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Biomedical subjects

C B Coulam

Publications and source records attributed to C B Coulam.

At least 19 recordsLinked to original sources
PubMed2002

Gestational sac diameter in very early pregnancy as a predictor of fetal outcome.

OBJECTIVE: To determine whether transvaginal sonographic measurement of gestational sac diameter in pregnancies 28-42 days from the last menstrual period can predict whether a pregnancy results in a normal term birth or a spontaneous miscarriage. DESIGN: Gestational sac diameter was measured during the 4th and 5th weeks of gestation from the last menstrual period in 67 women who had a total of 102 ultrasound scans. These pregnancies were followed until one of two outcomes occurred: term gestation (n = 32) or spontaneous miscarriage (n = 35). Gestational sac diameter as a function of gestational age was compared in each of the groups. RESULTS: The mean diameter of the gestational sac at 28-35 days from the last menstrual period among normal pregnancies did not differ significantly from that in those that subsequently miscarried (2.6 mm vs. 2.7 mm; P = 1.00). In pregnancies 36-42 days from the last menstrual period, the mean sac diameter was significantly different between the two groups (normal group, mean sac diameter, 8.2 mm and miscarriage group, mean sac diameter, 4.5 mm; P < 0.001). CONCLUSION: There is no difference in gestational sac diameter at 28-35 days from the last menstrual period in normal and abnormal pregnancies. However, smaller than expected sac diameter in pregnancies 36-42 days from the last menstrual period is predictive of spontaneous miscarriage.

Abortion, Spontaneous↗
PubMed2001

Activation of the novel prothrombinase, fg12, as a basis for the pregnancy complications spontaneous abortion and pre-eclampsia.

PROBLEM: Impaired trophoblast invasion during the first trimester of pregnancy is linked to spontaneous abortion, and defective invasion in the second trimester to hypertension + proteinuria (pre-eclampsia). Hypertension developing during the third trimester of human pregnancy represents, in part, a corrective response in the mother to provide adequate placental perfusion for fetal growth when trophoblast has not to invaded and converted the myometrial porprtion of maternal spiral arteries into to low resistance-high capacitance conduits. Deportation of vesicles from hypoxemic trophoblast is thought to cause hypertension plus proteinuria, vascular damage and a systemic coagulopathy. Trophoblast invasion may be inhibited by local cytokines, such as TGF-betas but Thl-type cytokines associated with pre-eclapmsia and spontaneous abortions (e.g., IL-1, TNF-alpha, IFN-gamma) are not known to inhibit migration at in situ concentrations. Trophoblast invasion is also inhibited by the binding of surface integrins to fibronectin and fibrin, and fibrin production is stimulated by these Th1 cytokines via up-regulation of prothrombinases(s) such as fg12 which directly and via TNF-alpha-facilitated inflamation compromise trophoblast cell integrity. We, therefore, asked if fg12 expression and TNF-alpha are increased in first trimester human miscarriage and in third trimester pre-eclampsia. METHODS: fg12 mRNA was detected using in situ hybridization and fg12 protein by immunohistochemistry. TNF-alpha mRNA and protein were similarly tested. The techniques were validated using uterine sections from day 8.5 of CBA x DBA/2 pregnancies, and then were applied to sections of placentae from normal and pre-eclamptic pregnancies with and without intrauterine fetal growth restriction (IUGR). Fibrin was detectectd by immunohistochemistry. RESULTS: Expression of fg12 protein correlated with fg12 mRNA expression in mouse uteri and in placentae from normal human pregnancies. Increased expression of fg12 and TNF-alpha mRNA and protein, and increased fibrin deposition was detected in placental trophoblast. CONCLUSIONS: Activation of fg12 prothrombinase by Th1-type cytokines in pregnancy may lead to spontaneous abortion, or in ongoing pregnancy, to pre-eclampsia and/or IUGR.

Abortion, Spontaneous↗
PubMed2000

Understanding the immunobiology of pregnancy and applying it to treatment of recurrent pregnancy loss.

