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Biomedical subjects

D Krebs

Publications and source records attributed to D Krebs.

At least 163 records · Page 9Linked to original sources

[Tolerance of intraoperative, intraperitoneal chemotherapy in advanced gynecologic malignancies].

Assuming that cells and portions of tumor may remain in the abdominal cavity after surgery to reduce tumor size in cases of ovarian carcinoma, and that a change in cell kinetics could result in accelerated growth in the event of a recurrence, 23 patients with advanced tumors were given local (intraperitoneal) treatment intraoperatively. The treatment consisted of 15 mg Mitomycin C or 30 or 40 mg of Mitoxantron, in 1000 ml normal saline. Since the observation time was so short, the tolerance and side effects of this form of treatment were of primary interest, rather than remission quotas and survival times. The principal abdominal complaints included two subileus conditions which responded well to therapy and the problem of postoperative nausea. Four patients reacted to the treatment described with temperatures of over 38 degrees C. Chemical changes detected in the laboratory included 18 cases of leukopenia, which in one case reached WHO Grade 4. Intermittent changes in liver values and electrolytes were observed in isolated cases. Wound-healing impairments occurred in three cases. In one of them, a patient who sustained a prolapse of the small intestine with tumor growth into the abdominal wall, reoperation was necessary. Taken overall, the side effects of the intraoperative, intraperitoneal cytostatic therapy were acceptable. In view of the courses observed and with the idea of employing a form of therapy to combat aggressive growth of tumor cells remaining after surgery, it appears justified to continue with this form of treatment.

Adolescent↗

[Transvaginal, ultrasound-controlled follicle puncture].

Between December 1986 and November 1987, 588 transvaginal sonographically-guided oocyte retrievals, using a vaginal transducer, were performed for in vitro fertilization at the University of Bonn. All follicles were accessible. No complication occurred except one case of pelviperitonitis in a patient with preoperatively diagnosed sactosalpinx. Because this technique is safe, non-invasive, and performable without general anaesthesia, we also retrieved eggs in patients despite poor hormonal values and endogenous LH-surge. In all, clinical pregnancies were diagnosed in 85 patients. Pregnancy rates per embryo transfer, oocyte retrieval and stimulated cycle, respectively were 19.0%, 14.5% and 12.0%. The advantages of the transvaginal technique, using a vaginal transducer compared with the laparoscopically-guided as well as with other sonographically-guided techniques of oocyte retrieval, are obvious (possibly without general anaesthesia, in general all follicles are accessible, very low complication rates, low discomfort to patient, and less amount of time and staff). Therefore, this technique seems to be the method of first choice. A laparoscopically-guided oocyte retrieval is only indicated, when a laparoscopic screening of pelvic organs or a gamete intrafallopian transfer are to be performed simultaneously.

Embryo Transfer↗

Ovarian stimulation using pure FSH in an in-vitro fertilization programme.

The therapeutic efficacy of stimulating ovarian follicular development by pure urinary FSH in an IVF programme was determined and compared with results of other therapeutic regimens. Forty-three patients selected for extracorporeal fertilization were treated with pure FSH after stimulation with clomiphene or HMG had proved to be unsuccessful. Treatment had to be discontinued in five patients before follicular puncture, and embryo transfer was performed in 32, of whom seven conceived. FSH stimulation evidently creates favourable conditions for in-vitro fertilization in patients with impaired follicular maturation following conventional stimulation with clomiphene or HMG. Levels of oestradiol, progesterone and androstenedione were measured in follicular fluid, and high progesterone concentrations were correlated with mature oocytes. The increased ratios of progesterone/androstenedione and progesterone/oestradiol in follicles containing mature oocytes are due to the onset of luteinization of mature follicles as a consequence of HCG administration.

Androstenedione↗

Combined GnRH-agonist/gonadotrophin stimulation for in-vitro fertilization.

The occurrence of a premature luteinizing hormone (LH) surge during gonadotrophin stimulation for in-vitro fertilization leads to cancellation of the cycle. Moreover, insufficient follicular maturation is often caused by elevated basal gonadotrophin levels. Therefore, the gonadotrophin-releasing hormone (GnRH) agonist, D-Trp-6-LHRH, was applied to patients exhibiting premature LH surges, hyperandrogenaemia or incipient premature menopause. A total of 119 cycles were treated using a long-acting versus a short-acting GnRH agonistic analogue. In protocol 1, patients received daily s.c. injections of 100-500 micrograms of a short-acting compound. In protocol 2, a long-acting bolus of 3.2 mg was given i.m. Concomitant human gonadotrophin stimulation was started in protocol 1 after clinical and biochemical evidence of pituitary suppression and in protocol 2 after a fixed suppression interval of 14 days. In protocol 1, higher oestrogen levels were reached with more oocytes harvested. The pregnancy rate per transfer was increased from 3.5 to 18%, with most pregnancies occurring with protocol 1. The cancellation rate of 13.4% was mainly due to insufficient follicular development in patients in whom premature menopause was suspected. Hyperandrogenaemic patients with an elevated LH/FSH ratio exhibited the best follicular recruitment with the highest pregnancy rate of 25% per transfer. Thus, combined GnRH-agonist/gonadotrophin stimulation offers a causal treatment for patients susceptible to premature LH surges and for hyperandrogenaemic patients.

