxis provides a mechanism for selective recruitment of functionally mature spermatozoa (i.e., of capacitated spermatozoa, which possess the potential to undergo the acrosome reaction and fertilize the egg). This study aimed to examine this possibility. Capacitated spermatozoa were identified by their ability to undergo the acrosome reaction upon stimulation with phorbol 12-myristate 13-acetate. Under capacitating conditions, only a small portion (2-14%) of the spermatozoa were found to be capacitated. The spermatozoa were then separated according to their chemotactic activity, which resulted in a subpopulation enriched with chemotactically responsive spermatozoa and a subpopulation depleted of such spermatozoa. The level of capacitated spermatozoa in the former was approximately 13-fold higher than that in the latter. The capacitated state was temporary (50 min < life span < 240 min), and it was synchronous with the chemotactic activity. A continuous process of replacement of capacitated/chemotactic spermatozoa within a sperm population was observed. Spermatozoa that had stopped being capacitated did not become capacitated again, which indicates that the capacitated state is acquired only once in a sperm's lifetime. A total sperm population depleted of capacitated spermatozoa stopped being chemotactic. When capacitated spermatozoa reappeared, chemotactic activity was restored. These observations suggest that spermatozoa acquire their chemotactic responsiveness as part of the capacitation process and lose this responsiveness when the capacitated state is terminated. We suggest that the role of sperm chemotaxis in sperm-egg interaction in vivo may indeed be selective recruitment of capacitated spermatozoa for fertilizing the egg.

Acrosome↗
PubMed1995

Endometrial blood flow response to hormone replacement therapy in women with premature ovarian failure: a transvaginal Doppler study.

OBJECTIVE: To evaluate the endometrial blood flow response to hormone replacement therapy (HRT) in women with premature ovarian failure who plan to enter an oocyte donation program. DESIGN: Transvaginal color Doppler ultrasound examinations were performed in women with ovarian failure before and during a cycle of standard HRT and in those with normal menstrual cycles. Blood flow response was assessed by visualization of arterial wave forms in the endometrial region. The transvaginal color flow mapping system was used. Resistance indexes were calculated for analysis and correlated with plasma E2 and P concentrations. PATIENTS: Eighteen women with ovarian failure (study group), and 12 volunteers with normal ovarian cycles (control group). RESULTS: Data for resistance indexes were divided into five phases according to the day of hormonal cycle: 0, pretreatment phase; I, early follicular phase (days 5 to 7); II, late follicular phase (days 11 to 13); III, early luteal phase (days 17 to 21); and IV, late luteal phase (days 23 to 25). All women with ovarian failure demonstrated continuous forward end-diastolic flow velocities at phase I, whereas none showed this pattern during the pretreatment period (phase 0). Women with ovarian failure in the early follicular phase had a significantly higher resistance index (0.85 +/- 0.1; mean +/- SD) than that in the late follicular phase (0.57 +/- 0.1), and the resistance index in the early luteal phase (0.67 +/- 0.1) was significantly higher than that of the late follicular phase. There was no difference in the resistance index between early and late luteal phases. A similar pattern of lower resistance index around midcycle was observed in the control group. However, a comparison of the resistance indexes between ovarian failure and control patients revealed a significant difference between values in the early follicular phase only (0.85 +/- 0.1 versus 0.68 +/- 0.1). In the late follicular phase and during the entire luteal phase, the mean resistance index did not differ between the study and control groups. CONCLUSIONS: The observed data suggest that standard HRT in women with premature ovarian failure enables restoration of endometrial blood flow to normal. This may imply uterine receptivity for oocyte donation.

Diastole↗
PubMed1995

Adjuvant growth hormone therapy in poor responders to in-vitro fertilization: a prospective randomized placebo-controlled double-blind study.

