Repeated Spontaneous Abortion Research Articles

Astragalus polysaccharides combined with Codonopsis pilosula polysaccharides modulates the physiological characteristics of trophoblasts via miR-92a-1–5p/CCR7 axis

BackgroundWhen the abnormality occurs in proliferation, differentiation and apoptosis of trophoblasts, the invasion ability of placental trophoblast is weakened, which is prone to trigger the occurrence of various pregnancy diseases such as repeated spontaneous abortion (RSA). Clinically, Astragalus and Codonopsis pilosula polysaccharides (APS and CPPS) are used for the treatment of unexplained recurrent spontaneous abortion (URSA). Therefore, we aimed to probe into the roles of APS and CPPS in biological behaviors of placental trophoblasts. MethodsThe trophoblasts were treated with APS and CPPS, and transfected with miR-92a-1–5p mimic and CCR7 plasmid to explore the roles of APS and CPPS. Cell viability and apoptosis were determined by CCK-8 and flow cytometry, respectively. The levels of miRNA/mRNA and protein were measured by qRT-PCR and western blot, respectively. The interaction between miR-92a-1–5p and CCR7 was analyzed by TargetScan and dual-luciferase reporter assay. Invasion and migration rates were assessed by Transwell and wound healing assays, respectively. ResultsAPS combined with CPPS enhanced viability, Bcl-2 expression, and migration and invasion capabilities, while suppressing apoptosis, and expressions of Bax, Bim and miR-92a-1–5p in trophoblasts. Nevertheless, miR-92a-1–5p mimic produced the inverse modulations in trophoblasts, and partially reversed the effects of APS and CPPS. Furthermore, overexpression of CCR7, the target of miR-92a-1–5p, partially offset the effect of miR-92a-1–5p mimic in trophoblasts. ConclusionAstragalus combined with Codonopsis pilosula polysaccharides modulates the biological behaviors of trophoblasts via miR-92a-1–5p/CCR7 axis. The regulatory axis we studied will be helpful for the treatment of URSA in the future.

A Case-Control Study on Chromosomal Anomalies in Parents Experiencing Repeated Spontaneous Abortions From Northern India

ObjectivesMany women lose their fetuses through miscarriage due to a variety of causes. The incidence of three or more consecutive pregnancy losses is often classified as repeated spontaneous abortion (RSA) and is considered the most frustrating and complex area in reproductive medicine. Parental chromosomal abnormalities, underlying medical condition, heritable or acquired thrombophilias, immunologic abnormalities, infections, and environmental factors are reported to be possible etiologies responsible for RSA. Gametes with unbalanced chromosomes, which are formed when abnormalities exist in parent chromosomes, are one such cause and are responsible for about 50-60% of first-trimester pregnancy loss. This paper aims to identify whether there is an association between chromosomal anomalies in parents and RSA.MethodA case-control study was performed on a total sample size of 600 individuals, including 150 couples with a history of RSA and 150 fertile couples as control. The participants were cytogenetically analyzed using G-banding. Associations between variables were tested using Chi-square and Fisher’s exact test (a p-value<0.05 was considered significant). Informed consent from participants and institutional ethical clearance was obtained before the research began.ResultsChromosomal anomalies were detected in 21 individuals (7%) with a history of RSA. Female preponderance was observed with a female to male ratio of 2.5:1. Structural chromosomal aberrations (SCAs) were detected in 17 patients, with nine (53%) cases showing balanced reciprocal translocation (involving chromosomes 1,3,6,8,12,13,15,16,18,22 and X) and three (17.65%) cases of Robertsonian translocation (exclusively in males). Mosaicism was observed in four (19.05%) cases. A statistically significant positive association (p-value <0.05) was observed between the presence of parental chromosomal anomalies and RSA.ConclusionThese results support an association between RSA and parental chromosomal abnormalities. Currently, clinicians treating cases of RSA face challenging clinical conditions. Identifying a cytogenetic cause for RSA may be of great help to clinicians who manage affected couples.

