Single Miscarriage Research Articles

Possible contributions of fibrogenesis to recurrent miscarriages – A transcriptome analysis

Recurrent miscarriages (RM) generally refer to two or more consecutive pregnancy losses. The risk of miscarriages grows with its frequency of occurrences, so as the future obstetric complications or longer-term health problems for patients. Most previous researches sought to discover the etiology of RM by making comparisons between patients with RM and fertile women. Our study collected decidua tissues from patients with RM and single miscarriage (SM) for transcriptome sequencing analysis and aimed at identifying vital factors contributing to additional miscarriages after previous miscarriage. Between the RM and SM group, a total of 122 differentially expressed genes (DEGs) were detected and pathways associated with cell adhesion and ECM remodeling were particularly enriched in the RM group, which indicated abnormally activated fibrogenesis process. Particularly, the enhancement of ITGB6, EGFLAM and COL3A1 in the RM group were validated by RT-qPCR. Our study discovered that fibrogenesis, which might be caused by intrauterine manipulation, could lead to recurrent miscarriages after a previous miscarriage. Therefore, we encourage higher attention to thorough prevention and prompt remedies towards fibrotic disorders related diseases.

Prevalence of toxoplasmosis among miscarried women and the effect on embryo in Thi -Qar province southern – Iraq

Toxoplasma gondii is a widespread worldwide and is one of the causes of miscarriage in women who are pregnant .Toxoplasma gondii infection among miscarried women in Thi-Qar province was investigated in this study. A total of 120 blood samples of aborted women and 80 samples of blood were taken from women who had not undergone miscarriage while pregnant (comparison group) and for the period from November 2018 to January 2019 and with ages ranging from 15 to 44 years. Anti-Toxoplasma IgM and IgG antibodies were detected using an enzyme-linked immunosorbant assay (ELISA).The results showed that the total incidence of T. gondii among women with miscarriage was 59/120 (49.1%) compared with the standard group (women without miscarriage) 5/80 (6.2%). The rate of infection was IgG 41.6%, IgM 5% and IgG & IgM togather 2.5% among miscarried women. The age group with the highest percentage was the range of (25-34) year ,was(45.7%) and the lowest percentage was 22 % in the range of ( 35-44 )year age range. The highest rate of infection was in the first period of pregnancy 52.5% and the lowest was in the third period of pregnancy 18.6% women who had a single miscarriage have the highest prevalence of infection (44%) and the lowest was in women who have multiple miscarriage (23.7%).

Restoration Treatment for Female Patients with Non-Bearing Pregnancy at the Early Terms of Gestatione

An important indicator of reproductive health is pregnancy failure, which has no decreasing trend worldwide [1-3]. Despite certain successes achieved in treatment and rehabilitation, the problem of pregnancy failure, especially in early gestation, is still urgent [4-6]. Thus, according to different authors, it ranges from 2 to 55%, reaching up to 80% in the first trimester. Statistically, 15 to 25% of all registered pregnancies are spontaneously miscarried, and 80% of pregnancies are terminated before 12 weeks of gestation. The incidence of spontaneous miscarriage remains consistently high, at 45-88.6% of early spontaneous miscarriages. Direct reproductive losses from non-pregnancy in Ukraine amount to 36-40 thousand unwanted children annually. It has been established that the state of reproductive health depends to a greater extent on the duration of pregnancy failure and the complex of rehabilitation measures [1-3]. When a pregnancy occurs within the first 6 months, after a previous miscarriage, a large number of repeated pregnancy losses have been noted. The rate of pregnancy loss after a single miscarriage is 13-17%, after two miscarriages 36-38%, and with recurrent miscarriage up to 45% [1-3]. After spontaneous abortion it is necessary to rehabilitate a woman's reproductive health regardless of the number of spontaneous miscarriages, taking into account all the causes and conditions that contribute to spontaneous pregnancy termination. The principles of the reproductive health rehabilitation program for women after spontaneous miscarriage include the earliest possible initiation of treatment and rehabilitation measures, the principle of an individual approach to rehabilitation measures for each patient [4-6]. The principle of dynamic control over the effectiveness of rehabilitation and therapeutic measures and the principle of continuity between inpatient, outpatient, and sanatoriumresort units of rehabilitation measures are important when using the methods and means of physical rehabilitation [4-7].

