Are neutrophil to lymphocyte ratio and platelet to lymphocyte ratio clinically useful for the prediction of early pregnancy loss?
Oğlak Süleyman Cemil,Aydın Mustafa Fırat
Ginekologia polska
OBJECTIVES:Red cell distribution width (RDW), mean platelet volume (MPV), plateletcrit (PCT), platelet distribution width (PDW), neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) have all been identified as systemic inflammatory markers. The aim of this study to investigate whether the use of systemic inflammatory markers can predict early pregnancy loss. MATERIAL AND METHODS:A total of 137 patients with early pregnancy loss was compared with 148 participants in the control group who had given birth at term. In the study group, CBC values were included in the study at the time of referral to the hospital for routine follow-up, while patients did not experience early pregnancy loss. In the control group, CBC values of the patient before the seventh week of pregnancy were included in the study. RESULTS:There was no significant difference between the two groups in terms of RDW, MPV, PCT and PDW values. The NLR and PLR values were significantly higher in the early pregnancy loss group than the control group (p < 0.05). CONCLUSION:Our findings suggest that high NLR and PLR values are potent markers for the prediction of early pregnancy loss.
10.5603/GP.a2020.0082
Urinary Concentrations of Phthalate Metabolites and Bisphenol A and Associations with Follicular-Phase Length, Luteal-Phase Length, Fecundability, and Early Pregnancy Loss.
Jukic Anne Marie,Calafat Antonia M,McConnaughey D Robert,Longnecker Matthew P,Hoppin Jane A,Weinberg Clarice R,Wilcox Allen J,Baird Donna D
Environmental health perspectives
BACKGROUND:Certain phthalates and bisphenol A (BPA) show reproductive effects in animal studies and potentially affect human ovulation, conception, and pregnancy loss. OBJECTIVES:We investigated these chemicals in relation to follicular- and luteal-phase lengths, time to pregnancy, and early pregnancy loss (within 6 weeks of the last menstrual period) among women attempting pregnancy. METHODS:Women discontinuing contraception provided daily first-morning urine specimens and recorded days with vaginal bleeding for up to 6 months. Specimens had previously been analyzed for estrogen and progesterone metabolites and human chorionic gonadotropin. A total of 221 participants contributed 706 menstrual cycles. We measured 11 phthalate metabolites and BPA in pooled urine from three specimens spaced throughout each menstrual cycle. We analyzed associations between chemical concentrations and outcomes using linear mixed models for follicular- and luteal-phase lengths, discrete-time fecundability models for time to pregnancy, and logistic regression for early pregnancy loss. RESULTS:Higher concentrations of monocarboxyoctyl phthalate (MCOP) were associated with shorter luteal phase [2nd tertile vs. 1st tertile: -0.5 days (95% CI: -0.9, -0.1), 3rd vs. 1st: -0.4 days (95% CI: -0.8, 0.01), p = 0.04]. BPA was also associated with shorter luteal phase [2nd vs. 1st: -0.8 days (95% CI: -1.2, -0.4), 3rd vs. 1st: -0.4 days (95% CI: -0.8, 0.02), p = 0.001]. CONCLUSIONS:BPA and MCOP (or its precursors) were associated with shorter luteal phase. Menstrual cycle-specific estimates of urinary BPA and phthalate metabolites were not associated with detrimental alterations in follicular-phase length, time to pregnancy, or early pregnancy loss, and in fact, DEHP [di(2-ethylhexyl) phthalate] metabolites {MEOHP [mono(2-ethyl-5-oxohexyl) phthalate] and ΣDEHP} were associated with reduced early loss. These findings should be confirmed in future human studies.
10.1289/ehp.1408164
Serum and placental periostin levels in women with early pregnancy loss.
Eroglu Semra,Colak Eser,Erinanc Ozgur Hilal,Ozdemir Duygu,Ceran Mehmet Ufuk,Tasdemir Umit,Kulaksizoglu Sevsen,Ozcimen Emel Ebru
Journal of reproductive immunology
OBJECTIVES:Periostin is secreted from the placenta in the embryonic period and it is emphasized that it may be involved in endometrial implantation. In this study, we aimed to investigate periostin serum levels and placental tissue expression in first trimester pregnancy losses. STUDY DESIGN:In this prospective case-control study, 30 patients who underwent dilatation and curettage with first trimester spontaneous abortion (<10 weeks of gestation) were included in the study group and 30 patients who had voluntary pregnancy termination (<10 gestational weeks) were included in the control group. Serum samples collected from the study and control groups were analyzed usingenzyme-linkedimmunosorbent assay (ELISA), and trophoblastic and decidual tissues were examined using immunohistochemical staining with streptavidin-biotin-peroxidase techniques. RESULTS:There were no significant differences between the groups in terms of age, gravida status, parity number, gestational week, and number of previous abortions. In the spontaneous abortion group, the serum level of periostin was significantly lower than in the voluntary termination group (6.56 ± 4.16 pg/mLvs. 9.51 ± 4.52 pg/mL, p = 0.03). There was no significant difference between the two groups in terms of periostin expression in decidual and trophoblastic tissue (p = 0.617, p = 0.274, p = 0.497). CONCLUSION:Periostin serum levels were significantly reduced in patients with spontaneous pregnancy loss. Periostin can be used as a predictive marker for the success of endometrial implantation.
10.1016/j.jri.2020.103138
The cellular immunity and oxidative stress markers in early pregnancy loss.
