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B Kovacic

Publications and source records attributed to B Kovacic.

At least 19 recordsLinked to original sources
PubMed2001

Value of the serum estradiol level on the day of human chorionic gonadotropin injection and on the day after in predicting the outcome in natural in vitro fertilization/intracytoplasmic sperm injection cycles.

OBJECTIVE: To predict the risk of premature ovulation and possibility of pregnancy in natural IVF/ICSI cycles on the basis of the estradiol (E2) level on the day of hCG injection and on the day after. DESIGN: A prospective study. SETTING: Hospital research program. PATIENT(S): One hundred sixty-four women undergoing 305 IVF/ICSI natural cycles. INTERVENTION(S): Serum E2 levels were measured approximately 12 h before (day 0) and 12-17 h after hCG administration (day 1). MAIN OUTCOME MEASURE(S): E2 levels on day 0 and day 1, the ratio of the day 1 to day 0 levels, and cycle outcome. RESULT(S): In cycles with premature ovulation and in conception cycles, the average E2 level on day 0 was statistically significantly higher than in other cycles, whereas the E2 ratio was statistically significantly lower. Multiple logistic regression was used to determine the connection of the E2 level on day 0 (B0 = -0.742, B = 2.147, P =.01) and the E2 ratio (B0 = -0.742, B = -3.135, P<.001) with premature ovulation. Only the E2 ratio (B0 = 0.659, B = -2.209, P =.0068) was significantly connected with conception. CONCLUSION(S): In predicting the outcome of natural IVF/ICSI cycles, the importance lies not in the E2 level on the day of hCG administration or on the day after, but rather in the E2 ratio.

Adult↗
PubMed2001

Subendometrial contractility is not predictive for in vitro fertilization (IVF) outcome.

OBJECTIVES: The aim of the study was to investigate whether endometrial thickness, endometrial pattern, endometrial movement and serum estradiol and progesterone affect the outcome of in vitro fertilization. METHODS: Prospectively collected data of endometrial thickness, endometrial pattern and subendometrial activity were analyzed in 122 consecutive in vitro fertilization cycles. All measurements were made on the day of hCG administration (day -2), day of embryo transfer (day +2), day +6 and day +12. RESULTS: It would appear that pregnant women tend to have a thicker endometrium on day +12 than non-pregnant women. There appears to be no appreciable difference between pregnant and non-pregnant women in endometrial movement and thickness, nor in serum estradiol and progesterone on day +2 and day +6. In combining three echographic variables (thickness, pattern and movement) and hormone level (estradiol and progesterone), only progesterone on day +12 could be used to predict the outcome. CONCLUSIONS: Subendometrial contractility plays no important role in implantation on the day of embryo transfer or 4 days later.

Adult↗
PubMed2001

Is there any benefit from the culture of a single oocyte to a blastocyst-stage embryo in unstimulated cycles?

BACKGROUND: The aim of the study was to test the influence of 2- and 5-day cultivation of a single oocyte on the pregnancy rate in a non-stimulated cycle. METHODS: A retrospective chart review of 391 consecutive patients undergoing IVF and intracytoplasmic sperm injection in unstimulated cycles was performed. The embryos were kept in MediCult universal IVF medium for day 2 transfers and in BlastAssist System for day 5 transfers. RESULTS: The oocyte recovery rate in the group for 2-day cultivation and in the group for 5-day cultivation was similar, being 79.4 (162/204) and 83.6% (154/187) respectively. The same is true of the fertilization rate (73.8 versus 77.7%). The blastulation rate was 52.8%. The embryo transfer rate per cycle was higher when day 2 embryos were transferred: 64.8% (105/162) compared with 35.7% (55/154) if blastocyst-stage embryos were transferred. The pregnancy rate per transferred embryo was higher when a blastocyst was transferred (40.0%) instead of a day 2 embryo (23.8%). CONCLUSION: The expected pregnancy rate calculated per embryo available on day 2 of cultivation was similar in both groups (23.8 versus 22.2%) and it was not affected by oocyte culture to the blastocyst stage.

Blastocyst↗
PubMed2001

Three protocols for monitoring follicle development in 587 unstimulated cycles of in vitro fertilization and intracytoplasmic sperm injection. A comparison.

