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Biomedical subjects

Eitan Lunenfeld

Publications and source records attributed to Eitan Lunenfeld.

15 recordsLinked to original sources

Obstetric outcome of twin pregnancies conceived by in vitro fertilization and ovulation induction compared with those conceived spontaneously.

OBJECTIVE: To compare the obstetric characteristics of twin pregnancies conceived by in vitro fertilization (IVF) and ovulation induction with those conceived spontaneously. DESIGN: Case control study. SETTING: Tertiary Medical Center. PATIENTS: All twin deliveries that were achieved by IVF (n=558) and ovulation induction (n=478) from January 1988 through December 2002 were evaluated. Each group was compared with a control group that conceived spontaneously (n=3694) and was delivered during the same period. INTERVENTIONS: Ovulation induction, IVF-ET. MAIN OUTCOME MEASURES: Obstetrical complications. RESULTS: Multivariate analysis showed that patients who conceived with the assistance of IVF and ovulation induction had a significantly higher risk for gestational diabetes mellitus (odds ratio [OR]=2.41, 95% confidence interval [CI]=1.77-3.29 and OR=1.71, CI=1.2-2.42, respectively), cesarean section (OR=2.17, 95% CI=1.74-2.70 and OR=1.76, CI=1.43-2.16, respectively), and a lower gestational age at birth in the IVF group (OR=0.91, 95% CI=0.88-0.94), compared with their controls. CONCLUSIONS: After controlling for maternal age, and nulliparity we demonstrated that twin pregnancies conceived with the assistance of IVF and ovulation induction are at increased risk for gestational diabetes mellitus, and delivery by cesarean section. In addition, IVF conceived pregnancies have a lower gestational age at birth.

Adult↗

Impact of hypnosis during embryo transfer on the outcome of in vitro fertilization-embryo transfer: a case-control study.

OBJECTIVE: To investigate whether hypnosis during ET contributes to successful IVF/ET outcome. DESIGN: Case-control clinical study. SETTING: Academic Fertility and IVF Unit, Soroka Medical Center, Beer-Sheva, Israel. PATIENT(S): Infertile couples undergoing IVF. INTERVENTION(S): Ninety-eight IVF/ET cycles with hypnosis during the ET procedure were matched with 96 regular IVF/ET cycles. MAIN OUTCOME MEASURES: Comparison of clinical pregnancy and implantation rates between the two groups. RESULT(S): We obtained 52 clinical pregnancies out of 98 cycles (53.1%) with an implantation rate of 28% among hypnosis IVF/ET cycles, and 29 out of 96 (30.2%) clinical pregnancies and an implantation rate of 14.4% in the control cycles. Our overall IVF program pregnancy rate for the same period was 32.1%. Logistic regression analysis was performed emphasizing the positive contribution of hypnosis to the IVF/ET conception rates. CONCLUSION(S): This study suggests that the use of hypnosis during ET may significantly improve the IVF/ET cycle outcome in terms of increased implantation and clinical pregnancy rates. Furthermore, it seems that the patients' attitude to the treatment was more favorable.

Adult↗

Induction of IL-1, in the testes of adult mice, following subcutaneous administration of turpentine.

PROBLEM: Interleukin-1 family is present in the testicular homogenates and its cellular compartments. It has been suggested that IL-1 is involved in physiological and pathological functions of the testicular tissues. In the present study we examined the effect of acute mostly localized inflammation, using turpentine, on the expression levels of testicular IL-1 system. METHODS OF STUDY: Mice were subcutaneously injected with steam-distilled turpentine or saline (control). Three hours to 10 days following the injection, mice were killed and testis and spleen were homogenized and examined for interleukin (IL)-1alpha, IL-1beta, and IL-1 receptor antagonist (IL-1ra) levels by enzyme-linked immunosorbent assay and polymerase chain reaction. RESULTS: Subcutaneous injection of turpentine induced mice systemic inflammation, as indicated by significant increase in serum IL-1beta levels, and IL-1alpha, IL-1beta and IL-1ra in spleen homogenates. The levels of IL-1alpha, IL-1beta and IL-1ra were significantly induced in testicular homogenates of adult mice following subcutaneous injection of turpentine. The significant induction of testicular IL-1alpha was detected after 3-24 hr of turpentine injection and decreased later (after 3-10 days) to levels similar to the control. However, significant induction of testicular IL-1beta was detected only after 3-10 days of turpentine injection, and for testicular IL-1ra levels was detected after 3 hr to 6 days of turpentine injection, and after 10 days the levels were similar to the control. These results were also confirmed by mRNA expression of these factors. CONCLUSION: Our results demonstrate for the first time the distant effect of acute localized inflammation on testicular IL-1 levels. Thus, transient inflammatory response to infectious/inflammatory agents at non-testicular sites that elicit systemic IL-1 response should be considered during clinical treatment as a possible factor of male infertility.

