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Selective use of leuprolide acetate in women undergoing superovulation with intrauterine insemination results in significant improvement in pregnancy outcome.

OBJECTIVE: To examine the incidence of premature luteinization in individuals undergoing hMG with IUI therapy, the association between premature luteinization, cycle fecundity, and pregnancy outcome, and to determine if the selective use of leuprolide acetate (LA) in women demonstrating premature luteinization improves pregnancy outcome in subsequent hMG with IUI cycles. DESIGN AND SETTING: Retrospective analysis of superovulation cycles from January 1990 until December 1991 at the University of Connecticut Health Center. PATIENTS: All women with ovulatory function undergoing hMG superovulation with IUI. INTERVENTIONS: All patients were tested for evidence of premature luteinization. Those demonstrating premature luteinization were started on LA in the luteal phase in their subsequent hMG with IUI cycle. MAIN OUTCOME MEASURES: Peak serum E2, the number of mature preovulatory follicles, the number of ampules of hMG, days of hMG therapy, cycle fecundity, and spontaneous abortion rate. RESULTS: Thirty-three percent of all hMG with IUI patients showed evidence of premature luteinization, with premature luteinization occurring in 22.2% of conception cycles and 37.4% of nonconception cycles. For those women who demonstrated premature luteinization in their conception cycle, 90.0% of the pregnancies ended with either spontaneous abortion or were biochemical in nature compared with 44.3% in the cycles without evidence of premature luteinization. Cycle fecundity was 11.1% in patients demonstrating premature luteinization compared with 26.3% for patients without premature luteinization. All women demonstrating premature luteinization and not conceiving were placed on LA in the luteal phase and had a subsequent cycle fecundity of 18.9% with the percent pregnancy wastage being significantly less (33.3% versus 90.0%) when LA was used. CONCLUSIONS: Premature luteinization is a common occurrence during hMG therapy and is associated with decreased cycle fecundity and an increased incidence of spontaneous abortion and biochemical pregnancies. The selective use of LA in those individuals demonstrating premature luteinization results in a significant increase in the percent of women conceiving a viable pregnancy.

Abortion, Spontaneous↗

Serum PAPP-A measurements in first-trimester screening for Down syndrome.

Serum PAPP-A measurements taken from 254 women in the first trimester are reported. Eleven chromosomal abnormalities were detected. The mean serum PAPP-A levels in cases of Down syndrome were 0.44 MOM at 9 weeks gestation, 0.15 MOM at 10 weeks, and 0.29 MOM at 11 weeks. The PAPP-A level at 10 weeks was below those of pregnancies which aborted spontaneously. At 11 weeks, the pregnancies with Down syndrome recorded the lowest PAPP-A levels at that gestation. On this small sample, offering chorionic villus sampling to women with singleton pregnancies and a PAPP-A level below 0.3 MOM (approximately 6.5 per cent of this at-risk group) would have detected all the Down syndrome fetuses at 10 weeks and 50 per cent at 11 weeks without selecting those cases destined to abort. This suggests that serum PAPP-A should continue to be investigated as a potential first-trimester screening test for Down syndrome.

Adult↗

Embryo infiltration by maternal macrophages is associated with selective expression of proto-oncogenes in a murine model of spontaneous abortion.

The causes and precise mechanisms leading to early embryo loss in mammals remain largely unknown, especially from a molecular point of view. Using the CBA/J x DBA/2 murine model of early spontaneous embryo loss (25-30% embryo loss), we have previously demonstrated the involvement of infiltrating activated macrophages and their cytolytic products such as nitric oxide and tumor necrosis factor alpha (TNF alpha) in the etiology of early embryo loss. On the other hand, far fewer of the CBA/J x Balb/c conceptuses (5-10% embryo loss) displayed significant cellular infiltration and nitric oxide and TNF alpha. Having used probes for cellular activation markers, we now present evidence indicating that significantly increased expression of AP-1 family members, Ha-ras, Ki-ras, v-erbA, v-raf, v-abl, and c-myc was present in 24.4% of the CBA/J x DBA/2 embryonic units that also harbored significant Mac-1, F4/80, and class II major histocompatibility complex (MHC) molecule cellular infiltration. In contrast, only 7% of CBA/J x Balb/c conceptuses displayed increased proto-oncogene expression and increased cellular infiltration. Therefore, macrophage infiltration, cellular activation as identified by the increased expression of proto-oncogenes, and the production of cytotoxic macrophage products are closely linked to early embryo loss. These data add to the evidence that activated maternal macrophages may be directly responsible for spontaneous pregnancy failure.

