Increase of ectopic pregnancy in Finland--combination of time and cohort effects.
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Biomedical subjects
Publications and source records attributed to C B Coulam.
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To evaluate the association between ectopic pregnancy and 22 potential risk factors, we conducted a population-based case-control study. The investigation included 274 cases diagnosed from 1935 through 1982 in residents of Rochester, Minn, and 548 matched controls selected from live-birth deliveries. Risk factor information documented prior to the last index menstrual period was obtained via medical record abstract. Univariate matched analyses revealed nine variables associated with a significantly elevated relative risk of ectopic pregnancy. Following conditional logistic regression, four variables remained as strong and independent risk factors for ectopic pregnancy: current intrauterine device use (relative risk, 13.7; 95% confidence interval, 1.6 to 120.6), a history of infertility (relative risk, 2.6; 95% confidence interval, 1.6 to 4.2), a history of pelvic inflammatory disease (relative risk, 3.3; 95% confidence interval, 1.6 to 6.6), and prior tubal surgery (relative risk, 4.5; 95% confidence interval, 1.5 to 13.9). Theoretically, any condition that prevents or retards migration of the fertilized ovum to the uterus could predispose a woman to ectopic gestation. Further research is needed to clarify the impact of other potential risk factors in the etiology of ectopic pregnancy.
In an attempt to reduce the number of couples whose basic infertility evaluation fails to reveal any abnormality, 57 couples with the diagnosis of unexplained infertility were further investigated by ultrasound monitoring for folliculogenesis, sperm antibody testing, hamster egg penetration assay, and major histocompatibility (human leukocyte antigen) typing. The use of these techniques allowed the diagnosis of luteinized unruptured follicle in 5% (three patients), sperm antibodies in 5% (three patients), low sperm penetration in 11% (six patients), and human leukocyte antigen-B locus homozygosity in 37% (21 couples). When the incidence of B locus homozygosity among the 57 couples with unexplained infertility was compared with that in 51 fertile couples, the difference was significant at p = 0.025. Thus by adding the diagnostic tools of ultrasound monitoring of folliculogenesis, sperm antibody testing, hamster egg penetration assay, and major histocompatibility antigen typing, the diagnosis of unexplained infertility can be reduced by 60%.
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Twenty women with the diagnosis of premenstrual syndrome (PMS) participated in a double-blind, placebo-controlled, crossover study to evaluate the efficacy of naltrexone, an oral opiate antagonist. This study was designed to test the hypothesis that inhibition of opiate withdrawal would aid in the treatment of PMS. The subjects received either placebo or naltrexone from days 9-18 of the cycle for three consecutive cycles. The mean scores of the three day-25 Menstrual Distress Questionnaires of 16 patients on naltrexone were compared with the mean scores of the same patients on placebo. Scores were at least ten points lower on naltrexone in 11 patients and at least ten points higher on naltrexone in two patients. Score changes of less than ten points were noted in the other three patients. The mean scores dropped 28 points on naltrexone (P = .016). The general acceptability of naltrexone was good, with side effects including nausea, decreased appetite, and dizziness. These results suggest that naltrexone alleviates many PMS symptoms and may be an effective treatment for this syndrome.
To determine the association between levels of major basic protein and onset of preterm labor, plasma levels of major basic protein were measured in 13 women from weeks 22 to 41 of gestation. Twelve of the 13 women studied experienced spontaneous onset of labor. All of these women demonstrated a late rise in serum levels of major basic protein characterized by an increase in concentration of 156% +/- 14%. A temporal association between a rise in concentrations of major basic protein and the onset of preterm labor, which was successfully treated with tocolytic agents, was observed in three patients. Increases in major basic protein began 3 to 4 weeks before delivery. The rise in levels of major basic protein was absent in one patient who was delivered of her infant at 30 weeks' gestation after induction of labor with oxytocin. Analysis of these data indicate that a protein marker is associated with the onset of human labor not only at term but also preterm.
The frequency of autoantibodies during pregnancy was studied. Sera from 136 women (84 pregnant and 52 nonpregnant) were tested for antibodies directed against nuclear antigens, smooth muscle antigens, gastric parietal cells, mitochondria, and striated muscle by indirect immunofluorescent microscopy. Rheumatoid factor was measured by a latex agglutination test, and thyroid microsomal and thyroglobulin antibodies were measured by a hemagglutination assay. Immunofluorescence assays were considered positive if antibodies were detected at a serum dilution of 1:20. All positive samples were retested at increasing dilutions until immunofluorescence or agglutination could not be detected. The control population consisted of 52 normal, healthy, ovulatory, and nonpregnant women. The study population consisted of 84 pregnant women, none of whom had a known autoimmune disorder. The mean ages of the two groups were 32 and 26 years, respectively. The frequency of autoantibody detection was not significantly different in comparing the study (46.2) and control groups (40.5). The results did not support the hypothesis that pregnancy has an effect on the induction or suppression of autoantibody production. Previous studies that suggested differences may have been influenced by the lack of a control group.