OBJECTIVE: To test the adequacy of unstimulated cycles for intracytoplasmic sperm injection (ICSI) and in vitro fertilization (IVF) and to evaluate implantation and pregnancy rates in three monitoring protocols. STUDY DESIGN: A retrospective chart review of 587 patients undergoing IVF and ICSI in unstimulated cycles was performed. In the first group (protocol A), all cycles were monitored by ultrasound only. Human chorionic gonadotropin (hCG) was given when the mean follicle diameter reached 18 mm. In protocol B, hCG was given when serum estradiol (E2) or follicle diameter reached the critical value (0.91 nmol/L and 18 mm). With a smaller follicle diameter, the E2 level had to be higher, and vice versa. In protocol C, hCG was administered when the serum E2 was > 0.49 nmol/L and follicle diameter at least 15 mm. Cycles with positive luteinizing hormone in urine before hCG was given were cancelled. RESULTS: The cancellation rate was lower in protocol C (33/335, 9.8%) than protocol B (42/151, 27.8%) and A (41/101, 40.5%). In protocol C the pregnancy rate per cycle was higher with IVF (n = 219) and ICSI (n = 116) cycles (10.5% and 12.1%) than when protocol B was used (3.8% and 4.3%). The pregnancy rate per transfer was highest when protocol C was used in the IVF (23/105, 21.9%) and ICSI group (14/53, 26.4%). CONCLUSION: Unstimulated cycles monitored by serum E2, urinary luteinizing hormone and ultrasound can produce an acceptable pregnancy rate after IVF and ICSI.

Adult↗
PubMed2000

Configuration of maternal and paternal chromatin and pertaining microtubules in human oocytes failing to fertilize after intracytoplasmic sperm injection.

The microtubules and chromosomes of 180 human oocytes failing to fertilize after intracytoplasmic sperm injection were observed in order to establish how sperm chromatin and sperm astral microtubule configuration is related to the phases of oocyte cell cycle, and to find the defects in those structures causing fertilization arrest. As many as 125 (69%) oocytes were arrested at metaphase II. In one-fourth of them, damages of the second meiotic spindle were noted. In their cytoplasm intact sperm were found in 38 (30%) cases, a swollen sperm head in 36 (29%) and prematurely condensed sperm chromosomes (G1-PCC)-a result of active mitosis promoting factor (MPF)-in 51 (41%) cases. G1-PCC were mostly (73%) surrounded by the bipolar paternal spindle instead of astral microtubules. A male pronucleus was never presented in metaphase II oocytes. In 19 (11%) oocytes, arrested at anaphase II, no intact sperm were found. As many as 9 (47%) oocytes contained sperm in G1-PCC form, which proves that anaphase II oocytes mostly retain active MPF, despite oocyte activation. As many as 78% of 36 monopronucleate oocytes contained sperm, with delay in the process of sperm nucleus decondensation. Sperm in G1-PCC form and a bipolar paternal spindle were never found in monopronucleate oocytes. From this we conclude that sperm that does not activate the oocyte may continue decondensing the chromatin, but the oocyte prevents male pronucleus formation before the female one, mostly by causing PCC in the sperm and by duplicating the sperm centrosome. Mol. Reprod. Dev. 55:197-204, 2000.

Cell Cycle↗
PubMed2000

Simplification of the clinical phase of IVF and ICSI treatment in programmed cycles.

OBJECTIVE: To evaluate the success of a protocol for controlled ovarian hyperstimulation allowing patient self-selection into groups for ovulation stimulation planned 8 weeks and more in advance following cycle synchronization, drug self-administration as well as a reduced number of folliculometries. METHODS: A total of 714 patients received the same stimulation protocol. In 260 cases GnRH-a was applied daily and in 454 as depot. In all patients FSH-HP was self-administered subcutaneously for ovarian stimulation. In 316 patients IVF and in 398 patients ICSI was performed. RESULTS: The delivery rate per started cycle was higher in patients receiving depot GnRH-a in the IVF and ICSI group (30.2 vs. 23.4) than in those receiving subcutaneous GnRH-a (20.2 vs. 22.1). CONCLUSION: Programming of the IVF/ICSI cycle greatly simplifies treatment. A comparison of pregnancy rate and delivery rate per cycle between depot and subcutaneous daily application of GnRh-a did not confirm any statistically significant difference.

Adult↗
PubMed1999

Number of oocytes retrieved and resulting pregnancy. Risk factors for ovarian hyperstimulation syndrome.

