*Abortion, Criminal ; *Abortion, Habitual ; *Abortion, Missed ; *Abortion, Septic ; *Abortion, Threatened ; *Malaysia ; *Maternal Mortality ; *Statistics ; *Adolescent ; *Pregnancy

OBJECTIVE: The study was carried out to assess whether a sudden rise in the serum CA 125 level might predict spontaneous abortion in the first trimester. In the process, we assessed the clinical value of maternal CA 125 in patients with missed abortion and evaluate the prognostic significance of CA 125 in early normal pregnancies, threatened abortions. The purpose of this study was to prospectively compare serum CA 125 levels among women who abort in the first trimester, who experience threateneda bortion and who go through normal pregnancy. METHODS: Between March 2001 and September 2001, a total of 133 patients were observed in the Department of Obstetrics and Gynecology at CHA Hospital. Fifty-eight with missed abortions, forty-five with threatened abortions and thirty normal pregnancies (no history of endometriosis or ovarian mass) were evaluated during gestational age 6 to 12 weeks and maternal serum samples were collected. All patients were sonographically assessed and CA 125 values were compared. RESULTS: There was no statistically significant difference in the CA 125 levels between the spontaneous aborted patients and the patients without abortion: missed abortion, 72.9 +/- 102.0IU/ml (range 7.3-487.6); threatened abortion, 46.6 +/- 37.9IU/ml (range 13.9-206.1); normal pregnancy, 63.4 +/- 61.2IU/ml (range 13.8-62.8). CONCLUSION: Our study shows that serum CA 125 levels are not predictive of spontaneous abortion in the first trimester and failed to discriminate among missed abortions, threatened abortions, and normal pregnancies.
Abortion, Missed ; Abortion, Spontaneous ; Abortion, Threatened ; Endometriosis ; Female ; Gestational Age ; Gynecology ; Humans ; Obstetrics ; Pregnancy Trimester, First* ; Pregnancy* ; Prospective Studies

OBJECTIVE: This study was conducted to determine the effectiveness and safety of medical treatment with sublingual misoprostol (MS) in the 1st trimester miscarriage under the approval by Health Insurance Review and Assessment Service (HIRA) for off-label usage by the single medical center in Korea. METHODS: A retrospective cohort study was performed in one institution between April 2013 and June 2016. Ninety-one patients diagnosed with miscarriage before 14 weeks of gestation and wanted to try medical treatment were included. A detailed ultrasound scan was performed to confirm the diagnosis. Patients took 600 microgram (mcg) of MS sublingually at initial dose, and repeated the same dose 4–6 hours apart. Successful medical abortion was defined as spontaneous expulsion of gestational products (including gestational sac, embryo, fetus, and placenta). If gestational products were not expelled, surgical evacuation was performed at least 24 hours later from the initial dose. Information about side effects was obtained by medical records. RESULTS: About two-thirds of patients had a successful outcome. The median interval time from pill to expulsion was 18 hours in the successful medical treatment group. There was no serious systemic side effect or massive vaginal bleeding. Presence or absence of vaginal spotting before diagnosis of miscarriage, uterine leiomyomas, subchorionic hematoma, or distorted shape of gestational sac on ultrasound scan were not statistically different between the two groups. CONCLUSION: Medical treatment with sublingual MS can be a proper option for the 1st trimester miscarriage, especially for the patient who want to avoid surgical procedure. We can reduce the unnecessary sedation or surgical intervention in the patients with the 1st trimester miscarriage.
Abortion, Incomplete ; Abortion, Missed ; Abortion, Spontaneous* ; Administration, Sublingual ; Cohort Studies ; Diagnosis ; Embryonic Structures ; Female ; Fetus ; Gestational Sac ; Hematoma ; Humans ; Insurance, Health ; Korea* ; Leiomyoma ; Medical Records ; Metrorrhagia ; Misoprostol* ; Off-Label Use* ; Pregnancy ; Retrospective Studies ; Ultrasonography ; Uterine Hemorrhage