With the induction of ovulation, clomiphene citrate and human menopausal gonadotropin have the potential to stimulate the endocervical glands. We have found that the degree of mucus production can occasionally be quite large and hence is detectable by sonographic evaluation as an anechoic cervical mass. The incidence of this specific ultrasonic finding was found to be approximately 5%. This physiologic process should be differentiated from disease states affecting the cervix.
Since the successful advent of in vitro fertilization and embryo transfer (IVF-ET), reproductive surgeons have been forced to compare pregnancy outcomes of surgical procedures for tubal infertility with those of IVF-ET. The current study reports pregnancy outcomes, with extended follow-up, in patients who had proximal oviductal obstruction. Twenty-seven patients who had proximal oviductal disease with limited distal disease were evaluated after microsurgical repair. The conception rate at the end of 3 years of observation was 69.3%. The live birth rate was 53.2% at 3 1/2 years. The results indicate that microsurgical reconstruction of proximal oviductal occlusion is a workable option for patients with infertility.
Thirty-one patients underwent microsurgery for correction of postinflammatory occlusion of both the proximal and the distal portions of the oviduct. Preoperative staging of tubo-ovarian adhesions, hydrosalpinges, and sites of oviductal occlusion was completed in each patient. Laparoscopic records were reviewed to correlate laparoscopic sites of occlusion with those found at the time of microsurgery. The conception rate at 2.5 years of observation was 12%, and there were no live births. The sensitivity of laparoscopy to predict proximal and distal disease was 65.6 and 55.2%, respectively. The poor surgical outcome in these patients suggests that IVF-ET should be strongly considered and that a careful preoperative laparoscopic examination is necessary for prospective counseling in these patients.
Major basic protein (MBP), the core of the eosinophil granule, is a potent toxin for parasites and mammalian cells; it also causes histamine release from mast cells and basophils. Plasma levels of MBP are increased in all pregnant women, and MBP has been localized by immunofluorescence to placental X cells and placental-site giant cells. Analyses of plasma MBP levels during pregnancy showed a striking correlation between increases late in the third trimester and spontaneous onset of labor. In one case with premature labor, the plasma MBP level also was increased coincidentally with labor. In contrast, in cases of prolonged gestation in which labor was induced, there were no late increases in MBP levels. Also, uterine contraction during spontaneous labor or oxytocin-induced labor did not cause elevations of plasma MBP. Measurement of plasma MBP levels in pregnancy may be useful for the prediction of labor and for the development of new means of intervention for premature labor and prolonged gestation.
Many studies have both supported and refuted an association between HLA antigens and reproductive performance. To clarify these discrepant results, HLA antigens from 59 couples experiencing recurrent spontaneous abortions and 79 couples with unexplained infertility were compared with 51 fertile couples. Patients with recurrent spontaneous abortions were classified as either primary (no children) or secondary (abortions after having children or stillbirths) aborters, and patients with unexplained infertility were classified as primary (never pregnant) or secondary (previously pregnant) infertiles. The amount of antigenic disparity, homozygosity, and the probability of producing a heterozygotic offspring were analyzed for each group. Significantly more disparities at combined HLA loci and at DR loci were observed when childbearing controls were compared with primary aborters. Significant disparity between controls and secondary aborters was at the DQ locus. Total homozygosity as well as homozygosity at DR and DQ loci were significantly increased among primary aborters, but not secondary aborters, and at the B locus among secondary, but not primary infertile couples. Significant association in probability of heterozygote production was seen at the DQ locus in patients with primary infertility. These results indicate that controversy involving association of HLA and reproductive performance can be explained by properly classifying recurrent spontaneous aborters and unexplained infertiles.