OBJECTIVE: To test whether the risk of developing clinically significant ovarian hyperstimulation syndrome (OHSS) is related to the number of oocytes retrieved by puncture and the resulting pregnancy and to determine the most suitable cutoff limit of the number of oocytes in predicting OHSS. STUDY DESIGN: The study included 973 patients who underwent ovarian stimulation for in vitro fertilization or intracytoplasmic sperm injection. Using the classification of Schenker and Weinstein, we identified patients who developed moderate and severe OHSS. By multiple logistic regression we established the risk of moderate or severe OHSS development in relation to the number of oocytes retrieved and the resulting pregnancy. A receiver operator characteristic curve was constructed to describe the relation between sensitivity and the false positive rate for the number of oocytes retrieved in the prediction of OHSS. RESULTS: We identified 35 (3.6%) patients who developed OHSS, 8 (0.8%) severe and 27 (2.8%) moderate. The risk of developing OHSS increased with the number of oocytes retrieved (odds ratio = 1.14) and with pregnancy (odds ratio = 1.14). The most suitable limit for predicting OHSS was 10 oocytes, with 81.9% specificity and 48.6% sensitivity. The risk of OHSS development in cycles with < or = 10 oocytes and no conception was 1.31% and, with conception, 5.12%. The risk of OHSS development in cycles with > 10 oocytes and no conception was 4.43% and with conception, 15.93%. CONCLUSION: The risk of OHSS development increases with the number of oocytes retrieved and with pregnancy. The most suitable limit for predicting OHSS is 10 oocytes; however, due to low sensitivity, it is also necessary to consider other factors when establishing the increased risk of OHSS.

Adult↗
PubMed1998

c-Src activation plays a role in endothelin-dependent hypertrophy of the cardiac myocyte.

Activation of the atrial natriuretic peptide (ANP) gene is regarded as one of the earliest and most reliable markers of hypertrophy in the ventricular cardiac myocyte. We have examined the role of the nonreceptor tyrosine kinases in the signaling mechanism(s) leading to hypertrophy using human ANP gene promoter activity as a marker. Endothelin (ET), a well known hypertrophic agonist, increased activity of c-Src, c-Yes, and Fyn within minutes and promoted a selective redistribution of each of these kinases within the cell. Overexpression of c-Src effected a significant increase in activity of a cotransfected human ANP promoter-driven chloramphenicol acetyl transferase reporter, while expression of either c-Yes or Fyn was considerably less effective in this regard. ET-dependent stimulation of the human ANP gene promoter was partially inhibited by co-transfection with dominant negative Ras or dominant negative Src or Csk or by treatment with the potent Src family-selective tyrosine kinase inhibitor PP1, suggesting that the Src family kinases are involved in signaling ET-dependent activation of this promoter. Both ET- and Src-dependent activation of the ANP promoter required the presence of a CArG motif in a serum response element-like structure between -422 and -413 but did not appear to require assembly of a ternary complex for full activity. These findings support a role for Src in the activation of ANP gene expression and suggest that this kinase may contribute in an important way to the signaling mechanisms that activate hypertrophy in the cardiac myocyte.

Animals↗
PubMed1992

In vitro fertilization program based on programmed cycles monitored by ultrasound only.

OBJECTIVE: Programmed oocyte retrieval was performed in order to make the in vitro fertilization (IVF) program cheaper and work of the IVF team easier. METHOD: In a group of 77 patients included in the IVF program, the menstrual cycle was modified with estrogen-progesterone contraceptive pills. For this reason, it was possible to start the stimulation protocol in all patients on the same day. The stimulation protocol was a combination of clomiphene (100 mg) for 5 days and HMG (150 IU) every other day. Cycles were monitored by ultrasound only. RESULT: The implantation rate per embryo transfer was 22.4%. The number of embryos per embryo transfer was low (2.6 +/- 1.4) and eliminated the need for cryopreservation. Fertilization rate (82%) and embryo transfer rate (87%) were high. The take home baby rate was 14.3%. CONCLUSION: Seventy percent of all punctures were performed in 3 days in the middle of the week. In our conditions, programmed oocyte retrieval is associated with significant economic benefits.

Clinical Protocols↗
PubMed1988

Suppression of neuroleptic-induced persistent abnormal movements in Cebus apella monkeys by enantiomers of 3-PPP.

Effects of the enantiomers of the dopamine (DA) autoreceptor agonist 3-PPP (0.5-8.0 mg/kg body weight, i.m.) were studied in three Cebus apella monkeys with persistent abnormal movements induced by prior long-term treatment with fluphenazine enanthate. In 2 of the animals, (-)-3-PPP abolished the abnormal movements while producing only negligible acute motor effects (trembling and stereotypy). (+)-3-PPP, administered to one of these monkeys, also produced a dose-dependent suppression of the persistent abnormal movements, along with the appearance of acute motor signs including tongue protrusions, hyperkinesia, and stereotypy; at the highest dose, there was a biphasic effect. In the first phase, there were pronounced acute motor signs but no persistent abnormal movements. In the second phase, there were neither acute nor persistent abnormal movements. One monkey was unaffected by (-)-3-PPP or low doses of (+)-3-PPP; a higher dose (4 mg/kg) produced hyperkinesia and increased persistent abnormal movements in one experimental setting. The suppression of neuroleptic-induced persistent abnormal movements by 3-PPP enantiomers may be related to their ability to act as autoreceptor agonists, while the acute motor signs produced by higher doses of (+)-3-PPP may be due to activation of postsynaptic DA receptors. The present findings suggest that (-)-3-PPP and drugs with a similar pharmacological profile might be effective as symptomatic treatments for tardive dyskinesia, with little chance of inducing acute extrapyramidal side-effects.

