Search PubMed⌕ Search

Biomedical subjects

B Imthurn

Publications and source records attributed to B Imthurn.

35 records · Page 2Linked to original sources

The chromosomal complements of multipronuclear human zygotes resulting from intracytoplasmic sperm injection.

Implementation of intracytoplasmic sperm injection (ICSI) in human in-vitro fertilization (IVF) has highlighted the need for information about the risk of nuclear spindle damage caused by this procedure. For this purpose we studied the final products of oocyte meiosis at the first cleavage division of multipronuclear zygotes arising after ICSI, and compared the results with abnormally fertilized oocytes after conventional in-vitro insemination. Of 37 successfully analysed tripronuclear zygotes, 18 had three individual metaphases. Abnormal complements of 11 zygotes in this group indicated that non-disjunction occurred predominantly at the second meiotic division of the oocytes. Nine of the 37 tripronuclear zygotes exhibited two individual metaphases. Seven were abnormal and there were some indications that non-disjunction took place during oocyte meiosis. Of the 37 tripronuclear zygotes, 10 had a single metaphase and three showed an aneuploid number of chromosomes. The overall rate of aneuploidy among tripronuclear microinjected zygotes was 56.7%. In addition, seven zygotes with more than three pronuclei arising after ICSI displayed severely depleted chromosome complements. The incidence of non-disjunction in oocytes fertilized by conventional in-vitro insemination was significantly lower (20.0%, P < 0.01), since only four zygotes had an aneuploid number of chromosomes. Our findings suggest that ICSI might interfere with regular chromosome segregation at the second meiotic division of the oocytes.

Aneuploidy↗

[Intracytoplasmic versus subzonal spermatozoa injection. A comparison of 2 different methods of micro-assisted fertilization].

In order to define the usefulness of subzonal sperm insertion (SUZI) and intracytoplasmic sperm injection (ICSI), we studied in a comparative trial 46 consecutive treatment cycles of microassisted fertilisation by SUZI and ICSI. By ICSI 9% of the oocytes in metaphase II were damaged in 26 treatment cycles, by SUZI, however, not one single egg in 20 cycles (p < 0.001). Fertilisation rate after ICSI (65%) was, particularly in cases with combined sperm defects as well, significantly higher than after SUZI (35%; p < 0.001). Additionally, after ICSI a higher transfer (100% vs. 75%; p < 0.05) and pregnancy rate could be obtained (38% vs. 10% per cycle; p < or = 0.05). At the moment, 3 healthy children are born (2 after SUZI, 1 after ICSI), 4 patients are in the 2nd and 3rd trimenon, respectively, the remaining 5 patients aborted. In conclusion, the ICSI technique yields better results than SUZI, especially in cases of very severe male subfertility.

Cytoplasm↗

Evidence for in vivo high-frequency periodicity of plasma beta-endorphin in humans.

OBJECTIVE: To investigate whether high-frequency periodic fluctuation in the release of plasma immunoreactive (ir)-beta-endorphin occurs in humans. DESIGN, PATIENTS AND MEASUREMENTS: Blood was collected at 90-sec intervals for 1 hour from the forearm vein of four healthy women and subsequently analysed for ir-beta-endorphin by radioimmunoassay. RESULTS: In all women circulating beta-endorphin release followed a high-frequency periodic rhythm pattern. The estimated spectral densities within the four subjects varied between 3.6 min to 4.9 min. CONCLUSIONS: Our results provide the first in vivo evidence that fluctuations in the release of beta-endorphin in humans cannot only be characterized by low-frequency pulses, but also by a high frequency periodic rhythm.

Adult↗

Effects of nitric oxide on human spermatozoa: evidence that nitric oxide decreases sperm motility and induces sperm toxicity.