P–383 Cytogenetic analysis of products of conception from miscarriages following natural conception and IVF pregnancy: a comparative study

Abstract Study question Do cytogenetic results from products of conception from miscarriages differ from patients conceiving by natural conception versus IVF? Summary answer: Cytogenetic results were similar, with no statistical difference from miscarriages following natural conception and assisted conception. What is known already Cytogenetic sampling of products of conception (POC) following recurrent miscarriages (RM) are recommended to rule out parental chromosomal rearrangements. The RCOG recommends cytogenetic testing in cases of recurrent miscarriages (3 consecutive miscarriages). However some units routinely request cytogenetic analysis following a single miscarriage following an IVF pregnancy. There is no evidence to support the routine sampling of POCs following assisted conception. Study design, size, duration: Retrospective cohort study of 117 cytogenetic samples, followed up by the outcome of parental karyotyping if applicable. Patients were categorised based on mode of conception into natural conception (NC) with recurrent miscarriages (≥3) or one miscarriage following IVF. Data collected between 2018–2020. Primary Outcome measure: Presence and type of cytogenetic abnormality; individual parental targeted G-band karyotyping result. Participants/materials, setting, methods: A total of 117 cytogenetic results were reviewed, of which 35 were unsuitable for analysis due to contamination (Total n = 79: NC = 60, IVF = 19). Main results and the role of chance: Cytogenetic analysis showed abnormal results in 59% of miscarriages following natural conception and 53% of miscarriages from IVF pregnancy (p = 0.46). Abnormal cytogenetic results were mainly sporadic. Trisomy 16 was the commonest abnormality in both groups. Others included Trisomy 15, 22, 21, 8, 13, 5, 9, 10, 14, 18, single X (Turner’s), all occurring in the same frequency in both groups. As expected 35 out of 45 abnormal cytogenetic results occurred with a maternal age greater than 35 years. One couple from the NC group were referred to a geneticist for a Trisomy 9 imbalance. All other parental karyotyping results were normal. Limitations, reasons for caution This study contains a small sample size, and would benefit from further data collection to account for a percentage of samples being inadequate for analysis. Wider implications of the findings: Cytogenetic results were similar from miscarriages following natural conception and assisted conception. IVF does not increase the risk of miscarriage from abnormal embryonic karyotype. Routine cytogenetic testing following one miscarriage in patients undergoing IVF is not cost effective. Trial registration number Not applicable

Adverse childhood experiences are associated with increased risk of miscarriage in a national population-based cohort study in England.

