Recurrent Miscarriage In Women Research Articles

A Novel Method to Repair Thin Endometrium and Restore Fertility Based on Menstruation-Derived Stem Cell.

Thin endometrium (TE), which mainly occurs as a result of severe damage to the endometrial basalis, is one of the prominent etiologies of menstrual abnormalities, infertility, and recurrent miscarriage in women. Previous studies have demonstrated that mesenchymal stem cells (MSCs) are considered ideal cells with multipotency for regenerative medicine and exhibit therapeutic effects on TE through their cellular secretions. However, there is limited research on strategies to enhance MSC secretion to improve their therapeutic efficacy. Herein, we isolated menstrual blood-derived mesenchymal stem cells (MenSCs) from menstruation and transformed them into decidualized stromal cells (DSCs), which are specialized cells with enhanced secretory functions. To assess the therapeutic potential of DSCs compared to MenSCs, we conducted a series of experiments in cells and animals. The results demonstrated that DSCs exhibited changes in morphology compared to MenSCs, with a decrease in cell proliferation but a significant improvement in secretion function. Furthermore, DSCs facilitated the restoration of endometrial thickness and increased the number of glands and blood vessel formation. Most importantly, the pregnancy rates in rats were effectively restored, bringing them closer to normal levels. These findings greatly contribute to our understanding of stem cell therapy for TE and strongly suggest that DSCs could hold significant promise as a potential treatment option for TE.

Prospective study on biochemical markers causing recurrent miscarriages in Iraqi women of reproductive age

Objective: To compare the levels of elemental calcium, vitamin D3, malondialdehyde and super oxide dismutaseenzymes in serum of women having recurrent miscarriages with normal healthy pregnant women.Method: The prospective study was conducted at Al-Karkh Maternity Hospital, Baghdad, Iraq, and Al-Alawia MaternityHospital, Baghdad, Iraq, from February to August 2022, and comprised adult pregnant women having recurrentmiscarriages without being hypertensive or diabetic in group A and normal healthy pregnant women in control groupB. Blood samples were obtained from all the subjects. Besides, placental tissues were obtained from some membersfrom both the groups. Levels of elemental calcium, vitamin D3, malondialdehyde and superoxide dismutase enzymesin serum were evaluated and compared between the groups. Malondialdehyde and super oxide dismutase enzymesin the placental tissues were also compared. Data was analysed using SPSS 20.Results: Of the 140 women, 70(50%) were in each of the 2 groups. The overall age range of the sample was 18-43years. Placental tissues were obtained from 40(57.14%) in group A and 30(42.85%) in group B. In group A, miscarriagewas reported in the first trimester in 45(62.3%) cases, 21(30%) in the second trimester and 4(5.7%) in the third trimester.Mean level of serum elemental calcium, vitamin D3, malondialdehyde and super oxide dismutase were significantlydifferent between the groups (p<0.05), and the same was the case with the placental tissues (p<0.05).Conclusion: The causes of recurrent miscarriage in women could be attributed to changes in the levels of elementalcalcium, vitamin D3, super oxide dismutase and malondialdehyde in serum and placental tissues.Keywords: Pregnancy, Abortion, Spontaneous, Malondialdehyde, Cholecalciferol, Placenta, Vitamins, Oxides.

The hormone-sensitive lipase C-60G polymorphism is correlated with recurrent spontaneous abortion in women with polycystic ovary syndrome

Objective(s)Disrupted lipid metabolism has been associated with the development of polycystic ovary syndrome (PCOS) in women of reproductive age. Hormone-sensitive lipase (HSL) is an intracellular lipase that has a crucial role in normal lipid metabolism. This study aimed to assess the frequency of C-60G polymorphism of HSL in healthy women and PCOS women, and its correlation with infertility and recurrent spontaneous abortion (RSA) in PCOS patients. Study designA total of 324 PCOS patients (including 199 infertile patients and 125 patients with a history of RSA and 144 healthy controls) were enrolled in this study. Biochemical parameters were measured, and the genotypes of C-60G polymorphism of the HSL gene were determined using PCR-restriction fragment length polymorphism (RFLP) techniques. ResultsThere was no significant difference in the genotype and allele frequencies of C-60G polymorphism between PCOS, PCOS-infertile woman, and non-PCOS subjects. However, a higher percentage of combined variants (CG + GG) and CG genotypes, as well as G allele was found in the PCOS-RSA group in comparison with non-PCOS women. The presence of the G allele conferred a 2.4-fold risk for RSA in women with PCOS (OR: 2.4, 95 % CI [1.22–4.70], P = 0.011). Furthermore, a significant correlation between CG or GG genotype of HSL and the level of free testosterone was observed. ConclusionAccording to the obtained results, the C-60G polymorphism in the HSL promoter was associated with PCOS-related RSA, possibly through increasing the level of free testosterone. Therefore, the rs34845087 polymorphism may be a promising prognostic biomarker for RSA in women with PCOS.