Animals↗
PubMed1986

Effect of neuroleptics and of potential new antipsychotic agents (MJ 13859-1 and MJ 13980-1) on a monkey model of tardive dyskinesia.

Two adult female cebus apella monkeys with persistent tardive dyskinesia (TD) were given acute i.m. injections of reference neuroleptics (chlorpromazine, haloperidol, thioridazine, and clozapine) or of potential new antipsychotic agents (MJ 13859-1 and MJ 13980-1). The drugs were assessed for their ability to modify TD symptoms or to produce acute neurologic reactions. Effects of three doses of MJ 13859-1 administered orally were also examined. At the doses used, thioridazine and clozapine had little or no effect. Chlorpromazine, haloperidol, MJ 13859-1 and MJ 13980-1 reduced or abolished TD and concomitantly produced hypokinesia, akinesia, mask expression, trembling, and reduced response to stimuli. Haloperidol also produced a mildly abnormal posture. In addition to the above effects, MJ 13859-1 also produced "slow motion" movement, sustained bizarre postures, sudden falls, and episodes of severe rigidity with trembling.

Animals↗
PubMed1985

Lack of clinically significant improvement of patients with tardive dyskinesia following phosphatidylcholine therapy.

A double-blind controlled study was undertaken to examine the value of phosphatidylcholine as a treatment for tardive dyskinesia (TD) in 19 psychiatric patients. All patients were maintained on their usual psychotropic medication throughout the entire study. In addition, they were given either phosphatidylcholine (30 g/day) or placebo for 6 weeks. Thirteen of the patients received the crossover treatment for 6 weeks, after which 10 of the 13 were continued on the crossover medication for an additional 6 weeks. At the end of the study, 5 patients had received phosphatidylcholine for 12 weeks and another 12 patients had received the drug for only 6 weeks. Plasma and red blood cell choline levels were monitored every 3 weeks as a measure of compliance. Although some patients showed clinical improvement of their TD, the results did not differ significantly between active drug and placebo. This was in spite of a marked elevation of plasma and red blood cell choline (up to 300% for the Lafayette Clinic patients and up to 400% for the patients from the Ypsilanti Regional Psychiatric Hospital) during treatment with phosphatidylcholine. Side effects of the drug included occasional gastrointestinal upsets and diarrhea but, in general, the medication was tolerated very well. The results indicate that large doses of phosphatidylcholine of soya origin are of no clinical value in treating symptoms of TD in spite of very large increases in blood choline.

Adult↗
PubMed1984

Fluphenazine-induced acute and tardive dyskinesias in monkeys.

Five Cebus apella monkeys were treated with biweekly injections of fluphenazine enanthate (0.1-3.2 mg/kg IM). Three of these completed 1 full year of treatment, one injured its leg after 6 months of treatment and was killed, and another died of unknown causes after 9 months of treatment. All monkeys displayed abnormal movements corresponding to the early appearing extrapyramidal symptoms of neuroleptic-treated patients. These consisted initially of slowing or absence of volitional movement, trembling of the hands, trembling of the entire body, and general drowsy behavior. As treatment progressed, a variety of abnormal postures and movements appeared after each injection that were not exacerbated by drug withdrawal and, as tested at the end of the year, could be abolished or prevented with benztropine mesylate (0.2-0.5 mg/kg IM). The three monkeys that completed 1 year of treatment with fluphenazine were then withdrawn from the drug. After withdrawal, all three developed movements similar in appearance to those of patients with tardive dyskinesia (TD). Reinstitution of fluphenazine treatment, as tested in one monkey, abolished all movements resembling TD.

Animals↗
PubMed1982

A monkey model of tardive dyskinesia (TD): evidence that reversible TD may turn into irreversible TD.

