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Biomedical subjects

C A Jansen

Publications and source records attributed to C A Jansen.

At least 19 recordsLinked to original sources

The chemotherapeutic agent bleomycin in a two-drug combination with zidovudine, ritonavir or indinavir synergistically inhibits HIV Type-1 replication in peripheral blood lymphocytes.

It has been suggested that the combination of cancer chemotherapy with antiviral therapy is helpful for the containment of lymphomas in HIV-infected patients. Since we have recently shown that the nucleic acid binding chemotherapeutic agent bleomycin in itself has antiviral properties, we looked to see if there was any possible synergy with current anti-HIV agents. Combinations of zidovudine, indinavir or ritonavir with bleomycin, synergistically inhibited HIV-1(AT) replication in stimulated peripheral blood lymphocytes (combination index at 50% virus inhibition was 0.427, 0.604 and 0.535, respectively) and this synergism was not accompanied by any synergistic effects on cytotoxicity. We conclude from these data that further studies to investigate the clinical efficacy of combinations of antiviral and cancer chemotherapeutic agents are warranted in relation to viral load improvement.

Anti-HIV Agents↗

Influence of group culture and culture volume on the formation of human blastocysts: a prospective randomized study.

The optimal culture conditions for embryos to reach the blastocyst stage are under investigation. One factor is the putative influence of autocrine or paracrine factors produced by the embryo itself. Studies in mice blastocysts showed a beneficial influence of micro-cultures and communal growth on pregnancy and implantation rates, attributed to these growth or survival factors. In humans, studies have only involved embryos up to day 2 or 3 without consistent results. Therefore a prospective, randomized study was designed to assess whether group culture or incubation volume would influence day 3 human embryos to develop into blastocysts. Embryos were initially cultured in groups until day 3, after which patients were randomly allocated to four groups. Group 1: group culture in a small volume; group 2: single culture in a small volume; group 3: single culture in a large volume; group 4: group culture in a large volume. No significant differences in blastocyst formation could be found between the four groups (35, 45, 36 and 36% respectively). Therefore any of the four modes can be used, whichever is most convenient. The only factor which made a statistically significant contribution was the number of embryos on day 3. An increase in the number of embryos by one embryo decreased the odds of obtaining a blastocyst by 6%. The overall pregnancy rate per transfer was 40%, and the implantation rate was 28%. Single culture in a small volume allows a direct and individual assessment of embryo morphology, and as such it seems preferable.

Adult↗

The predictive value of day 3 embryo morphology regarding blastocyst formation, pregnancy and implantation rate after day 5 transfer following in-vitro fertilization or intracytoplasmic sperm injection.

The transfer of blastocysts has been associated with a very high implantation rate. However, not all embryos achieve the blastocyst stage. Our study was set up to demonstrate whether embryo morphology on day 3 predicts subsequent blastocyst formation. A prospective study was carried out in 48 patients with a mean of 2.9 failed in-vitro fertilization (IVF) attempts. In this new cycle, the morphology of the embryos on day 3 was noted. After pre-selection of the embryos which would have been transferred on day 3, all embryos were cultured individually and allowed to develop further until transfer on day 5. The clinical pregnancy rate per transfer was 46%, and the overall implantation rate was 24%. When only blastocysts were transferred the pregnancy rate was 53% with an implantation rate of 30%. Thirty-nine per cent of all embryos reached the blastocyst stage on day 5; 47% of class 1 and 2 embryos (good quality) in contrast to 21% of class 3 and 4 embryos (poor quality). Respectively 45% of class 1 and 2 embryos and 69% of class 3 and 4 embryos arrested in development or degenerated. Only 51% of the embryos that were transferred on day 5 had been pre-selected for transfer on day 3. In conclusion, it appears that the predictive value of embryo morphology on day 3 for subsequent blastocyst formation is limited.

Adult↗

A prospective randomized clinical trial comparing recombinant follicle stimulating hormone (Puregon) and human menopausal gonadotrophins (Humegon) in non-down-regulated in-vitro fertilization patients.