Successful mammalian pregnancy depends upon tolerance of a genetically incompatible fetus by the maternal immune system. When tolerance is not achieved pregnancies fail. Repeated pregnancy failures are associated with high emotional and financial cost. To provide a better understanding of an approach to treatment for recurrent pregnancy loss this manuscript presents a review of current concepts of the immunobiology of successful pregnancies and the immunopathophysiology of unsuccessful pregnancies. Based upon information gleaned from these reviews an approach to diagnosis and treatment of recurrent pregnancy loss is presented.

Abortion, Habitual↗
PubMed2000

Increased pregnancy rates after IVF/ET with intravenous immunoglobulin treatment in women with elevated circulating C56+ cells.

Intravenous (IV) immunoglobulin (Ig) has been previously shown to increase pregnancy rates after previously failed in vitro fertilization (IVF) embryo (ET) attempts in women who are efficient embryo producers (fertilize at least 50% of oocytes retrieved and generate at least 3 embryos/cycle). Women experiencing implantation failure have a higher frequency of elevated percentage of circulating CD56+ (natural killer) cells (>12%) than fertile women (3-12%). To evaluate the effects of IVIg on pregnancy rates in women with elevated percentage of circulating CD56+ cells, 32 women who had previously failed IVF/ET (>12 embryos transferred without pregnancy) were studied. Pregnancy and live birth rates with and without IVIg were compared in the same woman. All 32 women had previously failed to conceive after at least 12 ET, were efficient embryo producers and had persistently elevated plasma concentrations of CD56+ cells. Each woman received IVIg 500mg/kg prior to ET. If serum hCG concentrations were positive for pregnancy, IVIg was continued at 500mg/kg/mo until 28 weeks gestation. Pregnancy rates with and without IVIg were 56% and 9% (P<0.0001). The rate of live birth was 38% with IVIg and 0% without IVIg (P<0.0001). IVIg enhances pregnancy and live birth rates in women with elevated circulating CD56+ cells who have a history of implantation failure. Despite technologic advances leading to enhancement of fertilization rates after in vitro fertilization (IVF) (1, 2) implantation rates after embryo transfer (ET) have not increased significantly (3) over the last 20 years (4). Implantation rates after IVF/ET are influenced by the quality of the embryos and receptivity of the endometrium (3-9). Endometrial receptivity involves both hormonal (10-13) and immunologic (14-29) factors. Among the immunologic factors that play a crucial role in successful implantation are natural killer (NK) cells (14-18). NK cells present within the decidua that express CD56(but lack CD 16) have been associated with successful implantation (14-18). A deficiency of decidual CD56+ CD16- cells (18) and an increase in circulating CD56+ cells (25, 26) have been observed in women experiencing implantation failure. Women experiencing implantation failure after IVF and multiple ET have been successfully treated with intravenous (IV) immunoglobulin (Ig) (27). IVIg reduces activation of NK cells and NK killing activity both in vitro (29) and in vivo (30-31). This reduction in activation of NK cells is essential for normal implantation to occur (14). To further define the role of IVIg for treatment of implantation failure, pregnancy and live birth rates were compared before and after IVIg treatment in women undergoing IVF/ET who had elevated levels of circulating CD56+ cells.

Adult↗
PubMed2000

Luteal estrogen supplementation in pregnancies associated with low serum estradiol concentrations.

