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Biomedical subjects

J M Brandes

Publications and source records attributed to J M Brandes.

At least 37 records · Page 2Linked to original sources

Transvaginal embryo aspiration--a safe method for selective reduction in multiple pregnancies.

OBJECTIVE: To evaluate pregnancy outcome after transvaginal selective embryo aspiration and to compare the results with those reported previously with other techniques for selective abortion. DESIGN: Retrospective case series. SETTING: University-based in vitro fertilization (IVF) program. PATIENTS: Nineteen women with multiple pregnancy who conceived after ovulation induction or IVF/gamete intrafallopian transfer. INTERVENTION: Transvaginal ultrasound-guided aspiration of the embryo(s) was performed at 7 to 8 weeks of gestation. MAIN OUTCOME MEASURES: Early and late complications related to the procedure, outcome of pregnancy, and birth weight. RESULTS: In 18 cases, the initial number of embryos (3 to 7) was reduced to two. In 1 case, the number of embryos was reduced from 4 to 3. None of the remaining fetuses vanished after the procedure. One patient delivered at 25 weeks and all other patients delivered healthy, viable infants (a pregnancy loss rate of 5.3%). CONCLUSIONS: Transvaginal embryo aspiration in early gestation appears to be a simple and relatively safe procedure for selective termination in patients with high-order multiple pregnancy. The cumulative loss rate of selective termination procedures previously reported by others is three times higher than the loss encountered in our series. This earlier procedure may be more acceptable to patients from emotional and religious points of view.

Abortion, Induced↗

Pregnancy after subzonal insertion of cryopreserved spermatozoa from a patient with testicular seminoma.

The first pregnancy established after subzonal insertion of frozen-thawed sperm obtained from a patient with seminoma and severe oligoasthenospermia is reported. A total of 800,000 sperm with a poor progressive motility were recovered after thawing. Three to seven motile spermatozoa were injected into the perivitelline space of each of 10 oocytes, and seven sibling oocytes were coincubated and inseminated with 200,000 motile sperm/mL. Only 1 of the manipulated oocytes fertilized and was transferred to the uterus 65 hours after insemination at the eight-cell stage. A healthy boy weighing 3,600 g was delivered spontaneously at 38 weeks of pregnancy. This report gives hope to patients with testicular malignancy and severely impaired sperm function to maintain their reproductive potential through sperm banking and assisted fertilization techniques.

Adult↗

Spontaneous fetal reduction in multiple gestations assessed by transvaginal ultrasound.

OBJECTIVE: To assess the occurrence of disappearance of one or more of the fetuses in pregnancies which start as multiple gestation. DESIGN: Observational study. SETTING: Infertility section, Rambam Hospital, Haifa. SUBJECTS: 88 women with multiple gestations, established after ovulation induction (54 twin, 26 triplet, five quadruplet, and three quintuplet) and diagnosed by transvaginal ultrasound at 5-6 weeks, in all of whom absorption of at least one gestation sac was detected at follow-up ultrasound scan. INTERVENTIONS: Follow-up by serial transvaginal and later abdominal ultrasound scan throughout pregnancy. RESULTS: Of the 54 twin gestations, 51 ended in the birth of a singleton and three in miscarriage. Of the 26 pregnancies starting as triplets, 12 ended in singleton births, 12 in twins and two miscarried. The five quadruplet gestations resulted in one singleton birth, one set of twins, two triplets, and one ended in late miscarriage. Of the three quintuplet pregnancies, two resulted in the birth of triplets, one of them after spontaneous, the other after iatrogenic fetal reduction. In the third quintuplet pregnancy, one fetus vanished spontaneously and another was subject to iatrogenic reduction, two fetuses survived and were liveborn. Of the 221 fetuses identified 107 (48%) vanished spontaneously. CONCLUSION: Iatrogenic fetal reduction should be delayed until 12 weeks gestation in quadruplet or higher multiple gestations, but is probably not indicated in twin and triplet gestations.