Effect of ADA1 mother–fetus and wife–husband phenotypic differences on the ratio birth weight/placental weight in fertile women and on reproductive success in couples with RSA

To study the effect Adenosine Deaminase locus 1 (ADA(1)) mother-fetus and wife-husband phenotypic differences on the ratio Birth Weight/Placental Weight (BW/PW) in fertile women and on reproductive success in couples with repeated spontaneous abortion (RSA). 209 couples with primary RSA and a consecutive series of 379 healthy puerperae with their newborn infants from the White Caucasian population of central Italy were studied. In primary RSA women reproductive success was indicated by the presence of at least one live-born infant within 5 years of follow up. Two way contingency tables were analyzed by chi-square. The proportion of primary RSA couples with at least a live-born infant shows the highest value in couples mother ADA(1)1/father carrier of ADA(1)*2 allele (55.2%) and the lowest value in reciprocal couples mother carrier of ADA(1)*2 allele /father ADA(1)1 (18.7%) (O.R. = 5.33; P = 0.023). The highest ratio BW/PW is observed in the class mother ADA(1)1/newborn carrier of ADA(1)*2 allele while the lowest ratio is observed in the reciprocal class mother carrier of ADA(1)*2 allele/ newborn ADA(1)1. Differences between mother and fetus in ADA(1) phenotype may influence the ratio BW/PW in healthy women and reproductive success in RSA women.

Adenylate kinase genetic polymorphism and spontaneous abortion

Recent studies on healthy puerperae suggest that Adenylate kinase locus 1 (Ak(1)) genetic polymorphism could be involved in intrauterine selection. In this article, we have searched for a possible relationship between Ak(1) polymorphism and spontaneous abortion. 178 women with primary repeated spontaneous abortion (RSA), 487 healthy consecutive puerperae, 251 puerperae with diabetes, and 361 consecutive healthy female newborns from the White Caucasian population of Central Italy delivered at the Maternal Department have been studied. In these subjects, Ak(1) phenotype was determined to study the relationship between this enzyme and spontaneous abortion. The proportion of Ak(1)2-1 phenotype is higher in women with history of two or more spontaneous abortion than in puerperae with a negative history of spontaneous abortion and in female newborns infants (O.R. 1.930; 95%C.I. 1.113-3.280). Moreover, RSA women carrying the Ak(1)2-1 phenotype have a reduced probability of having live-born infants. Our findings suggest a reduced reproductive efficiency of women carrying the Ak(1)2-1 phenotype: this observation could have practical importance in predicting the probability of reproductive success in couples with RSA and in the practice of in vitro fertilization.

ABH secretor status and reproductive success in couples with primary recurrent spontaneous abortion

FUT2 is an autosomal gene that controls the secretion of the ABH blood group antigens in organic fluids. The secretor gene plays an important role during intrauterine life. The aim of this study is to investigate a possible association between the ABH system and reproductive success in couples with primary repeated spontaneous abortion (RSA). Sixty-six couples with primary repeated spontaneous abortion and 356 consecutive healthy puerperae with their newborn infants from the white population of Rome were studied. All couples were seen at the Center for Reproductive Disorders of the Institute of Obstetrics and Gynecology of the University of Rome, La Sapienza. Secretor phenotype was determined by saliva in all subjects by laboratory standard procedures. In couples with primary RSA, the frequency of non-secretor phenotype of both husbands and wives (37.9%) were significantly higher than those of newborns from other couples (21.4% for male newborns and 29.4% for female newborns). In husbands, but not in wives, of the couples with primary RSA succeeding in having at least a live born infant after 5 years of follow up, the frequency of non-secretor phenotype was significantly lower than those without a liveborn infant (22.8% vs 54.8%). The presence of joint secretor phenotype in both husband and wife was positively associated with having a liveborn infant after 5 years of follow up (odds ratio = 4.57, 95% C.I.1.39-15.6). Secretor phenotype of couples with RSA, especially of the husband, could facilitate 'reproductive success'.

Immunologic factors and reproductive success in women with primary repeated spontaneous abortion

In 109 women with primary RSA the presence of at least one live-born infant within 5 years of follow-up has been found positively associated with ACA intensity.

