Reproductive technology--the price of progress.
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Adult↗
Biomedical subjects
J A Collins
Publications and source records attributed to J A Collins.
Sedation of horses with romifidine and butorphanol.
Combinations of romifidine and butorphanol were used to sedate 55 horses for a variety of surgical, therapeutic and diagnostic procedures. Eighteen of the horses were given the drugs separately, romifidine first followed by butorphanol four minutes later, and 37 were given the drugs together. The levels of sedation and ataxia were assessed and graded, and there were no statistically significant differences between the two methods of administration. The side effects were typical of the alpha-2 agonists, including bradycardia, heart block and some sweating. Box-walking was observed in one horse. The procedure attempted was successfully completed in 54 of the horses, and the combination of drugs was judged to be a safe and effective sedative for horses.
Analgesia↗
Cigarette smoking and the outcomes of in vitro fertilization: measurement of effect size and levels of action.
OBJECTIVE: To assess whether cigarette smoking in women or men affects the outcomes of IVF-ET and at what functional levels smoking is active. INTERVENTIONS: Demographic and smoking data were collected by questionnaire at the onset of consecutive treatment cycles (n = 462) and at the time of ET. In addition to routine endocrine and clinical data, circulating immunoreactive inhibin, follicular fluid E2 endometrial thickness, and morphology were assessed. Reported exposure to cigarettes was validated using a serum cotinine assay. RESULTS: Serum cotinine level at the onset of treatment correlated strongly with the number of cigarettes reported (r = 0.68). The duration and dose of gonadotropin treatment was greater among active smokers than never smokers: 10.2 versus 9.2 days and 24.7 versus 19.8 ampules, respectively. Fertilization, pregnancy, and abortion rates were similar between groups. Multivariate analyses demonstrated negative correlation between female age, but no such effect was seen with female or male smoking. Sperm concentration was significantly reduced in male smokers (prewash: 108 versus 130 x 10(6); postwash: 17.1 versus 21.6 x 10(6)), although fertilization rate was unaffected (66% versus 62%). Follicular function, assessed using serum inhibin and E2, as well as follicular fluid E2 levels showed no significant difference between active smokers and never smokers. Endometrial thickness and morphology also were similar between groups. CONCLUSIONS: These data suggest that among couples undergoing IVF neither female nor male smoking has a measurable deleterious effect on conception rate. Female age remains a far more potent prognostic factor in the current study. However, when all the published data are combined, a significant deleterious effect of smoking on conception is suggested, with a common odds ratio of 0.540 (95% confidence interval 0.385 to 0.757).
Adult↗
New treatments, preliminary results, and clinical practice.
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Feasibility Studies↗
Frequency and predictive value of antisperm antibodies among infertile couples.
Although sperm-associated antibody could impair fertility through various mechanisms, the results of follow-up studies do not uniformly confirm that pregnancy rates are lower when one of the infertile partners demonstrates antibody to spermatozoa. We conducted a prospective double-blind cohort comparative analysis in which antibody assay results were not available to physicians or patients for clinical management. The diagnostic protocol included mid-luteal progesterone, semen analysis, hysterosalpingogram and laparoscopy. The serum of each partner was assayed by immunobead testing, tray agglutination testing and a gelatin agglutination test. Data on relevant clinical characteristics and events during follow-up were collected prospectively. Among 471 couples in whom both partners were evaluated, 42 (8.9%) tested positive for anti-sperm antibodies by one or more assays, including 38 (8.1%) male partners and 6 (1.3%) female partners. The number of conceptions was 118/429 (27.5%) in antibody negative couples, 9/38 (23.7%) in male partner-positive couples and 1/6 (16.7%) in female partner-positive couples. With proportional hazards analysis, antibody status in either partner was not a significant independent predictor of time to pregnancy.
Adult↗
Occupation and the follow-up of infertile couples.