STUDY QUESTIONIs there an association between adverse childhood experiences (ACE) and the risk of miscarriage in the general population?SUMMARY ANSWERSpecific ACE as well as the summary ACE score were associated with an increased risk of single and recurrent miscarriages.WHAT IS KNOWN ALREADYThere is scarce evidence on the association between ACE and miscarriage risk.STUDY DESIGN, SIZE, DURATIONWe conducted a retrospective national cohort study. The sample consisted of 2795 women aged 55–89 years from the English Longitudinal Study of Ageing (ELSA).PARTICIPANTS/MATERIALS, SETTING, METHODSOur study was population-based and included women who participated in the ELSA Life History Interview in 2007. We estimated multinomial logistic regression models of the associations of the summary ACE score and eight individual ACE variables (pertaining to physical and sexual abuse, family dysfunction and experiences of living in residential care or with foster parents) with self-reported miscarriage (0, 1, ≥2 miscarriages).MAIN RESULTS AND THE ROLE OF CHANCEFive hundred and fifty-three women (19.8% of our sample) had experienced at least one miscarriage in their lifetime. Compared with women with no ACE, women with ≥3 ACE were two times more likely to experience a single miscarriage in their lifetime (relative risk ratio 2.00, 95% CI 1.25–3.22) and more than three times more likely to experience recurrent miscarriages (≥2 miscarriages) (relative risk ratio 3.10, 95% CI 1.63, 5.89) after adjustment for birth cohort, age at menarche and childhood socioeconomic position. Childhood experiences of physical and sexual abuse were individually associated with increased risk of miscarriage.LIMITATIONS, REASONS FOR CAUTIONGiven the magnitude of the observed associations, their biological plausibility, temporal order and consistency with evidence suggesting a positive association between ACE and adverse reproductive outcomes, it is unlikely that our findings are spurious. Nevertheless, the observed associations should not be interpreted as causal as our study was observational and potentially susceptible to bias arising from unaccounted confounders. Non-response and ensuing selection bias may have also biased our findings. Retrospectively measured ACE are known to be susceptible to underreporting. Our study may have misclassified cases of ACE and possibly underestimated the magnitude of the association between ACE and the risk of miscarriage.WIDER IMPLICATIONS OF THE FINDINGSOur study highlights experiences of psychosocial adversity in childhood as a potential risk factor for single and recurrent miscarriages. Our findings contribute to a better understanding of the role of childhood trauma in miscarriage and add an important life course dimension to the study of miscarriage.STUDY FUNDING/COMPETING INTEREST(S)ELSA is currently funded by the National Institute on Aging in USA (R01AG017644) and a consortium of UK government departments coordinated by the National Institute for Health Research. The funders had no role in the study design, data collection and analysis, decision to publish or preparation of the article. The authors have no actual or potential competing financial interests to disclose.

Evaluating the role of paternal factors in aetiology and prognosis of recurrent pregnancy loss: study protocol for a hospital-based multicentre case–control study and cohort study (REMI III project)

IntroductionRecurrent pregnancy loss (RPL) is defined as the spontaneous demise of two or more pregnancies before the fetus reaches viability. Despite investigation of multiple known maternal risk factors, in more...

Pregnancy loss and risk of later dementia: A nationwide cohort study, Denmark, 1977–2017

IntroductionPregnancy losses may be associated with increased risks of dementia. MethodsWe conducted a register-based cohort study in 1,243,957 women with ≥1 pregnancy in Denmark in the period 1977–2015. Using Cox regression, we estimated hazard ratios (HRs) comparing risks of dementia in women with and without pregnancy losses. ResultsDuring 21,672,433 person-years of follow-up, 261,279 women experienced a pregnancy loss, and 2188 women were diagnosed with dementia. Stillbirth was associated with an 86% increased risk of dementia overall (HR 1.86, 95% confidence interval [CI] 1.28–2.71). By contrast, miscarriage was not associated with later risk of dementia overall (single miscarriage, HR 0.99, 95% CI 0.87–1.12; recurrent miscarriages, HR 1.06, 95% CI 0.84–1.35). Adjustment for cardiovascular disease, hypertension, and diabetes did not meaningfully alter the association magnitudes. DiscussionStillbirth and dementia may share underlying mechanisms, suggesting that a history of stillbirth should be considered when assessing dementia risk in women.

Immunological and molecular study of Chlamydia trachomatis as causative agent of abortion in Al-Muthanna province

Chlamydiasis during pregnancy should be considered a significant risk factor for adverse pregnancy outcomes in humans. 120 women who had a single or repeated abortion were selected for this study, and they were referred with a physician report for TORCH tests to determine the final diagnosis of pregnancy loss. The control were (40) healthy pregnant women with a history of a normal pregnancy. The innate immunity in abortive women was higher than normal pregnancies, that was estimated by Nitroblue Tetrazolium test done to estimate the phagocytic activity, there was a significant increase (P=0.009) in phagocytic activity in the leukocytes of abortive women which was (22%) higher than that in control. Also, the cellular immune response was higher in abortive women than that in control. Methyl Thiazolyl Tetrazolium assay was performed to estimate lymphocyte transformation index of peripheral blood leukocytes in abortive women. The results of Methyl Thiazolyl Tetrazolium assay showed a significant increase (P=0.001) in the lymphocyte transformation index in the lymphocytes of abortive women which was (27%) higher than control. The serological detection by ELISA showed that anti-C. trachomatis IgG was (14.2%), and the molecular detection by Quantitive Real Time-Polymerase Chain Reaction showed positive results (17.5%) of total abortive women. The present study demonstrated a high level of relationship between C. trachomatis and abortion among women in the study samples. The age group (20-25years) was the most susceptible to chlamydial infection and the infection was higher in recurrent miscarriages than in single miscarriage.

