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Biomedical subjects

J Smitz

Publications and source records attributed to J Smitz.

At least 127 records · Page 7Linked to original sources

Receptors for corticotropin-releasing hormone in human pituitary: binding characteristics and autoradiographic localization to immunocytochemically defined proopiomelanocortin cells.

Using autoradiography combined with immunocytochemistry, we demonstrated that the target cells of CRH in the human pituitary were proopiomelanocortin cells. Scatchard analysis of [125I]Tyr0-oCRH saturation binding revealed the presence of one class of saturable, high affinity sites on pituitary tissue homogenate. The equilibrium dissociation constant (Kd) for [125I]Tyr0-oCRH ranged from 1.1-1.6 nM, and the receptor density was between 200-350 fmol/mg protein. Fixation of cryostat sections with 4% paraformaldehyde before tracer incubation improved both tissue preservation and localization of the CRH receptor at the cellular level. Additional postfixation with 1% glutaraldehyde inhibited tracer diffusion during subsequent immunocytochemistry and autoradiography. [125I]Tyr0-oCRH was found in cytoplasmic inclusions or at the cell periphery of ACTH/beta-endorphin cells in the anterior pituitary. Single cells of the posterior pituitary were also CRH receptor positive. Cells staining for PRL or GH were CRH receptor negative. We conclude that CRH binds only to high affinity receptors on ACTH/beta-endorphin cells in the human pituitary.

Adrenocorticotropic Hormone↗

Placental production of estradiol and progesterone after oocyte donation in patients with primary ovarian failure.

After oocyte donation 18 pregnancies were established in 17 patients with the absence of ovaries. Eight patients were delivered of nine healthy infants including one set of twins, six pregnancies were progressing normally, and four pregnancies were aborted. Four pregnancies were established after transfer of frozen-thawed embryos. In the simulated luteal phases, replaced with estradiol valerate and progesterone, pregnancies could be established and maintained as indicated by the profile of serum human chorionic gonadotropin concentrations. Weekly determinations of serum 17 beta-estradiol levels indicated significantly higher values at 7 weeks' gestation, as compared with week 5. This observation precludes that the luteoplacental shift occurred before 7 weeks' gestation. The weekly serum determinations of progesterone were significantly higher week 9, as compared with week 5. Two pregnancies were achieved after the vaginal administration of micronized progesterone.

Adult↗

Endocrinology in luteal phase and implantation.

The normality of the luteal phase after superovulation depends on the method and adequacy of the stimulation regimen. In comparison with natural cycles, the luteinisation of multiple follicles produces higher concentrations of steroids in blood, and soon after ovulation a correct ratio of serum oestradiol (E2) to progesterone is critical to establish viable pregnancies. Out of phase and asynchronous endometria can arise after stimulation with clomiphene (CC) alone or in association with human menopausal gonadotrophin (HMG), and pregnancies mostly arose in patients with advanced endometrial characteristics and elevated post-ovulatory levels of serum progesterone after HMG stimulation. Increasing plasma progesterone concentrations in the early luteal phase with natural progesterone can thus be considered as a rational approach to improve rates of implantation. Premature luteal regression is frequently observed after HMG stimulation whether or not in association with gonadotrophin releasing-hormone agonists (GnRHa). Support to the theca lutein cells is mandatory before sufficient human chorionic gonadotrophin (HCG) is produced by the embryo. Deficient luteal phases can be treated with hormonal support, but the efficacy of routine luteal supplementation after ovarian hyperstimulation has still to be proven in larger controlled trials.

Corpus Luteum↗

Short-term use of buserelin in combination with human menopausal gonadotrophins for ovarian stimulation for in-vitro fertilization in endocrinologically normal women.