Animals↗

Relationship between the duration of sexual abstinence and semen quality: analysis of 9,489 semen samples.

OBJECTIVE: To evaluate the relationship between duration of sexual abstinence and various characteristics of normal and subnormal semen. DESIGN: A retrospective study based on computerized data. SETTING: Fertility and IVF unit at a university medical center. PATIENT(S): Nine thousand, four hundred eighty-nine semen samples from 6,008 patients were analyzed according to the World Health Organization (WHO) manual and grouped according to sperm concentration (10(6)/mL) into severe (0.2-4 x 10(6)), moderate (>4-10 x 10(6)), and mild (>10-19.99 x 10(6)) oligozoospermia, and normozoospermia (> or =20-250 x 10(6)) groups. MAIN OUTCOME MEASURE(S): In each group mean values of semen volume, sperm concentration, percentage of motile sperm and of normal morphology (according to WHO or Kruger criteria), total sperm count, and total motile sperm count per ejaculate were related to duration of abstinence. RESULT(S): Among the 3,506 oligozoospermic samples, the peak mean sperm motility of 30.3% was observed after 1 day of abstinence. Similarly, the mean percentage of normal morphology among mild-moderate oligozoospermic samples (n = 2,260) reached peak values of 7.4%-8.6% between 0-2 days of abstinence. The 5,983 normozoospermic samples showed a significant decrease in the percentage of sperm motility and normal morphology to mean values of 33.1% and 7.0%, respectively, on days 11-14 of sexual abstinence. CONCLUSION(S): Our data challenge the role of abstinence in male infertility treatments and suggest that to present the best possible semen samples, patients with male factor infertility should collect the semen after just 1 day of sexual abstinence. Patients presenting normal sperm analysis or sperm donors for cryopreservation purposes should be advised not to exceed 10 days of sexual abstinence.

Adult↗

Increased prevalence of gestational diabetes mellitus in in vitro fertilization pregnancies inadvertently conceived during treatment with long-acting triptorelin acetate.

Thirty-five pregnancies were inadvertently conceived during the midluteal application of the long-acting gonadotropin-releasing hormone agonist triptorelin acetate before ovarian stimulation for in vitro fertilization. Most of the conceptions occurred before the first or second IVF trial, and were associated with a significantly increased tendency to develop gestational diabetes. No increase in pregnancy wastage or appearance of congenital malformations occurred.

Adult↗

Zinc-regulating proteins, ZnT-1, and metallothionein I/II are present in different cell populations in the mouse testis.

Zinc ions play an important role in testis development and spermatogenesis. Thus, nutritional zinc deficiency leads to aberrant testicular development, reduced spermatogenesis, and male sterility. The precise actions of zinc in mediating these functions and the mechanisms by which zinc is itself regulated in the testis, however, have not been adequately elucidated. We have assessed the distribution of the zinc-regulating proteins ZnT-1 and metallothionein I/II (MT I/II) in the mouse seminiferous tubule. Co-labeling for ZnT-1 and MT I/II demonstrated unique patterns of distribution for these proteins, with ZnT-1 present in Sertoli cells in addition to luminal spermatozoa and MT I/II restricted to spermatocytes. These findings were confirmed by dual-label immunofluorescence for ZnT-1 and the Sertoli cell marker, vimentin, and by immunoelectron microscopy. The differential expression patterns of ZnT-1 and MTs support the hypothesis that ZnT-1 and MTs play different roles in the regulation of intracellular zinc in this organ. The specific expression of ZnT-1 in the Sertoli cells, moreover, is consistent with their role in maintaining a nurturing, closely regulated environment for spermatogenesis.

