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Biomedical subjects

N Laufer

Publications and source records attributed to N Laufer.

At least 19 recordsLinked to original sources

Angiotensin-I-converting enzyme and its correlation with human follicular fluid steroids.

Angiotensin-I-converting enzyme (ACE) is a peptidyl-dipeptide hydrolase which splits off the dipeptide His-Leu from the decapeptide angiotensin I and thus converts it to angiotensin II. We determined ACE activity in human preovulatory follicular fluid to further establish the intraovarian activity of the renin angiotensin system. Follicular fluids (n = 18) were obtained from eight patients undergoing in vitro fertilization (IVF) and embryo transfer (ET). ACE activity in follicular fluid and serum was determined by fluorescent spectrophotometry. The median follicular fluid ACE activity was 1.12 (range: 0.19-1.56) nmol/min/ml. This value was significantly lower than ACE activity in serum, 1.50 (range: 1.22-1.57) nmol/min/ml (P less than 0.001). In contrast to this 3:4 ratio between follicular fluid and serum ACE when expressed per ml fluid, the values were very similar when expressed per mg of protein: 0.025 vs. 0.023 nmol/min/mg in follicular fluid and serum, respectively. Correlations were sought between follicular fluid ACE activity and both serum and follicular fluid E2 and P4. A highly significant correlation (P less than 0.0005, r = 0.73) was found between ACE activity in follicular fluid and follicular fluid P4. The presence of significant ACE activity in human follicular fluid further supports the local-ovarian activity of the renin angiotensin cascade.

Embryo Transfer

Enhancing in vitro fertilization of mouse oocytes by partial zona pellucida digestion.

This work was undertaken in order to evaluate the effect of partial zona digestion on fertilization in vitro of mouse oocytes and assess zona surface changes induced by the procedure. Three hundred forty-six oocytes allocated for treatment were exposed to Ham's F-10 medium supplemented with 0.5% Pronase for either 3 min (188 oocytes) or 5 min (158 oocytes); 324 oocytes served as controls. Oocyte losses incurred as a result of the procedure were small (15 oocytes; 4.3%). Control and Pronase-treated oocytes were each divided into four subgroups and inseminated with 5 x 10(5), 5 x 10(4), 5 x 10(3), or 5 x 10(2) sperm cells/ml. Fertilization was assessed 8 hr following insemination by the appearance of two pronuclei and development to the two- to four-cell stage the following day. The morphology of the zona pellucida following Pronase treatment was assessed by phase-contrast and scanning electron (SEM) microscopies performed immediately after treatment. Fertilization rate of control oocytes was 80% at a sperm concentration of 500,000/ml and gradually declined to approximately 30% at 500 cells/ml. In contrast, treated oocytes inseminated with 500 sperm cells/ml demonstrated a normal rate of fertilization. At this low sperm concentration the longer Pronase treatment was significantly (P less than 0.05) more efficient in enhancing fertilization (69 and 88% for 3 and 5 min of Pronase treatment, respectively). Polyspermic fertilization was not observed in any of the subgroups. Phase-contrast microscopic examination of oocytes at the time of Pronase treatment showed an initial swelling of the zona pellucida for 30-60 sec with a time-dependent increase in its transparency.

Animals

Artificial endometrial preparation for oocyte donation: the effect of estrogen stimulation on clinical outcome.

Morphologic studies of the endometrium have demonstrated that varying the duration of an artificial follicular phase (AFP) in women with ovarian failure did not adversely affect its developmental capacity. The aim of this study was to evaluate whether such manipulations of endometrial stimulation could influence the pregnancy rate in women undergoing oocyte donation (OD). Twenty-nine women were investigated in 51 cycles of OD. Endometrial preparation was performed with a fixed dose of micronized estradiol, 4 mg/day, administered for 5-35 days in accordance with oocyte availability. On the day of donation progesterone in oil, 50 mg/day, was added to the regimen. Oocytes were donated anonymously by patients undergoing routine in vitro fertilization. Fifteen clinical pregnancies were achieved, for a success rate of 29.4%. Using logistic regression analysis the success rate was found to be closely associated with the duration of estrogen stimulation. The pregnancy rate was 7.7, 52, and 7.7% after an AFP of 4-11, 12-19, and 20-29 days, respectively. It seems that for optimal results in an OD program, estrogen stimulation should be kept at between 12 and 19 days. These results also imply that, contrary to endometrial morphology, which seems to be tolerant to extreme AFP durations, functional receptivity is less permissive and is adversely affected by such manipulations.