Adult↗

Transvaginal sonographically guided oocyte retrieval for in-vitro fertilization.

Between December 1986 and November 1987, 588 transvaginal sonographically guided oocyte retrievals using a vaginal transducer were performed for in-vitro fertilization. All follicles were accessible. No complication occurred except for one case of pelviperitonitis in a patient with preoperatively diagnosed sactosalpinx. Because this technique is safe, non-invasive and can be performed without general anaesthesia, eggs were also retrieved from patients despite poor hormonal values and endogenous LH surge. In all, clinical pregnancies were diagnosed in 85 patients. Pregnancy rates per embryo transfer, oocyte retrieval and stimulated cycle, respectively, were 19.0, 14.5 and 12.0%. The advantages of the transvaginal technique compared with laparoscopically guided and with other sonographically guided techniques of oocyte retrieval are obvious, e.g. no general anaesthesia, in general all follicles accessible, very low complication rates, little discomfort to patient, less time and fewer staff. Therefore, this technique seems to be the method of choice. Laparoscopically guided oocyte retrieval is only indicated when a laparoscopic screening of pelvic organs or a gamete intra-Fallopian transfer are to be performed simultaneously.

Embryo Transfer↗

Acrosomal proteinase activity of human spermatozoa and relation of results to semen quality.

An assay for measuring the acrosomal proteinase activity of human spermatozoa with the use of a microscope slide coated with a thin layer of gelatin as a protein substrate was developed and applied to study the semen of 82 males from infertile couples and 15 normal donors. Acrosomal protease activity is indicated by a clear area of proteolyzed gelatin (halo) about the sperm head. Probit analysis revealed two populations divided at a halo diameter of 14 microns. The patient samples were grouped according to semen quality. The mean proteinase activity for most of the infertile groups was significantly below the control and more of the infertile men had a halo diameter less than 14 microns. Decreased activity was also found in 37% of patients with normal semen analysis. It is concluded that low acrosomal proteinase activity is associated with infertility. This reliable, inexpensive and rapid assay may prove to be helpful as an adjunct to semen analysis in the infertility work-up.

Acrosome↗

The effect of general anaesthesia on the success of embryo transfer following human in-vitro fertilization.

In this study the effect of general anaesthesia on the success of embryo transfer was investigated. Between January and August 1986, in a preliminary trial using general anaesthesia for embryo replacement (sodium thiopentone and alfentanyl), the overall pregnancy rate was 36% (n = 86), compared to 21% in a group of matched controls without anaesthesia (n = 131). Following the preliminary study in a larger series of patients between August 1986 and December 1987, all embryo transfers were performed using general anaesthesia. In a total of 795 embryo replacements the pregnancy rate was 19%. This was neither significantly different from the overall pregnancy rate of the non-anaesthetic controls of the preliminary study (21%), nor from a group of 603 patients who received embryo replacement without anaesthesia between June 1984 and December 1985. The results of this study indicate no obviously adverse effect of the anaesthesia on the induction of pregnancy. The results of the preliminary study even indicate a beneficial effect of anaesthesia on the pregnancy rate. However, to assess accurately the effect of general anaesthesia, a large prospective randomized study is needed. The type of anaesthesia used in this study, however, may be useful in cases of difficult transfer procedures, due to psychological stress to the patient, or technical/mechanical problems during the embryo transfer procedure.

Anesthesia, General↗

Ovarian stimulation for in-vitro fertilization.

In-vitro fertilization (IVF) and embryo transfer has become an accepted clinical method for the treatment of sterility. Different types of ovarian stimulation have been used successfully. The therapeutic principles behind the stimulation treatment in an IVF programme are the same as those applied in the treatment of normal and hypogonadotrophic ovarian insufficiency. These include clomiphene therapy with subsequent HCG administration, combined clomiphene/HMG administration and stimulation with HMG alone, followed by HCG. A new approach to the stimulation of follicular development and oocyte maturation is the use of pure FSH and GnRH analogues. The principal indications, results, advantages and disadvantages of these different schemes of ovarian stimulation for oocyte retrieval are discussed.