Human Cytomegalovirus and Vitamin D Deficiency Implicated in Recurrent Miscarriages in Women of Basrah, Iraq

Objectives: Human cytomegalovirus (HCMV) and vitamin D (VD) deficiency are implicated in miscarriages. This study aims to determine the seroprevalence of CMV in miscarriage and investigate the effect of VD deficiency risks in pregnant women. Materials and Methods: The study was conducted from February 2020 to April 2021. The study included 75 participants, with 50 women with recurrent miscarriages (the case group) and 25 healthy women (the control group), all of whom had abortions between the ages of 15 and 40. Results: The CMV IgM and IgG antibodies were seropositive at 6% and 98%, respectively. The CMV IgM and IgG prevalence among women with abortions were 0.4 ± 0.21 for IgM antibodies and 259.5 ± 169.9 for IgG antibodies at higher levels compared to the control group, which was 0.18 ± 0.07 for IgM antibodies and 98 ± 89.7 for IgG antibodies. The VD level was evaluated in the case group (7.1 ± 8.24) and the control group (25.5 ± 6.02) based on two age ranges: 28 (56%) in 15–27 years, and 22 (44%) in 28–36 years. On the other hand, the results for the control group were 15-27 years and 28-36 years, with 13 (52%) and 12 (48%), respectively. Conclusions: CMV IgG positive was associated with younger ages because potential reproductive increases with age. Recurrent miscarriages have a strong relationship with VD deficiency. The greater the VD deficiency, the greater the risk for women with more than two abortions in a row.

Association between non-O blood type and early unexplained recurrent spontaneous abortion in women with and without inherited thrombophilia

We retrospectively evaluated the prevalence of non-O blood type – the most frequently inherited prothrombotic factor – and inherited thrombophilia (IT) in a group of women with recurrent spontaneous abortion (RSA). All consecutive women with a history of early unexplained RSA who underwent a screening for IT between December 2008 and December 2021 were considered for enrolment. A group of healthy, age-matched women with ≥1 normal pregnancy and no adverse pregnancy outcomes acted as controls. Two hundred and seventeen women were enrolled. The adjusted odds ratio (aOR) of RSA in non-O vs. O blood type was 1.37 (95% CI, 1.04-2.78), and in women with vs. without IT was 1.26 (95% CI, 1.08-3.61); aOR of RSA in women with non-O blood type and IT was 2.52 (95% CI, 1.12-5.47). We observed a significant association between non-O blood group or IT and RSA. The concomitant presence of non-O blood group and IT further increases RSA risk.

Human Endometrium-Derived Adventitial Cell Spheroid-Loaded Antimicrobial Microneedles for Uterine Regeneration.

Asherman's syndrome (AS) occurs as a consequence of severe damage to the endometrial basalis, usually leading to menstrual abnormalities, infertility, and recurrent miscarriage in women. Currently, human endometrium-derived adventitial cells (En-ADVs) are considered ideal seed cells with high pluripotency for regenerative medicine. However, critical issues such as noninvasive repair of tissues, targeting of native stem cells, and continuous action in the injured sites are not well resolved. Herein, En-ADV spheroid-loaded hierarchical microneedles (MN/En-ADV) for in situ intrauterine repair are developed. The flexible microneedles are fabricated with gelatin methacryloyl and lactoferrin, imparting the characteristics of rapid degradation and antimicrobial activity. Benefiting from an array of microwells on microneedles, En-ADVs can rapidly form 3D cell spheroids, which display higher potential for cell proliferation, differentiation, and migration than dissociated cells. With the application of MN/En-ADV, the repaired uteri show well-defined myometrial regeneration, angiogenesis, and an increase of endometrial receptivity in a rat AS model. Notably, embryos are able to implant in the reconstructed sites and remain viable, indicating that this system promotes the restoration of both normal morphology and reproductive function in the injured uterus. It is anticipated that multifunctional MN/En-ADV can be an ideal candidate for versatile in situ tissue regeneration.

Long-read Oxford nanopore sequencing reveals a de novo case of complex chromosomal rearrangement involving chromosomes 2, 7, and 13.