Adult↗

The influence of mercury on the secretion of human chorionic gonadotropin in superfused young placental tissue.

The effect of mercury (Hg), as HgCl2, in levels ranging from 0.75 to 12 micrograms/ml medium, on the secretion of human chorionic gonadotropin (hCG) was examined in first-trimester placental explants, after 6 or 24 hr incubation, employing both static and dynamic systems (the latter by superfusion). Later the unbound Hg was washed for 45 min. with fresh medium devoid of Hg, followed by superfusion with the latter medium for 75 min., during which time samples were collected for hCG assay. For the superfusion experiments the parameters used for evaluating the hCG secretion pattern were: mean peak amplitude, pulse frequency and the area under the hCG secretion curve (AUC). The results observed after 24 hr incubation indicate that in the dynamic system the hCG secretion increased significantly, and this increase was dose-dependent. There was also a dose-related increase in mean total hCG secreted by the explants exposed to Hg. Maximal hCG secretion was observed after 24 hr exposure of explants to 6 micrograms of the metal/ml. Both the mean peak amplitude and AUC parameters showed a statistically-significant increase for this dose level. At 12 micrograms/ml, the pulsatile secretion of hCG decreased, but the value for the mean hCG secretion was still higher than that observed for 0.75 and 3 micrograms/ml. After 6 hr incubation, however, there were no significant changes from the control, as judged by all of the above parameters. The levels of hCG secreted by the explants into the media in the static system were not significantly different from their respective controls, for both incubation periods and Hg levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Chorionic Gonadotropin↗

Enzyme activities in the term human placenta: in vitro effect of cadmium.

The effect of cadmium (Cd) as CdCl2 on some placental enzyme activities were studied after explants had been incubated with the salt for 6 or 24 hr. The results indicated that, for both incubation periods, Cd at low doses had a stimulatory effect on aryl hydrocarbon hydroxylase (AHH) (a phase I enzyme) and on quinone reductase and catecholamine-O-methyltransferase (COMT) (both phase II enzymes). This effect was dose- and time-dependent. Only the activities of AHH and COMT showed a biphasic response, (i.e., increases at the lower dose levels and decreases with the higher ones), whereas that of quinone reductase continually increased with all the dose levels of the metal administered. Glucose-6-phosphate dehydrogenase (G-6-PD) activity was found to be inhibited at all the dose levels of Cd tested, the effect also being time- and dose-dependent. In conclusion, it appears that the use of placental explants can serve as a valuable means for studying the toxic effects of certain xenobiotics, as reflected in the activity of various important enzymes.

Analysis of Variance↗

Growth hormone (GH)-binding protein regulation by estrogen, progesterone, and gonadotropins in human: the effect of ovulation induction with menopausal gonadotropins, GH, and gestation.