Haptoglobin phenotype and reproductive success in repeated spontaneous abortion

Objective To study the reproductive success of couples with a history of repeated spontaneous abortion (RSA) with respect to the haptoglobin (Hp) phenotypes of both the wife and husband. Study design This study examined maternal and paternal Hp in 194 couples with primary and secondary RSA recruited from the Center for Reproductive Disorders of the Institute of Obstetrics and Gynaecology at the University of Rome, La Sapienza. Reproductive success was indicated by the presence of at least one live-born infant after more than 5 years of follow-up. Results The proportion of wives carrying Hp2/1 phenotype and with at least one live-born infant is significantly lower than that of wives without a live-born infant. Moreover, the proportion of couples in which both wife and husband possess the Hp2/1 phenotype is much lower in those with at least a live-born infant than in those without a live-born infant. Both maternal and paternal Hp contribute to reproductive success. However, the contribution of maternal Hp appears stronger than that of paternal Hp. Conclusions Hp may play an important role in implantation and/or embryo survival. Couples in which both partners carry the Hp2/1 phenotype have a low probability of producing a live-born infant.

Evidence of an association between the adenylate kinase genetic polymorphism and primary repeated spontaneous abortion

A recent study of healthy pueperae suggests that the adenylate kinase locus 1 (Ak1) genetic polymorphism may be involved in intrauterine selection. This prompted us to search for a possible relationship between this polymorphism and primary repeated spontaneous abortion. Ak1 catalizes the reaction ATP+AMP <—>2ADP, and has an important role in the synthesis of nucleotides involved in several metabolic functions as well as in DNA and RNA synthesis.

Repeated Spontaneous Abortion. Cooperative Effects of ADA and ACP1 Genetic Polymorphisms

In consideration of the effect of adenosine deaminase (ADA) and ACP1 (a low-molecular-weight protein tyrosine phosphatase) on T-cell receptor activity, we have analysed the joint distribution of these polymorphisms in a sample of women with primary repeated spontaneous abortion (RSA) to search for possible interactive effects on susceptibility to RSA. ACP1 and ADA phenotypes were determined in 170 women with primary RSA in 79 healthy consecutive puerperae and in 160 female newborns from the Caucasian population of Rome and in 357 healthy consecutive puerperae from the Caucasian population of Penne. Chi-square test of independence and three way contingency table analysis by a log-linear model were performed. Women with low-ADA activity and high-ACP1 activity show the lowest susceptibility to RSA. Women with high-ADA activity and low-ACP1 activity, on the contrary, show the highest susceptibility to RSA and also the highest incidence of auto antibodies and of A blood group incompatibility. The data are in agreement with those expected on the basis of the effects of ACP1 and ADA genetic variability on T-cell receptor activity and suggest a cooperative effect of the two polymorphic systems in the susceptibility/resistance to repeated spontaneous abortion.

Relationship between genetic polymorphism of homocysteine metabolism enzyme and unexplained repeated spontaneous abortion

目的 探讨胱硫醚β合成酶(cystathionine β synthase,CBS)基因844ins68、甲硫氨酸合成酶(methione synthase,MS)基因A2756G、亚甲基四氢叶酸还原酶(methylene tetrahydrofolate reductase,MTHFR)基因C677T三种同型半胱氨酸代谢相关酶基因突变与习惯性流产的关系. 方法用PCR扩增50例习惯性流产患者(习惯性流产组)及56例正常孕妇(对照组)的CBS、MS、MTHFR基因突变点,直接或经限制性内切酶消化后行凝胶电泳确定其基因型.结果习惯性流产组MTHFR C677T突变纯合子(12/50,24.0%)较对照组(4/56,7.1%)明显升高(P＜0.05),且等位基因突变频率习惯性流产组(26/100,26.0%)较对照组(20/112,17.9%)升高(P＜0.05).CBS844ins68、MS A2756G各种基因型频率在流产组与正常对照组之间的差异无统计学意义.结论MTHFR C677T纯合子突变与习惯性流产有明确的相关关系;CBS 844ins68、MS A2756G突变可能不足以构成习惯性流产的独立遗传性危险因子。