The role of luteal phase estrogen in pregnancy outcome has been a matter of considerable debate. In order to evaluate the effectiveness of estrogen supplementation in gonadotropin releasing hormone agonist (GnRHa)/human menopausal gonadotropin (hMG)-stimulated cycles associated with low luteal estrogen concentration, a study was performed comparing the ongoing pregnancy rates in cycles with serum concentrations of estradiol (E2) <100 pg/ml 11 days post embryo transfer (p-ET), treated with luteal phase progesterone (P4) vs. E2 and P4 supplementation. Among 1106 serum samples studied, 951 were from women receiving GnRHa and follicle stimulating hormone (FSH) prior to oocyte retrieval and P4 (50 mg-100 mg IM daily) as luteal phase supplementation beginning day 11 after retrieval. The remaining 155 were from women receiving both E2 (2 mg-6 mg estrace orally each day) and P4 during the luteal phase. Significantly greater frequencies of preclinical losses were observed among women with human chorionic gonadotropin (hCG) concentrations>5 mIU/ml and concurrent E2 concentrations <100 pg/ml compared with E2 >100 pg/ml (p<0.00001). Among the 128 women who had hCG concentrations >5 mIU/ml and E2 concentrations <100 pg/ml, 102 received P4 only during the luteal phase and 26 were treated with estrace 2 mg-6 mg daily, as well as P4 during the luteal phase. The frequency of preclinical pregnancy losses among the 102 women with hCG >5 mIU/ml and E2 <100 pg/ml who did not receive luteal E2 supplementation was 72%, compared with 50% who received luteal E2 supplementation (p=0.04) The increase in preclinical pregnancy loss rates among women not receiving luteal E2 resulted in a decrease in ongoing pregnancy rate (8%), compared to those receiving luteal E2 supplementation (31%) (p=0.002). Our results indicated that a subset of women losing pregnancies preclinically after GnRHa and FSH stimulation due to low luteal phase serum E2 level may benefit from luteal estrogen supplementation. More sensitive and specific markers are needed to identify prospectively women in this risk group.

Administration, Oral↗
PubMed2000

First trimester diagnosis of acardiac twins.

OBJECTIVE: To describe ultrasonographic findings from 5 to 17 weeks of gestation in monozygotic twin pregnancy resulting in acardia of one twin. METHODS: Transvaginal ultrasonographic examinations were performed using a 7.5 MHz probe at weekly intervals from week 5-11. Uterine artery PI were measured using color Doppler flow. Embryonic heart rates were determined with M-mode. RESULTS: A monochorionic gestational sac containing 2 embryos demonstrated embryonic cardiac activity between 5 and 7 weeks. One twin lost cardiac activity at 7 weeks. A diagnosis of acardiac twins was made at 1 weeks when growth of the lower extremities and no development above the thorax as well as reversal of blood flow through the umbilical cord of the acardiac twin was noted by 14 weeks. CONCLUSION: Ultrasonographic demonstration of independent embryonic heart rates from 5-6 weeks and reversal of blood flow through the umbilical cord of the acardiac twin suggest that the primary pathogenesis in acardia is cardiac dysmorphogenesis secondary to reversal of blood flow rather than primary cardiac agenesis. Acardiac twins can spontaneously ligate connection with their viable twin. Acardiac twinning is a rare complication of multifetal gestation occurring in 1% of monozygotic twin pregnancies or 1 in 35000 births (1). Acardius, as the name implies, is anomaly in which the heart is absent. Acardius can only occur in multiple gestations since its circulation must be maintained by vascular anastomosis with an accompanying fetus (2). Although little doubt exists that intrauterine growth of the acardiac twin is achieved by the perfusion afforded from the normal co-twin via vessel anastomosis in the placenta, the pathogenesis of acardia has been disputed. Some authors (3-5) have presented evidence supporting the concept that the primary defect is one of cardiac embryogenesis (dysmorphogenesis) and that the vascular anastomosis between the vessels, although necessary for the intrauterine survival of the acardiac twin, is not responsible for the cardiac findings. Others (6-8) believe that the primary cause is an abnormal vascular communication between embryos leading to reversed flow of blood to the hemodynamically disadvantaged or recipient twin, with the resulting secondary atrophy of the heart and dependent organs. Inadequate perfusion of the recipient twin is responsible for the development of characteristic set of anomalies including acardia and acephalus. The hemodynamically advantaged or pump twin is structurally normal, but is at risk for in utero cardiac failure and without treatment dies on 50% to 75% of cases (9). Ultrasonography has assumed increasing importance in prenatal diagnosis of congenital anomalies (10). Using this technique, intrauterine diagnosis of acardiac twins has been made as early as 18 weeks of gestation allowing umbilical cord ligation of the acardiac twin at 19 weeks of gestation and uncomplicated birth of abnormal twin at 36 weeks of gestation (11). We now report intrauterine diagnosis of acardiac twins during the first trimester of pregnancy. Unique aspects of the case suggest the pathogenesis of acardia involves arterioarterial anastomosis of placental vessels with retrogade blood flow into the recipient twin and not primary arrest in cardiac development. Further, spontaneous ligation of the vascular connection is documented followed by an uncomplicated delivery of a normal infant at term.