The recently described serum GH-binding protein (GH-BP) may reflect the GH-receptor level. To assess the serum GH-BP levels under various physiological and supraphysiological levels of sex steroids, we have evaluated its concentration in 26 patients undergoing 34 cycles of ovulation induction with either human menopausal gonadotropins (hMG)/hCG or GH/hMG/hCG. The latter ovulation induction protocol was undertaken in "Clonidine negative" patients in a prospective, randomized, crossed-over manner, between GH/hMG/hCG or hMG/hCG. The increase in GH-BP levels in patients' sera undergoing ovulation induction directly correlated with peripheral estradiol (E2) (r = 0.577; P < 0.001), and with peripheral progesterone (P4) (r = 0.542; P < 0.001; n = 174) concentrations in hMG/hCG cycles, and also in GH/hMG/hCG cycles (r = 0.669, P < 0.001 for E2, and r = 0.722, P < 0.001 for P4, n = 84). GH-BP levels did not change significantly in response to 0.15 mg Clonidine ingestion. The baseline GH-BP levels significantly correlated with the body mass index of 47 patients (r = 0.547; P < 0.001). The insulin-like growth factor-I (IGF-I) concentrations increased in correlation with increasing E2 levels up to 5500 pmol/L but decreased thereafter, at very high E2 concentrations. In gestations generated by ovulation induction with hMG/hCG or GH/hMG/hCG, longitudinal measurements of GH-BP levels showed an initial sharp increase during early gestation, followed by a gradual decrease beginning around the end of the first trimester and continuing during the mid and late trimesters. In normal spontaneous pregnancies, GH-BP levels, measured from the fifth week until term, were negatively correlated with gestational age (r = -0.581; P < 0.001; n = 84). This pattern is highly suggestive of the possibility that GH-BP is coregulated not only with E2 and P4 but also with hCG, and possibly other gonadotropins as well. Indeed, in patients with "resistant ovaries", pharmacological amounts of hMG failed to increase E2 concentrations but moderately increased GH-BP levels. These data provide good indirect evidence for coregulation of the GH-BP with both sex steroids and gonadotropins. The mid and late trimesters decrease in GH-BP levels in spite of increasing sex steroids concentrations, may be attributed to the decreasing hCG concentrations, and/or to the increasing secretion of placental lactogen (PL) and placental GH with the advancing gestation.

Carrier Proteins↗

Growth and development of children conceived by in vitro fertilization.

To assess the physical and mental development of infants born after in vitro fertilization (IVF), we performed a general physical and developmental examination (Bayley and Stanford-Binet scales) on a cohort of 116 IVF children, conceived and born at our institution between February 1985 and March 1989, and on 116 non-IVF matched controls. Study and control groups were each composed of 66 singletons, 19 pairs of twins and 4 sets of triplets, whose age at examination ranged from 12 to 45 months. The developmental indices of IVF infants were within the normal range and did not differ from those of their matched controls. The indices were positively correlated to gestational age, birth weight, head circumference at birth and at examination, and mother's education. Mean birth weight, gestational age, and birth weight percentile of IVF infants were lower than the mean of the healthy population. Mean percentiles of weight and length at examination (mean age 22.4 months) were equally low but did not differ from those of the matched controls. However, mean percentiles of head circumference at birth and at examination compare well with the normal mean, both in IVF and control groups. Twins and triplets (IVF and controls) had significantly lower physical and mental indices as compared to singletons.

Analysis of Variance↗

Parathion transfer and acetylcholinesterase activity in an in-vitro perfused term human placenta.

Organophosphate transport through the placenta was investigated in an in-vitro placental perfusion system. The system consisted of maternal and fetal reservoirs in which Krebs Ringer bicarbonate buffer with heparin, albumin and glucose was circulated at a constant pH, temperature and pO2. Parathion was analysed by means of gas chromatography with a N-P detector. 14C Antipyrine, a lipid soluble salt, was used as an internal standard, which allowed for the difference in placental size and permeability. A certain amount of parathion passed the placenta and reached the fetal compartment. Glucose consumption was not influenced by the introduction of parathion; neither was the water content of the placental tissue. Acetylcholinesterase activity in placental tissue decreased 50%. The amount of parathion transferred was not negligible and could have caused damage to a fetus.

Acetylcholinesterase↗

Differentiating malignant from benign ovarian tumors with transvaginal color flow imaging.

The impedance to blood flow was examined by transvaginal color flow imaging in 53 ovarian masses before exploratory laparotomy. Serum CA 125 levels were measured in all subjects. Thirty-six had benign ovarian tumors and 17 had malignant ovarian tumors confirmed by histopathologic examination. Intratumoral blood vessels, detected in 16 of the malignant tumors, consistently demonstrated low impedance to flow, with a pulsatility index (PI) always below 1. The PI of the intraovarian or intratumoral blood vessels was greater than 1 in 35 of the 36 benign tumors, although 11 had suspicious sonographic findings (P less than .01) and 14 had elevated CA 125 levels (P less than .001). The sensitivity and specificity of the preoperative PI in detecting malignant ovarian tumors were 94 and 97%, respectively. The sensitivity and specificity of preoperative suspicious sonographic findings in detecting malignant ovarian tumors were 94 and 69%, and those of elevated preoperative serum CA 125 levels were 82 and 61%, respectively. Our results suggest that transvaginal color flow imaging may be a useful clinical tool in the preoperative evaluation of ovarian masses.