The objective of the study was to assess the effect of growth hormone (GH) supplementation to a combined gonadotrophin-releasing hormone agonist/human menopausal gonadotrophin (GnRHa/HMG) treatment protocol on ovarian response in 'poor responders' undergoing in-vitro fertilization (IVF). GH or a placebo were administered in a prospective randomized double-blind manner. A total of 14 poor-responder patients (oestradiol < 500 pg/ml, less than three oocytes retrieved in two previous IVF cycles) were randomly allocated to a combined treatment of either GnRHa/HMG/GH (18 IU on alternate days, total dose 72 IU) or GnRHa/HMG placebo. No difference was found between the study and control groups in the number of HMG ampoules used, the number of follicles (> 14 mm) and serum oestradiol concentrations on the day of administration of human chorionic gonadotrophin (HCG), the number of oocytes retrieved and fertilized, and the number of embryos transferred. The GH group (n = 7) did not show a better ovulatory response in the study cycles; mean +/- SD serum oestradiol on day of HCG 411 +/- 124 versus 493 +/- 291 pg/ml, aspirated oocytes 2.2 +/- 1.5 versus 1.9 +/- 2.0. Interestingly, when the above results for the placebo group were compared with their previous cycles (serum oestradiol 403 +/- 231 pg/ml; 0.4 +/- 0.5 aspirated oocytes), a non-specific effect was found. Follicular recruitment, oestradiol secretion by mature follicles and the number of oocytes retrieved in poor responders were not improved by GH supplementation.

Adult↗
PubMed1995

A cytosolic protein tyrosine kinase activity is induced by follicle stimulating hormone and insulin like growth factor-I in human granulosa cells.

Follicle stimulating hormone (FSH) induces estradiol (E2) production in rat, porcine and human granulosa cells with a concomitant increase in cAMP. In human granulosa cells insulin like growth factor-I (IGF-I) induces E2 production without cAMP accumulation. In the current study we report that IGF-I and FSH effects on aromatase activity both involve activation of a cytosolic soluble protein tyrosine kinase (CytPTK). This FSH and IGF-I stimulated CytPTK activity was blocked by AG-82 (a tyrosine kinase inhibitor) and by staurosporine (STS) (a non specific protein kinase inhibitor) at concentrations which inhibited E2 production. These new findings strengthen the concept of fail-safe mechanism in E2 production in human granulosa cells by an involvement of tyrosine kinase(s) activity downstream of cAMP formation and protein kinase A (PKA) activation.

Alkaloids↗
PubMed1995

Polycystic ovarian syndrome: pregnancy outcome following in vitro fertilization-embryo transfer.

A retrospective study of a series of pregnant patients with polycystic ovarian syndrome following in vitro fertilization-embryo transfer was conducted to assess the outcome after ovarian stimulation by different protocols. Forty-one pregnancies were evaluated in patients with polycystic ovarian syndrome who conceived during in vitro fertilization-embryo transfer using human menopausal gonadotropin alone (17 pregnancies), or combined with gonadotropin releasing hormone analog (24 pregnancies). The demographic data of in vitro fertilization-embryo transfer cycles and pregnancy outcome were compared with the use of Student's t-test, the Mann-Whitney U test and Fisher's exact test, where appropriate. Among the pregnancies that were initiated following treatment, the protocol of the combination of the two was not associated with a higher rate of deliveries. The rate of first-trimester abortions was not statistically different between the two groups. These results suggest that the combined use of gonadotropin releasing hormone agonist and human menopausal gonadotropin in an in vitro fertilization program may not have beneficial effects on pregnancy outcome in patients with polycystic ovarian syndrome.

Adult↗
PubMed1994

Congenital bilateral absence of vas deferens in the absence of cystic fibrosis.

The high frequency of mutations in the cystic fibrosis gene in patients with congenital bilateral absence of vas deferens (CBAVD) has raised the question whether all of them have a genital form of cystic fibrosis. We investigated 47 CBAVD patients by ultrasonography, 10 (21%) had renal malformations and 37 (79%) did not. In the former group, no cystic fibrosis mutations were found and sweat chloride concentrations were normal. In the latter group, 18 patients (49%) carried at least one cystic fibrosis mutation and sweat chloride was high in 17 of 26 tested (65%). Our findings suggest that CBAVD patients with renal malformations do not necessarily have cystic fibrosis.

Cystic Fibrosis↗
PubMed1994

Hormonal treatment in pregnancy: a possible risk factor for neuroblastoma.

In the last 4 years, 24 cases of neuroblastoma were treated in the Pediatric Hematology-Oncology Unit at the Chaim Sheba Medical Center, 8 of whom were under 1 year of age. Four of them were the product of a pregnancy-induced or preserved by gonadotropins, clomiphene citrate, or progestational hormones. These drugs are known to produce a higher than normal level of estradiol or progesterone in the early stages of pregnancy. Our observation led to the hypothesis that high levels of progestational hormones given during pregnancy are a risk factor for neuroblastoma in infancy.

20-alpha-Dihydroprogesterone↗
PubMed1994

Complete failure of fertilization in couples with mechanical infertility: implications for subsequent in vitro fertilization cycles.