Adult

Defective oocytes: a new subgroup of unexplained infertility.

OBJECTIVE: To define a new category of unexplained infertility and its potential treatment. DESIGN: Normal infertile couples underwent prospectively, cross-fertilization attempts in which the wife's oocytes were inseminated by the husband and donor semen. After recurrent failure of fertilization, cross insemination of donor oocytes was attempted with the husband sperm. SETTING: In vitro fertilization unit at a teaching hospital. PATIENTS: Three couples who were diagnosed as suffering of unexplained infertility and treated by in vitro fertilization (IVF). RESULTS: The female partner of these couples produced morphologically normal oocytes that were demonstrated to be functionally defective and failed to fertilize in vitro with both husband and donor sperm. Donated oocytes inseminated by the husband's sperm were fertilized in all patients, demonstrating the normal fertilizing ability of the husbands' semen. One patient conceived and delivered after an oocyte donation. CONCLUSIONS: Conclusive diagnosis of defective oocytes as a cause of infertility may be made only after IVF and oocyte donation.

Adult

Ovarian hyperstimulation syndrome in novel reproductive technologies: prevention and treatment.

OBJECTIVE: To overview the world literature on ovarian hyperstimulation syndrome (OHSS) and modes of prevention and treatment of OHSS. STUDY SELECTION: All the pertinent literature on OHSS, its prevention, and strategies for treatment were reviewed. PREVENTION: Key to prevention is proper identification of the population at risk, which includes women with either the hormonal or the morphological signs of polycystic ovarian disease, high serum estradiol (E2) before human chorionic gonadotropin (hCG) administration (E2 greater than 4,000 pg/mL), multiple follicular response (greater than 35), younger age, and lean habitus. When a high risk situation is recognized, ovulatory dose of hCG may be reduced, avoided (with cycle cancellation), or substituted by gonadotropin-releasing hormone or its agonist. Luteal support with hCG is to be bypassed. To minimize risk of OHSS, endogenous pregnancy-drived hCG may be eluded by judicious cryopreservation of all embryos. Last, follicular aspiration will allow higher levels of E2 and larger number of follicles to be matured with lesser risk of OHSS than conventional ovulation induction without follicular aspiration. TREATMENT: In-house for the severe and intensive care for the critical form. Meticulous fluid and electrolyte balance using both crystalloids and colloids (albumin) until hemoconcentration abates. Paracentesis is indicated for tight ascites, deteriorating kidney functions, and symptomatic relief. Diuretics may be prudently used once hemodilution is achieved. Dopamine drip may be used as a renal rescue, whereas heparin is indicated for thromboembolic phenomena and surgery reserved for abdominal catastrophies. Therapeutic interruption of an early gestation may be lifesaving when all other measures have failed. CONCLUSIONS: Although severe and critical OHSS may not be completely avoided, early recognition of high-risk factors, judicious prevention schemes, and treatment strategies should reduce the complication and long-term sequelae of this iatrogenic syndrome.

Chorionic Gonadotropin

Effects of melatonin on progesterone production by human granulosa lutein cells in culture.

OBJECTIVE: To test the hypothesis that melatonin modulates steroid synthesis in the human ovary. DESIGN: Granulosa lutein cells obtained from in vitro fertilization cycles were cultured in medium containing melatonin and human chorionic gonadotropin (hCG). RESULTS: Progesterone (P) secretion by granulosa lutein cells increased progressively in both basal and hCG-stimulated conditions, up to 96 hours in culture, plateaued at 144 and decreased thereafter. Melatonin (10(-7), 10(-9), 10(-11) M) had no effect on basal P or 17 beta-estradiol production. The addition of melatonin to the hCG-treated granulosa lutein cells significantly (P less than 0.05) potentiated the stimulatory effect of hCG on P production. The effect was most prominent after 144 and 196 hours of incubation. CONCLUSION: This observation suggests a role for melatonin in the intraovarian control of P production in the human ovary.

Cells, Cultured

The effect of growth hormone supplementation on in vitro fertilization outcome: a prospective randomized placebo-controlled double-blind study.