Adult↗

The physical and psychomotor development of children conceived by IVF and exposed to high-frequency vaginal ultrasonography (6.5 MHz) in the first trimester of pregnancy.

We examined the physical and psychomotor development of 33 infants conceived by in vitro fertilization (IVF) who were exposed to high-frequency transvaginal ultrasonography (HFTVS) (6.5 MHz) in the first trimester of pregnancy. The study group was composed of 21 singletons and six sets of twins. Thirty-three non-IVF controls were matched for birth weight, gestational age, sex, birth order, order in multiple delivery, mode of delivery, age at examination and parental age and education. Forty-five IVF infants who were not exposed to HFTVS and their matched controls also served as comparison groups. The Bayley scales were used to assess the psychosocial development of the infants studied. Increases in preterm delivery, low birth weight and Cesarean section rates were within the acceptable range for IVF babies. Mean birth weight, gestational age and birth weight percentiles of exposed IVF infants were lower than the expected mean for a normal population, but did not differ from that of non-exposed IVF infants. Mean percentiles of weight and length at examination were also low but not different from those of non-exposed IVF and matched control groups. However, percentiles of head circumference were normal at birth and at examination both in study and control groups. Overall, Bayley scores of exposed IVF infants were within the normal range and did not differ significantly from those of their matched controls and non-exposed peers. These scores were significantly correlated to birth weight, percentiles of birth weight and head circumference at birth and at examination, and to the mother's education. Twins had lower physical and mental indices than singletons, but did not differ from their controls.

Journal Article↗

Transfer and accumulation of cadmium, and the level of metallothionein in perfused human placentae.

The purpose of the present study was to investigate the effect of perfusion with a medium containing 12 or 24 micrograms Cadmium (as CdCl2) per ml on this metal's accumulation, transfer rate and metallothionein (MT) level. The experiments were performed with an isolated lobule of a dually-perfused human term placenta. Placental cell integrity and viability were characterised by their morphology and metabolic function, manifested in the tissue's electron microscopic structure and glucose and oxygen (O2) consumption, respectively. Perfusion with 24 micrograms Cd/ml medium for 5 h resulted in significant elevation in MT. The transfer rate of Cd to the fetal side of the placenta was very slow, and not until 40 min after the addition of Cd into the maternal side was a significant increase in the metal's level observed in the fetal perfusate. Thereafter, the level of the metal increased gradually and reached a steady state about 1 h later, at a level which was less than 1/20th of its concentration in the maternal perfusate. There was a 60-fold increase in Cd level in the cytosolic fraction obtained from the Cd-treated samples. At 12 micrograms Cd/ml no significant changes were noted in morphology, metabolic function and MT content. None of the Cd levels caused a significant change in O2 and glucose consumption, in spite of the fact that with the higher Cd dose the microstructure of the tissue showed some pathological changes. The observed elevation in MT may provide the fetus some protection against the harmful effects of the metal.

Cadmium↗

Dopa reaction test in hair bulbs of fetuses and its application to the prenatal diagnosis of albinism.

No information is available on the amount of tyrosinase normally present in fetuses. A dopa reaction test in hair bulbs from the scalp of normal fetuses obtained after abortion showed that tyrosinase is present in fetuses as early as 17 weeks. Only faint activity was detected in skin specimens other than from the scalp. This assay can serve as a quick and reliable method for the prenatal diagnosis of tyrosinase-negative albinism.

Albinism, Oculocutaneous↗

Management of triplet pregnancies in the 1980s--are we doing better?