Endogenous nitric oxide (NO) is an important functional mediator in several physiological systems, including the reproductive system. However, when generated in excessive amounts for long periods, mainly during immunological reactions, NO is cytotoxic and cytostatic for invading microbes, as well as for the cells generating it and the tissues present around it. Since infertility associated with urogenital tract infection in males and females is also accompanied by reduced sperm motility and viability, it is possible that reduced fertility in these patients is due to NO-induced sperm toxicity. We therefore evaluated the direct effects of NO, chemically derived from S-nitroso-N-acetylpenicillamine (SNAP, 0.012-0.6 mM) and sodium nitroprusside (SNP, 0.25-2.5 mM), on the motility and viability of human spermatozoa. Furthermore, we tested whether inhibition of NO synthesis prevents sperm motility and viability by incubating washed total cells present in the semen (spermatozoa, round cells) with N-nitro-L-arginine-methyl-ester (L-NAME), a NO synthesis inhibitor. Treatment of purified spermatozoa with SNAP or SNP decreased forward progressive sperm motility and straight line velocity, and also increased the percentage of immotile spermatozoa in a concentration-dependent manner. Furthermore, the percentage of immotile spermatozoa positively correlated with the percentage of dead spermatozoa. In contrast to freshly prepared SNAP, SNAP preincubated for 48 h had no effect on the motility and viability of the spermatozoa. Furthermore, as compared to untreated controls, a significantly higher percentage of forward progressive sperm motility as well as viability (P < 0.05) was maintained in washed semen incubated with L-NAME (0.15 mM).(ABSTRACT TRUNCATED AT 250 WORDS)

Arginine↗

Circulating nitric oxide (nitrite/nitrate) levels in postmenopausal women substituted with 17 beta-estradiol and norethisterone acetate. A two-year follow-up study.

Postmenopausal women (PMW) have an increased risk of cardiovascular disease that is attenuated by hormone replacement therapy (HRT). Inasmuch as hypertension and atherosclerosis are associated with diminished endothelium-derived nitric oxide (NO), we investigated whether HRT augments NO release in PMW. We determined serum levels of nitrite/nitrate (NO2 + NO3) at baseline and during the 6th, 12th, and 24th months of the study in two groups of PMW. One group (HRT-PMW, n = 13) received continuous transdermal administration of 17 beta-estradiol (Estraderm-TTS-50) supplemented with oral norethisterone acetate (NETA) on days 1 through 12 of each month, and the other group (control PMW, n = 13) did not receive HRT. Blood samples in the HRT-PMW group were collected without regard to whether subjects were taking NETA at the time of blood sampling. Serum NO2 + NO3 levels increased in HRT-PMW for the duration of the study, whereas serum NO2 + NO3 levels remained unchanged in control PMW. When all samples regardless of timing of collection with respect to NETA treatment were included in the statistical analysis, the change in NO2 + NO3 levels in HRT-PMW was significantly greater compared with the change in control PMW (P = .037). Likewise, when only those samples collected when estradiol-treated subjects were not taking oral NETA were included in the statistical analysis, the change in NO2 + NO3 levels in the HRT-PMW group remained significant (P = .047) compared with control PMW.(ABSTRACT TRUNCATED AT 250 WORDS)

Drug Therapy, Combination↗

Endogenous nitric oxide modulates endothelin-1 induced contraction of bovine oviduct.

We recently reported that oviduct epithelial cells in culture produce endothelin (ET) and postulated that ET could play an important role in the contraction of the oviduct. In the present study using an organ chamber myograph system, we evaluated the contractile effects of ET-1 on bovine oviduct ampullary-isthmus segments. Additionally, the possibility whether the basal release/synthesis of nitric-oxide (N(O)) and/or prostacyclin modulates the contractile effect of ET-1 was investigated. ET-1 (10(-10) to 10(-7) M) contracted oviduct rings in a concentration dependent manner (P < 0.05). ET-1 (10(-7) M) induced contractions were significantly enhanced in presence of nitric oxide synthase inhibitor N-nitro-L-arginine-methyl-ester (10(-4) M), but remained unaltered in the presence of indomethacin (10(-5) M), an inhibitor for prostacyclin synthesis. In conclusion, ET-1 induced contraction of the oviduct is reduced/modulated by endogenous basal release/synthesis of N(O).

Acetylcholine↗

Endothelin production by bovine oviduct epithelial cells.