Ten endocrinologically normal women were injected subcutaneously with 500 micrograms D-Ser(TBU)6-EA10-LHRH (buserelin) on days 3,4 and 5 after the start of the menses. Two types of response were observed. Five women (group A) responded promptly and had a mean number of 13.4 oocytes retreived after 11.4 days of stimulation. In the second group (B), two to three times more HMG was needed to obtain a mean number of 7.3 oocytes after 17.2 days of stimulation. The response upon stimulation could be predicted by the serum gonadotrophin output on days 4 and 5 of the cycle. One woman from group B had a premature LH rise on day 16 and luteinization; her cycle was abandoned. In the four other patients of group B, serum and urinary LH concentrations showed that pituitary gonadotrophin secretion had recovered before the ovulatory stimulus, without signs of premature luteinization. Two women in each group became pregnant, one of whom aborted. This short-term GnRH agonist treatment could be an alternative method for ovarian stimulation, although it did not totally prevent the occurrence of an endogenous LH surge.

Adult↗

Effects of natural progesterone on the morphology of the endometrium in patients with primary ovarian failure.

In 43 patients without ovaries, endometrial biopsies at day 21 of 75 substituted cycles were studied by light and electron microscopy. The morphology of the endometrium was compared after oral, vaginal or intramuscular administration of progesterone, and correlated with the serum levels of 17-beta oestradiol and progesterone and the pregnancies obtained after oocyte donation. After vaginal application of micronized progesterone, endometrial morphology closely matched that of a natural cycle. This therapy was able to support two ongoing pregnancies. No adequate endometrial response was noted after oral ingestion of progesterone. The maturation of the endometrium after intramuscular injections of progesterone in oil was heterogeneous. It was concluded that the vaginal route for administering micronized progesterone can be advised as the treatment of choice in patients without ovarian function.

Administration, Oral↗

Incidence of severe ovarian hyperstimulation syndrome after GnRH agonist/HMG superovulation for in-vitro fertilization.

In 1673 treatment cycles stimulated with buserelin and HMG, for IVF, GIFT or ZIFT, the severe ovarian hyperstimulation syndrome (OHSS) occurred in 10 cycles (0.6%). Eight patients were hyperandrogenic and showed an increased ovarian response to HMG. After replacement of a maximum of three embryos or zygotes, seven women became pregnant. Three women had a multiple gestation. All patients recovered uneventfully with conservative treatment. Support with progesterone or continuation of the agonist during the luteal phase did not prevent OHSS, confirming that the ovulatory HCG dose is the most important factor in inducing this severe complication. Luteal supplementation with HCG and/or HCG production during implantation could exacerbate OHSS.

Adult↗

An 18-month survey of infertility treatment by in vitro fertilization, gamete and zygote intrafallopian transfer, and replacement of frozen-thawed embryos.

An 18-month survey of infertility treatment by in vitro fertilization (IVF) and related procedures at the Centre for Reproductive Medicine of the Vrije Universiteit Brussel is described. During this period, 1326 treatment cycles were started in patients with long-standing infertility and 1135 oocyte retrievals were performed in 771 different patients. IVF and embryo transfer (ET) after laparoscopic (N = 793) or ultrasonically guided (N = 342) ovum pickup, gamete intrafallopian transfer (GIFT; N = 284), or zygote intrafallopian transfer (ZIFT; N = 15) combined with IVF as well as the replacement of cryopreserved embryos yielded an overall pregnancy rate of 21.8% per started cycle. Echographic and laparoscopic oocyte retrieval gave similar results except for a higher fertilization rate after echographic-guided retrieval. For in vitro fertilization and embryo transfer an overall pregnancy rate of 26% per transfer was obtained. For GIFT and ZIFT the pregnancy rates were, respectively, 27.8 and 46.7% per replacement. For each procedure one-third of the pregnancies aborted. After the replacement of frozen and thawed embryos, during a natural cycle, a significantly lower fetal loss was observed.

Adult↗

Synchronization of donor's and recipient's cycles with GnRH analogues in an oocyte donation programme.