Epidemiological Survey and Risk Factor Analysis of Recurrent Spontaneous Miscarriages in Infertile Women at Large Infertility Centers.

Background:A higher frequency of spontaneous miscarriage has been observed in infertile couples, and there is a higher prevalence of infertility among patients with a history of recurrent spontaneous miscarriages (RSMs; ≥2 miscarriages). This study aimed to determine the proportion of infertile patients with RSM and examine risk factors associated in patients with RSM being treated with assisted reproductive technologies.Methods:This cross-sectional observational study was conducted at six reproductive medicine centers in three cities of China. Data of 751 patients with at least one spontaneous miscarriage were analyzed. Demographic data and etiological factors associated with infertility were compiled and compared between patients with a single spontaneous miscarriage (SSM) and those with RSM.Results:Two hundred (26.6%, 95% confidence interval [CI]: 23.50–29.95%) patients experienced RSMs and 551 (73.4%) had a single miscarriage. The odds of RSM increased with increasing age (odds ratio [OR] = 1.06), uterine disorders (OR = 2.09), endocrine disorders (OR = 2.48), and immune disorders (OR = 2.98). Higher education level, masters or above, and a pelvic cavity disorder were associated with lower risk of RSM (OR = 0.27 and 0.46, respectively). Late spontaneous miscarriages were more frequent in patients with RSM than in those with a SSM (31.5% vs. 14.2%, respectively, P < 0.001) and were associated with a history of uterine cavity procedures (OR = 2.095) and cervical factors related to infertility (OR = 4.136, 95% CI: 1.012–16.90).Conclusions:Compared to patients with only a SSM, the conditions of patients with RSM are more complicated. To increase the success rate of assisted reproductive technology, factors including uterus cavity adhesion, cervical relaxation, endocrine disorders, and immune disorders should be treated before assisted reproduction is initiated. These data may provide treatment guidance for infertile patients with a history of RSM.

P220 A previous miscarriage and a previous successful pregnancy have a different impact on HLA antibody formation during a subsequent successful pregnancy

Aim Inherited paternal HLA antigens from the semi-allogeneic fetus may trigger maternal immune responses during pregnancy, leading to the production of child-specific HLA antibodies. The prevalence of these HLA antibodies increases with the number of successful pregnancies. In the present study we investigated the effect of a single prior miscarriage on HLA antibody formation during a subsequent successful pregnancy. Methods Women with a successful pregnancy with one or more prior miscarriages (n = 58) and women with a successful pregnancy without a prior miscarriage (n = 229) and their children were HLA typed. HLA-antibody analyses were performed in these women to identify whether HLA antibodies were formed against mismatched HLA class-I antigens of the last child. Results The percentage of immunogenic antigens was significantly lower after a single successful pregnancy that was preceded by a single miscarriage (n = 18 women) compared to a successful pregnancy that was preceded by a first successful pregnancy (n = 62 women). Conclusions Our data suggest that a previous miscarriage has a different impact on child-specific HLA antibody formation during a subsequent successful pregnancy than a previous successful pregnancy. The lower immunogenicity in these women cannot be explained by reduced numbers of immunogenic B-cell and T-cell epitopes. Our observations indicate that increasing gravidity is not related to an increased prevalence of HLA antibodies in a single successful pregnancy that was preceded by a single prior miscarriage.

A Previous Miscarriage and a Previous Successful Pregnancy Have a Different Impact on HLA Antibody Formation during a Subsequent Successful Pregnancy.