The production of immunoreactive-endothelin by bovine oviduct epithelial cells in culture was studied. The minimum amount of endothelin detected in the supernatant of cultured bovine oviduct epithelial cells after 6 h of incubation was 97.3 +/- 10 pg endothelin mg-1 protein and the amounts increased significantly (P < 0.01) with time of incubation. Pretreatment of bovine oviduct epithelial cells with the calcium ionophore A23187 increased the production of endothelin (P < 0.05). These results provide the first evidence that bovine oviduct epithelial cells produce endothelin and, therefore, may be locally involved in the muscular oviduct wall contractility and play an important role in the transport of gametes and embryos.

Animals↗

[Micro-insemination--a novel treatment method for sterility in severe male subfertility].

Microinsemination is a new method of treating sterility. It improves the chance of fertilization in cases of severe male subfertility and of unexplained infertility. Fertilization is assisted by opening the zona pellucida with a microneedle (PZD), by introducing a small number of sperms with a micropipette into the perivitelline space (SUZI) or by direct insertion of a spermatozoon into the ooplasm (ICSI). We report on the first delivery achieved by microinsemination (SUZI) at the University Hospital Zurich and, as far as we know, in Switzerland.

Adult↗

Chromosomal constitution of mouse blastocysts derived from oocytes inseminated by multiple sperm insertion into the perivitelline space.

PURPOSE: Our purpose was to evaluate the rate of chromosomal aberrations in mouse blastocysts obtained after microinjection of multiple spermatozoa under the zona pellucida of mature oocytes. Without detecting the appearance of pronuclei, the microinjected mouse oocytes containing two polar bodies were cultivated to the blastocyst stage and then analyzed cytogenetically. RESULTS: A chromosome study was carried out in a total of 109 blastocysts derived after microinjection of motile spermatozoa into the perivitelline space. Fifty-five blastocysts (50.5%) exhibited normal diploid chromosome complements, 30 (27.5%) showed different forms of mosaicism, and 24 (22%) exhibited haploidy caused by parthenogenetic activation. Compared to in vivo and in vitro control groups there was a significant increase in the parthenogenesis and mosaic forms of embryos produced by micromanipulation (P < 0.001). A total of 360 well-spread metaphases of 103 blastocysts was analyzed to determine whether the micromanipulation procedure increased the chance of aneuploidy. Aneuploid numbers of chromosomes were absent in all the metaphases analyzed. CONCLUSION: Mosaicism and parthenogenesis appear to be increased significantly following microinjection of multiple spermatozoa under the zona pellucida of mouse oocytes, and there was no evidence of aneuploidy.

Animals↗

[In-vitro fertilization--progress in a method of sterility treatment].

UNLABELLED: The first IVF-baby (in-vitro fertilization) was born in England in 1978 and was greeted enthusiastically. But, despite the enormous effort invested, pregnancy rates were disappointingly low. Although in recent years the clinical pregnancy rate has increased worldwide to 15-20% per retrieval, a vast number of people remained unaware of this improvement. To demonstrate and analyze the progress of IVF we evaluated all 196 IVF treatments effected from 1988-1991 at Zürich University Hospital. With an initial clinical pregnancy rate of only 6% per retrieval in 1988, the rate improved to 35% (p < 0.025) in 1991. The crucial factors relating to this improvement were the 1990 introduction of the programmed short-term protocol for ovarian stimulation and reevaluation of the previously used embryo freezing technique. CONCLUSION: After a difficult start, IVF has become, if accurately indicated, a method of sterility treatment with a realistic pregnancy and delivery prospect.

Antibodies↗

A transdermal regimen for continuous combined hormone replacement therapy in the menopause.

Transdermal systems for oestrogen therapy in the menopause have become very popular. The compliance, however, is impeded by the cyclic addition of oral progestins which leads to monthly withdrawal bleeds. In this pilot study a skin patch releasing 0.05 mg oestradiol and 0.25 mg norethisterone acetate per day, which was originally designed for sequential therapy, was used in a continuous manner. Results were quite favourable. Menopausal complaints were efficiently relieved and the Kupperman score dropped from 27.6 to 5.0. Out of 10 women, 1 had mild breakthrough bleeding, and 7 patients recorded one or several spotting episodes, mainly within the first 3 treatment months. No endometrial hyperplasia was observed and there was no significant change in plasma lipids, i.e. cholesterol, triglycerides, HDL-, HDL2-, HDL3-cholesterol, LDL-cholesterol and apolipoproteins A1 and B. The regimen might be a useful alternative to oral continuous combined replacement therapy.