Daglar Korkut,Biberoglu Ebru,Kirbas Ayse,Dirican Aylin Onder,Genc Metin,Avci Aslihan,Biberoglu Kutay
The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians
OBJECTIVE:We investigated whether changes in cellular immunity and oxidative stress in pregnancy have any association with spontaneous miscarriage. MATERIAL AND METHODS:Circulating adenosine deaminase (ADA) activity as a marker of cellular immunity and malondialdehyde (MDA) and catalase (CAT), glutathione peroxidase (GPx) as markers of T lymphocyte activation and parameters of oxidative stress and antioxidant defense were compared between 40 women with early pregnancy loss and another 40 women with ungoing healthy pregnancy. RESULTS:Women with miscarriage had higher serum ADA and GPx levels when compared with women with normal pregnancy (p = 0.034 and p < 0.001, respectively). Although serum MDA level was slightly higher in women with miscarriage, the difference was not significant (p = 0.083). CAT levels were alike in both groups. CONCLUSION:We have demonstrated an increased cellular immunity and perhaps a compensated oxidative stress related to increased antioxidant activation in women with early spontaneous pregnancy loss.
10.3109/14767058.2015.1064886
ACOG Practice Bulletin No. 200 Summary: Early Pregnancy Loss.
Obstetrics and gynecology
Early pregnancy loss, or loss of an intrauterine pregnancy within the first trimester, is encountered commonly in clinical practice. Obstetricians and gynecologists should understand the use of various diagnostic tools to differentiate between viable and nonviable pregnancies and offer the full range of therapeutic options to patients, including expectant, medical, and surgical management. The purpose of this Practice Bulletin is to review diagnostic approaches and describe options for the management of early pregnancy loss.
10.1097/AOG.0000000000002900
ACOG Practice Bulletin No. 200: Early Pregnancy Loss.
Obstetrics and gynecology
Early pregnancy loss, or loss of an intrauterine pregnancy within the first trimester, is encountered commonly in clinical practice. Obstetricians and gynecologists should understand the use of various diagnostic tools to differentiate between viable and nonviable pregnancies and offer the full range of therapeutic options to patients, including expectant, medical, and surgical management. The purpose of this Practice Bulletin is to review diagnostic approaches and describe options for the management of early pregnancy loss.
10.1097/AOG.0000000000002899
Impaired Placentation and Early Pregnancy Loss in Patients with MTHFR Polymorphisms and Type-1 Diabetes Mellitus.
Gurbuz Rumeysa Hekimoglu,Atilla Pergin,Orgul Gokcen,Tanacan Atakan,Dolgun Anil,Cakar Ayse Nur,Beksac Mehmet Sinan
Fetal and pediatric pathology
To evaluate the impact of type-1 diabetes mellitus (DM) and methylenetetrahydrofolate reductase (MTHFR) polymorphisms on impaired placentation leading to early pregnancy loss. Miscarriage materials were obtained from eight pregnant women with type-1 DM without MTHFR polymorphism, eight with MTHFR polymorphisms without type-1 DM, and eight controls with neither DM nor MTHFR polymorphisms. Insulin-like growth factor-1 (IGF-1), leukemia inhibitory factor (LIF), and Beclin-1 expression were assessed to evaluate placentation. Cytoplasmic LIF, IGF-1, and Beclin-1 expression were decreased in the superficial and glandular epithelial cells of the decidua in both study groups. LIF expression was increased in interstitial trophoblasts in the MTHFR group. IGF-1 expression was decreased in the decidual cells and interstitial trophoblasts in both study groups, while the decrease in stromal cells was noted only in type-1 DM group. Beclin-1 expression was increased in interstitial and villous trophoblasts in both study groups. The expression of IGF-1, LIF, and Beclin-1 are altered in both the decidua and the trophoblasts in pregnancies of women with type-1 DM and MTHFR polymorphisms, compared to normal pregnancies undergoing (elective) terminations.
10.1080/15513815.2019.1600623
Expression of TET and 5-HmC in Trophoblast Villi of Women with Normal Pregnancy and with Early Pregnancy Loss.
Wu Ai-Hua,Yang Dong-Yu,Liu Yu-Dong,Chen Xin,Chen Xu-Long,Lu Shan,Chen Shi-Ling
Current medical science
Increasing evidence suggests that epigenetic dysfunction may influence the stability of normal pregnancy. The ten-eleven translocation (TET) family and 5-hydroxymethylcytosine (5-hmC) were found to be linked with epigenetic reprogramming. The present study aimed to examine the expression of the TET family and 5-hmC in the villi of human embryos and compared their expression between normal pregnancy and early pregnancy loss (EPL). Embryonic villi were collected from normal pregnant women (control) experiencing medical abortion and from EPL patients at gestation ages of 6, 7 and 8 weeks. The mRNAs of TET family were analysed using quantitative polymerase chain reaction (qPCR), and TET proteins using Western blotting and immunohistochemical analysis. The MethylFlash™ Kit was used to quantify the absolute amount of 5-methylcytosine (5-mC) and 5-hmC. Our results showed that the expression of the TETs and 5-hmC in the normal villus decreased with increasing gestational age. Immunohistochemistry revealed that the TET proteins were expressed in the cytoplasm of trophoblasts and their expression was the highest in the 6-week tissue samples, which was consistent with the qPCR and Western blot results. The expression of TET1, TET2, and TET3 was lower in the villi in EPL group than in normal pregnancy group (P<0.05 for all). It was concluded that the TET family and 5-hmC are critical in epigenetic reprogramming of human embryo. The findings also suggest that a deficiency of TETs in the villus might be associated with human EPL.
10.1007/s11596-018-1907-0
Proteomics study reveals that the dysregulation of focal adhesion and ribosome contribute to early pregnancy loss.