BackgroundComplex chromosomal rearrangements (CCRs) are associated with high reproductive risk, infertility, abnormalities in offspring, and recurrent miscarriage in women. It is essential to accurately characterize apparently balanced chromosome rearrangements in unaffected individuals.MethodsA CCR young couple who suffered two spontaneous abortions and underwent labor induction due to fetal chromosomal abnormalities was studied using long‐read sequencing(LRS), single‐nucleotide polymorphism (SNP) array, G‐banding karyotype analysis (550‐band resolution), and Sanger sequencing.ResultsSNP analysis of the amniotic fluid cells during the third pregnancy revealed a 9.9‐Mb duplication at 7q21.11q21.2 and a 24.8‐Mb heterozygous deletion at 13q21.1q31.1. The unaffected female partner was a carrier of a three‐way CCR [46,XX,? ins(7;13)(q21.1;q21.1q22)t(2;13)(p23;q22)]. Subsequent LRS analysis revealed the exact breakpoint locations on the derivative chromosomes and the specific method of chromosome rearrangement, indicating that the CCR carrier was a more complex structural rearrangement comprising five breakpoints. Furthermore, LRS detected an inserted fragment of chromosome 13 in chromosome 7.ConclusionsLRS is effective for analyzing the complex structural variations of the human genome and may be used to clarify the specific CCRs for effective genetic counseling and appropriate intervention.

Antioxidant nanozyme microneedles with stem cell loading for in situ endometrial repair

Endometrial injury could result in infertility as well as recurrent miscarriage in women of reproductive age. Stem cells are valuable for the treatment of the endometrial injury; while their effective transplantations and functions displaying are still challenges. Herein, we present novel antioxidant cerium oxide (CeO2) nanozyme microneedles with stem cell loading for in situ endometrial repair. The MNs were made of gelatin methacryloyl (GelMA) with nanozyme and stem cells in the backing layer and tips, respectively, imparting the MNs with distinctive features including antioxidant activity, high cell viability, and rapid degradation. With the MN patch, the damaged endometrium shows the well-defined regeneration of smooth muscle and neovascularization. Notably, embryos can be implanted in the regenerated sites and stay alive to the late pregnancy stage, indicating that the hybrid microneedles not only promote the morphological reconstruction of injured uterus, but also increase the pregnancy rate and restore the reproductive function. These features indicated that the flexible multifunctional biohybrid MNs could serve as an ideal candidate for versatile in situ tissue repair and regeneration.

Study of some microbial infections of recurrent miscarriage in women

Background: some microbial infections can be passed to the fetus before or during birth and damage the fetus or cause a miscarriage, like infection with ToRCH agents and salmonella enterica. The current study aims to investigate the extent of the involvement of salmonella enteria serovars, proteus spp. and Brucella spp. in recurrent miscarriage in women during first trimester. Material and method: The 50 blood samples were collected from women age rage (19-39), who had repeated miscarriages during the first trimester during periods extended from October 2021 to February 2022,. The study control includes the 20 fertile women with no miscarried history. Two tests were conducted which are ToRCH IgM and febril antigen slid test for identification infectious agents associated with pregnancy loss. Results: The present results showed that the most frequent recurrent miscarriage (RM) was in the age group 35-39 years at a percentage 34%, while the lowest abortion rate was 18% at the age group of 25-29 years.

Can we accurately diagnose endometriosis without a diagnostic laparoscopy?

Endometriosis is a progressive, estrogen-dependent, chronic inflammatory disease that affects approximately 6-10% of reproductive age women. Patients usually presents with symptoms, such as non-menstrual pelvic and abdominal pain, ovulatory pain, dyspareunia, dysmenorrhea, dyschezia, and/or changes to bowel or bladder function, which can be exacerbated during ovulation or menses. Endometriosis is a leading cause of unexplained infertility, accounting for up to 50-80% of cases. Currently, altered endometrial receptivity and progesterone resistance are some of the leading theories that could explain endometriosis-related implantation failure. In the endometrium, the B-cell chronic lymphocytic leukemia/lymphoma 6 (BCL-6) protein forms a complex that binds to and inactivates regulators of the progesterone pathway, leading to progesterone resistance, aberrant decidualization, implantation failure, and recurrent miscarriages in women diagnosed with endometriosis. Surgical diagnosis consisting of laparoscopy, with or without histologic confirmation, is still considered the gold standard for diagnosis of endometriosis. Development of noninvasive screening and diagnostic tests to accurately identify patients with endometriosis has become increasing popular. A screening test for endometriosis has been developed to detect endometrial BCL-6 overexpression in asymptomatic women with unexplained infertility or recurrent pregnancy loss. Positive endometrial BCL-6 testing has been associated with recurrent miscarriages and poor in vitro fertilization outcomes. When the underlying cause of endometrial inflammation secondary to endometriosis was treated, an improvement in subsequent live birth rates was seen. Endometrial BCL-6 testing has a high positive predictive value that could help physicians and patients undergoing infertility treatment to seek surgical evaluation for endometriosis, to improve their reproductive outcomes.