OBJECTIVE: To determine the effect of growth hormone (GH) supplementation to a long gonadotropin-releasing hormone agonist (GnRH-a)/human menopausal gonadotropin (hMG) treatment protocol, on ovarian response, embryo quality, and clinical outcome in in vitro fertilization (IVF). DESIGN: Growth hormone or placebo were administered in a prospective randomized double-blind manner. PATIENTS: Forty-two normal ovulatory, women who were 38 years of age or less with mechanical factor infertility and a normal male factor were selected for this study. INTERVENTIONS: Gonadotropin-releasing hormone agonist, 0.5 mg/d, was initiated in the midluteal phase of the preceding cycle and continued until the day of human chorionic gonadotropin (hCG) administration. Ovulation induction with hMG was started 14 days after pituitary down regulation (17 beta-estradiol [E2] serum level less than 30 pg/mL). Growth hormone (12 IU/d) or placebo were administered on days 1, 3, 5, and 7 of hMG treatment. RESULTS: Breaking the code at the completion of the study revealed that 20 women received GH and 22 placebo. The age and duration of infertility did not differ between the two groups. Follicular phase duration, hMG ampules used, serum E2, and number of follicles (greater than or equal to 14 mm) on day of hCG as well as number of oocytes and embryos achieved were similar in both groups. Embryo morphology and rate of cleavage were also similar. Insulin-like growth factor-I (IGF-I) serum levels did not change after pituitary down regulation and increased significantly both after GH/hMG and placebo/hMG ovulation induction treatment. Clinical pregnancy rate (PR) per embryo transfer and implantation rate were 40% versus 32% and 17.9% versus 11.3% in the GH and placebo groups, respectively, and were not statistically different. CONCLUSIONS: In normo-ovulatory women undergoing ovulation induction for IVF, GH supplementation to hMG after GnRH-a pituitary down regulation does not seem to augment ovarian response or improve embryo quality. The effect of this regimen on actual PRs and implantation rates needs further clarification.

Adult

Interleukin-1: local production and modulation of human granulosa luteal cells steroidogenesis.

OBJECTIVES: To investigate the possibility of local interleukin-1 (IL-1) and IL-1 inhibitor production by human granulosa and cumulus cells and to assess their direct effects on the steroidogenesis of these cells in vitro. DESIGN: Prospective study. PARTICIPANTS: Normal ovulatory women undergoing ovulation induction for in vitro fertilization. INTERVENTION: Pretreatment of patients with gonadotropin-releasing hormone analogue, human menopausal gonadotropin, and human chorionic gonadotropin (hCG). MAIN OUTCOME MEASURES: Retrieval and isolation of granulosa luteal cells and follicular fluid (FF). Granulosa luteal cells and cumulus cells cultured and analyzed by fluorescent activated cell sorter. Follicular fluid separated and bioassayed for IL-1 and IL-1 inhibitory activity. Steroid measurement performed. Interleukin-1 inhibitor purified. Interleukin-1 and IL-1 inhibitor bioassay performed. Statistical analysis made and interpreted. RESULTS: Interleukin-1, but not IL-1 specific inhibitory activity, was found in granulosa and cumulus cell cultures and also in FF, only after its purification on a high-pressure liquid chromatography column. Under nonstimulated conditions, neither IL-1 nor IL-1 inhibitor had any effect on basal progesterone (P) or estradiol (E2) secretion. However, IL-1 inhibitor demonstrated significant (P < 0.01) inhibition of hCG-stimulated P secretion (from 200 to 110 ng/10,000 cells per 24 hours). In addition, IL-1 demonstrated a significant (P < 0.05) and dose-dependent inhibition of hCG-stimulated E2 production (from 6,832 +/- 460 to 4,237 +/- 141 pg/10,000 cells per 24 hours). CONCLUSIONS: Interleukin-1 may exert a significant local autocrine regulatory role in the human ovary.

Cells, Cultured

Treatment of male infertility by gamete micromanipulation.

Over the past decade, in vitro fertilization (IVF) has become a routine and acceptable tool in the treatment of infertility. However, major limitations in solving certain infertility problems still remain. Male infertility is one area in which only a small fraction of patients have benefited from IVF. Union of male and female gametes, either in vivo or in vitro, requires sperm penetration through the cumulus oophorus and the zona pellucida. Failure of fertilization despite the increased number of spermatozoa introduced into the oocyte's vicinity by IVF, has been shown to be directly related to abnormalities in sperm cell morphology and motility. The improved technology for micromanipulation of gametes has made it possible to circumvent the oocyte barriers to sperm penetration, thereby greatly reducing the number of normal sperm cells needed to achieve fertilization. This paper reviews the three major micromanipulative strategies which have been developed over the past five years, patient selection for the different procedures and the methods of sperm preparation to improve the yield of the applied technique.