The incidence of triplet pregnancies has increased with the introduction of ovulation induction agents and is expected to further increase with the implementation of multiple embryo transfer in the in vitro fertilization programs. We review our experience with 29 triplet pregnancies in the last 10 years. Despite early sonographic diagnosis, close follow-up, increased use of tocolytics, and prophylactic cervical suture, we could not document prolongation of pregnancy, increased infants' weight, or a significantly decreased perinatal mortality, which still remains about 14%. Furthermore, the use of cesarean section as the delivery method of choice did not change the well-documented unfavorable relationship between birth order and fetal outcome. There is an urgent need for prospective assessment of the value of different treatment modalities, which nowadays becomes possible with the increasing incidence of triplet pregnancies. The prevention of triplet pregnancies or treatment by selective fetal reduction deserves a second thought.

Adult↗

In vitro effect of mercury on aryl hydrocarbon hydroxylase, quinone reductase, catecholamine-O-methyltransferase and glucose-6-phosphate dehydrogenase activities in term human placenta.

The effect of HgCl2 on human term placental aryl hydrocarbon hydroxylase (AHH), quinone reductase (QR), catecholamine-O-methyltransferase (COMT), and glucose-6-phosphate dehydrogenase (G-6-PD) enzyme activities was studied after incubation of placental explants with the salt for either a 6 or 24 hr period. Mercury (Hg) increased the activities of AHH, QR and COMT, but decreased that of G-6-PD. The increases in enzyme activities, as well as the decrease in G-6-PD activity observed were in all cases time- and dose-dependent. The data suggest that Hg exerts an enhancing effect on the activity of placental phase I enzyme (AHH) and phase II enzymes (QR and COMT). This enhancement may be due to increased de novo synthesis, elimination of some suppressing agent(s), or the decreased breakdown of enzyme protein. Also, the inhibitory effect of Hg on G-6-PD activity appears to indicate that this enzyme is appreciably more sensitive to Hg than the other three enzymes. These findings may imply increased cellular resistance to Hg toxicity. The altered state of activity may also be used as a tool for monitoring exposure to this metal.

Aryl Hydrocarbon Hydroxylases↗

Synergistic effect of growth hormone and gonadotropins in achieving conception in "clonidine-negative" patients with unexplained infertility.

Based on preliminary reports by others and by us of a potentiating effect of growth hormone (GH) on human menopausal gonadotropin (hMG)-induced ovulation, a study using a randomized, prospective, cross-over protocol between GH + hMG/human chorionic gonadotropin (hCG) and hMG/hCG was undertaken. The study included patients with long-standing (2-11 years) unexplained infertility with a negative or reduced GH response to clonidine (up to 150 micrograms of clonidine orally). The first cycle was randomly assigned between GH/hMG/hCG (study cycle) and hMG/hCG alone (control cycle), and after an interval cycle the patient's treatment was crossed over. All patients who completed the study had previously undergone 1-20 attempts at ovulation induction for in vitro fertilization (IVF) and 5-40 cycles of ovulation induction for in vivo fertilization at three different medical centers. Three patients conceived on the combined GH/hMG cycle, with diminution in the hMG consumption needed for ovulation induction in the study cycles. Another patient with long-standing mechanical infertility underwent 11 abortive attempts at ovulation induction with hMG for IVF but has never achieved egg retrieval. On the GH/hMG/hCG ovulation induction cycle, three mature ova were retrieved as opposed to no response and cancellation of the "hMG only" cycle. Another patient with 11 years of primary infertility who had undergone 21 previous attempts at ovulation induction and had reached follicular aspiration in only three of those cycles conceived spontaneously on the first cycle after the GH/hMG/hCG IVF/ET cycle. All four pregnancies that have been achieved by now in seven GH/hMG-treated patients ended in cesarean deliveries of four normal male neonates. No correlation was found between the follicular fluid levels of insulin-like growth factor I (IGF-I) and the fertilization rate in vitro. The peripheral IGF-I levels were significantly higher during the follicular phase of the study cycles than during the respective stage of the control cycles or the luteal phase of either cycle. A study of serum GH-binding protein (GH-BP) levels revealed gradual increases in the late follicular phase, in the luteal phase, and in early pregnancy. On the basis of this study and in keeping with earlier reports, we conclude that the addition of GH to hMG/hCG may serve as a contributory adjunct in selected patients. However, in contrast to others who could not find a correlation between the response to acute tests for GH release and the ovarian response to combined treatment, we conclude that the clonidine test can play a discriminatory role in identifying patients who may benefit from this innovative combination.