OBJECTIVE: To determine whether complete failure of fertilization of oocytes in couples with mechanical infertility during the first IVF cycle indicates a poor prognosis for subsequent IVF cycles. DESIGN: A retrospective study of 172 cycles of IVF in 50 couples with mechanical infertility and complete failure of fertilization during their first IVF trial. SETTING: In vitro fertilization unit of the Sheba Medical Center. PATIENTS: Fifty couples undergoing one to eight cycles of IVF for mechanical infertility. MAIN OUTCOME MEASURE(S): Fertilization rate of retrieved oocytes and pregnancy rate. RESULTS: Of the initial 50 couples, 44 underwent additional IVF cycles, and 43 (97.7%) achieved fertilization during the second or third cycle. Twenty-four patients conceived during the study period as a result of IVF. CONCLUSIONS: Complete failure of fertilization in couples with mechanical infertility does not necessarily persist during subsequent IVF cycles. Therefore, at least two more IVF cycles should be attempted before reverting to other therapeutic options. Complete failure of fertilization during the first cycle of IVF in couples with mechanical infertility is accompanied by a good prognosis for subsequent cycles.

Female↗
PubMed1994

How often should infertile men have intercourse to achieve conception?

OBJECTIVE: To clarify how often infertile men should have intercourse to achieve conception, the effect of sequential ejaculation on total motile sperm counts was investigated. DESIGN: Case-control study. SETTING: Infertility and IVF unit, tertiary care center. PARTICIPANTS: Five hundred seventy-six men who produced two closely spaced sequential ejaculates. MAIN OUTCOME MEASURE: The total motile sperm counts of the second ejaculates were compared with the total motile sperm counts of the first ejaculates. RESULTS: In normospermic men (n = 359), the total motile sperm counts decreased significantly from 93 (18 to 601) (median [minimum to maximum] x 10(6)) in the first ejaculate to 42 (1.2 to 387) in the second ejaculate, produced 24 hours later. In contrast to the normospermic men, in the asthenospermic group (24 hours difference, n = 81) and in both oligospermic groups, (1 to 4 hours difference, n = 27; and 24 hours difference, n = 45), there were no significant changes in the total motile sperm counts (24 [5.9 to 229] versus 30 [0.8 to 150], 6 [0.8 to 18] versus 3.6 [0.1 to 63] and 13 [2.5 to 32] versus 10 [0.1 to 66], respectively). Moreover, in both oligoasthenospermic groups (1 to 4 hours difference, n = 23; and 24 hours difference, n = 41) the total motile sperm counts increased significantly (3.2 [0.6 to 7.9] versus 8 [0.4 to 48] and 4 [0.2 to 13] versus 4 [0.1 to 101], respectively). In all groups, pooling sequential ejaculates significantly increased the total motile sperm counts, over and above that of the first ejaculate, by 49% in the normospermic group, 95% in the asthenospermic group, 67% and 75% in the oligospermic groups (1 to 4 hours and 24 hours difference, respectively), and 233% and 139% in the oligoasthenospermic groups (1 to 4 hours and 24 hours difference, respectively). CONCLUSIONS: Sequential ejaculation may overcome the impaired sperm transport causing low total motile sperm counts observed in some oligospermic and/or asthenospermic men. Most of these infertile men may significantly increase their fertility potential, assessed by the total motile sperm counts, either by pooling sequential ejaculates for IUI, GIFT, and IVF, or by having intercourse every day or even twice a day, at the time of ovulation.

Case-Control Studies↗
PubMed1994

Chemotaxis and chemokinesis of human spermatozoa to follicular factors.

Human spermatozoa accumulate in vitro in diluted follicular fluids obtained from follicles from which the eggs have been fertilized. Using capillary assays under a variety of experimental conditions (ascending or descending gradients of follicular fluid, or no gradient at all) and microscopic assays in which individual spermatozoa could be followed, we found that the sperm accumulation in follicular fluid was the result of both sperm chemotaxis and chemokinesis and eventually hyperactivation-like motility. We determined the optimal conditions for sperm accumulation, which involved sperm preincubation (possibly to induce sperm capacitation) and proper dilution of follicular fluid. In all the assays, the net accumulation was low, probably reflecting the chemotactic responsiveness of only a small fraction of the sperm population at any given time. We partially fractionated follicular fluid in a Centricon microconcentrator (Amicon, Danvers, MA) and by acetone precipitation, and found that at least one of the chemotactic factors is a small (< 10-kDa) molecule that is probably nonhydrophobic. This is the first time that sperm chemotaxis and chemokinesis in response to a follicular factor(s) in mammals has been established and has been distinguished from other processes that might cause sperm accumulation. The physiological significance of these findings is discussed.