OBJECTIVE: To evaluate the influence of socioeconomic factors on the outcomes of infertility, including pregnancy, adoption, resolution, and loss to follow-up. DESIGN: Prospective observational study. SETTING: Infertility clinics in 11 teaching hospitals. PATIENTS: Newly registered couples with infertility of > 1 year. INTERVENTIONS: Demographic, clinical, and occupational data were recorded at registration, and events including treatment, pregnancy, adoption, and resolution were recorded during up to 7 years of follow-up. MAIN OUTCOME MEASURES: Time to outcomes was evaluated by means of proportional hazards analyses with respect to the occurrence of conception of livebirth, adoption, resolution, or loss to follow-up. RESULTS: [1] The clinical predictors of pregnancy included duration of infertility, pregnancy history, female partner's age, diagnosis of tubal defect or endometriosis, and treatment; [2] the likelihood of livebirth was 1.38 times greater in partnerships with a male professional; [3] adoption was 1.64 times more likely with male professional partners; [4] loss to follow-up was 1.61 times more likely if the female partner was unemployed; and [5] the likelihood of resolution was unrelated to occupation or income variables. CONCLUSION: Socioeconomic factors, as expressed by occupation, are significantly associated with important outcomes among infertile couples.
Adult↗
A quantitative overview of controlled trials in endometriosis-associated infertility.
OBJECTIVE: To undertake quantitative overviews of the following commonly used treatments for endometriosis-associated infertility: ovulation suppression, laparoscopic ablation, and conservative laparotomy. DESIGN: A protocol was prospectively defined detailing the research question, mode of study identification, inclusion and exclusion, data extraction, and pooling methods. Studies were assessed for relevance and validity by independent reviewers and their findings compared. Data were extracted in a similar fashion. PATIENTS: Women with visually diagnosed endometriosis, complaining of infertility. MAIN OUTCOME MEASURE: Pregnancy as defined by positive pregnancy test. RESULTS: Twenty-five relevant randomized controlled trials and cohort studies were identified with a total of 37 treatment comparisons. The common odds ratio (OR) from seven studies comparing ovulation suppression (danazol, medroxyprogesterone acetate [MPA], or gestrinone) versus placebo or no treatment was 0.85, suggesting no treatment benefit. The common OR for pregnancy after ovulation suppression (MPA, gestrinone, or GnRH agonist) versus danazol was also nonsignificant: 1.07. Although pooled data from trials of laparoscopic surgery suggested a treatment benefit, significant heterogeneity between studies undermines this conclusion. Laparoscopic data were similar to those from conservative laparotomy studies. Studies assessing conservative surgery plus danazol versus danazol alone showed no significant benefit from this adjunct. CONCLUSION: Ovulation suppression is an ineffective treatment for endometriosis-associated infertility. Well-designed trials of laparoscopic ablation deserve a high priority.
Combined Modality Therapy↗
Intratumoral and whole-body distributions of C110 anti-carcinoembryonic antigen radioimmunotoxin after intraperitoneal and intravenous injection: a quantitative autoradiographic study.
The intratumoral and whole-body distributions of 90Y-labeled C110 anticarcinoembryonic antigen immunotoxin after i.p. and i.v. injection were compared by quantitative autoradiography. During in vitro incubation of spherical tumor nodules of LS174T human colon cancer (about 5 mm in diameter) in a medium containing C110 radioimmunotoxin (RIT), the direct penetration of the immunotoxin increased with time but was limited to the outer 300 microns of the tumor nodule after 12 h of incubation. In vivo experiments were performed in nude mice bearing LS174T xenografts as i.p. tumor nodules. Injection of C110 RIT i.p. resulted in a ring-like distribution, i.e., high uptake at the tumor periphery and considerably lower uptake at the tumor center (ratio of peripheral to central concentration, 7:1 at 1 day and 2:1 at 5 days). In contrast, i.v. injection provided a much smaller gradient in C110 RIT distribution from peripheral to central regions (ratio of peripheral to central concentration, 3:1 at 1 day and 1:1 at 5 days). Estimates of total tumor uptake of C110 RIT by quantitative autoradiography demonstrated almost equivalent tumor uptake after either i.p. or i.v. injection, while i.v. injection was associated with increased C110 RIT uptake in various normal organs, especially in the liver, as compared to i.p. injection. The results in this study suggest that (a) i.v. injection may produce more homogeneous distribution of C110 RIT in i.p. tumor nodules of LS174T but may also result in increased liver toxicity, and (b) i.p. injection may decrease C110 RIT exposure of normal tissues, which can reduce systemic toxicity, but may also produce more restricted intratumoral distribution of C110 RIT. In addition, current methods using a nude mouse model of i.p. tumor nodules and quantitative autoradiography allow us to assess intratumoral and whole-body distributions of radiolabeled immunoconjugates from various administration routes.
Animals↗
A comparison of ovulation suppression and ovulation stimulation in the treatment of endometriosis-associated infertility.