Abortion, Spontaneous↗

Risk factors associated with Neospora caninum abortion in Ontario Holstein dairy herds.

The objective of this epidemiological study was to identify risk factors for Neospora caninum-related abortions in Ontario Holstein dairy herds. A total of 88 herds, consisting of 5080 cattle, and utilizing Dairy Herd Improvement (DHI) services, were divided into three groups. Case (n = 30) and first control (n = 31) herds were selected from 1998 and 1999 fetal abortion submissions to the Animal Health Laboratory, University of Guelph, that were histopathologically positive or negative, respectively, for N. caninum. A second control group (n = 27) was selected from multiple sources of herds sampled within the previous 4 years that had a low seroprevalence (<7%) to N. caninum. Between May and December 1999, all available cows on all farms, in parity one or greater, were blood sampled. The sera were then analyzed for antibody to N. caninum using a kinetic ELISA. A survey administered at the time of sampling recorded information on housing, animal species present, manure management, reproduction, biosecurity practices, wildlife observations, peri-parturient cow management, herd disease history and nutrition. Production and other herd parameters were obtained from DHI records. Logistic regression indicated that the following parameters were positively associated with a N. caninum abortion in a herd: the N. caninum herd seroprevalence (OR = 1.1), the total number of dogs on a farm (OR = 2.8), the frequency that dogs were observed defecating in mangers (OR = 2.8), the number of horses on a farm (OR = 3.1), the observed annual rate of retained fetal membranes (OR = 1.2) and the observed annual rate of cows returning to estrus after pregnancy confirmation (OR = 1.2). Factors negatively associated were the frequency of stray cats and wild canids observed on a farm (OR = 0.4 and OR = 0.7, respectively) and the housing of heifers on loafing packs (a housing pen divided into feed manger, scrape alley and bedded pack areas, OR = 0.1).

Abortion, Veterinary↗

[Comparison of the effectiveness of metal and flexible plastic cannulas in abortion by vacuum aspiration].

A total of 300 abortions were performed--150 with each kind of cannula, selected at random. Except for the cannula, all other elements of abortion were the same and did not change during the whole study. The characteristics of women undergoing abortion did not differ either. The occurrence of complications in women having undergone abortion by the use of metal or the use of flexible plastic cannulas did not differ significantly, the duration of the procedure was the same, but the amount of the tissue exceeding 10 g which was obtained by the subsequent exploration of the uterus was significantly higher with the use of metal than with the use of flexible plastic cannulas. Also the metal cannula got obstructed in the course of the procedure significantly more frequently. The authors conclude that everything considered, the flexible plastic cannula is somewhat more efficacious than the metal one when used for the interruption of pregnancy up to the tenth week of gestation.

Abortion, Induced↗

A Swiss case-control study to assess Neospora caninum-associated bovine abortions by PCR, histopathology and serology.