Embryo Implantation↗

Glass wool column filtration of human semen: relation to swim-up procedure and outcome of IVF.

The number and viability of spermatozoa recovered by glass wool column filtration and a swim-up procedure were compared using different types of ejaculates, such as normal, asthenozoospermic and very viscous oligozoospermic semen. The filtration procedure resulted in significantly (P less than 0.01) higher recovery of viable spermatozoa than the swim-up procedure from all types of ejaculates studied. Further, the spermatozoa from 50 (78.1%) of the 64 ejaculates filtered through glass wool column fertilized at least one intact human egg in an in-vitro fertilization (IVF) procedure. It is concluded that glass wool column filtration is superior to the swim-up procedure since it yields a higher recovery of viable spermatozoa that are potentially fertile. Therefore, the glass wool column filtration procedure used to prepare spermatozoa may be of benefit for IVF, intra-uterine insemination, in-vitro fertilization and GIFT (gamete intra-Fallopian transfer), especially in cases of poor quality semen.

Cell Separation↗

[Experiences with PAC and PEC polychemotherapy in the treatment of advanced and recurrent breast cancers].

At the department of gynecology of the universities of Lübeck and Bonn 18 in part pretreated patients with advanced or relapsing cancer of the breast were treated with a DDP-containing polychemotherapy. For 14 of the 18 women the PAC or PEC regime was beneficial: 9 had complete or partial remission and 1 patient had a no change situation; 4 women showed no evidence of disease. The time of survival after the chemotherapy treatment was two month in the minimum and more than 50 month in the maximum (20 month in the average). As side effects, in particular leucocyte-depression and nausea as well as vomiting of various degrees were observed; alopecia was seen in every case. The success of DDP-containing chemotherapy in the treatment of breast cancer is of note, but in the future it will be important to define subgroups that would most benefit from PAC- or PEC-treatment without substantial negative side effects.

Adult↗

Electro-rotation of mouse oocytes: single-cell measurements of zona-intact and zona-free cells and of the isolated zona pellucida.

Passive electrical properties of oocytes and of zonae pellucidae, and the mechanical coupling between them, can be elucidated by means of rotating-field-induced rotation. In low-conductivity media (25-100 microS/cm) rotation of mouse oocytes (with or without their zonae) requires fields in the 1-100 kHz frequency range. However, an isolated zona shows weak rotation in the opposite direction to that of a cell, and in response to much higher field frequencies (approx. 1 MHz). In zona-intact mouse oocytes, the rotation of cell and zona are not rigidly coupled: thus rotation of the cell can still be induced when the zona is held stationary. However, rotation of freely suspended zona-intact cells is much slower than that of zona-free cells and requires an optimum field frequency that is approximately 1.5 kHz higher. These observations show that the electrical properties of the oocyte that are measured by rotation are altered by the presence of the zona pellucida, even though no such influence has been detected using micro-electrodes. The data are consistent with the zona acting as a porous shell with a conductivity of 40 microS/cm (preliminary estimate made at a single medium conductivity of 26 microS/cm). Measurements on cells from which the zonae had been removed gave values for the membrane capacity and resistivity of 1.2-1.3 microF/cm2 and 400 omega.cm2, respectively. These values may reflect the presence of plasmalemma microvilli. The results strongly suggest that the technique may be useful for studies of cell maturation and for in vitro fertilization, because the cells may be further cultured after measurement.

Animals↗

Leucospermia and the fertilizing capacity of spermatozoa.

Ejaculates obtained from men attending an in vitro fertilization (IVF) program were analyzed to determine the effect of the presence of leucocytes in semen on the ability of sperm in that semen to fertilize oocytes. The mean (+/- S.E.) concentration of leucocytes in 103 ejaculates was 0.62 X 10(6)/ml (+/- 0.09) with a range of 0.1 X 10(6) or less per ml to 7.0 X 10(6)/ml. The leucocyte concentration demonstrated a significant (p less than 0.05) but inverse relationship with the fertilizing capacity of spermatozoa. Though not statistically significant, the leucocyte concentration also demonstrated an inverse relationship to sperm motility and normal morphology. These results suggest that the presence of leucocytes in an ejaculate cannot be used as the sole indicator of the fertilizing capacity of spermatozoa in that ejaculate.

Female↗

[Ovarian stimulation with pure FSH in an in vitro fertilization program].