This study compares ovulation stimulation or suppression with the pregnancy rate among infertile couples with endometriosis. The design is a nonrandomized, prospective, multicentered cohort analytic study. Two hundred and ninety-seven couples with laparoscopy-proven endometriosis were analyzed: 68 received no therapy, 42 received clomiphene and 74 received danazol. Forty patients (22%) conceived and pregnancy rates were similar in each treatment group. The relative likelihood of pregnancy associated with clomiphene was 2.9 (95% confidence limits 1.2-7.1); the relative likelihood of pregnancy with danazol was 1.02 (95% confidence limits 0.5-2.3). This study suggests that pregnancy rates during clomiphene treatment could be superior to expectant therapy, while pregnancy rate after danazol is similar to no treatment.
Adult↗
Unexplained infertility: a review of diagnosis, prognosis, treatment efficacy and management.
The dilemma of unexplained infertility posed by Southam in 1960 remains today: despite advances in the diagnostic assessment of infertility, many couples still have no explanation for their infertility. Even the most sophisticated evaluation of semen, ovulation and genital tract competence cannot reveal all of the possible defects in the complex process leading to conception. Because it arises from these shortcomings in our knowledge of fertilization and from our inability to utilize all of the current knowledge, unexplained infertility is a challenge for both biological and clinical research. This paper attempts to summarize some clinical issues in the management of unexplained infertility: the prevalence of the disorder, problems in the definition and possible explanations for the existence of this diagnostic category. It reviews outcome-based clinical publications as a guide to decision-making on what diagnostic tests to use, provides a summary of the untreated prognosis and evaluates study results that may serve as a basis for treatment decisions in this puzzling diagnostic category of infertility.
Age Factors↗
The routine use of gonadotropin-releasing hormone agonists prior to in vitro fertilization and gamete intrafallopian transfer: a meta-analysis of randomized controlled trials.
OBJECTIVE: To assess the efficacy of gonadotropin-releasing hormone agonists (GnRH-a) used in ovulation induction for in vitro fertilization and embryo transfer (IVF-ET) and gamete intrafallopian transfer (GIFT). DESIGN: Meta-analysis of 10 trials comparing treatment cycle outcomes after GnRH-a (n = 914) with other ovulation induction protocols (n = 722) and 7 trials comparing outcomes after short flare-up (n = 368) with longer suppression (n = 476) GnRH-a protocols. MAIN OUTCOME MEASURES: The outcome of primary interest was clinical pregnancy rate (PR) per treatment cycle commenced. Data describing the amount of gonadotropin used, cycle cancellation rate, clinical pregnancy per ET, and multiple pregnancy and abortion rates were also analyzed. RESULTS: Clinical PR per cycle commenced was significantly improved after GnRH-a use for IVF (common odds ratio [OR] 1.80, 95% confidence interval [CI] 1.33 to 2.44) and GIFT (common OR 2.37, 95% CI 1.24 to 4.51). Clinical PR per embryo transfer was also significantly improved with GnRH-a use (common OR 1.40, 95% CI 1.01 to 1.95). Cycle cancellation was decreased (common OR 0.33, 95% CI 0.25 to 0.44), whereas spontaneous abortion rate was similar with and without GnRH-a use. Cycle cancellation and PRs after short flare-up and longer suppression protocols were similar between groups. CONCLUSIONS: This meta-analysis supports the routine use of GnRH-a for IVF and GIFT. Further research is needed, however, to assess the potential for increased rates of multiple pregnancy and ovarian hyperstimulation syndrome, which may be associated with this treatment.
Abortion, Spontaneous↗
Prognostic factors in assessment and management of male infertility.
Evaluation of 304 infertile couples with at least one abnormal semen analysis (sperm density < 20 x 10(6)/ml and/or motility < 50%) and no apparent female factors was performed in a multicentre prospective cohort study. In 73 cases therapeutic donor insemination was performed (TDI group) with a resulting pregnancy rate of 48%. The remaining 231 couples (non-TDI group) had an overall pregnancy rate of 25%. The TDI group had a shorter duration of infertility. The ages of both partners were comparable in TDI and non-TDI groups. In the non-TDI group, univariate analysis resulted in identification of six clinical variables associated with a change in pregnancy rates. The strongest association was noted for length of infertility. There was a weaker association for semen volume, concentration of leukocytes in semen, history of pregnancy in the female partner and laparoscopy. Multiple variable analysis of data from the non-TDI group revealed that independent predictors of pregnancy were 'duration of infertility' and 'history of pregnancy in the female partner'. The multiple variable modelling suggested that (i) an increase in the length of infertility by 1 month prolongs the time to pregnancy by an additional 1.6% (95% confidence interval: 1.5-1.7%); and (ii) a history of past pregnancy in the female partner reduces the time of pregnancy by 51% (95% confidence interval: 47-56%).