Neospora caninum is one of the most frequent infectious organisms causing abortion in cattle worldwide. The present case-control study was designed to assess the importance of bovine neosporosis for causing abortion in Swiss cattle and to identify selected risk factors. Infection was primarily diagnosed by a N. caninum-specific PCR and serology, complemented with histopathology and immunohistochemistry. A total of 113 case and 113 corresponding control-farms were studied for 1.5 year. During this time period, 242 abortions were reported and referred for bacteriological, virological, parasitological and pathohistological examinations. N. caninum was detected by PCR in the brains of 21% of all aborted fetuses. Microscopic lesions indicative for cerebral protozoa infection were detected in 84% of PCR-positive fetal brains. Bovine viral diarrhea virus (BVDV) was demonstrated in 7% of the cases, and bacterial infections were detected in 4% of the abortions. One or more N. caninum-abortions occurred in 20% of the herds (41 case-farms and 3 control-farms). Serological examination of aborting mother cows revealed a significantly higher percentage of N. caninum-seropositive animals (44%) in comparison to the prevalence in a randomly selected population (12%). However, in eight cases (4% of all investigated abortions) seronegative cows aborted N. caninum PCR-positive fetuses, and in 50 cases the fetus remained negative although the respective mother cow was N. caninum-seropositive. Repetitive serological investigations (at a 3-12 months interval) of 3551 cows from case- and control-farms showed a decrease of the overall N. caninum-seroprevalence from 17 to 12%. Ninety out of 3008 seronegative animals were converted to N. caninum-seropositivity. Conversely, 212 out of 543 initially seropositive animals became seronegative for their second serum sample. The obtained data underlined the importance of N. caninum as a causative agent for abortion in Swiss cattle. Furthermore, PCR was confirmed to be a valuable diagnostic tool for the primary diagnosis of N. caninum in aborted fetuses. On the other hand, the value of serology appears to be hampered by the temporal instability of N. caninum antibody concentrations in adult cattle, including especially seronegativity of some individual animals. Thus, seronegativity in a mother cow or heifer does not exclude N. caninum-associated abortions.

Abortion, Veterinary↗

Fraction of the peripheral blood concentration of CD56+/CD16-/CD3- cells in total natural killer cells as an indication of fertility and infertility.

OBJECTIVE: To determine whether the peripheral blood concentration of CD56(+)/CD16(-)/CD3(-) cells, the main natural killer (NK) subpopulation that colonizes the endometrium in the middle and late secretory phase, can be related to fertility or infertility status. DESIGN: A case control study. SETTING: Immunopathology department of an infertility laboratory. PATIENTS: A total 99 women were selected (group I: consecutive spontaneous aborters, n = 25; group II: sporadic spontaneous aborters, n = 30; group III: infertile, n = 33; group IV: controls, n = 11). INTERVENTION: Immunophenotyping of women grouped according to their fertility status. MAIN OUTCOME MEASURES: Peripheral blood lymphocytes were examined by two- and three-color flow cytometry. RESULTS: A statistically significant association between endometrial-type peripheral blood (PB) NK cell concentrations and fertility status (groups I and IV vs. groups II and III) was documented. The %(/TOTAL PB)(CD56+CD16-CD3-) NK cells was significantly higher [1] in fertile (groups I and IV) than in sporadic aborters/infertile (groups II and III) women, [2] in group I when compared with groups II and III, and [3] in group IV when compared with groups II and III. CONCLUSIONS: This study indicates that diminished numbers of the %(/TOTAL PB)(CD56+CD16-CD3-) NK cells are related to sporadic aborters and infertile women. Thus, the fraction could be used as an indicator of subsequent successful implantation and maintenance of gestation.

Abortion, Habitual↗

Leon C. Chesley and hypertension in pregnant women.