A randomized clinical trial was performed comparing recombinant follicle stimulating hormone (rFSH, Puregon, n = 54) and human menopausal gonadotrophin (HMG, Humegon, n = 35) in infertile women undergoing in-vitro fertilization without the use of a gonadotrophin-releasing hormone (GnRH) agonist. Most patients had a tubal or idiopathic infertility, the latter always longer than 4 years' duration. Patients with sperm abnormalities were excluded. None of the between-group differences in treatment outcome was statistically significant. In the rFSH group, a mean number of 11.2 oocytes was retrieved compared with 8.3 in the HMG group. Ongoing pregnancy rates per started cycle were higher in the rFSH group (22.2%) than in the HMG group (17.1%). Implantation rates were 27.5% in the rFSH group in comparison with 16.7% in the HMG group. In the rFSH group, a mean total dose of 1410 IU during 6.2 days was administered compared with 1365 IU in 6.0 days in the HMG group. Oestradiol concentrations on the day of human chorionic gonadotrophin administration were 3889 pmol/l in the rFSH group and 3145 pmol/l in the HMG group. In 15 subjects (rFSH: n = 9, 16.7%; HMG: n = 6, 17.1%) luteinizing hormone concentrations higher than 10 IU/l were seen during stimulation. In two of them, both from the rFSH group, ongoing pregnancies were achieved. The results indicate that rFSH (Puregon) is at least as efficacious as HMG and that acceptable pregnancy rates can be achieved without the use of a GnRH agonist.

Adult↗

External validation of prognostic models for ongoing pregnancy after in-vitro fertilization.

This study aimed to validate prognostic models for predicting ongoing pregnancy after the first and second in-vitro fertilization cycles. Models were developed using data from the University Hospital, Nijmegen, 1991-1994 and tested using more recent data from the same centre and data from two other centres. Although the variables included in the models seemed plausible, the predictions of the models were unsatisfactory. The models did not discriminate between women who had achieved pregnancy and women who did not achieve pregnancy; neither could they indicate which women had a (very) low probability of ongoing pregnancy. Taking into account the success rate of a specific clinic or the success rate during a specific period did not show any advantage. The predictions were even inaccurate in the same hospital during another period. It is obvious that these prognostic models should not be used. This study shows the importance of validating prognostic models before their implementation in clinical practice.

Adult↗

A case of a neurological complication after transvaginal oocyte retrieval.

A patient is described who developed neurological signs of the left leg following transvaginal ultrasound-guided puncture. A hypodense lesion of the obturator space above the lumbosacral plexus was seen on ultrasound which could explain her signs, due to compression by a hematoma. She recovered completely.

Adult↗

Renal clearance of the thyrotropin-releasing hormone-like peptide pyroglutamyl-glutamyl-prolineamide in humans.

TRH-like peptides have been identified that differ from TRH (pGlu-His-ProNH2) in the middle amino acid. We have estimated TRH-like immunoreactivity (TRH-LI) in human serum and urine by RIA with TRH-specific antiserum 8880 or with antiserum 4319, which binds most peptides with the structure pGlu-X-ProNH2. TRH was undetectable in serum (< 25 pg/mL), but TRH-LI was detected with antiserum 4319 in serum of 27 normal subjects, 21 control patients, and 12 patients with carcinoid tumors (range 17-45, 5-79, and 18-16,600 pg/mL, respectively). Because serum was kept for at least 2 h at room temperature, which causes degradation of TRH, pGlu-Phe-ProNH2, and pGlu-Tyr-ProNH2, serum TRH-LI is not caused by these peptides. On high-performance liquid chromatography, serum TRH-LI coeluted with pGlu-Glu-ProNH2 (< EEP-NH2), a peptide produced in, among others, the prostate. Urine of normals and control patients also contained TRH-LI (range 1.14-4.97 and 0.24-5.51 ng/mL, respectively), with similar levels in males and females. TRH represented only 2% of urinary TRH-LI, and anion-exchange chromatography and high-performance liquid chromatography revealed that most TRH-LI in urine was < EEP-NH2. In patients with carcinoid tumors, increased urinary TRH-LI levels were noted (range 1.35-962.4 ng/mL). Urinary TRH-LI correlated positively with urinary creatinine, and the urinary clearance rate of TRH-LI was similar to the glomerular filtration rate. In addition, serum TRH-LI was increased in 17 hemodialysis patients (43-373 pg/mL). This suggests that serum < EEP-NH2 is cleared by glomerular filtration with little tubular resorption. The possible role of the prostate as a source of urinary TRH-LI was evaluated in 11 men with prostate cancer, showing a 25% decrease in urinary TRH-LI excretion after prostatectomy (0.19 +/- 0.02 vs. 0.15 +/- 0.01 ng/mumol creatinine, mean +/- SEM). However, TRH-LI was similar in spontaneously voided urine and in urine obtained through a nephrostomy cannula from 16 patients with unilateral urinary tract obstruction (0.15 +/- 0.01 vs. 0.14 +/- 0.01 ng/mumol creatinine). These data indicate that: 1) TRH-LI in human serum represents largely < EEP-NH2, which is cleared by renal excretion; 2) part of urinary < EEP-NH2 is derived from prostatic secretion into the blood and not directly into urine; and 3) urinary < EEP-NH2 can be used as marker for carcinoid tumors.

Adult↗

Maternal serum screening for fetal Down syndrome in IVF pregnancies.