Administration, Cutaneous↗

[Programmed stimulation for in vitro fertilization].

A programmed stimulation protocol for in vitro fertilisation was evaluated in order to perform oocytes aspiration from Tuesday to Friday only. For this purpose, norethisterone acetate (Primolut-Nor) was given in a daily dose of 10 mg for 10-25 days, starting on the 2nd day of the preceding cycle and ending on a Monday. The stimulation was started on the following Friday by administering daily 0.1 mg D-Trp-6-LHRH s. c. (Decapeptyl). In group A (preliminary study) the treatment with HMG 150 IU/d (Pergonal) was initiated two days later. In group B the treatment with HMG was individualised with respect to the initial dose and the starting point. 10 ultrasonographic, needle-guided, transvaginal aspirations were performed from January to March 1990 in Group A, 29 aspirations from April to December 1990 in Group B. Indication for IVF in all patients was tubal infertility. All aspirations were possible from Tuesday to Friday. In Group A 5 of 15 cycles (33%) had to be cancelled. A total of 53 oocytes (5.3 +/- 2.3 per aspiration) were retrieved. Cleavage per oocyte took place in 62%. There was no pregnancy. In Group B, the cancellation rate could be reduced to 3% (1/30 cycles; p less than 0.025). 227 oocytes were recovered (7.8 +/- 3.1 per aspiration; p less than 0.05) and there was a higher cleavage rate (74%, n.s.). The clinical pregnancy rate (with allowance for progressive introduction of freezing) increased to 30% per stimulation cycle (9/30, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Developmental capacities of two-cell mouse embryos frozen by three methods.

The following three methods were evaluated in order to obtain a most efficient freezing protocol for the preservation of two-cell mouse embryos: (a) slow cooling and slow thawing in 1.5 M dimethyl sulfoxide, (b) slow cooling and fast thawing in 1.5 M propanediol (PROH), and (c) ultrarapid freezing and fast thawing in either 3.5 M DMSO or 3.0 M PROH. In the slow-cooling procedures (a and b) ice nucleation (seeding) was induced manually or automatically. With method a, only a slight difference, 51.8% for manual and 58.9% for automatic seeding, was observed in survival rates, while the development to blastocysts was significantly affected: 35.4% with manual and less than 10% with automatic induction (P less than 0.001). Method b gave high survival (86.2%) and developmental rates (69.0%) with manual seeding compared with automatic seeding (20.7 and 9.8%, respectively; P less than 0.001). Using protocol c, higher survival and developmental rates were obtained with DMSO (84.8 and 55.9%) than with PROH (39.8 and 19.4%, P less than 0.001). These results demonstrate that inducing nucleation manually is superior to the use of a highly sophisticated autoseeding system and that method b with manual seeding is most effective in preserving the developmental capacity of two-cell mouse embryos after freezing and thawing. There is evidence that this is also true of human embryo cryopreservation.

Animals↗

Abnormal chromosomal arrangements in human oocytes.

Ninety-one human oocytes, lacking signs of fertilization 50 h after insemination in vitro, were investigated cytogenetically to assess the frequency and type of chromosomal abnormalities. Chromosome spreading permitted adequate karyotyping in 55 oocytes. Non-determined numerical aberrations occurred with the following frequencies: hypohaploidy, 10.9% (6/55), hyperhaploidy, 14.5% (8/55) and hyperdiploidy, 3.6% (2/55). Total aneuploidy occurred with a frequency of 29.1% and was observed in oocytes from 30 patients. No correlation was found between specific chromosomal aberrations and type of infertility, stimulation treatment or gonadotrophin levels. On the other hand, the frequency of aneuploidy was significantly higher (P less than 0.05) in patients greater than 35 years of age. Two chromosomal complements (3.6%) had structural rearrangements; one oocyte had both structural and numerical chromosomal abnormalities and the other had differently condensed regions on the long arms of three chromosomes from group C. The overall frequency of chromosomal aberrations was 32.7%. Only two samples contained an additional set of polar body chromosomes. Thirteen oocytes presented sperm chromosomes in an arrested stage of premature chromosome condensation of the G1 phase and four oocytes showed asynchronous condensation of pronuclear chromosomes. Finally, it was concluded that the high proportion of chromosomal aberrations observed in human oocytes may contribute significantly to abnormal embryonic development in vitro.