Adult↗

Transplacental transfer of ritodrine and its effect on placental glucose and oxygen consumption in an in vitro human placental cotyledon perfusion.

Maternofetal transfer of ritodrine and its effect on placental glucose and oxygen consumption were studied using a recycling perfusion of maternal and fetal circulations of an isolated cotyledon of a term human placenta. 3H-labeled ritodrine was introduced into the maternal side of the perfusion system. Transfer was calculated from the linear rise of ritodrine concentrations on the fetal side and was found to be 7.31 +/- 1.02 ng/g placental wet weight/min (SEM) when 1.4 micrograms/ml of ritodrine was used (n = 3) and 14.7 +/- 1.06 ng/g placental wet weight/min when the concentration was 2.8 micrograms/ml (n = 5). The antipyrine transfer rate, 4.1 +/- 0.51 mg/kg/min (n = 8), was used to demonstrate perfusion adequacy and served as an internal standard. Upon computing the mass balance of ritodrine and antipyrine at the end of the experiment, it was found that 17% of ritodrine disappeared from the perfusion system compared to 0.7% of antipyrine (p less than 0.01). The introduction of ritodrine into the perfusion system did not affect placental glucose and oxygen consumption rates of 0.35 +/- 0.01 mumol/g/min (n = 7) and 0.19 +/- 0.013 mumol/g/min (n = 5), respectively.

Antipyrine↗

Induction of preovulatory luteinizing hormone surge and prevention of ovarian hyperstimulation syndrome by gonadotropin-releasing hormone agonist.

OBJECTIVE: To use gonadotropin-releasing hormone agonist (GnRH-a) instead of human chorionic gonadotropin (hCG) to induce oocyte maturation for in vitro fertilization (IVF). DESIGN: Pituitary and ovarian responses to GnRH-a and the outcome of IVF were studied prospectively. Data from patients injected with hCG were analyzed retrospectively. SETTING: Program of IVF at the Rambam (Governmental) Hospital, Haifa, Israel. PATIENTS AND INTERVENTIONS: One or two doses of buserelin acetate 250 to 500 micrograms were administered to six patients with moderate response (Estradiol [E2], 1,494 +/- 422 [+/- SD] pg/mL) and 8 patients with exaggerated response (E2, 7,673 +/- 3,028 pg/mL) to gonadotropin stimulation. Progesterone (P) and E2 were administered for luteal support. MAIN OUTCOME MEASURES: Gonadotropin-releasing hormone agonist effectively triggered luteinizing hormone (LH)/follicle-stimulating hormone (FSH) surge. Mature oocytes were recovered in all patients. Luteal E2 and P were lower than in patients injected with hCG. No signs of ovarian hyperstimulation syndrome were observed. RESULTS: Serum LH and FSH rose over 4 and 12 hours, respectively, and were significantly (P less than 0.05) elevated for 24 hours. Of all mature oocytes, 67% fertilized and 82% cleaved. Four pregnancies were obtained. CONCLUSIONS: A bolus of GnRH-a is able to trigger an adequate midcycle LH/FSH surge, resulting in oocyte maturation and pregnancy. Our preliminary results also suggest that it allows a more accurate control of ovarian steroid levels during the luteal phase and may prevent the clinical manifestation of ovarian hyperstimulation syndrome.

Buserelin↗