Animals↗

Interleukin-6 expression during normal maturation of the mouse testis.

In this study, we examined the cellular origin and the expression levels of interleukin-6 (IL-6) during normal maturation of mouse testis. The levels of IL-6 (protein and mRNA) were higher in testicular homogenates of sexually immature than mature mice. Immunohistochemical staining of testicular tissues of sexually immature and adult mice show that testicular germ cells, at different stages of differentiation, Leydig cells/interstitial cells and peritubular cells express IL-6. Our results demonstrate, for the first time, overexpression of IL-6 in testicular tissues of immature mice, as compared to mature mice, as well as the expression of IL-6 in germ cells of testicular tissues of adult and sexually immature mice. Thus, our results may indicate the involvement of the endocrine system (gonadotropins and testosterone) in the regulation of IL-6, which is involved in the regulation of testicular development, functions and spermatogenesis.

Animals↗

Testicular interleukin-6 response to systemic inflammation.

Spermatogenesis is a highly controlled process of proliferation, meiosis, and differentiation. Systemic infection and chronic inflammation can impair testicular steroidogenesis and spermatogenesis. In this study, we examined the effect of systemic infection--intraperitoneal (i.p.) injection of lipopolysaccharide (LPS)--on the expression levels of IL-6 in the testis of sexually immature and adult mice. IL-6 levels in testicular homogenates of immature mice were significantly higher than in mature mice (both protein and RNA levels), before and after LPS injection. Injection of LPS (i.p.) into mature mice over 3 hours, significantly increased testicular IL-6 protein and mRNA levels (as demonstrated by ELISA and RT-PCR respectively) compared to the control group. Injection of LPS over 24 hours significantly increased IL-6 mRNA expression, but it did not significantly affect IL-6 protein levels in the homogenates. In contrast, stimulation of immature mice with LPS (2, 20 or 100 microg/mL) over 3 hours or LPS (2 or 20 microg/mL) over 24 hours, significantly increased testicular IL-6 (both protein and mRNA expression). The levels of testicular IL-6 (protein) in the homogenates were not significantly increased after stimulation with 100 microg/mL over 24 hours, but they were significantly increased at the mRNA level. Our results demonstrate, for the first time, the over-expression of IL-6 in testicular homogenates of mature and immature mice following systemic inflammation (i.p. injection of LPS). These results suggest the possibility of the involvement of systemic infection/inflammation, through the elevation of testicular IL-6, in testicular functions, which may affect male fertility. Also, high levels of IL-6 during pathological conditions, could play a role in protecting testicular tissue.

Animals↗

Blastocyst-stage embryo transfer in patients who failed to conceive in three or more day 2-3 embryo transfer cycles: a prospective, randomized study.

OBJECTIVE: To compare blastocyst-stage embryo transfers (ETs) with day 2-3 ETs in patients who failed to conceive in three or more day 2-3 IVF/ET cycles. DESIGN: Prospective, randomized. SETTING: Fertility unit in a university medical center. PATIENT(S): Fifty-four patients with an adequate ovarian response underwent oocyte retrievals. The patients were prospectively and randomly divided into blastocyst-stage and day 2-3 ET groups. INTERVENTION(S): Ovarian down-regulation was obtained using GnRH agonist, and controlled ovarian hyperstimulation was achieved using daily administration of gonadotropins. MAIN OUTCOME MEASURE(S): The rate of blastocyst formation, ET cancellations, pregnancies, implantation, multiple gestation, and live births. RESULT(S): The clinical pregnancy rates per oocyte retrieval were 21.7% and 12.9% per blastocyst and day 2-3 ETs, respectively. Although there was a significantly higher implantation rate for blastocyst embryos (21.2%) as compared with 48- to 72-hour embryos (6%), the multiple-pregnancy rate was not significantly different between both groups. An ET cancellation rate of 26% and 6.4% for blastocyst and day 2-3 ETs, respectively, was observed. The presence of two or more 8-cell embryos on day 3 in culture carried a high probability of obtaining blastocysts for transfer. CONCLUSION(S): This prospective randomized study suggests that in patients with an adequate ovarian response who failed to conceive in at least three IVF/ET cycles [1]. transfer of blastocyst-stage embryos carries a significantly higher implantation rate; [2]. the pregnancy rate per oocyte retrieval and ET are higher in the blastocyst-stage group, even if it did not reach statistical significance; [3]. a higher ET cancellation rate was observed in the whole blastocyst-stage group; [4]. the ET cancellation rate was reduced significantly if the decision to proceed to blastocyst transfer was made on day 3 after oocyte retrieval, which is a post hoc conclusion.