BACKGROUND: Recurrent spontaneous abortion (RSA) is defined as the occurrence of three or more consecutive spontaneous abortion before 20 gestational weeks. But, 40-50% of RSA still remain "unex-plained". Cytokines seem to play a critical role in the pathogenesis of unexplained RSA, and Th1 cytokines have been shown to exert deleterious effects on pregnancy. NK cytotoxicity has been reported to be predictive of subsequent abortion in women who had unexplained recurrent abortions. The aim of this study was to investigate immunophenotypic characteristics of peripheral blood mononu-clear cells and evaluate Th1 cytokine (TNF-alpha) production in women with RSA. METHODS: The study group comprised 93 women with RSA, and the control group consisted of 40 healthy pregnant women. The population of CD56/CD16 cells was observed by using a two-color scattergram in FACScan (Becton Dickinson, San Jose CA, USA). Concentration of TNF-alpha was measured by an enzyme-linked immunoabsorbant assay (ELISA) using commercial kits (NEOGEN corporation, Lexington KY, USA). RESULTS: The percentage of CD56+/CD16-cells were significantly higher (P<0.05) in the patients with RSA (13.40+/-7.95%) than in the pregnant control group (9.12+/-3.93%). We observed a significantly higher level of TNF-alpha (medians: 85.59+/-8.29 pg/mL versus 44.80+/-9.78 pg/mL; P<0.05) in RSA women compared to controls. CONCLUSIONS: This study indicates that an increased proportion of CD56+/CD16-mononuclear cells and increased level of serum TNF-alpha are related to RSA. Thus, the two factors could be used as an indicator of subsequent successful implantation and maintenance of gestation.
Abortion, Habitual ; Abortion, Spontaneous* ; Cytokines ; Female ; Humans ; Pregnancy ; Pregnant Women ; Tumor Necrosis Factor-alpha*

OBJECTIVE: To assess the value of BACs-on-Beads (BoBs) technique for the detection of chromosomal abnormalities in abortus tissues from recurrent pregnancy loss. METHODS: A total of 109 abortus samples were collected and analyzed with the BoBs technique. The incidence and types of chromosomal abnormalities for different age groups and gestational weeks were compared. RESULTS: The BoBs assay has succeeded in all cases, with an incidence for chromosomal abnormalities reaching 62.39% (68/109). The major findings included trisomy 16 (12/68), trisomy 22 (9/68), trisomy 13 (9/68) and trisomy 21 (8/68). The abnormal rate was significantly higher in those above 35-year-old compared with that of the <35-year-old group (P<0.05). More aberrations were found among abortus tissues derived from 42-70 days of pregnancy albeit with no statistical significance (P>0.05). The aberration rates were similar for samples derived from second, third and fourth time abortions (P>0.05). CONCLUSION BoBs technique can detect chromosomal aberrations in miscarriages and may be routinely used for the analysis of early spontaneous abortions.
Abortion, Habitual ; Abortion, Spontaneous ; Adult ; Chromosome Disorders ; Down Syndrome ; Female ; Humans ; Karyotyping ; Pregnancy ; Prenatal Diagnosis

OBJETIVE: To analyze the antithrombin III deficiency in patients with recurrent spontaneous abortion. MATERIALS AND METHOD: The blood samples were tested by chromogenic assay to evaluate the activity of antithrombin III. RESULTS: There was only one case of antithrombin III deficiency. This patient experienced one neonatal death after delivery and one FDIU (fetal death in utero). And also this patient showed a lupus anticoagulant and the prolongation of PTT. CONCLUSIONS: Women with recurrent miscarriage who have no obvious identified cause should consider hematologic screening. Antithrombin III deficiency could be a cause of recurrent spontaneous abortion. But the incidence is very rare in Korean patients.
Abortion, Habitual ; Abortion, Spontaneous* ; Antithrombin III Deficiency* ; Antithrombin III* ; Female ; Humans ; Incidence ; Lupus Coagulation Inhibitor ; Mass Screening ; Pregnancy

BACKGROUNDGenetic factors are the main cause of early miscarriage. This study aimed to investigate aneuploidy in spontaneous abortion by fluorescence in situ hybridization (FISH) using probes for 13, 16, 18, 21, 22, X and Y chromosomes.

METHODSA total of 840 chorionic samples from spontaneous abortion were collected and examined by FISH. We analyzed the incidence and type of abnormal cases and sex ratio in the samples. We also analyzed the relationship between the rate of aneuploidy and parental age, the rate of aneuploidy between recurrent abortion and sporadic abortion, the difference in incidence of aneuploidy between samples from previous artificial abortion and those from no previous induced abortion.