Three Cebus apella monkeys were treated with biweekly injections of fluphenazine enanthate for 1 year. Two distinct motor syndromes were produced. The first consisted of acute dystonic, dyskinetic, parkinsonian, and akathisia-like reactions, which worsened after each injection, were not exacerbated by drug withdrawal, and could be abolished or prevented with benztropine. The second appeared after cessation of neuroleptic treatment and consisted of abnormal movements very similar to those of patients with tardive dyskinesia (TD). This syndrome was abolished completely by reinstitution of fluphenazine treatment. One monkey was given a second and third course of fluphenazine, each course lasting 4 weeks. The second syndrome was seen after but not during each course and remained robust for a longer period after the third than after the first or second courses of treatment. We conclude that the first syndrome is analogous to the early appearing extrapyramidal symptoms of neuroleptic-treated patients and that, according to preliminary evidence, reversible TD may turn into irreversible TD with continued periods of on and off neuroleptic treatment.

Animals↗
PubMed1979

Naloxone enhancement of DMT and LSD-25 induced suppression of food-rewarded bar pressing behavior in the rat.

The narcotic antagonist naloxone was tested to determine its possible interaction with N,N-dimethyltryptamine (DMT) and lysergic acid diethylamide-25 (LSD) in adult male Holtzman rats trained to press a bar on a fixed-ratio four schedule (FR4), i.e., every fourth press earned a reward of 0.01 ml sugar sweetened milk. LSD (0.1 mg/kg) or increasing doses of DMT (1.0, 3.2, and 10.0 mg/kg) were administered i.p. to disrupt food-rewarded fixed ratio bar pressing in a dose related fashion. Pretreatment (5--10 min) with behaviorally ineffective doses of naloxone (1.0--5.6 mg/kg) dramatically enhanced the effects of DMT and LSD. The content of DMT in the brain and liver of rats injected with DMT alone (10 mg/kg) and with a 5 min pretreatment of naloxone (3.2 mg/kg) was determined by radiochemical analysis at 30 and 90 min after 14C-DMT injection. There was no significant difference for either brain or liver 14C-DMT levels when control DMT rats were compared with the naloxone pretreated rats. These results seem to rule out interference by naloxone with the metabolism of DMT as a mechanism of the observed behavioral potentiation.

Animals↗
PubMed1978

Interactions of partial LSD analogs with behavioral disrupting effects of LSD and DMT in the rat.

Adult male Holtzman rats were trained to barpress on a schedule whereby every fourth press earned a reward of 0.01 ml of sugar-sweetened milk (FR4). After an i.p. injection of LSD (0.1 mg/kg) or DMT (3.2 or 10 mg/kg) such barpressing is abolished completely and resumed, usually within an hour, at a rate near the preinjection control rate of pressing. It continues at a steady, uninterrupted pace until the animals are removed from the operant chamber one-half hour later. A series of N,N-diethylnipecotamide derivatives were synthesized and tested for their ability to modify the disruptive effect of these hallucinogens. N,N-diethylbutyramide (DBA) and 1-methyl-1,2,5,6-tetrahydropyridine-3-(N,N-diethylcarboxamide) (THPC) were also tested. Pretreatment with a single i.p. injection of any of these compounds (5--40 mg/kg) either had no effect on or else prolonged the duration of hallucinogen-induced cessation of barpressing.

Animals↗
PubMed1977

Effects of various neuroleptics on rabbit hyperthermia induced by N, N-Dimethyltryptamine (DMT) and d-amphetamine.

The effects of various neuroleptics were studied on N, N-dimethyltryptamine (DMT, 3.2 mg/kg) and d-amphetamine (3.2 mg/kg) induced hyperthermia in the rabbit. Complete dose-effect curves were obtained. The order of potency for antagonism of DMT-induced hyperthermia was: methiothepin greater than octoclothepin greater than or equal to oxyprothepin greater than perathiepin greater than dokloxythepin greater than mianserine greater than loxapine greater than oxypertine greater than chlorpromazine greater than pipamperone greater than fluphenazine greater than thiothixene greater than haloperidol greater than molindone. The order of potency for antagonism of d-amphetamine hyperthermia was: haloperidol greater than chlorpromazine greater than oxypertine greater than octoclothepin and methiothepin. For these five drugs, the order of potency for antagonism of amphetamine hyperthermia was the reverse of the order for antagonism of DMT hyperthermia. Methiothepin reduced d-amphetamine-induced hyperthermia effectively at a very high dose (0.32 mg/kg) and variably at lower doses. The results indicate that neuroleptics differ markedly in their specificity of antagonism of DMT and d-amphetamine which may act through different neurotransmitter mechanisms (tryptaminergic vs. adrenergic).

Animals↗