Xin Lingli,Xu Benhong,Ma Li,Hou Qingxiang,Ye Mei,Meng Shu,Ding Xiaoping,Ge Wei
Proteomics. Clinical applications
PURPOSE:Early pregnancy loss (EPL) affects 50-70% pregnant women in first trimester. The precise molecular mechanisms underlying EPL are far from being fully understood. Therefore, we aim to identify the molecular signaling pathways relating to EPL. EXPERIMENTAL DESIGN:We performed proteomics and bioinformatics analysis of the placental villi in women who have undergone EPL and in normal pregnant women. The proteomics data were validated by Western blot analysis. RESULTS:We identified a total of 5952 proteins in placental villi, of which 588 proteins were differentially expressed in the EPL women. Bioinformatics analysis revealed that these differentially expressed proteins participated in a variety of signaling pathways, including the focal adhesion pathway and ribosome pathway. Moreover, results of the Western blot confirmed that Desmin, Lamin A/C, MMP-9, and histone H4 were upregulated in EPL and the Lamin C/ Lamin A ratio decreased obviously in EPL. These proteins could be associated with the pathophysiology of EPL. The data have been deposited to the ProteomeXchange with identifier PXD002391. CONCLUSION AND CLINICAL RELEVANCE:Our study demonstrated that the focal adhesion pathway and ribosome pathway are involved in EPL, and these findings might contribute to unveil the pathophysiology of EPL.
10.1002/prca.201500136
Association of DNMT3B and DNMN3L Gene Polymorphisms with Early Pregnancy Loss.
Bulletin of experimental biology and medicine
A total of 100 women with early pregnancy loss were recruited and further classified into two subgroups: sporadic pregnancy loss and recurrent pregnancy loss; each subgroup consisted of 50 women. The control group included 56 women with normal pregnancies. Genotyping was performed by PCR with restriction fragment length polymorphism analysis. A statistically significant increase in the frequencies of TT genotype and T allele for DNMT3B rs2424913 polymorphism was found in the total patient group and in both patient subgroups in comparison with the control. Moreover, homozygous TT genotype was associated with increased risk of early pregnancy loss (both sporadic and recurrent). DNMT3B rs2424913 gene polymorphism in women can be used a marker of predisposition to early pregnancy loss and recurrent pregnancy loss.
10.1007/s10517-019-04553-6
Down-regulation of miR-378a-3p induces decidual cell apoptosis: a possible mechanism for early pregnancy loss.
Hong Lihua,Yu Tiantian,Xu Haiyan,Hou Ningning,Cheng Qi,Lai Lihua,Wang Qingqing,Sheng Jianzhong,Huang Hefeng
Human reproduction (Oxford, England)
STUDY QUESTION:Do microRNAs (miRNAs) contribute to human early pregnancy loss (EPL)? SUMMARY ANSWER:miR-378a-3p expression is regulated by progesterone and is down-regulated in ducidua of EPL patients which may contribute to decidual apoptosis through Caspase-3 activation. WHAT IS KNOWN ALREADY:A variety of miRNAs have been demonstrated to be associated with the development of decidualization and placental formation. However, little has been reported on the roles of miRNA in the pathogenesis of EPL. STUDY DESIGN, SIZE, DURATION:Normal and EPL decidual tissues were collected from patients with normal pregnancies undergoing elective termination of gestation, and from patients with EPL, respectively. PARTICIPANTS/MATERIALS, SETTING, METHODS:miRNA microarrays were used to identify the differentially expressed miRNAs between normal and EPL decidua, and miRNA expression was confirmed by qRT-PCR, qRT-PCR, western blotting and luciferase reporter assays were employed to validate the downstream targets of miR-378a-3p. The effects of miR-378a-3p were evaluated using miR-378a-3p-transfected decidual cells. MAIN RESULTS AND THE ROLE OF CHANCE:Of note, 32 up-regulated miRNAs and 38 down-regulated miRNAs were identified by microarray analysis when comparing EPL to normal decidua. MiR-378a-3p was significantly down-regulated in the EPL decidua and was found to inversely regulate the expression of Caspase-3 by directly binding to its 3'-UTRs. In decidual cells, transfection of miR-378a-3p mimics resulted in the inhibition of cell apoptosis and in the increase of cell proliferation through Caspase-3 suppression. Moreover, we found that progesterone could induce the expression of miR-378a-3p in decidual cells. LIMITATIONS, REASONS FOR CAUTION:This study focused on the function of miR-378a-3p and its target Caspase-3, however, numerous other targets and miRNAs may also be responsible for the pathogenesis of EPL. Therefore, further studies are required to elucidate the role of miRNAs in EPL. WIDER IMPLICATIONS OF THE FINDINGS:Our findings indicate that miR-378a-3p may contribute to the development of EPL, and that it could serve as a new potential predictive and therapeutic target of progesterone-treatment for EPL. STUDY FUNDING/COMPETING INTEREST:This study was supported by National Basic Research Program of China (No.2012CB944900); National Science Foundation of China (No.31471405 and 81490742, No.81361120246); The National Science and Technology Support Program (No.2012BA132B00). Authors declare no competing interests.
10.1093/humrep/dex347
Early pregnancy loss in 15-hydroxyprostaglandin dehydrogenase knockout (15-HPGD) mice due to requirement for embryo 15-HPGD activity.