RESULTSA total of 832 samples were finally analyzed. 368 (44.23%) were abnormal, in which 84.24% (310/368) were aneuploidies and 15.76% (58/368) were polyploidies. The first was trisomy 16 (121/310), followed by trisomy 22, and X monosomy. There was no significant difference in the rate of aneuploidy in the advanced maternal age group (≥ 35 years old) and young maternal age group (<35 years old). However, the rate of trisomy 22 and the total rate of trisomies 21, 13, and 18 (the number of trisomy 21 plus trisomy 13 and trisomy 18 together) showed significantly different in two groups. We found no skewed sex ratio. There was no significant difference in the rate of aneuploidy between recurrent miscarriage and sporadic abortion or between the samples from previous artificial abortion and those from no previous artificial abortion.

CONCLUSIONSAneuploidy is a principal factor of miscarriage and total parental age is a risk factor. There is no skewed sex ratio in spontaneous abortion. There is also no difference in the rate of aneuploidy between recurrent abortion and sporadic abortion or between previous artificial abortion and no previous induced abortion.

Abortion, Habitual ; genetics ; Abortion, Spontaneous ; genetics ; Adult ; Aneuploidy ; Female ; Humans ; In Situ Hybridization ; Middle Aged ; Pregnancy ; Sex Ratio

OBJECTIVE: To explore the genetic etiology and related factors in 1 065 women with spontaneous abortions. METHODS: All patients have presented at the Center of Prenatal Diagnosis of Nanjing Drum Tower Hospital from January 2018 to December 2021. Chorionic villi and fetal skin samples were collected, and the genomic DNA was assayed by chromosomal microarray analysis (CMA). For 10 couples with recurrent spontaneous abortions but normal CMA results for abortive tissues, non-in vitro fertilization-embryo transfer (IVF-ET) pregnancies and no previous history of live births and no structural abnormalities of the uterus, peripheral venous blood samples were collected. Genomic DNA was subjected to trio-whole exome sequencing (trio-WES). Candidate variants were verified by Sanger sequencing and bioinformatics analysis. Multifactorial unconditional logistic regression analysis was carried out to analyze the factors that may affect chromosomal abnormality in spontaneous abortions, such as the age of the couple, number of previous spontaneous abortions, IVF-ET pregnancy and history of live birth. The incidence of chromosomal aneuploidies in spontaneous abortions during the first trimester was compared in young or advanced-aged patients by chi-square test for liner trend. RESULTS: Among the 1 065 spontaneous abortion patients, 570 cases (53.5%) of chromosomal abnormalities were detected in spontaneous abortion tissues, which included 489 cases (45.9%) of chromosomal aneuploidies and 36 cases (3.4%) of pathogenic/likely pathogenic copy number variations (CNVs). Trio-WES results have revealed one homozygote variant and one compound heterozygote variants in two pedigrees, both of which were inherited from the parents. One likely pathogenic variant was detected in the patient from two pedigrees. Multifactorial unconditional Logistic regression analysis suggested that age of patient was an independent risk factor of chromosome abnormalities (OR = 1.122, 95%CI: 1.069-1.177, P < 0.001), the number of previous abortions and IVF-ET pregnancy were independent protective factors for chromosomal abnormalities (OR = 0.791, 0.648; 95%CI: 0.682-0.916, 0.500-0.840; P = 0.002, 0.001), whilst the age of husband and history of live birth were not (P > 0.05). The incidence of aneuploidies in the abortive tissues has decreased with the number of previous spontaneous abortions in young patients (χ² = 18.051, P < 0.001), but was not significantly correlated with the number of previous spontaneous abortions in advanced-aged patients with spontaneous abortions (P > 0.05). CONCLUSION Chromosomal aneuploidy is the main genetic factor for spontaneous abortion, though CNVs and genetic variants may also underlie its genetic etiology. The age of patients, number of previous abortions and IVF-ET pregnancy are closely associated with chromosome abnormalities in abortive tissues.
Pregnancy ; Humans ; Female ; Aged ; Abortion, Spontaneous/genetics* ; DNA Copy Number Variations ; Chromosome Aberrations ; Chromosome Disorders/genetics* ; Aneuploidy ; Abortion, Habitual/genetics*