Birth Rate↗

Regulation of spermatogenesis by paracrine/autocrine testicular factors.

Spermatogenesis is a complex process regulated by endocrine and testicular paracrine/autocrine factors. Gonadotropins are involved in the regulation of several testicular paracrine factors, mainly of the IL-1 family and testicular hormones. Testicular cytokines and growth factors (such as IL-1, IL-6, TNF, IFN-gamma, LIF and SCF) were shown to affect both the germ cell proliferation and the Leydig and Sertoli cells functions and secretion. Cytokines and growth factors are produced by immune cells and in the interstitial and seminiferous tubular compartments by various testicular cells, including Sertoli, Leydig, peritubular cells, spermatogonia, differentiated spermatogonia and even spermatozoa. Corresponding cytokine and growth factor receptors were demonstrated on some of the testicular cells. These cytokines also control the secretion of the gonadotropins and testosterone in the testis. Under pathological conditions the levels of pro-inflammatory cytokines are increased and negatively affected spermatogenesis. Thus, the expression levels and the mechanisms involved in the regulation of testicular paracrine/autocrine factors should be considered in future therapeutic strategies for male infertility.

Animals↗

GESDOR - a generic execution model for sharing of computer-interpretable clinical practice guidelines.

We developed the Guideline Execution by Semantic Decomposition of Representation (GESDOR) model to share guidelines encoded in different formats at the execution level. For this purpose, we extracted a set of generalized guideline execution tasks from the existing guideline representation models. We then created the mappings between specific guideline representation models and the set of the common guideline execution tasks. Finally, we developed a generic task-scheduling model to harmonize the existing approaches to guideline task scheduling. The evaluation has shown that the GESDOR model can be used for the effective execution of guidelines encoded in different formats, and thus realizes guideline sharing at the execution level.

Decision Making, Computer-Assisted↗

Involvement of intratesticular IL-1 system in the regulation of Sertoli cell functions.

The Interleukin-1 (IL-1) system has been suggested to be involved in the cell-cell cross talk within the testis. To investigate the testicular autocrine, paracrine and endocrine factors involved in the regulation of Sertoli cell functions, we have examined the capacity of Sertoli cell cultures, from immature mice, to produce IL-1alpha, IL-1beta and IL-1 receptor antagonist (IL-1ra) under in vitro cultures and in the presence of testicular physiological and pathological factors. Our investigation revealed that Sertoli cells produce large amounts of IL-1alpha, IL-1ra but not IL-1beta under basal culture conditions, as examined by ELISA and immunohistochemical staining. Liposaccharides (LPS), as well as IL-1alpha and IL-1beta were found to stimulate IL-1alpha and IL-1ra, but not IL-1beta production, in Sertoli cells from immature mice. Maximum concentration of IL-1alpha and of IL-1ra was observed after 2 and 8 h after the stimulation, respectively. The addition of IL-1ra to Sertoli cells did not alter their capacity to constitutively produce IL-1alpha. However, the stimulatory effects of recombinant IL-1alpha on IL-1alpha production by Sertoli cells were reversed by the concomitant addition of recombinant IL-1ra. FSH is capable to induce IL-1ra production in Sertoli cells in a dose-dependent manner but not IL-1alpha or IL-1beta. As expected, Sertoli cell cultures were also shown to constitutively secrete transferrin. Stimulation of these cultures with IL-1alpha, IL-1beta significantly increased their capacity to secrete transferrin. Addition of IL-1ra to unstimulated Sertoli cell cultures did not affect their capacity to secrete transferrin. Stimulation of Sertoli cell cultures with a combination of both IL-1alpha and FSH or IL-1beta and FSH showed additive effect between IL-1 and FSH in their capacity to induce transferrin secretion by these cells. However, stimulation of Sertoli cells with a combination of both IL-1ra and FSH did not affect their capacity to secrete transferrin as compared with FSH-stimulated cultures. Our results with Sertoli cells, in addition to previous data on Lydig cell and germ cells, may suggest the involvement of the IL-1 system in testicular paracrine/autocrine regulation, which could be involved in the regulation of spermatogenesis and spermiogenesis processes and male fertility.