The therapeutic efficacy of stimulating ovarian follicular development by pure urinary FSH in an IVF programme was determined and compared with results of other therapeutic regimes. 43 patients selected for extracorporeal fertilization were treated with pure FSH after stimulation with clomiphene or HMG had proven not be successful. Only in 5 patients (12%) treatment had to be discontinued before follicular puncture. In 32 women an embryo transfer was performed, and 7 patients conceived. This result demonstrates that, applying pure FSH stimulation, favourable conditions can be created for an in-vitro fertilization in patients with impaired follicular maturation following conventional stimulation with clomiphene or HMG. On the strength of the values determined for progesterone and estradiol during the luteal phase one has to conclude that a normal corpus luteum function was achieved in all our patients following FSH-stimulation.

Embryo Transfer↗

[Fertilization of human ova in capillary tubes with a very small number of spermatozoa. A new treatment possibility in severe oligospermia?].

In contrast to the in vivo situation the current in vitro fertilization techniques require large numbers of spermatozoa per oocyte to achieve successful fertilization. In this study a culture system was developed in which successful fertilization was performed in haematocrit capillary tubes (75 mm length, 0.8-0.9 mm inner diameter) even if only low numbers of spermatozoa were used. Oocytes were fertilized in 5-10 microliters of different sperm suspension containing a total number of 500, 1000, 2000 and 4000 spermatozoa per oocyte (0.1-0.4 X 10(6) sperms/ml). In 10 patients participating in an in vitro fertilization programme 32 oocytes were fertilized in capillary tubes and 32 oocytes were cultured using standard methods (1 ml culture medium in tissue culture tubes, 0.1-0.2 X 10(6) spermatozoa/ml). The overall fertilization rate of oocytes cultured in tissue culture tubes was 78% (25/32) and the fertilization rates in capillary tubes using 4000, 2000, 1000 or 500 spermatozoa per oocyte were: 71% (5/7), 86% (6/7), 60% (6/10) and 50% (4/8), respectively. The fertilization rate of mature oocytes was higher compared to immature oocytes when fertilization was performed in culture tubes (83% and 63%) or in capillary tubes (74% and 44%). Fertilization in capillary tubes using a volume of the sperm oocyte suspension of 10 microliters compared to 5 microliters seems to provide better culture conditions resulting in higher fertilization and cleavage rates (75 and 91% versus 62.5 and 60%). These preliminary results indicate that fertilization of human oocytes under in vitro conditions can be achieved even with very low numbers of spermatozoa.(ABSTRACT TRUNCATED AT 250 WORDS)

Embryo Transfer↗

Cryopreservation of human oocytes.

Three different methods were used for freezing human excess oocytes (320 frozen, 205 thawed) in our IVF programme and the results of these methods were compared. A high fertilization rate (75%) could be achieved after thawing, using 1,2 propanediol as a cryoprotectant. Polyploidy rates of 20% and 40% were observed using DMSO and 1,2-propanediol as cryoprotectants, respectively. Using the ultracooling method, the survival rate was poor (4%).

Cryoprotective Agents↗

Oocyte retrieval for in vitro fertilization.

Present methods to monitor follicular development, and to determine the time for oocyte retrieval are described: LH and estradiol determinations, ultrasonography. The two techniques, available for oocyte pick-up, namely laparoscopic and ultrasound guided follicle aspiration, are reviewed. The methods and results of the University of Bonn IVF team are discussed, e.g. ovarian stimulation schemes, including the use of pure FSH for patients with a high LH/FSH ratio, and the use of GnRH analogues, for patients with premature LH discharges; the reasons for failed oocyte retrieval; pregnancy rates.

Chorionic Gonadotropin↗

[Significance of atypical hemorrhage in ovarian cancer].

UNLABELLED: In a retrospective study on 167 ovarian cancer patients the presenting symptom was defined via anamnesis. This parameter was correlated to others characterising the cancer and the patient: age, parity, menopause, stage, extent of operation, tumor residue, postoperative therapy, induction of remission and several morphological data. The prognostic significance was analysed using Hazard-models (Cox 1972, Carter 1983) and contingency tables. RESULTS: The presenting signs and symptoms were: atypical bleeding in 44 patients, pain in 75 patients and other signs in 48 patients. These signs and symptoms were significantly correlated with tumor residue, and were more frequently seen in mucinous and endometrioid carcinomas. There were no significant correlations to the other examined parameters, but there was a trend for patients with atypical bleedings to be diagnosed at early stages and their survival prognosis was significantly (p less than 0.01) better compared with that for patients with pain or other presenting signs or symptoms.

Female↗