Leon C. Chesley's first paper opened with the title 'Pregnancy in the patient with hypertensive disease'(1). Leon C. Chesley PhD, John E. Annitto, MD, MSc (Med), Jersey City, NJ, USA (from the Margaret Hague Maternity Hospital) [Am J Obstet Gynecol 1947;53:372-381]. We quote some lines from this important paper and pioneering work: "We have thought it worth while to survey our experience with pregnancy in women with hypertensive disease. There are relatively few such studies based upon any considerable series, and in most studies extant there has been a selective factor in that therapeutic abortion has been done in the more severely hypertensive patients. It has not been our policy to abort such women, and our large material therefore offers an almost unique opportunity for the study of the natural history of pregnancy in hypertensive women. From the opening of the hospital in October 1931 through to 1944 there were a total of 218 patients in whom recorded blood pressures established the diagnosis of 'hypertensive toxemia,' as defined by the American Committee on Maternal Welfare. A detailed analysis has been made of the 301 pregnancies in which these patients have been seen. The gross fetal loss: in prior pregnancies, 35%; in first hypertensive pregnancy, 38%; in subsequent pregnancies, 40%. Of 47 sisters of these hypertensive patients, who delivered here, 45% had at least one toxic pregnancy. Nearly 40% of the hypertensive patients showed drops in the blood pressure in midpregnancy. Proteinuria of some degree occurred in half of the pregnancies. Renal function was normal in 93% of the pregnancies. Premature separation of the placenta occurred in 5.6% of the pregnancies. Fetal loss increased with: higher initial blood pressure, second trimester rises in blood pressure, higher pressures near delivery, decreased renal function, proteinuria, and superimposed toxemia. There were six immediate maternal mortalities (2.0%) and seven late puerperal deaths. Thus the mortality was 20 times that of the whole hospital experience." From here we will start our "hypertensive journey".

Eclampsia↗

Seroprevalence of antibodies against Neospora caninum in diagnostic equine serum samples and their possible association with fetal loss.

A case-control study of the association between the presence of serum antibodies against Neospora spp. and fetal loss was performed on serum samples submitted to a veterinary diagnostic laboratory in northwestern United States. Control sera were randomly selected from those submitted from healthy horses for routine equine infectious anemia testing required for regulatory health certification. Case sera were randomly selected from those submitted from aborting mares for diagnostic workup. Based on a 1:50 or greater titer on the indirect fluorescent antibody test, 8% of the 160 control sera and 13% of the 140 case sera were titer positive. The association odds ratio of 1.67 fell short of statistical significance (p=0.124).

Abortion, Veterinary↗

A comprehensive ethical framework for fetal research and its application to fetal surgery for spina bifida.

The transition from innovation to standard of care for fetal surgery should be guided by ethical considerations. We provide an ethical framework that identifies criteria for the investigation of fetal surgery. This framework addresses the initiation and assessment of clinical trials to determine whether they establish a standard of care, describes an appropriate informed consent process, considers whether selection criteria should include the abortion preferences of the pregnant woman, and considers whether physicians have an obligation to offer referral to such investigation. This ethical framework, in a clinically comprehensive fashion, takes account of the physician's obligations to the fetal patient, the pregnant woman, and future fetal and pregnant patients. We apply this framework to clinical investigations of fetal surgery for spina bifida.

Abortion, Induced↗

Cytomegalovirus infects human lymphocytes and monocytes: virus expression is restricted to immediate-early gene products.

In this investigation, we studied the ability of human cytomegalovirus to infect peripheral blood mononuclear cells. With monoclonal antibody technology, we demonstrated that cytomegalovirus could infect human lymphocytes of T- and B-cell lineage, natural killer cells, and monocytes. Furthermore, virus expression was limited to the synthesis of immediate-early cytomegalovirus polypeptides. These peripheral blood mononuclear cells did not produce infectious virus, nor were mature virions visualized by electron microscopy. This abortive infection of mononuclear cells was most convincingly shown with stocks of cytomegalovirus that had been recently isolated from infected patients and passaged minimally in fibroblasts. This argues for an increased lymphotropic effect of some isolates of cytomegalovirus, compared to strains of virus that are extensively adapted to growth in fibroblasts. Furthermore, immunocompetent cells that were shown to be abortively infected with cytomegalovirus lost selected differentiated functions.

Antibodies, Monoclonal↗

Management of headaches. Focus on new strategies.

Migraine headaches can be successfully treated both abortively and prophylactically with carefully selected pharmaceutical agents. Mixed headache syndrome is complex and difficult to manage. Treatment is often complicated by patients' susceptibility to dependency and accompanying sleep disturbances, as well as by troublesome drug interactions. Cranial neuralgias can be successfully treated in the majority of cases. Since many patients with cranial neuralgias are elderly, careful monitoring of serum drug levels and frequent blood cell counts during therapy are crucial.

Anti-Inflammatory Agents, Non-Steroidal↗