Roizen Jeffrey D,Asada Minoru,Tong Min,Tai Hsin-Hsiung,Muglia Louis J
Scientific reports
Prostaglandins (PGs) have critical signaling functions in a variety of processes including the establishment and maintenance of pregnancy, and the initiation of labor. Most PGs are non-enzymatically degraded, however, the two PGs most prominently implicated in the termination of pregnancy, including the initiation of labor, prostaglandin E2 (PGE) and prostaglandin F2α (PGF), are enzymatically degraded by 15-hydroxyprostaglandin dehydrogenase (15-HPGD). The role of PG metabolism by 15-HPGD in the maintenance of pregnancy remains largely unknown, as direct functional studies are lacking. To test the hypothesis that 15-PGDH-mediated PG metabolism is essential for pregnancy maintenance and normal labor timing, we generated and analyzed pregnancy in 15-HPGD knockout mice (Hpgd). We report here that pregnancies resulting from matings between 15-HPGD KO mice (Hpgd X HpgdKO mating) are terminated at mid gestation due to a requirement for embryo derived 15-HPGD. Aside from altered implantation site spacing, pregnancies from KO matings look grossly and histologically normal at days post coitum (dpc) 6.5 and 7.5 of pregnancy. However, virtually all of these pregnancies are resorbed by dpc 8.5. This resorption is preceded by elevation of PGF but is not preceded by a decrease in circulating progesterone, suggesting that pregnancy loss is a local inflammatory phenomenon rather than a centrally mediated phenomena. This pregnancy loss can be temporarily deferred by indomethacin treatment, but treated pregnancies are not maintained to term and indomethacin treatment increases maternal mortality. We conclude that PG metabolism to inactive products by embryo derived 15-HPGD is essential for pregnancy maintenance in mice, and may serve a similar function during human pregnancy.
10.1038/s41598-019-54064-7
Aberrant methylation of IGF2-AS promoter in early pregnancy loss.
Wu Ai-Hua,Guo Long-Yi,Lu Shan,Chen Xu-Long,Wang Ai-Ai,Wang Xiao-Ying,Liang Xue-Fang
Taiwanese journal of obstetrics & gynecology
OBJECTIVE:The present study aimed to evaluate insulin-like growth factor 2 antisense (IGF2-AS) in the villi of human embryos and compared its expression between normal pregnancy and early pregnancy loss (EPL). MATERIALS AND METHODS:The present study conducted a microarray analysis to identify the expression profiles of lncRNAs in villi from EPL and normal controls (controls, n = 10 and EPL patients, n = 10). Embryonic villi were collected from women who underwent artificial abortion. QPCR was used to confirm the results. The DNA methylation patterns were analyzed using pyrosequencing and bisulfite sequencing polymerase chain reaction. The percentage of methylation was compared in chorionic villi from the two groups. RESULTS:A total of 57 deregulated differentially expressed lncRNAs were detected, of which 33 were upregulated, and 24 were downregulated. The expression of lncRNA IGF2-AS was downregulated significantly in EPL villi compared with the normal villi. Negative regulation of IGF2-AS may be involved in the development of EPL. Methprimer predicted that IGF2-AS promoter had CpG islands and dense CG sites. Increased methylation at CpG islands present in IGF2-AS gene promoter was observed in EPL villi. CONCLUSION:An increase in methylation of IGF2-AS likely leads to its downregulation in chorionic villi of EPL. The findings suggest that a deficiency of IGF2-AS in the villi is associated with human EPL.
10.1016/j.tjog.2019.11.017
DNA methyltransferase 3A promoter polymorphism is associated with the risk of human spontaneous abortion after assisted reproduction techniques and natural conception.
Journal of assisted reproduction and genetics
PURPOSE:The aim of this study was to explore the association of the DNA-methyltransferase (DNMT)-3A and DNMT3B promoter polymorphisms with the risk of human spontaneous abortion after assisted reproduction techniques (ARTs) and natural conception. METHODS:We collected tissues from women who underwent abortion procedures: (a) chorionic villus samples (CVS) and muscle samples (MS) from spontaneous abortions conceived by ART and natural cycle (study group), n = 152; and (b) CVS and MS from normal early pregnancy and second trimester (control group), n = 155. The single-nucleotide polymorphism (SNP) -448A > G in the DNMT3A promoter region and -149C/T polymorphism of DNMT3B were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and confirmed by sequencing. RESULTS:The allele frequency of -448A among pregnancy loss group and control group was 34.2 % vs. 16.5 %, respectively. Compared with GG carriers, the DNMT3A -448AA homozygotes had an about 16-fold increased risk of spontaneous abortion [odds ratio (OR) = 16.130, 95 % confidence interval (CI), 3.665-70.984], and AG heterozygotes had an OR of 2.027 (95 % CI, 1.247-3.293). However, the distribution of -448A > G in individuals derived from ART pregnancies was not statistically significantly compared with those derived from spontaneous pregnancies (P = 0.661). For DNMT3B, we observed genotype frequencies of 100 % (TT) in the study group and the control group. CONCLUSIONS:The DNMT3A -448A > G polymorphism may be a novel functional SNP and contribute to its genetic susceptibility to spontaneous abortion in Chinese women, and ART may not affect the distribution of -448A > G in pregnancy loss and normal pregnancy. The observed TT genotype of DMNT3B suggests that this is the predominant genotype of this population. The findings provide new insights into the etiology of human spontaneous abortion.
10.1007/s10815-016-0837-7
Social work intervention for women experiencing early pregnancy loss in the emergency department.