Animals↗

Induction of transferrin secretion in murine Sertoli cells by FSH and IL-1: the possibility of different mechanism(s) of regulation.

In the present study we examined the capacity of interleukin-1 (IL-1) alpha, beta, interleukin-1 receptor antagonist (IL-1ra) and follicle stimulating hormone (FSH) to induce transferrin secretion by Sertoli cells under in vitro conditions. Primary Sertoli cell (SC) cultures from immature mice secreted constitutively transferrin. Stimulation of these cultures with IL-1alpha, IL-1beta significantly increas\d their capacity to secrete transferrin. Addition of IL-1ra to unstimulated SC cultures did not affect their capacity to secrete transferrin. Stimulation of SC cultures with a combination of both IL-1alpha and FSH or IL-1beta and FSH showed additive effect between IL-1 and FSH in their capacity to induce transferrin secretion by these cells. However, stimulation of Sertoli cells with a combination of both IL-1ra and FSH did not affect their capacity to secrete transferrin compared with FSH-stimulated cultures. Our results may suggest the involvement of testicular paracrine/autocrine factors (IL-1) and endocrine (FSH) factors in the regulation of transferrin secretion by SC. This capacity seems to be differently regulated by these factors. Thus, IL-1alpha and beta may directly affect physiological functions of the testis; which may suggest their involvement in the regulation of spermatogenesis and spermiogenesis processes and male fertility.

Animals↗

Autoimmune progesterone dermatitis manifested as erythema annulare centrifugum: Confirmation of progesterone sensitivity by in vitro interferon-gamma release.

Autoimmune progesterone dermatitis was manifested as deep-type erythema annulare centrifugum. Sensitivity to progesterone was studied in vivo by means of intradermal and patch tests, which revealed immediate-type and delayed-type hypersensitivity, respectively. Sensitivity to progesterone was further confirmed in vitro by results of an interferon-gamma release test, which imply a possible role for T(H)1-type cytokines in autoimmune progesterone dermatitis.

Adult↗

Over expression of interleukin-1alpha, interleukin-1beta and interleukin-1 receptor antagonist in testicular tissues from sexually immature mice as compared to adult mice.

The levels of IL-1alpha, IL-1beta and IL-1Ra were higher in homogenates of testicular tissue from sexually immature than those from mature mice. Immunohistochemical staining of testicular tissues from sexually immature and adult mice show that differentiated germ cells express higher levels of IL-1alpha compared to Sertoli cells and Leydig cells/interstitial cells. Peritubular cells of sexually immature and adult mice did not express IL-1alpha. Testicular tissue cells of adult mice showed high levels of expression of IL-1beta, mainly in the cytoplasm and nucleus of the spermatogonia and in spermatocytes. Sertoli cells and Leydig/interstitial cells were also highly stained for IL-1beta. However, peritubular cells did not express IL-1beta. On the other hand, testicular tissue cells from sexually immature mice, showed high levels of IL-1beta, mainly in spermatocytes. Spermatogonia showed low levels of IL-1beta expression. Also, high levels of IL-1beta expression were detected in Leydig/interstitial cells. Peritubular cells clearly showed IL-1beta expression. Testicular tissue cells from adult mice, showed IL-1Ra expression in spermatogonia, Sertoli and Leydig/interstitial cells. IL-1Ra expression was clearly present in the Golgi apparatus of spermatogonia and Sertoli cells. However, peritubular cells did not show IL-1Ra expression. Testicular tissue cells from sexually immature mice, also showed high levels of IL-1Ra expression mainly in the cytoplasm and nucleus of the spermatogonia and Sertoli cells. In addition, Leydig/interstitial cells and peritubular cells also expressed IL-1Ra. Our results demonstrate, for the first time, the expression of IL-1beta in germ and Sertoli cells, and IL-1Ra in Leydig/interstitial cells of testicular tissues from adult and sexually immature mice, under in vivo conditions. In addition, the relative elevated levels of the IL-1 system in the testis of immature mice compared to mature mice may indicate its involvement in the spermatogenesis.

Animals↗