Inherited paternal HLA antigens from the semi-allogeneic fetus may trigger maternal immune responses during pregnancy, leading to the production of child-specific HLA antibodies. The prevalence of these HLA antibodies increases with the number of successful pregnancies. In the present study, we investigated the effect of a single prior miscarriage on HLA antibody formation during a subsequent successful pregnancy. Women with a successful pregnancy with one or more prior miscarriages (n = 229) and women with a successful pregnancy without a prior miscarriage (n = 58), and their children were HLA typed. HLA antibody analyses were performed in these women to identify whether HLA antibodies were formed against mismatched HLA class-I antigens of the last child. The percentage of immunogenic antigens was significantly lower after a single successful pregnancy that was preceded by a single miscarriage (n = 18 women) compared to a successful pregnancy that was preceded by a first successful pregnancy (n = 62 women). Thus, our data suggest that a previous miscarriage has a different impact on child-specific HLA antibody formation during a subsequent successful pregnancy than a previous successful pregnancy. The lower immunogenicity in these women cannot be explained by reduced numbers of immunogenic B-cell and T-cell epitopes. In conclusion, our observations indicate that increasing gravidity is not related to an increased prevalence of HLA antibodies in a single successful pregnancy that was preceded by a single prior miscarriage.

Miscarriage and recurrent miscarriage in patients with congenital factor V deficiency: a report of six cases in Iran.

Miscarriage and recurrent miscarriage have not been reported in women with congenital factor V (FV) deficiency. Here we describe cases of both miscarriage and recurrent miscarriage in women with congenital FV deficiency (FVD). We investigated six women with FVD from the southeast of Iran who had experienced miscarriage and recurrent miscarriage. Consequent diagnosis was made by routine coagulation tests as well as FV activity and antigen assays. To evaluate the presence of an inhibitor, a mixing study via prothrombin time (PT) assay was performed. All patients were investigated, and found to be negative for antiphospholipid syndrome. Demographic data and clinical presentations were obtained by standard questionnaire. The factor assays determined that all six women were suffering from moderate FVD. One had experienced eight miscarriages, while the others experienced two (two patients), three, and four episodes. Only one patient had a single miscarriage. Three of the women experienced successful delivery without medical intervention. Miscarriage and recurrent miscarriage should be considered as possible presentations of FVD to prevent its life-threatening consequences.

Tourch Infections in Mothers with Bod as a Cause of Neonatal Miscarriages and Fetal Malformation in Duhok Province, Kurdistan Region/ Iraq

This study was performed to demonstrate the effect of TORCH agents on pregnancy outcome of 84 mothers with BOD, the number of single, twice, triple, four and more miscarriages were 102 (55.4%), 50 (27.2%), 27 (14.7%) and 5 (2.7%), respectively. Out of 102 BOH pregnant women with single miscarriage, 43 (42.2%) and 2 (4.9%) were seropositive for anti T. gondii IgG and IgM, respectively, 89 (87.3%) and 17 (16.7) were seropositive for anti CMV IgG and IgM, respectively, 63 (61.8%) and 3 (2.9%) were seropositive for anti Rubella IgG and IgM, respectively and 63(61.8%) and 14(13.7) were seropositive for HSV-2 IgG and IgM, respectively. Regarding women with twice miscarriage, 1 (2.0%), 14 (28.0%) were seropositive for T. gondii anti IgG and IgM, respectively, 16 (8.0%), 43 (86.0%) were seropositive for CMV anti IgG and IgM, 29(58.0%), respectively. The IgG of anti Rubella was recorded in 29 (58.0%) no any case for anti IgM. and 29 (58%) and 3 (6.0%) were positive for HSV-2 anti IgG and IgM, respectively. The number of cases with triple miscarriages, 8 (11.1%) were seropositive for anti T. gondii IgG antibodies, while no any case was found against IgM antibodies. Only, 3 (4.2%), 22 (30.6%) were seropositive for anti CMV IgG and IgM respectively. The seropositivity of anti Rubella, anti HSV-2 IgG and IgM antibodies in group with triple miscarriages were recorded in 12 (16.7%), 10 (13.9%), 0 (0.0%) and 3 (4.2%) respectively. The number of cases with four and more miscarriages, all (100%) were seropositive for CMV anti IgG and IgM, and one (20%) for T. gondii anti IgG and IgM, while 2 (40%) and 4 (80%),were seropositive for anti Rubella and anti HSV-2 IgG, respectively. Also the results indicated that 134 (72.8%) of all examined pregnant women with BOH have history of miscarriages,14 (7.6%) congenital malformation, 13 (7.1%) intrauterine growth retardation,10 (5.4%) premature labor and 13 (7.1%) still birth. with the predominant of anti CMV IgG and IgM antibodies.