Phosphoglucomutase genetic polymorphism of newborns

An association of the phosphoglucomutase locus 1 (PGM1) genetic polymorphism with repeated spontaneous abortion (RSA), with intrauterine development in both normal and diabetic pregnancies, and with fertility has been reported in previous studies. In view of the evolutionary interest and of a possible clinical relevance of PGM1 selection during intrauterine life, this study considers healthy puerperae, consecutive newborns, and couples with RSA as well as two alleles (PGM1*1 and PGM1*2). The joint maternal–neonatal PGM1 distribution in a sample from an Italian rural population is significantly different from that expected assuming Hardy–Weinberg conditions for equilibrium. Deviation is dependent on maternal age and parity. The joint mother–newborn PGM1 genotype distribution is significantly associated with a positive history of previous spontaneous miscarriage, suggesting that the presence of the PGM1*2 allele in the father predisposes to spontaneous abortion. This hypothesis is also supported by the observation that in couples with RSA, the delivery of a live born infant within 5 years from the first episode of miscarriage is negatively associated with the presence of a PGM1*2 allele in the husband. Altogether these observations suggest the hypothesis of PGM1 maternal selection at the reproductive level involving a differential role of PGM1*1 and PGM1*2 alleles of paternal origin. Am. J. Hum. Biol. 13:9–14, 2001. © 2001 Wiley-Liss, Inc.

Phosphoglucomutase genetic polymorphism of newborns.

An association of the phosphoglucomutase locus 1 (PGM1) genetic polymorphism with repeated spontaneous abortion (RSA), with intrauterine development in both normal and diabetic pregnancies, and with fertility has been reported in previous studies. In view of the evolutionary interest and of a possible clinical relevance of PGM1 selection during intrauterine life, this study considers healthy puerperae, consecutive newborns, and couples with RSA as well as two alleles (PGM1*1 and PGM1*2). The joint maternal-neonatal PGM1 distribution in a sample from an Italian rural population is significantly different from that expected assuming Hardy-Weinberg conditions for equilibrium. Deviation is dependent on maternal age and parity. The joint mother-newborn PGM1 genotype distribution is significantly associated with a positive history of previous spontaneous miscarriage, suggesting that the presence of the PGM1*2 allele in the father predisposes to spontaneous abortion. This hypothesis is also supported by the observation that in couples with RSA, the delivery of a live born infant within 5 years from the first episode of miscarriage is negatively associated with the presence of a PGM1*2 allele in the husband. Altogether these observations suggest the hypothesis of PGM1 maternal selection at the reproductive level involving a differential role of PGM1*1 and PGM1*2 alleles of paternal origin.

The effect of male factors in repeated spontaneous abortion: lesson from in-vitro fertilization and intracytoplasmic sperm injection.

Between 6.5 and 21% of pregnancies result in spontaneous abortion. The incidence of repeated spontaneous abortion (RSA) is, however, lower: 0.05-1.0% of pregnancies. These values vary, not only according to the populations studied and the means of diagnosing the miscarriages, but also to the age and the parity of the patient: 4% at 20 years of age versus 16% after 35 years. These differences are greater if biochemical pregnancies are taken into account. The aetiologies of RSA are multiple and at times even multifactorial. While certain aetiologies, such as chromosomal, anatomic, hormonal, immunological or unexplained anomalies, have been extensively explored, the sperm characteristics likely to influence the quality of the conceptus have rarely been examined. This review examines the male factor's contribution in RSA.

Importance de la qualité du sperme

The semen quality and sperm chromatin alteration have added a new dimension to the evaluation of male factors in repeated spontaneous abortion (RSA). The aim of the study was to evaluate the importance of the sperm quality in RSA conjugal partners.

Examination of allogenic immunological reaction of repeated spontaneous abortion (RSA)

Examination of allogenic immunological reaction of repeated spontaneous abortion (RSA)