Appraisals of Sero-detection of Treponema pallidum Antibodies IgG and IgM and CBC parameters among Spontaneous Recurrent Miscarriage in Women- Case-Control Study in Gezira State 2018

Objectives: We determined Sero-detection of Treponema pallidum (IgG and IgM antibodies) using ELIZA techniques women with recurrent Miscarriage in Gezira state and appraisal of other risk factors.
 Methods: in this case-control, a hospital-based study conducted at Wad Madani teaching hospital Department of Obstetrics gynecological, Gezira State, Sudan. Ninety subjects were involved, 45 were women with recurrent Miscarriage, and controls were healthy pregnant women (no miscarriage). Serum Treponema pallidum antibodies were estimated by the ELIZA method.
 Results: Sero-detection of IgG and IgM antibodies by using ELIZA techniques, a total of 45 miscarriage women (cases) for IgM 6 (13.3%) were positive, and 39 (48.8%) were negative for Treponema pallidum by using ELISA techniques. A total of 45 non-miscarriage women (control) for IgM 4 (8.9%) were positive, and 41(91.1%) were negative For Treponema pallidum by using ELISA techniques. A total of 45 miscarriage women (cases) for IgG 13(28.9%) were positive, 32(71.1%) were negative. Furthermore, IgG for non-miscarriage, like IgM 4(8.9%), was positive, and 41(91.1%) were negative.
 Conclusion: Higher prevalence of Treponema pallidum IgG seropositivity among pregnant women who reported miscarriages compared to those who did not report miscarriages (p < 0.001) while no association between IgM seropositivity and pregnant women who reported miscarriages.

EP253: Incidence of miscarriages and recurrent miscarriages in women with children with 47,XXY, 48,XXXY, or 49,XXXXY

Approximately 15% of clinically recognized pregnancies end in a miscarriage, with two or more failed clinical pregnancies established as recurrent miscarriage (RM), as defined by the American Society for Reproductive Medicine (ASRM). RM affects 1-2% of women who are childbearing age. The leading cause of miscarriages, approximately 60%, seem to arise from chromosomal errors. Previous history of miscarriages increases the incidence of euploid miscarriages. However, a prior study showed that aneuploid miscarriages occur randomly so that the risk of subsequent aneuploid miscarriage is not increased based on previous history.

Study of relationships between HLA-G gene polymorphism, intrauterine infection and recurrent miscarriage in women

The relationship between the HLA-G gene polymorphism (rs41551813, rs12722477, rs41557518), intrauterine infection and recurrent miscarriage (RM) in women were studied. The case group consisted of 180 patients with RM, defined as two or more consecutive miscarriages (min = 2; max = 8) at up to 20 weeks of gestation, and with clinically confirmed pregnancies and non-viable fetuses. At the time of examination. the women were enrolled from the Genetic Counseling Center at the Kemerovo Regional Clinical Hospital, Kemerovo, Russia, and were not pregnant. Each patient underwent a gynecological examination. We excluded women with a history of medical abortion, birth, and ectopic pregnancies. In addition, we excluded women with endocrine (e.g. diabetes) disorders. To exclude other known causes of spontaneous abortion, the following tests were performed: ultrasound examination of pelvic organs, and karyotyping in women and men. The women’s mean age in the RM group, was 29.6±4.8 (SD) years. The control group comprised 408 fertile women. These women didn’t have a history of spontaneous abortion, or a family history of congenital malformations. They have born, at least, 1-2 healthy children. Women’s mean age at birth of last child was 26.8±5.2 (SD) years. Influence of the intrauterine infection was analyzed on the basis of laboratory tests. Diagnostics of bacterial vaginosis and vulvo-vaginal candidiasis by microscopic examination was conducted. Viral agent infections (herpes simplex virus type 2, cytomegalovirus, human papilloma virus type 16/18), Chlamydia trachomatis, Mycoplasma hominis, Ureaplasma urealyticum, Gardnerella vaginalis and Trichomonas vaginalis were detected by enzyme-linked immunoassay and polymerase chain reaction (PCR). The data were obtained from the medical cards of the surveyed women. All the women gave a written informed consent before participating in the study. Typing of polymorphisms of Thr31Ser (rs41551813, HLA-G*01:03) in exon 2, Leu110Ile (rs12722477, HLA-G*01:04) and 1597 delС (rs41557518, HLA-G*01:05N) in exon 3 HLA-G genes were performed by realtime PCR followed by melting analysis. The study showed that the intrauterine infection was not a risk factor for RM (p = 0.30) in the examined women. It was found that the 110 Ile allele (HLA-G *01:04) was a risk factor for RM both in women with intrauterine infection [ORa = 4.50 (2.41-8.38), p = 2.09e-06], and in women without infection [ORa = 2.46 (1.44-4.21), p = 0.0009]. The cooperative influence of genetic and infections factors with the risk of RM in women was revealed [ORa+f = 3.50 (2.01-6.09), p = 8.78e-06]. Our results will be useful in understanding the molecular mechanisms of immune disorders in fetomaternal interface, and for choosing the strategy of management and treatment in women with RM.