Diseases in Twins↗
PubMed1999

Murine embryos as a direct target for some human autoantibodies in vitro.

The involvement of one or another autoantibody in reproductive failure have long been thought to be through post-implantation thrombosis and/or peri-implantation trophoblast dysfunction and/or maternal hormonal imbalance. It can be postulated that the embryo may be a direct target for some autoantibodies prior to implantation. Mouse embryos have been labelled and cultured with affinity purified immunoglobulin (IgG) and IgA from positive for antiphospholipid antibody sera, as well as IgG from positive for antinuclear antibody sera and positive for antithyroid antibody sera. Intact IgG and IgA from healthy individuals were used as controls. All embryos cultured with purified antiphospholipid IgG or IgA, and anti-nuclear IgG exhibited strong immunofluorescence. No difference in fluorescent intensity was observed whether antiphospholipid or anti-nuclear antibodies were used, but the pattern of antibody distribution seemed to be different. Antiphospholipid IgG was more dominant on the zona pellucida, while antiphospholipid IgA and antinuclear IgG had predominant distribution on the embryonic cells. None of the embryos cultured with antithyroid IgG or with control immunoglobulins showed strong immunofluorescence. Embryos cultured with purified antiphospholipid and antinuclear immunoglobulins experienced significant growth impairment or death compared to those cultured with antithyroid or control immunoglobulins.

Animals↗
PubMed1999

Colour Doppler indices of follicular blood flow as predictors of pregnancy after in-vitro fertilization and embryo transfer.

Peak systolic velocity (PSV) of individual follicles has been correlated with oocyte recovery, fertilization rate and embryo quality [in women undergoing in-vitro fertilization (IVF) and embryo transfer]. The present study assessed the role of quantitative and qualitative indices of follicular vascularity in predicting pregnancy after IVF and embryo transfer. A total of 106 women undergoing IVF treatment for infertility who were considered to be at risk of failure (>37 years of age, history of low response to gonadotrophin stimulation, or multiple failed IVF cycles) constituted the study group. PSV was measured from the three largest follicles on both the right and left ovaries on the day of human chorionic gonadotrophin (HCG) administration using an Acuson Sequoia with a 4-8 MHz transvaginal probe. The quality of follicular flow was graded from 1 to 4 according to the amount of visible colour flow around the follicle (grade 1 when one-quarter of the follicle, grade 2 when one-half, grade 3 when three-quarters, and grade 4 when the entire follicle was surrounded by colour). Clinical pregnancies resulted in 11 (10%) of the 106 high-risk women. Women who had PSV >/= 10 cm/s in at least one follicle on the day of HCG administration more often became pregnant than those with PSV <10 cm/s (P = 0.05). All pregnancies occurred in women with grade 3 or 4 follicular blood flow. Qualitative as well as quantitative measurements of follicular flow predict pregnancy after IVF and embryo transfer.

Adult↗
PubMed1999

The emerging role of immunoregulation of fibrinogen-related procoagulant Fgl2 in the success or spontaneous abortion of early pregnancy in mice and humans.