Female↗
Thromboembolism following multiple trauma.
The true incidence of thromboembolic complications following multiple trauma is unknown, and no method of prophylaxis has been shown to be both safe and effective in managing seriously injured patients. In this prospective study, 113 trauma patients were assigned on admission to receive either low-dose heparin (LDH), (5,000 U subcutaneously every 12 hours) or to wear sequential compression devices (SCDs) as prophylaxis against the development of deep venous thrombosis (DVT). Both groups of patients were serially studied with duplex venous ultrasound imaging to detect thrombus in the veins of the thigh. Ventilation-perfusion lung scans and pulmonary angiograms were performed when pulmonary embolism (PE) was suspected clinically. There were 12 patients who had thromboembolic complications, including 9 of 76 in the SCD group (12%) and 3 of 37 in the LDH group (8%). Five patients had DVT only, four had PE without detectable DVT, and three had both DVT and PE. None of the patients with PE died, and there were no major complications associated with either method of prophylaxis. Compared with the patients who did not develop DVT/PE, those with thromboembolic complications were older (49 +/- 23 vs. 36 +/- 17 years, p less than 0.02), spent more hospital days immobilized (24 +/- 15 vs. 10 +/- 13 days, p less than 0.001), received more transfusions (11 +/- 12 vs. 3 +/- 5 U, p less than 0.001) and had clotting abnormalities on admission, as demonstrated by prolonged PTT values (39 +/- 28 vs. 26 +/- 5 seconds, p less than 0.001). It appears that there is an identifiable subgroup of injured patients at highest risk for PE who warrant both prophylaxis and close surveillance for DVT.
Adolescent↗
Preclinical assessments of 90Y-labeled C110 anti-carcinoembryonic antigen immunotoxin: a therapeutic immunoconjugate for human colon cancer.
We have synthesized 90Y-labeled immunotoxin (IT) containing ricin A chain and C110 anti-carcinoembryonic antigen monoclonal antibody (MAb) to produce a therapeutic immunoconjugate for human colon cancer. The C110 IT was labeled with 90Y via a benzylisothiocyanate derivative of diethylenetriaminepentaacetic acid. The efficiency of 90Y labeling was consistently 90 to 98%, with a specific activity of about 1 microCi/microgram. In in vitro stability studies, more than 80% of 90Y remained bound to the C110 IT for up to 5 days after incubation. The percentage of binding of 90Y-labeled C110 IT to carcinoembryonic antigen-coated microbeads was 86%, indicating good retention of the initial immunoreactivity of the C110 MAb. In in vitro protein synthesis inhibition assays, 90Y-labeled C110 IT was approximately 3.7-fold more toxic to the LS174T human colon carcinoma cell line than unmodified C110 IT and 1380-fold more toxic than 90Y-labeled C110 MAb. Biodistribution studies of 90Y-labeled C110 IT in LS174T tumor-bearing mice showed that, at 24 h following i.p. injection, high accumulation of radioactivity was seen in the i.p. tumor and liver and, thereafter, high accumulation in these tissues remained almost unchanged until up to 168 h, with percentage of injected dose/g ranging from 15 to 18% in the tumor and 10 to 15% in the liver. The radioactivity in the spleen and bone gradually increased with time and reached their highest levels (approximately 8% of injected dose/g) at 168 h. Estimation of absorbed radiation doses to the tissues showed that i.p. tumor would have received an approximately 1.5 to 7 times higher radiation dose than normal organs. In in vivo therapeutic trials, 90Y-labeled C110 IT provided survival prolongation of LS174T tumor-bearing mice superior to that with either unmodified C110 IT or 90Y-labeled C110 MAb (4 less than 0.01; Mann-Whitney U test). These results indicate that 90Y-labeled C110 anti-carcinoembryonic antigen IT may be a potent therapeutic immunoconjugate for human colon cancer and that it may have direct relevance for i.p. treatment of peritoneal carcinomatosis from colon cancers.