Placental Leucine Aminopeptidase/Oxytocinase Expression in Miscarriage

Objectives: To evaluate the role of placental leucine aminopeptidase (P-LAP) in miscarriage and searching to select the gene of this enzyme in miscarriage to exclude direct or indirect effects of abortion. Methods: Total RNA is purified from the fresh placental tissue sample according to the protocol of the QIAamp®RNA Tissues Mini Kit (Qiagen). The sample is visualized by 0.7% agrose gel containing. Total RNA is reverse-transcribed RT-PCR carried out on the previously extracted RNA samples using (QIAGEN One Step RT –PCR Kit). Aliquots (1ml) of RT reaction samples are amplified by PCR, the PCR products (10μl) per lane are resolved by using electrophoresis on 2.0% agrose gel .Later the product is detected and examined under UV transiluminator. Results: The obtained results indicate that there is an expression of P-LAP mRNAs in placentas of normal pregnancy women (28±SE0.45) and there is a decrease in miscarriage. Furthermore, there is a difference between single miscarriage and those with recurrent miscarriage, the mean values in single miscarriage (1 and 2) are (16.1%±SE0.84) and (13%±SE0.24) respectively while the mean values in recurrent miscarriage (1 and 2) are (12%±SE0.19) and (9%±SE0.52) respectively. The expression of P-LAP is significantly lower (p=0.05) in miscarriage and highly significant decrease in recurrent than in single miscarriage women. Original Research Article British Journal of Medicine & Medical Research, 4(17): 3283-3292, 2014 3284 Conclusion: The decrease of P-LAP mRNA levels in miscarriage placentas could be a sign that p-LAP function is an important step in pregnancy regulation.

Coping after recurrent miscarriage: uncertainty and bracing for the worst

BackgroundThe aim of this study was to understand how women with single or recurrent miscarriages cope during the waiting periods after miscarriage – waiting for pregnancy or waiting for pregnancy...

Clinical risk prediction for pre-eclampsia in nulliparous women: development of model in international prospective cohort

Objectives To develop a predictive model for pre-eclampsia based on clinical risk factors for nulliparous women and to identify a subgroup at increased risk, in whom specialist referral might be...

Obstetric outcome after early placental complications

To evaluate the impact of early pregnancy complications involving placentation and early placental development on adverse obstetric outcome in ongoing and subsequent pregnancies. We found an increased risk of adverse outcome (odds ratio >2.0) in ongoing pregnancies of preterm delivery (PTD), very preterm delivery (VPTD), placental abruption, small for gestational age (SGA), low birth weight (LBW) and very LBW (VLBW) after a threatened miscarriage episode; pregnancy-induced hypertension, preeclampsia, placental abruption, PTD, SGA and low 5-min Apgar score following the detection of an intrauterine haematoma; and VPTD, VLBW and perinatal death after a vanishing twin phenomenon. In subsequent pregnancies, the risk of perinatal death was increased (odds ratio >2.0) after a single miscarriage, the risk of VPTD after two or more miscarriages, the risk of placenta previa, premature preterm rupture of membranes, PTD, VPTD and LBW after recurrent miscarriage and the risk of VPTD after two or more terminations of pregnancy. Our analysis of the literature review indicates a link between early pregnancy complications involving the placenta and subsequent adverse obstetric and perinatal outcomes. Some of these associations are based on limited or small uncontrolled studies. Larger population-based prospective controlled studies have recently been published confirming most of these findings. This suggests that the early detection of these risk factors could improve the screening of women at high risk of specific obstetric complications in ongoing and subsequent pregnancies.

Myasthenia Gravis in Pregnancy: Report on 69 Cases

Obstetrical & Gynecological Survey 58(3):p 156-157, March 2003. | DOI: 10.1097/01.OGX.0000055745.76455.47