Palmer Ashley D,Murphy-Oikonen Jodie
Social work in health care
Often referred to as miscarriage, Early Pregnancy Loss (EPL) is the spontaneous death of a fetus experienced within the first 20 weeks of gestation and is the most common complication in pregnancy. Symptoms of an impending EPL are routinely managed in the Emergency Department (ED). EPL can have a substantial impact on women, potentially leading to psychological and emotional health issues and risks to future pregnancies. Despite the high prevalence of EPL, many women suffer in silence due to the common societal belief that EPL are insignificant. Many women experience EPL as an ambiguous loss and are at risk for disenfranchised grief. Compassionate, patient-centred care has been identified by women as an essential and often missing aspect of ED care and can have a profound impact on the overall well-being of women after EPL. Social workers play a critical role in the ED given that they prioritize the psychosocial well-being of patients in a system that is structured to primarily address trauma care. In an effort to reduce the psychological impact and complicated grief reactions of women experiencing EPL, specific recommendations for social work intervention to address the individual needs of women experiencing EPL in the ED are presented. These include acknowledging the loss, providing psychoeducation, honouring the loss, assessing resources, referral and additional information, and building capacity in the ED.
10.1080/00981389.2019.1580237
Maternal serum amyloid A level as a novel marker of primary unexplained recurrent early pregnancy loss.
International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics
OBJECTIVE:To assess maternal serum amyloid A (SAA) levels among women with primary unexplained recurrent early pregnancy loss (REPL). METHODS:A prospective study was conducted among women with missed spontaneous abortion in the first trimester at Ain Shams University Maternity Hospital, Cairo, Egypt, between January 21 and December 25, 2014. Women with at least two consecutive primary unexplained REPLs and no previous live births were enrolled. A control group was formed of women with no history of REPL who had at least one previous uneventful pregnancy with no adverse outcomes. Serum samples were collected to measure SAA levels. The main outcome was the association between SAA and primary unexplained REPL. RESULTS:Each group contained 96 participants. Median SAA level was significantly higher among women with REPL (50.0 μg/mL, interquartile range 26.0-69.0) than among women in the control group (11.6 μg/mL, interquartile range 6.2-15.5; P<0.001). The SAA level was an independent indicator of primary unexplained REPL, after adjusting for maternal age and gestational age (odds ratio 1.12, 95% confidence interval 1.06-1.19; P<0.001). CONCLUSION:Elevated SAA levels found among women with primary unexplained REPL could represent a novel biomarker for this complication of pregnancy.
10.1002/ijgo.12076
Follistatin-like 3, an activin A binding protein, is involved in early pregnancy loss.
Xu Yuqing,Xie Jiamin,Wan Liuxia,Wang Miaomiao,Xu Yanfei,Wang Huihua,Dong Minyue
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
BACKGROUND:Early pregnancy loss (EPL), a common and severe complication in pregnancy, has a long-term personal and social impact. It was previously reported that follistatin-like 3(FSTL3), an activin A binding protein, contributes to the invasion and migration of trophoblast. Simultaneously, activin A induces the release of FSTL3 and the elevated activin A is found to be associated with pregnancy loss in women. This study aimed to identify the roles of FSTL3 in the establishment and maintenance of pregnancy, and to determine whether FSTL3 is involved in the pathophysiology of EPL. METHODS:Endometrial Ishikawa cells and JAR cells were cultured and FSTL3 siRNA was used to silence FSTL3. The trophoblast spheroids mimicking embryos were used in an embryonic adhesion system. The system aimed to investigate the role of FSTL3 silence on embryonic adhesion onto endometrial cell in vitro. The ICR mice model in vivo was used to investigate whether the FSTL3 works in embryonic implantation. The western blotting was used to determine the expression of FSTL3 and activin A. RESULTS:In the in vitro study, silence of FSTL3 in JAR cells significantly reduced the number of trophoblast spheroids adhered onto Ishikawa cells compared with the scramble siRNA. For the in vivo study, the number of embryos implanted in the uterine horn injected with FATL3 siRNA mixture was significantly less than that in control group. In the case control study, both the expression of FSTL3 and activin A in EPL women were significantly higher than that in controls. CONCLUSIONS:FSTL3 plays a biological role in the establishment and maintenance of normal pregnancy. Moreover, FSTL3 may be involved in the early pregnancy loss via neutralizing the elevated activin A.
10.1016/j.biopha.2019.109577
Predictive value of fetal fibronectin on the embryonic loss of patients with recurrent spontaneous abortion in early pregnancy.
Zhang S,Fu S,Liu Y,Chen L,Zhu L,Tan J,Chen H,Zhang J
Clinical and experimental obstetrics & gynecology
OBJECTIVE:This work aims to investigate the predictive value of fetal fibronectin (fFN) in embryonic loss of patients with recurrent spontaneous abortion (RSA) in early pregnancy. MATERIALS AND METHODS:Eighty-four patients with RSA in early pregnancy were selected as the test group and 31 healthy women in early pregnancy were selected as the control group. The ages and number of previous abortions, along with other information, were recorded. These patients underwent a fFN test, and their pregnancy outcome was followed up until 14 weeks. RESULTS:The incidence of spontaneous abortion was 20.24% in the test group and 9.68% in the control group. The positive fFN [fFN (+)] rate was 57.14% in the test group and 12.90% in the control group, indicating a statistically significant difference (p < 0.01, chi2 = 17.89). The incidence of spontaneous abortion was 29.17% (14/48) in the fFN (+) group and 8.33% (3/36) in the fFN (-) group, indicating a statistically significant difference (p < 0.05, chi2 = 5.53). The sensitivity, specificity, and positive and negative predictive values in the prediction of abortion in fFN (+) patients of the test group were 82.35%, 49.25%, 29.17%, and 91.67%, respectively. CONCLUSION:If detected at an early stage of pregnancy, fFN in patients with RSA is largely related to the prediction of abortion and facilitates the evaluation of pregnancy outcomes.