Animals↗
Use of prescription drugs in the first trimester and congenital malformations.
A prospective survey of prenatal use of prescription drugs in Tasmania yielded detailed information on drug exposure, delivery and outcome for 56,037 births from 1982 to 1989. First trimester drug use was reported by 30.9% of women, and 17.9% used only supplements of vitamins and/or minerals; 40% used alcohol during the first trimester, and 28.8% smoked cigarettes. There were 1,035 (1.85%) congenital malformations, of which 885 (85.5%) were major. The malformation rate was not significantly different in the following exposure categories: supplements only (1.62%); other pharmaceuticals (1.92%); smokers (1.88%); alcohol users (1.89%); and maternal age 35 or more years (1.95%). Adjusting for alcohol use, smoking, maternal age and diabetes mellitus, significant associations [expressed as adjusted odds ratio and 95% confidence intervals (CI)] were found between aspirin and hypospadias (3.5, 95% CI 1.4 to 8.8); dicyclomine and phocomelia (4.4, 95% CI 1.0 to 19.5); and between oral contraceptive use and pes cavus (9.7, 95% CI 2.3 to 40.4). Although significant, these associations were based on very few cases and no direct supporting evidence could be found from other data sources.
Abnormalities, Drug-Induced↗
Initial clinical study of indium-111-labeled clone 110 anticarcinoembryonic antigen antibody in patients with colorectal cancer.
A murine monoclonal antibody directed against carcinoembryonic antigen (CEA) was labeled with indium-111 (111In) by means of a benzylisothiocyanate derivative of diethylenetriamine penta-acetic acid (DTPA) and used for clinical radioimmunodetection studies. Twenty-one patients having a history of surgically resected colorectal cancer and rising serum CEA levels suggestive of tumor recurrence were studied. Patients were infused over 20 minutes with 5, 10, or 20 mg of the monoclonal antibody labeled with 5 mCi of 111In. The mean radiochemical purity was greater than 96%. No toxicity was seen. The stability of the radiolabel on antibody in patient serum was demonstrated by high-performance liquid chromatography (HPLC), sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) with autoradiography, and immunoprecipitation for up to 96 hours after infusion. Tumor sites were identified in 20 of 21 patients. Sites of antibody accumulation in 20 patients were confirmed as tumor either by resection at laparotomy (16 patients) or fine-needle biopsy (four patients). Nine patients who had the identified lesion resected or irradiated showed return of the serum CEA antigen level to normal or near normal values. In the absence of high levels of circulating CEA (greater than 500 ng/mL), the disappearance of radioactivity from patient serum demonstrated first order elimination kinetics, with a mean half-life of 38 hours. The serum half-life was not affected by the dose of antibody administered or by serum CEA titers below 500 ng/mL. Despite a mean liver uptake of 18% injected dose (ID) 24 hours after administration, hepatic metastases were easily visualized as areas of increased uptake of radioactivity. Radioimmunodetection of recurrent colorectal cancer, not detected by computed tomographic (CT) scans, appears achievable with this agent. This may allow successful clinical intervention in selected patients.
Adult↗
Performance and fecal flora of calves fed a Bacillus subtilis concentrate.
Eighty-four Holstein calves were assigned at 2 d of age to one of three treatments: 1) control with no additives; 2) 10 g of a mixed microbial concentrate containing Lactobacillus acidophilus, Lactobacillus lactis, and Bacillus subtilis; or 3) 10 g of a B. subtilis concentrate. The microbial concentrates were mixed with milk replacer during the a.m. feeding. The milk replacer was offered twice daily at 5% BW per feeding; the reconstituted replacer contained 12.5% DM. Volume of replacer fed was based on initial weight of calf and held constant until weaning. Water and starter ration were offered for ad libitum intake throughout the trial. Calves were weaned abruptly at 30 d of age and received only water and starter from d 31 to 44. General health and performance of all calves were good. Although differences in weight gain and feed efficiency were not significant, the B. subtilis concentrate tended to have a positive effect on feed efficiency during wk 1 to 4 and on immediate postweaning gain. A higher fecal bacilli count at 6 wk in calves fed the microbial concentrates may be related to their tendency for improved gain during d 31 to 44, the immediate postweaning period.
Animals↗
Overview of surgery: 1991.
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Breast Neoplasms↗