In this oocyte donation programme nine female donors were stimulated using a combination of GnRH analogues and human menopausal gonadotrophins. A total of 149 oocytes were retrieved. Thirty fresh embryos were transferred in 14 uterine replacements, resulting in four pregnancies and 15 fertilized oocytes were placed in the Fallopian tube of six recipients, yielding two pregnancies. A mean number of 2.2 embryos was replaced. The implantation rate per embryo was 13%. Furthermore 36 embryos were cryopreserved for later use. Following 20 replacements, six pregnancies were established (30% per transfer); since two patients aborted, the ongoing pregnancy rate was 20%.

Adult↗

The effect of pneumoperitoneum gases on fertilization, cleavage and pregnancy in human in-vitro fertilization and gamete intra-fallopian transfer.

A prospective, randomized study was carried out, creating a pneumoperitoneum with 100% CO2 or with 5% CO2 in air and evaluating the effect(s) of these gas phases on fertilization, cleavage and pregnancy outcome in this in-vitro fertilization and embryo transfer programme. There was no significant difference in the fertilization rate when either 100% CO2 or 5% CO2 in air was used for insufflation during laparoscopy. Further, embryonic development and pregnancy rates also indicated no significant differences between the two groups. Similarly, the oocytes which were retrieved and replaced with spermatozoa in the gamete intra-Fallopian transfer programme using either 100% or 5% CO2, gave similar pregnancy rates. Furthermore, the fertilization and cleavage rates of the supernumerary oocytes were not significantly different in both groups.

Carbon Dioxide↗

Time of insemination and its effect on in-vitro fertilization, cleavage and pregnancy rates in GnRH agonist/HMG-stimulated cycles.

In this prospective study, we compared the effect of delayed inseminations on fertilization, cleavage and pregnancy rates in two groups of patients. In one group, the ovarian stimulation was performed with a clomiphene citrate/human menopausal gonadotrophin/human chorionic gonadotrophin (CC/HMG/HCG) protocol. The other group was pre-treated with gonadotrophin-releasing hormone agonist (GnRHa) and ovarian stimulation was carried out with an HMG/HCG protocol. Under both protocols, a delay of 2, 4 or 6 h in insemination showed no significant differences in the fertilization, cleavage or pregnancy rates. To find out which type of oocyte has the potential for better fertilization, cleavage and implantation, a simple oocyte classification scheme is proposed. In the GnRHa/HMG group, 9% post-mature, 90% mature and only 1% immature oocytes were retrieved. The post-mature oocytes showed a tendency towards reduced fertilization when insemination was delayed. The mature and slightly immature oocytes fertilized equally well when spermatozoa were added 2, 4 or 6 h after retrieval. Similarly, no significant difference was observed in the cleavage (80%) or fragmentation (20%) rates of these oocytes. The pregnancy rates after inseminations delayed for 2, 4 and 6 h were 14, 27 and 26%, respectively. Though these figures were not statistically significant, the 4- and 6-h groups in both the IVF and zygote intra-Fallopian transfer treatments showed a slightly improved pregnancy rate compared to the 2-h group. An insemination delay of 4 h is advocated on a routine basis.

Adult↗

Recurrent pancreatitis secondary to hypercalcemia following vitamin D poisoning.

A 66-year-old patient had been admitted four times for recurrent episodes of acute pancreatitis. At each time, elevated serum calcium levels, between 13.5-14.5 mg/dl, were found. Surgical drainage of necrotic pancreatic tissue had to be done on one occasion. Extensive investigations failed to disclose any conventional hypercalcemic disease. At his latest admission, the serum calcium level was 13.4 mg/dl, and the serum amylase level was 440 IU/L (N, less than 85). This time, the serum 25-OH vitamin D levels were investigated using radioimmunology and proved to be raised to 330 micrograms/L (normal, 16-74 micrograms/L). Specific questioning of the patient revealed that he had been taking regularly excessive quantities of vitamin supplements as a self medication. After stopping vitamin intake, his serum amylase levels returned to normal, and he had no more episodes of pancreatitis. This case illustrates vitamin D intoxication as a cause of recurrent pancreatitis. Measuring serum 25-OH vitamin D levels is advocated in pancreatitis associated with hypercalcemia of unclear origin.