To assess the influence of in vitro fertilization (IVF) on maternal serum human chorionic gonadotrophin (hCG) and alpha-fetoprotein (AFP), the maternal serum hCG and AFP values were studied in 67 IVF pregnancies and compared with the results of a control group of 4732 spontaneously conceiving patients. Maternal serum hCG was significantly higher and AFP significantly lower in the IVF group. Possible explanations and implications for prenatal diagnosis in IVF pregnancies are discussed.

Chorionic Gonadotropin↗

Transport intracytoplasmic sperm injection (ICSI): a cost-effective alternative.

PURPOSE: Transport in vitro fertilization (IVF) programs are operational in a lot of countries and especially popular in The Netherlands, where IVF activities are strictly regulated. Since the introduction of intracytoplasmic sperm injection (ICSI) in the IVF laboratory, many laboratories are now setting up this new technique, which necessitates major investments in terms of infrastructure and specialized personnel. METHODS: We present a cost effective alternative, consisting of patient selection, preparation, and oocyte retrieval at one center and transport of oocytes to a second center, where the ICSI procedure and embryo transfer are performed. Since early 1994 several Dutch centers have a transport ICSI program running with the Gent University Infertility Center, and we wish to present the results of our cooperation with two major centers, comparing them to our local results, for the first 10 months of 1994. Patient selection was similar at all three centers: only couples with previously failed in vitro fertilization or having been refused for routine IVF were enrolled in the program. Stimulation schemes and follow-up of the stimulation were different at all three centers. Transport of oocytes was carried out in a transport box or by attaching the closed tubes containing the follicular aspirates to the chest of the husband. Transport times varied between 1.5 and 3 hr, depending on traffic conditions. RESULTS: Up to November 1, 1994, a total of 77 transport ICSI cycles and 294 own ICSI cycles were carried out. Although locally significantly more oocytes were retrieved and thus available for ICSI than in transport cycles, fertilization and pregnancy rates were not different between the two groups. CONCLUSIONS: These results suggest that long-distance transport of human oocytes seems not to be harmful to their capacity to be successfully injected and to further embryonic development and their implantation potential. Transport ICSI seems to be a valuable and cost-effective approach to treat high numbers of patients at a restricted number of highly specialized IVF laboratories, especially in countries where ICSI is not commonly available.

Academic Medical Centers↗

The crown-rump length in early human pregnancy: a reappraisal.

The crown-rump length (CRL) was measured by means of transvaginal sonography in 41 pregnancies resulting from in-vitro fertilization (IVF). The embryonic CRL could be determined as early as 25 days after follicle aspiration. A reference chart was constructed relating the CRL to the number of days following follicle aspiration. Comparison with the CRL chart by Robinson & Fleming (1975) currently in use revealed that transvaginal sonography allows earlier and more accurate measurement of embryonic CRL.

Adult↗

Abnormal embryonic heart rate pattern in early pregnancy associated with Down's syndrome.

The case history of a 35-year-old woman with a pregnancy following IVF treatment is presented. Transvaginal sonography revealed an abnormal pattern of the embryonic heart rate between 28 and 50 days following follicular aspiration. At term, a male infant with the characteristics of Down's syndrome was born. The diagnosis was confirmed by chromosome analysis. The implications of this observation are discussed.

Adult↗

Embryonic heart activity: appearance and development in early human pregnancy.

The appearance and development of embryonic cardiac activity was studied in early human pregnancies established by in-vitro fertilization (IVF) using transvaginal sonography. Embryonic cardiac activity could be detected as early as 25 days after follicle aspiration. The range in appearance of embryonic cardiac activity in normal continuing pregnancies was 5 days. There was no correlation with maternal age, day of embryo transfer, or cell stage at embryo transfer. As the difference in appearance of embryonic cardiac activity was associated with a difference in crown-rump length whilst the subsequent growth curve was normal we ascribe these findings to different duration of the implantation stage. The later cardiac activity was detected the greater the risk of miscarriage. Reference curves were created relating embryonic heart rate to the number of days after follicle aspiration, the number of days that cardiac activity is present and the crown-rump length. In pregnancies ending in miscarriage heart rate patterns fell away from the reference curve. Embryonic factors seem to play an essential role in these observations.

Adult↗

Value and limitations of vaginal ultrasonography--a review.

Vaginal ultrasonography has become an indispensable method in infertility and early pregnancy investigations, in spite of its comparatively recent introduction. Initially this technique was introduced as an alternative for abdominal ultrasonography in in-vitro fertilization treatment for monitoring follicle growth and harvesting oocytes. In due course, the technique was used in many other fields of gynaecology and obstetrics, e.g. ovulation induction, early detection of (ectopic) pregnancy, oncology and placenta localization. The value and limitations of vaginal ultrasonography are discussed as well as patients' acceptance.

Female↗