Early pregnancy loss in Belagavi, Karnataka, India 2014-2017: a prospective population-based observational study in a low-resource setting.
Dhaded Sangappa M,Somannavar Manjunath S,Jacob Jane P,McClure Elizabeth M,Vernekar Sunil S,Yogesh Kumar S,Kavi Avinash,Ramadurg Umesh Y,Moore Janet L,Wallace Dennis P,Derman Richard J,Goldenberg Robert L,Goudar Shivaprasad S
Reproductive health
BACKGROUND:The prevalence of early pregnancy loss through miscarriage and medically terminated pregnancy (MTP) is largely unknown due to lack of early registration of pregnancies in most regions, and especially in low- and middle-income countries. Understanding the rates of early pregnancy loss as well as the characteristics of pregnant women who experience miscarriage or MTP can assist in better planning of reproductive health needs of women. METHODS:A prospective, population-based study was conducted in Belagavi District, south India. Using an active surveillance system of women of childbearing age, all women were enrolled as soon as possible during pregnancy. We evaluated rates and risk factors of miscarriage and MTP between 6 and 20 weeks gestation as well as rates of stillbirth and neonatal death. A hypothetical cohort of 1000 women pregnant at 6 weeks was created to demonstrate the impact of miscarriage and MTP on pregnancy outcome. RESULTS:A total of 30,166 women enrolled from 2014 to 2017 were included in this analysis. The rate of miscarriage per 1000 ongoing pregnancies between 6 and 8 weeks was 115.3, between 8 and 12 weeks the miscarriage rate was 101.9 per 1000 ongoing pregnancies and between 12 and 20 weeks the miscarriage rate was 60.3 per 1000 ongoing pregnancies. For those periods, the MTP rate was 40.2, 45.4, and 48.3 per 1000 ongoing pregnancies respectively. The stillbirth rate was 26/1000 and the neonatal mortality rate was 24/1000. The majority of miscarriages (96.6%) were unattended and occurred at home. The majority of MTPs occurred in a hospital and with a physician in attendance (69.6%), while 20.7% of MTPs occurred outside a health facility. Women who experienced a miscarriage were older and had a higher level of education but were less likely to be anemic than those with an ongoing pregnancy at 20 weeks. Women with MTP were older, had a higher level of education, higher parity, and higher BMI, compared to those with an ongoing pregnancy, but these results were not consistent across gestational age periods. CONCLUSIONS:Of women with an ongoing pregnancy at 6 weeks, about 60% will have a living infant at 28 days of age. Two thirds of the losses will be spontaneous miscarriages and one third will be secondary to a MTP. High maternal age and education were the risk factors associated with miscarriage and MTP. TRIAL REGISTRATION:The trial is registered at clinicaltrials.gov. ClinicalTrial.gov Trial Registration: NCT01073475 .
10.1186/s12978-018-0525-4
The anti-Mullerian hormone as a predictor of early pregnancy loss in subfertile women.
Hong Soyeon,Chang Eunmi,Han E Jung,Min Seung Gi,Kim Sohyun,Kang Min Kyu,Cha Dong Hyun,Shim So Hyun,Park Hee Jin
Systems biology in reproductive medicine
The aim of this study was to evaluate the predictive value of the anti-Mullerian hormone (AMH) level for early pregnancy loss and to compare the significance of AMH level to age as prognostic factors of pregnancy loss in subfertile women. The outcome of 848 subfertile patients confirmed with intrauterine pregnancies by ultrasound within 1 year of measuring serum AMH level were retrospectively analyzed. Among 848 patients, 206 women were diagnosed with early pregnancy loss. The mean age of the 848 patients was 35.66 ± 3.61 years (range: 26-46 years), and the mean AMH level was 2.95 ± 1.89 (range: 0.14-8.82 ng/mL). There were no significant differences in gravidity, parity, body mass index (BMI), and previous abortion history depending on early pregnancy loss. However, multivariable logistic regression analysis confirmed that the probability of early pregnancy loss is significantly affected by age (odd ratio, 1.079: 1.025-1.135, P = 0.004) and AMH (odd ratio, 0.885: 0.797-0.982, p = 0.022). According to this study, AMH level and age are both powerful predictors of early pregnancy loss. While chronological age is already well known as a factor related to early pregnancy loss, AMH was also considered when individualizing risk prediction for early pregnancy loss.
10.1080/19396368.2020.1806944
Thyroid-stimulating hormone (TSH) serum levels and risk of spontaneous abortion: A prospective population-based cohort study.
Kianpour Maryam,Aminorroaya Ashraf,Amini Massoud,Feizi Awat,Aminorroaya Yamini Sima,Janghorbani Mohsen
Clinical endocrinology
OBJECTIVE:Thyroid dysfunction, a common complication of pregnancy, is associated with adverse obstetric and neonatal consequences. This study aimed to determine the effect of TSH levels on early pregnancy outcome in a prospective population-based cohort study. DESIGN AND METHODS:The serum TSH, free thyroxine, free triiodothyronine, thyroid peroxidase antibody levels and urinary iodine concentration of 418 pregnant women in their first trimester of pregnancy were measured. According to the American Thyroid Association (ATA) and the local reference ranges for TSH, women were divided into two groups of 0.1-2.5, >2.5 mIU/L and 0.2-4.6, >4.6 mIU/L. The risk of spontaneous abortion (SA) was calculated for each group. RESULTS:Spontaneous abortion was detected in 7.2% (n = 30) of total 418 pregnancies. Women with TSH levels > 2.5 mIU/L had an increased risk of SA, compared to women with TSH levels of 0.1-2.5 mIU/L (relative risk [RR] 3.719, 95% confidence interval [CI]:1.713-8.074). The risk of SA was increased in women with TSH levels > 4.6 mIU/L (RR 5.939, 95% CI: 1.711-20.620). The rate of SA was increased by 78% for every unit increase in standard deviation of TSH concentration (RR 1.35, 95% CI: 1.09-1.70). The rate of miscarriages in the treated group by levothyroxine was 9.8% (n = 6) compared to 28.6% (n = 8) in the untreated group (P = 0.024). CONCLUSIONS:Our finding suggests that the upper limit for the TSH normal range should be redefined to <2.5 mIU/L during the first trimester of gestation. The local upper limit was 4.6 mIU/L, consistent with 4.0 mIU/L cut-off value recommended by the ATA.