Acute Disease↗

The respective effects of serum thyroxine and triiodothyronine on serum thyrotropin and lipid parameters in endemic juvenile hypothyroidism.

The respective effects of serum total T4 concentration and of serum total T3 concentration on serum TSH concentration and on lipid parameters were compared in 84 7- to 16-year-old children of the Northern Zaire goitre endemia classified in group A (T4 greater than 77 nmol/l and T3 greater than 1.69 nmol/l), B (low T4, normal T3) and C (low T4, low T3). Mean serum TSH level was normal in group A (2.3 mU/l), it raised to 39.4 mU/l in group B (p less than 0.001) and to 166.3 mU/l in group C (p less than 0.001 vs A and B). Low density lipoprotein cholesterol and apoprotein B were increased in group B vs A (p less than 0.05) and in group C vs A (p less than 0.001) and B (p less than 0.001 for apoprotein B; not significant for cholesterol). High density lipoprotein cholesterol and apoprotein A1 were similar in the three groups. Mean serum triglyceride level, not different in groups A and B, was doubled in group C (p less than 0.001). Multiple regression analysis showed that serum TSH, apoprotein B, and triglyceride levels were influenced by both thyroid hormones concentrations with a predominant effect of serum T4 on the first two parameters and of serum T3 on the last one. In conclusion, low serum T4 with normal T3 concentrations resulted in an increase in serum TSH and in an altered lipid metabolism; it clearly represented an hypothyroid state.

Adolescent↗

Hemodynamics of patients with renal failure treated with recombinant human erythropoietin.

Hemodynamics were evaluated in 8 patients with uncomplicated renal failure on regular dialysis before and after partial correction of anemia by treatment with recombinant human erythropoietin (r-huEPO). Under r-huEPO treatment, mean (+/- SD) hemoglobin increased from 7.51 (0.60) to 10.27 (0.92) g/dl. Mean blood pressure, body weight, total blood volume and extracellular fluid compartment remained unchanged. Cardiac output as measured with a radionuclide method increased significantly from 4622 (1069) to 5393 (1285) units (p less than 0.02) and peripheral resistance decreased from 22 (4) to 19 (3) units (p less than 0.02). 6-keto-1-alpha-prostaglandin decreased from 96.9 (54.4) to 61.6 (18.0) pg/ml (p less than 0.05) but plasma renin activity, noradrenalin and atrial natriuretic peptide remained unchanged comparing pre- and post-treatment levels. This observation suggests that an increase of red blood cell mass can improve heart function in patients undergoing regular dialysis treatment.

Adult↗

Perurethral ultrasound-guided ovum pickup.

Either a percutaneous-transvesical, a transvaginal, or a perurethral-transvesical approach can be used for oocyte recovery under ultrasound guidance in an in vitro fertilization and embryo transfer program. After having experienced these three different approaches in our program, we preferentially used the perurethral-transvesical approach as our routine technique for oocyte recovery under ultrasound guidance. We feel that this method is easier to perform and also carries less risk for contamination. From January to December 1986, 186 oocyte retrievals under ultrasound guidance were performed. In 7 cases no oocytes were found despite normal ovarian stimulation. A total of 767 oocytes was collected; the fertilization rate was 71.8%. Forty pregnancies were achieved (21.5% per attempt or 27.7% per embryo replacement). Except for transient hematuria, no complications were observed.

Chorionic Gonadotropin↗

Inhibition of gonadotropic and ovarian function by intranasal administration of D-Ser (TBU)6-EA10-LHRH in normo-ovulatory women and patients with polycystic ovary disease.