Humans

The correlation of interleukin 1 and tumour necrosis factor to oestradiol, progesterone and testosterone levels in periovulatory follicular fluid of in-vitro fertilization patients.

Data has accumulated suggesting reciprocity between cytokines and the reproductive system. The present study was performed in order to evaluate the correlation between interleukin 1 (IL-1) and tumour necrosis factor (TNF) concentrations in follicular fluid and its oestradiol, progesterone and testosterone levels. A total of 39 follicular fluid samples, from eight patients undergoing in-vitro fertilization and embryo transfer were evaluated. All of the patients were treated by a midluteal (long) protocol involving a gonadotrophin releasing hormone agonist (GnRHa) coupled with follicular phase human menopausal gonadotrophin. Mean levels in follicular fluid of IL-1, TNF, oestradiol, progesterone and testosterone were 1.58 +/- 0.42 fmol/0.1 ml, 4.69 +/- 4.18 pg/ml, 28.5 +/- 58.1 ng/ml, 2360.5 +/- 2846.3 ng/ml and 7.22 +/- 7.08 ng/ml respectively. There was a significant (P less than 0.01) positive correlation between IL-1 and progesterone levels. There was no significant correlation between the different lymphokines and oestradiol secretion, oocyte fertilization, embryo quality and pregnancy rates. It is concluded that IL-1 and TNF exist in follicular fluid. It may be hypothesized that IL-1 has a local regulatory action, possibly promoting luteinization.

Adult

The correlation between interleukin 2 and soluble interleukin 2 receptors to oestradiol, progesterone and testosterone levels in periovulatory follicles of in-vitro fertilization patients.

The present study was performed to evaluate the correlation between follicular fluid levels of interleukin 2 (IL-2) and IL-2 soluble receptor (sIL-2R), oestradiol, progesterone and testosterone levels, oocyte fertilization, embryo quality and pregnancy rates. Twenty-eight patients with a pure tubal factor and undergoing in-vitro fertilization and embryo transfer were randomly chosen and treated with gonadotrophin releasing hormone agonist (GnRHa) in the midluteal phase (long protocol) coupled with follicular phase administration of human menopausal gonadotrophin. Transvaginal follicular aspiration was performed 36 h after human chorionic gonadotrophin administration, followed 48 h later by embryo transfer. One hundred and twenty-three follicular fluids were sampled. The mean follicular fluid levels (+/- SD) were 2.30 +/- 0.80 fmol for IL-2, 458.2 +/- 236.0 units/ml for sIL-2R, 28.5 +/- 58.1 ng/ml for oestradiol, 2360.5 +/- 2846 ng/ml for progesterone and 7.22 +/- 7.08 ng/ml for testosterone. There was a significant (P less than 0.01) correlation between IL-2 and testosterone levels. No correlation was found between the lymphokines and serum oestradiol, follicular fluid progesterone, oocyte fertilization, embryo quality and pregnancy. It may be concluded that significant concentrations of IL-2 and sIL-2R exist in follicular fluid. Wide variations in follicular IL-2 and sIL-2R concentrations of different follicles were found in the same patients.

Estradiol

Births in Israel resulting from in-vitro fertilization/embryo transfer, 1982-1989: National Registry of the Israeli Association for Fertility Research.

Our objective was to describe the characteristics of pregnancies, deliveries and children at birth following in-vitro fertilization (IVF) and related technologies in Israel, from 1982 to 1989. A national survey with collaboration from all IVF units in the public hospitals was designed and data were collected on individual patients. Comparison of results was made with data from a national delivery census and from other national IVF registries. During the period covering this survey, 1149 deliveries resulted in 1475 newborns; 98% of deliveries occurred following conventional IVF and embryo transfer (IVF-ET), 2% after in-vivo fertilization and gamete intra-Fallopian transfer. Following IVF-ET, 23% of the pregnant women were hospitalized due to a complication of pregnancy and 47.3% of the deliveries were by Caesarean section (41% if multiple births are omitted). The male to female birth ratio was 1.07:1.0; 23.6% of the deliveries were multiple births, 28.6% of deliveries were pre-term and the median length of gestation decreased with multiple births. At delivery, 23.8% of newborns weighed less than 2500 g. The incidence of low birthweight newborns was significantly higher in multiple births. The ratio of perinatal mortality (22.8/1000), double the incidence found in a national census (13/1000), increased dramatically with multiple births (12.7, 24.5 and 75.8/1000 for singleton, twins and triplets respectively). The incidence of a major congenital malformation was 2.2%, no higher than in the general population. A survey of published national IVF registries from Australia and New Zealand, Great Britain, USA and France showed much similarity in all aspects of pregnancy outcome following IVF and related technologies.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Maternal hemorrhagic complications following prophylactic low-dose aspirin and dipyridamole therapy.