Capillary Action↗
PubMed1994

Sequential acquisition of chemotactic responsiveness by human spermatozoa.

Recent studies have indicated that human spermatozoa respond to follicular fluid by attraction to chemotactic factor(s) in the fluid, accompanied by enhancement of motility and ultimately hyperactivation. In this study, we quantified the sperm response. We exposed spermatozoa to a gradient of a chemotactically active fraction of follicular fluid (denoted as "the attractant") and separated the spermatozoa that accumulated in the attractant and those that did not. We thus obtained two subpopulations: one enriched with chemotactically responsive spermatozoa, and one deficient in such spermatozoa. The fraction of the responsive spermatozoa out of the total sperm population was 2-12% at any measured time point. With time, the responsive spermatozoa lost their ability to be attracted, while such activity was gradually acquired by the subpopulation originally deficient in responsive spermatozoa. These results indicate that the identity of responsive spermatozoa is continuously changing. If the in vitro results are representative of the physiological conditions in vivo, they imply that the role of sperm chemotaxis combined with enhanced motility may be to select capacitated spermatozoa and bring them to the egg. Such a mechanism may, over an extended period of time, increase the prospect that an egg will meet capacitated spermatozoa as soon as it ovulates.

Cell Separation↗
PubMed1994

Induction of aromatase in human granulosa cells by both follicle stimulating hormone and insulin-like growth factor-I involves tyrosine phosphorylation.

Evaluation of the intracellular signalling mechanisms of follicle stimulating hormone (FSH) and insulin-like growth factor-I (IGF-I) was performed in luteinized and non-luteinized human granulosa cells. A severalfold increase in estradiol production from androstenedione was induced by both hormones in these cells, while only FSH led to a concomitant increase in cAMP. IGF-I bound specifically to its receptor in these cells. Specific tyrosine kinase inhibitors (tyrphostins) blocked the effects of both FSH and IGF-I on aromatase activity without altering FSH-induced cAMP accumulation. These findings demonstrate an involvement of a tyrosine kinase pathway in the intracellular signalling mechanism of the IGF-I effect on aromatase activity. Furthermore, since FSH induction of aromatase activity can be blocked by a tyrosine kinase inhibitor without affecting the level of cAMP production, it can be suggested that tyrosine kinase(s) act downstream of cAMP production and protein kinase A activation.

Adenylyl Cyclases↗
PubMed1993

Complete failure of fertilization in couples with unexplained infertility: implications for subsequent in vitro fertilization cycles.

OBJECTIVE: To determine whether complete failure of fertilization of oocytes in couples with unexplained infertility persists during subsequent in vitro fertilization (IVF) cycles. DESIGN: A retrospective study of 120 cycles of IVF in 44 couples with unexplained infertility and complete failure of fertilization during their first IVF trial. SETTING: In vitro fertilization unit of the Sheba Medical Center. PATIENTS: Forty-four couples undergoing IVF for unexplained infertility. MAIN OUTCOME MEASURE(S): Fertilization rate of retrieved oocytes and pregnancy rate. RESULTS: Of the initial 44 couples, 37 underwent additional IVF cycles and 30 (81.1%) achieved fertilization. Seven patients conceived during the study period as a result of IVF and two conceived spontaneously. CONCLUSIONS: Complete failure of fertilization does not necessarily persist during subsequent IVF cycles. Therefore, at least two more IVF cycles should be attempted before reverting to other therapeutic options. However, although fertilization can be achieved in most couples, the mean oocyte fertilization rate during subsequent cycles in this group is low. This suggests an underlying undiagnosed pathology of oocyte/sperm interaction in some of these patients.

Female↗
PubMed1993

Immunoreactive endothelins in human follicular fluid.

Endothelin levels were measured by means of [125I]endothelin-1,2,3 radioimmunoassay in the follicular fluids of 22 mature ovarian follicles of 11 patients, obtained during ovum pickup. In all but 1 of the follicles, endothelin levels were detectable and ranged between 0.2 and 3.6 pg/ml (mean 1.47 +/- 0.99). In this preliminary study, no correlation was found between follicular endothelin levels and oocyte fertilization or the hormonal ovarian response during the follicular phase.

Endothelins↗