PROBLEM: Abortion of chromosomally normal embryos in the CBA X DBA/2 mating combination is triggered by release of Th1 cytokines (tumor necrosis factor [TNF]-alpha, interferon [IFN]-gamma, and interleukin [IL]-1), which cause abortion via a novel prothrombinase, Fgl2, and polymorphonuclear leukocytes. The site of activation may be maternal vascular endothelium on arteries and veins nourishing the placenta. Activation of coagulation is also prominent in spontaneous abortion of chromosomally normal human embryos. We asked where is Fgl2 up-regulated in the uterus in murine abortions, and if similar Fgl2 expression occurs in human pregnancy failure. METHODS: Control CBA X DBA/2 pregnant mice, or from mice injected with TNF-alpha + IFN-gamma on day 7.5 of gestation, were removed on day 8.5, fixed, sectioned, and subject to in situ hybridization for Fgl2. Sections were also stained for fibrin. Elective first trimester termination samples or biopsies taken early in the course of a recurrent miscarriage were similarly fixed, sectioned, and analyzed by in situ hybridization. Control and cytokine-treated mice were anticoagulated with heparin, an activator of antithrombin III, and/or the direct anti-thrombin inhibitor hirudin. RESULTS: Low level Fgl2 expression localized to basal decidua remote from the embryo was noted in control mice; cytokine treatment, which causes greater than 80% of abortions, produced a striking up-regulation in this area as well as in a band at the junction of decidua and myometrium. Trophoblast also became strikingly positive. Fgl2 expression was associated with increased fibrin staining. Anticoagulation significantly protected against abortions, but doses were limited by the complication of retroplacental hemorrhage. In tissue from normal first trimester pregnancy, minimal Fgl2 positivity was seen in some villous syncytiotrophoblast, in villous stroma, cytotrophoblast, and in some cells in decidua. In spontaneous abortion of normal embryo, striking Fgl2 positivity was seen in syncytiotrophoblast and extravillous cytotrophoblast, in association with areas of thrombus formation. CONCLUSIONS: Fgl2 appears to be physiologically expressed and may protect against the internal danger of maternal and/or fetal bleeding during pregnancy and at parturition; a role in inhibiting transplacental traffic is also possible. External dangers in the form of stress, endotoxin, and antigens eliciting Th1 cytokine responses upregulate Fgl2 prothrombinase in trophoblast as well as in decidua, which results in spontaneous abortion of immunogenetically "weaker" embryos.

Abortion, Spontaneous↗
PubMed1999

Progress in characterization of pre-implantation factor in embryo cultures and in vivo.

PROBLEM: Pre-implantation factor (PIF), a small, embryo-derived peptide is detected in the maternal serum prior to implantation and is associated with successful pregnancy outcome. However, its identity is not known. METHOD OF STUDY: PIF was isolated from mouse embryo conditioned media and from pregnant porcine sera, using high-performance liquid chromatography (HPLC) followed by mass spectrometry. RESULTS: Conditioned culture media was separated by gel filtration chromatography followed by reversed phase chromatography. At each step, PIF activity was determined by the lymphocyte/platelet binding autorosette assay (LPBA). Mass spectrometry yielded a single peak with a mass of 1300 Da. The peptide is, however, present in very low concentrations (fM), which has so far precluded complete identification. Pregnant porcine sera that exhibit potent PIF activity were deproteinated by acetone and further fractionated by reversed phase HPLC. Active fractions contain peptides of molecular masses 523 and 551 Da. CONCLUSION: PIF, likely to be peptides, represents a novel substance related to pregnancy initiation and maintenance.

Animals↗
PubMed1998

What is a preclinical pregnancy loss?

PURPOSE: To evaluate the contribution of embryo quality to preclinical loss rates after in vitro fertilization (IVF)/embryo transfer (ET) pregnancy, multiple gestation, and clinical loss rates were compared to preclinical pregnancy loss rates over a 3-year period. METHODS: The pregnancy outcomes after 1675 fresh ETs from 1994 to 1997 were studied. While establishment of a clinical pregnancy confirms uterine receptivity, multiple gestation rates reflect embryo quality. Because the majority of clinical losses are chromosomally abnormal, clinical loss rates serve as another indicator of embryo quality. RESULTS: The overall preclinical pregnancy loss rate was 5% (78/1675) of ETs and 17% (78/472) of pregnancies. During the 3-year period the pregnancy rates per ET increased from 19 to 36% (P < 0.0001), multiple gestation rates increased from 21 to 48% (P < 0.008), clinical loss rates decreased from 20 to 6% (P < 0.0001), and preclinical pregnancy loss rates remained unchanged from 13 to 19% (P = 0.1). CONCLUSIONS: Preclinical pregnancy loss more likely reflects abnormalities in uterine receptivity rather than embryo quality. If recurrent preclinical pregnancy loss occurs after IVF/ET, evaluation for abnormalities of uterine receptivity should be performed.