10.1111/cen.13979
Advances in the management of early pregnancy loss.
Henkel Andrea,Shaw Kate A
Current opinion in obstetrics & gynecology
PURPOSE OF REVIEW:To describe recent advances in management of early pregnancy loss. RECENT FINDINGS:Addition of mifepristone to current protocols for medical management of miscarriage increases effectiveness of a single dose of misoprostol and significantly reduces subsequent aspiration procedures. Women with an incomplete evacuation after medical management may be treated expectantly with similar rates of complete expulsion compared with surgical management at 6 weeks. As cytogenetic analysis improves, analysis of products of conception can be performed whether collected after surgical or medical management and is an efficient strategy in starting a recurrent pregnancy loss work-up. For those seeking pregnancy after miscarriage, conception immediately following an early pregnancy loss is not associated with increased risk of subsequent miscarriage. However, recent studies suggest that the original intendedness of the pregnancy resulting in miscarriage does not predict future reproductive goals of the woman, so family planning should be discussed at the time of miscarriage. SUMMARY:Miscarriage is a common experience among reproductive-aged women and advances in medical management and modern-day aspiration techniques make the use of the sharp curette obsolete.
10.1097/GCO.0000000000000501
Maternal antithyroid antibodies and euploid miscarriage in women with recurrent early pregnancy loss.
Cueva Shirley,Burks Channing,McQueen Dana,Barkoff Marla S,Stephenson Mary D
Fertility and sterility
OBJECTIVE:To determine whether an association exists between maternal antithyroid antibodies and euploid miscarriage in women with recurrent early pregnancy loss (REPL). DESIGN:Observational cohort study. SETTING:Two academic medical centers. PATIENT(S):Women seen between 2004-2015 with a history of REPL, who were euthyroid or had subclinical hypothyroidism, had maternal antithyroid antibody testing and had at least one subsequent early pregnancy loss (<10 weeks' gestation). INTERVENTION(S):Thyroid function and antibodies were measured at consultation. Subsequent miscarriages were assessed by conventional cytogenetic analysis, and when indicated, microsatellite analysis and/or comparative genomic hybridization/single nucleotide polymorphisms were performed. MAIN OUTCOME MEASURE(S):Determine whether maternal antithyroid antibodies are associated with euploid miscarriage. RESULT(S):Cohort consisted of 74 subjects with REPL who had 130 subsequent early pregnancy losses. The prevalence of maternal antithyroid antibodies in the cohort was 17.6%. Mean TSH was significantly higher among subjects with maternal antithyroid antibodies. Otherwise, no significant differences in demographics were noted. When comparing types of early pregnancy losses between the two groups, a trend toward having more miscarriages than nonvisualized pregnancy losses was noted among subjects with maternal antithyroid antibodies (70% and 30%) compared with subjects without maternal antithyroid antibodies (55% and 43%). No significant difference was noted in the frequency of euploid miscarriage between subjects with and without maternal antithyroid antibodies (42% vs. 56%). CONCLUSION(S):Our study did not demonstrate an association between euploid miscarriage and maternal antithyroid antibodies in subjects with a history of REPL. Therefore, testing or treatment in this cohort may not be warranted.
10.1016/j.fertnstert.2018.04.026
Abnormal Expression of TRAIL Receptors in Decidual Tissue of Chlamydia trachomatis-Infected Rats During Early Pregnancy Loss.
Lu Jinzhi,Zhu Liya,Zhang Lei,Jiang Jinpeng,Xie Fang,Huang Qing,Li Xiaolan,Yi Cunjian
Reproductive sciences (Thousand Oaks, Calif.)
Chlamydia trachomatis is the scientific name of pathogenic bacteria causing infection that has been linked to spontaneous abortion. In this study, the expression pattern of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL; a cytokine related to cell apoptosis) and its receptors was monitored in the decidua of C trachomatis-infected pregnant rats during early gestation to investigate the potential role of this molecular system in C trachomatis-induced spontaneous abortion. The data showed that C trachomatis infection significantly altered the messenger RNA (mRNA) expression of the receptors; death receptor (DR) 4 and DR5 increased, but decoy receptor (DcR) 1 and DcR2 decreased. Consistent with mRNA data, immunohistochemical staining of TRAIL and its receptors indicated that both DR4 and DR5 protein levels were elevated in infected tissues, primarily, decidual cells, decidual vessel wall, and uterine glands, whereas DcR1 and DcR2 showed lower levels compared to the noninfected group. Although receptor expression was altered, there was no difference detected in TRAIL expression. The observed altered expression of TRAIL receptors in C trachomatis-infected rats compared to noninfected rats during the embryo implantation phase suggests a possible mechanism for spontaneous abortion due to apoptosis and therefore failed embryo implantation. In addition, the observed increase in caspase-3 levels in infected cells further supports this finding. Taken together, the data presented in this study suggests C trachomatis infection altered the expression of TRAIL receptors, thus representing a general mechanism for C trachomatis-induced spontaneous abortion in C trachomatis-infected rats during early pregnancy loss.