A case is reported of a severe postpartum maternal hemorrhagic complication, which was related to prophylactic antithrombotic therapy with daily low-dose aspirin (75 mg) combined with dipyridamole (225 mg) for the prevention of preeclampsia. The postpartum course was complicated by recurrent episiotomy site hematomas of nonclotted blood and prolonged bleeding time. Transfusion of platelet concentrates was necessary to control the bleeding. This case report draws attention to maternal hemorrhagic complications which may be associated with prophylactic low-dose aspirin and dipyridamole in pregnancy.

Adult

The value of an electronic microcomputerized basal body temperature measurement device (Bioself) in in vitro fertilization cycles.

The Bioself 110 electronic basal body temperature (BBT) measurement device was employed in 18 women undergoing in vitro fertilization (IVF). This microcomputer-operated device records, charts and accurately analyzes the mean temperature measurements. These temperature recordings were used in addition to transvaginal ovarian sonography and serum estradiol and progesterone levels. The BBT rise correlated significantly (p < 0.0002) with progesterone elevation following human chorionic gonadotropin (hCG) administration. It is suggested that this electronic device may be used as an additional tool in the detection of premature progesterone secretion in IVF cycles.

Body Temperature

Multicenter registry of angioplasty therapy of cardiogenic shock: initial and long-term survival.

This retrospective multicenter study reviews the role of acute percutaneous transluminal coronary angioplasty in the treatment of cardiogenic shock complicating acute myocardial infarction to determine whether early reperfusion affects in-hospital and long-term survival. From 1982 to 1985, 69 patients were treated with emergency angioplasty to attempt reperfusion of the infarct-related artery. Balloon angioplasty was unsuccessful in 20 patients (group 1) and successful in 49 patients (group 2). Initial clinical and angiographic findings in the groups with unsuccessful and successful angioplasty were similar with respect to age (60.5 +/- 2.3 versus 57 +/- 1.8 years), infarct location (65% versus 65% anterior) and gender (65% versus 67% male). Hemodynamic variables in the two groups, including systolic blood pressure (68 +/- 4.3 versus 73 +/- 1.6 mm Hg), left ventricular end-diastolic pressure (24.4 +/- 2.4 versus 27 +/- 1.0 mm Hg) and initial ejection fraction (28.5 +/- 4% versus 32 +/- 2%), were also similar. Twenty-nine patients received thrombolytic therapy with streptokinase; the overall rate of reperfusion was 34%. Group 1 patients had a short-term survival rate of 20%, compared with 69% in group 2 patients (p less than 0.0005). Thirty-eight patients survived the hospital period and were followed up for 24 to 54 months (mean 32.5 +/- 2.4). Five patients (all in group 2) died during follow-up. The long-term incidence rate of congestive heart failure was 19%, arrhythmia 21%, need for repeat angioplasty 17% and coronary artery bypass grafting 26%. Twenty-four month survival was significantly better in group 2 patients (54%) versus group 1 patients (11%, p = 0.003).(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon, Coronary

Technique for cellular microsurgery using the 193-nm excimer laser.

A new cell surgery technique has been developed to produce well-defined alterations in cells and tissue without detectable heating and/or other structural damage in the surroundings. The technique involves the use of an argon fluoride excimer laser, in the deep ultraviolet (UV) region of the spectrum at 193 nm, which is guided through a glass pipette filled with a positive air pressure. To demonstrate the method, holes were drilled in the zona pellucida of mouse oocytes. The diameter of the drilled hole was determined by the pipette tip size, and its depth by an energy emitted per pulse and number of pulses. Scanning electron microscopy of the drilled mouse oocytes showed uniform, round, well-circumscribed holes with sharp edges. Oocytes that had their zona pellucida drilled with this new method fertilized in vitro and developed to the blastocyst stage in a rate similar to that of control group. These results demonstrate the nonperturbing nature of this cold laser microsurgical procedure. In addition to the extension of our results for clinical in vitro fertilization purposes, such as enhancement of fertilization and embryo biopsy, there are wide-ranging possible uses of our method in fundamental and applied investigations that require submicron accuracy in cellular alteration.

Animals