This paper describes a nuclear binding assay (NB assay) which measures not only the presence of a steroid receptor in a tissue, but also the quantity of that receptor which is biologically active or functional, i.e. able to bind to nuclear acceptor sites. The assay involves the isolation viable cells from tissues and their incubation with an excess of radiolabeled steroid to encourage the activation and nuclear binding of all cellular receptors. The nuclei are isolated under conditions that remove unactivated (unbound) steroid-receptor complexes. This NB assay demonstrates, in both animal and human steroid target tissues, a saturable, tissue- and steroid-specific, and temperature- and time-dependent nuclear binding of radiolabeled steroids. These properties support a receptor-dependent nuclear binding of steroids. This assay is reproducible and requires relatively small amounts of tissue. The patterns of nuclear binding of the progesterone receptor, achieved with the assay in the avian oviduct model system, are shown to correlate with the nuclear binding of progesterone in vivo, the ability of the steroid to alter transcription, and the expression of a specific gene product, the protein avidin. The assay has been used to identify the existence of nonfunctional steroid receptors in endometrial and breast carcinomas. Therefore, this NB assay combined with the standard charcoal/hydroxylapatite methods of quantitating total cellular receptors should provide a means of assessing changes in the regulation of the biological activity of steroid receptors. Further, the assay should be useful to assess the ability of steroid analogs to properly activate their respective receptors for subsequent nuclear binding.
The objective of this paper is to consider several categories of biomarkers of human pregnancy. The design of the report is to discuss useful and promising markers and techniques. Research gaps, needs, and priorities are also defined. Useful markers are mixed lymphocyte culture reactions, measures of lymphocytotoxic antibodies, histocompatibility (HLA) typing, and immunohematological evaluations. Promising markers are measures of major basic protein and early pregnancy factor, as well as determinations of trophoblast-lymphocyte cross-reactive (TLX) antigens. Promising techniques are fluorescence-activated cell-sorter analysis of maternal blood for fetal and extraembryonic tissues and immunotherapy with TLX and other antigens to prevent spontaneous abortion. It is concluded that immunology has much to offer the development of biomarkers of human pregnancy.
To examine the effects of cryopreservation on unfertilized oocytes, oocytes were collected from hamsters after injection of 25 IU of pregnant mare serum gonadotropin and 50 IU of human chorionic gonadotropin. Oocytes were placed in French straws containing Hepes-buffered Tyrode's medium and 2 mol/L of dimethyl sulfoxide at room temperature (method 1) or at 0 degree C (method 2). They were cooled to -6 degrees C at a rate of -2 degrees C/min (method 1) or at -0.5 degree C/min (method 2). The freezing rate was -0.3 degree C/min to a temperature of -80 degrees C, and then it was plunged to -196 degrees C. After thawing 1 to 21 days later at 8 degrees C/min, 52% (method 1) and 64% (method 2) of the oocytes showed normal morphologic features, 87% (method 1) and 89% (method 2) were viable by trypan blue staining, and 56% (method 1) and 59% (method 2) were viable by fluorescein diacetate staining. Comparable values for freshly collected oocytes were 95%, 100%, and 100%, respectively. Frozen-thawed oocytes were fertilized in vitro at a level of 26% (17/66) compared with 76% (51/67) for freshly collected controls. When the penetration rate of human spermatozoa was examined, frozen-thawed oocytes were penetrated at about one third of the fresh controls (14% or 18/129 compared to 42% in method 1 and 22% or 21/95 compared to 58% in method 2). The ability of oocytes to tolerate storage at -196 degrees C could be important in regard to various genetic studies, supply for hamster egg penetration assay, and cryopreservation of human oocytes.
CA-125 is a cellular antigen detected in many patients with ovarian cancer, but it has also been detected in patients with endometriosis. Preoperative CA-125 levels were drawn from 113 patients before they underwent laparoscopy. Patients were categorized into diagnostic groups on the basis of pathologic findings. CA-125 levels in patients with evidence of intraabdominal adhesions were not statistically different from those in patients with normal pelvic anatomy. However, patients with advanced endometriosis had significantly elevated levels of CA-125 when compared with patients with normal pelvic anatomy (P less than 0.05). The clinical and immunologic implications of elevated CA-125 levels in patients with advanced endometriosis are discussed.
The conception rate in 21 patients who underwent repeat tuboplasty after a primary macrosurgical procedure was evaluated. These data were compared with those of 161 patients who underwent primary microsurgical tuboplasty. Eighteen percent of the patients in the repeat tuboplasty group conceived, and all pregnancies resulted in live births. The conception rate for those patients who underwent primary microsurgical tuboplasty was 51%: 33% live births, 11% spontaneous abortions, and 9% ectopic pregnancies. The conception rate for the repeat tuboplasty group with previous macrosurgery was significantly lower (P = 0.0095) than that of the primary microsurgical group. Three patients underwent a primary microsurgical procedure followed by a second microsurgical tuboplasty. There were no conceptions in this group.