OBJECTIVES: Methylenetetrahydrofolate reductase (MTHFR) mutation are commonly associated with hyperhomocysteinemia, and through their defects in homocysteine metabolism, they have been implicated as a risk factor for recurrent spontaneous abortion. Recent report describe that 28-bp tandem repeat polymorphism in thymidylate synthase enhancer region (TSER) that influence enzyme activity would affect plasma homocysteine level. We have investigated the relationship between TSER genotype and plasma homocysteine level in 54 patients with recurrent spontaneous abortion. METHODS: Plasma homocysteine level was measured by fluorescent polarizing immunoassay. MTHFR mutation (C677T and A1298C) was identified by PCR-restriction fragment length polymorphism assay and TSER mutation was analyzed by PCR method. The data were analyzed using the program SAS 8.2 for Windows. RESULTS: Total homocysteine level was significantly higher in MTHFR 677TT genotype (9.80+/-3.87 mumol/L) than MTHFR 677CC genotype (8.14+/-1.74 mumol/L) in Korean patients with unexplained recurrent spontaneous abortion (p=0.0143). However, the plasma homocysteine level was not significantly different in the MTHFR 1298AA (8.42+/-2.65 mumol/L) and 1298CC (6.09+/-0.32 mumol/L; p=0.2058) and, TSER 2R2R (8.61+/-1.68 mumol/L) and 3R3R (8.05+/-2.81 mumol/L; p=0.9319) mutant genotypes, respectively. In this study, we found the combination effects of TSER and MTHFR C677T genotypes. Plasma homocysteine levels were the highest (11.47+/-4.66 mumol/L) in individuals with TSER 3R3R (8.05+/-2.81 mumol/L) and MTHFR 677TT (9.80+/-3.87 mumol/L) genotypes. Individuals with a combination of both TSER 2R2R/2R3R and MTHFR 677CC/CT genotypes (7.69+/-1.77 mumol/L) had lower plasma homocysteine levels than TSER 2R2R (8.61+/-1.68 mumol/L) and MTHR 677CC (8.14+/-1.74 mumol/L) genotypes, respectively. The effect of MTHFR polymorphism in the homocysteine metabolism appears to be stronger than that of TSER polymorphism. CONCLUSION: Although statistically not significant, we found the elevated level of plasma homocysteine in combined genotypes with TSER and MTHFR (C677T and A1298C) in Korean patients with unexplained habitual abortion. In this study, we reported the possibility that TSER polymorphism is a genetic determinant of plasma homocysteine levels in the Korean patients as well as MTHFR C677T polymorphism. A large prospective study is needed to verify our findings.
Abortion, Habitual ; Abortion, Spontaneous* ; Female ; Genotype ; Homocysteine* ; Humans ; Hyperhomocysteinemia ; Immunoassay ; Metabolism ; Methylenetetrahydrofolate Reductase (NADPH2) ; Plasma* ; Polymerase Chain Reaction ; Pregnancy ; Risk Factors ; Tandem Repeat Sequences ; Thymidylate Synthase*

OBJECTIVE: Successful implantation depends on a complex interaction between the developing blastocyst and the endometrium. Among the steroid hormones, growth factors, and cytokines which participate in preparing the uterus for implantation, leukemia inhibitory factor (LIF) plays an essential role in implantation. We compared the expression of LIF in normal pregnancies to that of recurrent abortions in placenta to elucidate whether spontaneous abortion and expression of LIF has correlation. METHODS: Placental tissues from normal pregnancies and recurrent abortions were fixed and embedded in paraffin. Standard immunohistochemical staining was used to identify LIF. RESULTS: LIF expressions on cytotrophoblast of recurrent abortion were lower than those of normal pregnancy. There were no expressions on syncytiotrophoblast and stroma in the both groups. In the decidua and gland, LIF was expressed in mild degree and there were no differences in LIF expression between normal pregnancy and recurrent abortion. CONCLUSION: LIF expression on cytotrophoblast of recurrent abortion was lower than that of normal pregnancy. LIF may provide paracrine and autocrine signals to both embryonic tissues and uterine epithelium during implantation. The dysfunction of LIF production may be a cause of the unexplained recurrent abortions.
Abortion, Habitual* ; Abortion, Spontaneous ; Blastocyst ; Cytokines ; Decidua ; Endometrium ; Epithelium ; Female ; Humans ; Intercellular Signaling Peptides and Proteins ; Leukemia Inhibitory Factor* ; Leukemia* ; Paraffin ; Placenta ; Pregnancy* ; Trophoblasts ; Uterus