Adult↗

Absence of Yq microdeletions in infertile men.

Microdeletions of the long arm of the Y chromosome (Yq) were described in men with idiopathic azoo- or oligozoospermia and seem to cause impairment of spermatogenesis. Deletion frequencies differ considerably among selected infertile men. The aim of this study was to investigate the prevalence of Yq microdeletions in patients with idiopathic infertility. Men with azoospermia or oligozoospermia resulting from endocrine or obstructive causes or with a constitutional cytogenetic anomaly were excluded. Ninety-seven patients presenting at infertility centers in Leipzig and Zurich were included in the study. Sixty-four (66%) of them were severely oligozoospermic (sperm concentrations < 5 x 10(6)/mL) and 33 (36%) were azoospermic. A sequence-tagged site (STS) PCR strategy was applied for the microdeletion screening. Thirteen STS markers spanning the whole euchromatic region of Yq were used. No Y-chromosomal microdeletion could be detected in these 97 infertile men. This result suggests a much lower Yq deletion frequency than previously thought, even among strictly selected patients with idiopathic azoo- or oligozoospermia.

Adolescent↗

Cellular and biochemical mechanisms by which environmental oestrogens influence reproductive function.

The biology and physiology of the male as well as female reproductive system is hormonally regulated. Abnormalities in the dynamics of hormone production, metabolism and elimination, as well as their binding to certain target tissues, has been associated with pathophysiological conditions of the reproductive system. Although oestrogens are known to be one of the major hormone groups in regulating the reproductive function and the fertilization process, the cellular and biochemical mechanism or mechanism(s) via which oestrogens induce their effects are still not fully defined. Moreover, in a modern environment we are also exposed to a wide battery of environmental agents which are structurally similar to oestrogens, and termed 'environmental oestrogens'. Because environmental oestrogens have been shown to mimic some of the effects of oestradiol, it has been postulated that these exogenous chemicals may influence or interfere with the oestrogen-dependent reproductive processes, and may be associated with beneficial as well as deleterious effects on the reproductive system. In this regard, two classes of environmental oestrogens have been widely studied, i.e. phyto-oestrogens (plant-derived dietary oestrogens) and xeno-oestrogens (industrial chemicals, including polychlorinated biphenyls, DDT, TCDD, dioxins, etc.). The main focus of this review is to provide an overview on the cellular and biochemical mechanism(s) by which xeno-oestrogens and phyto-oestrogens influence the oestrogen-dependent reproductive functions and induce their deleterious or protective effects on the reproductive system.

Animals↗

Vascular effects of environmental oestrogens: implications for reproductive and vascular health.

Environmental oestrogens are defined as xenobiotics structurally resembling oestrogen, and are divided into two broad categories, xeno-oestrogens and phyto-oestrogens. Environmental oestrogens may contribute importantly to the increased incidence of reproductive disorders in the modern environment. Although the mechanisms by which environmental oestrogens induce their deleterious effects on the reproductive system remain poorly defined, it is likely that the vascular effects of these compounds play a critical role. In this regard, oestradiol strongly regulates both angiogenesis and vascular remodelling by influencing the growth and function of vascular endothelial cells (EC) and smooth muscle cells (SMC). Since blood vessels, by undergoing angiogenesis, vascular regression and vascular remodelling, actively participate in the normal functioning of reproductive organs, environmental oestrogens-by mimicking or antagonizing the vascular effects of oestradiol-may induce abnormalities in vascular function and structure leading to reproductive disorders such as pre-eclampsia, endometriosis, impaired follicular development, inefficient implantation, impotence and infertility. The purpose of the present review is to summarize the evidence regarding the vascular effects of xeno-oestrogens and phyto-oestrogens and to discuss the implications for these effects on the reproductive system.

Animals↗