10.1177/1933719116676393
Women's experiences of health care utilization in cases of early pregnancy loss: A scoping review.
Freeman Angela,Neiterman Elena,Varathasundaram Shya
Women and birth : journal of the Australian College of Midwives
BACKGROUND:Approximately 25% of pregnancies end in miscarriage, most occurring within the first trimester (<13 weeks). For many women early pregnancy loss has implications for short- and long- term mental health, and women's well-being following early pregnancy loss is impacted by their experiences within the healthcare setting. To improve quality of care, it is crucial to understand women's' experiences within the healthcare system in cases of early pregnancy loss. QUESTIONS:What does the research literature tell us about the experiences of early pregnancy loss within healthcare settings? Are these experiences positive or negative? 'How can care improve for those experiencing early pregnancy loss?' METHODS:A scoping review of the research literature was undertaken. Three research databases were searched for relevant articles published in English since 2009, with key words related to 'Experience', 'Healthcare' and 'Early Pregnancy Loss'. A thematic analysis was undertaken to identify and summarize key findings emerging from the research literature. FINDINGS:Twenty-seven (27) articles met our inclusion criteria. Three main themes were identified: (1) issues related to communication, (2) challenges within care environments, and (3) inadequacies in aftercare. DISCUSSION:The literature suggests that women's experiences related to healthcare for early pregnancy loss are largely negative, particularly within emergency departments. Recommendations to improve women's experiences should extend beyond attempts to improve existing care structures, to include emerging environments and providers. CONCLUSION:Women's experiences identified within the literature provide further insights on what women are seeking from their care, and how care models can be improved.
10.1016/j.wombi.2020.07.012
Management of early pregnancy loss with mifepristone and misoprostol: clinical predictors of treatment success from a randomized trial.
Sonalkar Sarita,Koelper Nathanael,Creinin Mitchell D,Atrio Jessica M,Sammel Mary D,McAllister Arden,Schreiber Courtney A
American journal of obstetrics and gynecology
BACKGROUND:Early pregnancy loss is a common event in the first trimester, occurring in 15%-20% of confirmed pregnancies. A common evidence-based medical regimen for early pregnancy loss uses misoprostol, a prostaglandin E1 analog, with a dosage of 800 μg, self-administered vaginally. The clinical utility of this regimen is limited by suboptimal effectiveness in patients with a closed cervical os, with 29% of patients experiencing early pregnancy loss requiring a second dose after 3 days and 16% of patients eventually requiring a uterine aspiration procedure. OBJECTIVE:This study aimed to evaluate clinical predictors associated with treatment success in patients receiving medical management with mifepristone-misoprostol or misoprostol alone for early pregnancy loss. STUDY DESIGN:We performed a planned secondary analysis of a randomized trial comparing mifepristone-misoprostol with misoprostol alone for management of early pregnancy loss. The published prediction model for treatment success of single-dose misoprostol administered vaginally included the following variables: active bleeding, type of early pregnancy loss (anembryonic pregnancy or embryonic and/or fetal demise), parity, gestational age, and treatment site; previous significant predictors were vaginal bleeding within the past 24 hours and parity of 0 or 1 vs >1. To determine if these characteristics predicted differential proportions of patients with treatment success or failure, we performed bivariate analyses; given the small proportion of treatment failures in the combined treatment arm, both arms were combined for analysis. Thereafter, we performed a logistic regression analysis to assess the effect of these predictors collectively in each of the 2 treatment groups separately as well as in the full cohort as a proxy for the combined treatment arm. Finally, by using receiver operating characteristic curves, we tested the ability of these predictors in association with misoprostol treatment success to discriminate between treatment success and treatment failure. To quantify the ability of the score to discriminate between treatment success and treatment failure in each treatment arm as well as in the entire cohort, we calculated the area under the curve. Using multivariable logistic regression, we then assessed our study population for other predictors of treatment success in both treatment groups, with and without mifepristone pretreatment. RESULTS:Overall, 297 evaluable participants were included in the primary study, with 148 in the mifepristone-misoprostol combined treatment group and 149 in the misoprostol-alone treatment group. Among patients who had vaginal bleeding at the time of treatment, 15 of 17 (88%) in the mifepristone-misoprostol combined treatment group and 12 of 17 (71%) in the misoprostol-alone treatment group experienced expulsion of pregnancy tissue. Among patients with a parity of 0 or 1, 94 of 108 (87%) in the mifepristone-misoprostol treatment group and 66 of 95 (69%) in the misoprostol-alone treatment group experienced expulsion of pregnancy tissue. These clinical characteristics did not predict treatment success in the combined cohort alone (area under the curve=0.56; 95% confidence interval, 0.48-0.64). No other baseline clinical factors predicted treatment success in the misoprostol-alone treatment arm or mifepristone pretreatment arm. In the full cohort, the significant predictors of treatment success were pretreatment with mifepristone (adjusted odds ratio=2.51; 95% confidence interval, 1.43-4.43) and smoking (adjusted odds ratio=2.15; 95% confidence interval, 1.03-4.49). CONCLUSION:No baseline clinical factors predicted treatment success in women receiving medical management with misoprostol for early pregnancy loss. Adding mifepristone to the medical management regimen of early pregnancy loss improved treatment success; thus, mifepristone treatment should be considered for management of early pregnancy loss regardless of baseline clinical factors.
10.1016/j.ajog.2020.04.006