Abortion, Spontaneous↗
PubMed1997

Antiphospholipid antibodies associated with implantation failure after IVF/ET.

PURPOSE: Our purpose was to determine the specific antiphospholipid antibodies (APAs) that should be evaluated to identify individuals at risk for implantation failure associated with reproductive autoimmune failure syndrome (RAFS). METHODS: The prevalence of APAs among 312 women with implantation failure was compared with that of 100 fertile control women. To be included in the implantation failure group, each woman had to have had at least 12 embryos transferred without subsequent positive pregnancy test. Enzyme-linked immunoabsorbant assay was used to measure IgG, IgM, and IgA anticardiolipin, antiphosphatidyl ethanolamine, antiphosphatidyl inositol, antiphospatidic acid, anti-phosphatidyl glycerol, antiphosphatidyl choline, and antiphosphatidyl serine. RESULTS: When the values for each of the seven APAs in three isotypes were compared between women with implantation failure and the control population, all of the APAs tested had a significantly higher frequency among women with implantation failure. Positive APAs were detected in 69 (22%) of the 312 women with implantation failure compared with 5 (5%) of the 100 control women (P < 0.0001). Anticardiolipin antibodies were found in 13 (4%) of the 312 women with implantation failure and none of the controls. Fifty-six (18%) of the 312 with implantation failure were negative for anticardiolipin antibodies but had positive values of other APAs. CONCLUSIONS: A complete APA panel using seven isotypes is necessary for diagnosing implantation failure associated with RAFS. If only anticardiolipin antibody is measured, 4% (13/312) of the positive APAs are detected, and 81% (56/69) of women with implantation failure associated with RAFS will have the diagnosis missed.

Antibodies, Antiphospholipid↗
PubMed1997

Comparison of ultrasonographic findings in spontaneous abortions with normal and abnormal karyotypes.

To determine whether ultrasonographic findings can predict the karyotype of spontaneous abortions, 137 pregnancies (54 spontaneous, 83 assisted ovulatory cycles) that subsequently aborted and had chromosome analysis performed on the products of conception were studied ultrasonographically. Transvaginal ultrasound was performed using an Acuson 128XP/10 with 7.5 MHz probe. The numbers of empty gestational sacs, small and normal for gestational size, embryonic poles and embryos with documented cardiac activity were calculated. The frequency of each of these findings in pregnancies with normal and abnormal karyotypes was compared. Of the 137 spontaneous abortions, 51 had normal chromosome analyses and 86 had abnormal karyotypes (68 aneuploidies and 18 polyploidies). Ultrasonographic findings in the 51 karyotypically normal pregnancies included 16 (31%) with empty gestational sacs, and 35 (69%) with embryonic poles, of which 24 (69%) were at least 1 week smaller than expected for gestational age and 11 (31%) were the expected size. Embryonic cardiac activity was documented in 22 (63%) of the 35 embryonic poles. Amongst 86 pregnancies with abnormal karyotypes, similar frequencies of ultrasound findings were found: 23 (27%) with empty gestational sacs, 42 (67%) with embryonic poles smaller than expected for gestational age, and 50 (79%) embryos lost after documentation of embryonic cardiac activity. No differences in the frequency of ultrasonographic findings of empty gestational sacs, small embryonic pole and embryonic cardiac activity were observed between karyotypically normal and abnormal spontaneous abortions. Ultrasonographic findings cannot predict the karyotype of spontaneous abortions.

Abortion, Spontaneous↗