We investigated the effectiveness of D-Ser (TBU)6-EA10-LHRH (Buserelin) intranasally 600 micrograms/day given 6 times daily in desensitizing normal ovulatory women and patients with polycystic ovarian disease (PCOD) before initiation of ovarian stimulation for in vitro fertilization. We found that this regimen was sufficient to suppress the gonadotrophs in the normal women and in 8 out of 10 PCOD patients. In PCOD ovarian hormones became normal after Buserelin administration. Adrenal steroidogenesis was not affected by the GnRH agonist. We suggested that the frequency of administration of Buserelin was important to achieve a constant receptor binding and consequently a rapid desensitization. The choice of a monoclonal immunoradiometric assay for luteinizing hormone (LH) and follicle stimulating hormone (FSH) in association with the estradiol-benzoate provocation test were essential in evaluating desensitization.

Administration, Intranasal↗

Hormonal monitoring for in-vitro fertilization and related procedures.

Details of the endocrine monitoring of patients during in-vitro fertilization are analysed. Hormones usually measured are 17 beta-oestradiol, FSH, LH, progesterone and HCG. The assays must be rapid, robust, and have satisfactory precision and reproducibility. Radioimmunoassays have become standardized but immunoradiometric assays are being introduced, where the antibodies can be more easily labelled than antigens, but need care with very high concentrations of antigen. Enzyme immunoassays also have advantages: they are less hazardous than radioimmunoassays and the labelled materials have longer shelf-lives. Chemiluminescence has also been introduced, together with time-resolved fluoroimmunoassays, representing simpler, perhaps cheaper and improved methods. Immunoassays by latex particle counting offer the advantage of being completely automated. Practical examples of these methods are given with details of the treatment of individual patients.

Chorionic Gonadotropin↗

Addition of Buserelin to human menopausal gonadotrophins in patients with failed stimulations for IVF or GIFT.

The combined therapy of a gonadotrophin-releasing hormone agonist (GnRHa) D-Ser(TBU)6-EA10-LHRH (Buserelin) and human menopausal gonadotrophins (HMG) for ovarian stimulation for in-vitro fertilization and gamete intra-Fallopian transfer was evaluated during 84 cycles. All women selected for this therapy had previously failed stimulations with clomiphene citrate/HMG. The GnRHa prevented spontaneous luteinizing hormone surges and premature luteinization in all patients. After addition of the agonist to HMG, the cancellation rate dropped from 17 to 7% and improved the results in 72.6% of the cycles. Twenty-six per cent of the started cycles resulted in a pregnancy. Eighteen healthy children were born at term.

Buserelin↗

Hyperstimulation: the need for cryopreservation of embryos.

Successful application of in-vitro fertilization (IVF), zygote intra-Fallopian transfer (ZIFT) and gamete intra-Fallopian transfer (GIFT) requires ovarian hyperstimulation for the maturation of multiple follicles. To control the risk of multiple pregnancies, the number of gametes (GIFT) or embryos (IVF, ZIFT) replaced is limited to three. For the supernumerary embryos resulting from IVF, ZIFT or GIFT, the strategy is cryopreservation for a later transfer. Cryopreservation was performed using either dimethylsulphoxide or 1,2-propanediol as a cryoprotective agent. Embryos were frozen either in the pronucleate stage with 1,2-propanediol or in the multicellular stage with dimethylsulphoxide or 1,2-propanediol. Survival after thawing was scored for both cryoprotective agents as a function of the developmental stage of the embryo and the embryonic quality. Evaluation of survival after thawing was performed on the basis of morphological intactness of the 1-cell pronucleate embryo or of the blastomeres of multicellular embryos. For pronucleate stage embryos, the use of 1,2-propanediol resulted in a 60% survival after thawing. For 2-cell stage embryos the survival was similar for dimethylsulphoxide and 1,2-propanediol. Later stage embryos survived better when dimethylsulphoxide was the cryoprotectant. For all stages, embryo quality before freezing was a crucial factor in survival after thawing. The pregnancy rate (12.2%) was similar for the two cryopreservation protocols. In conclusion, the choice of an appropriate cryoprotective agent can increase the survival after thawing when embryos are of good quality before freezing.

Cryoprotective Agents↗