The SERPINA4 rs2070777 AA Genotype is Associated with an Increased Risk of Recurrent Miscarriage in a Southern Chinese Population.

BackgroundMany inflammation-related gene polymorphisms are associated with susceptibility to recurrent miscarriage. SERPINA4 is involved in inflammation and is associated with susceptibility to a variety of diseases, but its relevance in recurrent miscarriage is unclear. Therefore, this study aimed to investigate the relationship between SERPINA4 gene polymorphisms and susceptibility to recurrent spontaneous abortion.MethodsTwo SERPINA4 polymorphisms were genotyped in 631 patients with recurrent miscarriage and 771 controls by TaqMan real-time polymerase chain reaction, and the strength of each association was evaluated through 95% confidence intervals (CIs) and odds ratios (ORs).ResultsThe results showed that SERPINA4 rs2070777 AA genotypes were associated with an increased risk of recurrent miscarriage (AA vs AT/TT adjusted OR=1.409, 95% CI=1.032–1.924, P=0.0309), and we also found a significant association between the rs910352 T allele in the SERPINA4 gene and susceptibility to recurrent miscarriage (CT vs CC adjusted OR=1.579, 95% CI=1.252–1.992, P=0.0001; TT vs CC adjusted OR=1.524, 95% CI=1.134–2.049, P=0.0052). The combined analysis of two SNPs of the SERPINA4 gene revealed that carriers with one to two unfavorable genotypes were associated with a higher risk for recurrent miscarriage compared with individuals with no unfavorable genotypes (adjusted OR=1.257, 95% CI=1.019-1.550). Moreover, our study indicates that having one to two unfavorable genotypes is associated with an increased risk of recurrent miscarriage in women 35–40 years of age.ConclusionOur study suggests that SERPINA4 rs2070777AA genotypes might contribute to an increased risk of recurrent miscarriage in a southern Chinese population.

Aspirin and heparin in the treatment of recurrent spontaneous abortion associated with antiphospholipid antibody syndrome: A systematic review and meta-analysis.

The present study aimed to review relevant, randomized, controlled trials in order to determine the effects of aspirin and heparin treatment on recurrent spontaneous abortion (RSA) in women with antiphospholipid syndrome (APS). Previous relevant studies were identified using PubMed, Cochrane, Embase, CNKI, VANFUN and VIP by retrieving appropriate key words. Additionally, key relevant sources in the literature were reviewed and articles published before May 2019 were included. The 22 selected studies included 1,515 patients in the treatment group and 1,531 patients in the control group. These previous studies showed that heparin and aspirin significantly improved live birth rate when compared with treatments using intravenous immunoglobulin, aspirin alone or aspirin combined with prednisone. Moreover, heparin and aspirin greatly increased the birth weight compared with placebo and improved vaginal delivery relative to intravenous immunoglobulin. The gestational age at birth was significantly higher in the heparin and aspirin group compared with the placebo group and the incidence of intrauterine growth restriction was lower in the heparin and aspirin group compared with the placebo group. Furthermore, heparin and aspirin markedly reduced the incidence of miscarriage compared with the aspirin group and the placebo group, and the incidence of pre-eclampsia was lower in the heparin and aspirin group than the placebo group. Thus, heparin and aspirin could be further examined for the treatment of RSA in women with APS.

Prevention of recurrent miscarriage in women with antiphospholipid syndrome: A systematic review and network meta-analysis.

To compare and rank currently available pharmacological interventions for the prevention of recurrent miscarriage (RM) in women with antiphospholipid syndrome (APS). A search was performed using PubMed, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, CNKI, ClinicalTrials.gov, and the UK National Research Register on December 15, 2019. Studies comparing any types of active interventions with placebo/inactive control or another active intervention for the prevention of RM in patients with APS were considered for inclusion. The primary outcomes were efficacy (measured by live birth rate) and acceptability (measured by all-cause discontinuation); secondary outcomes were birthweight, preterm birth, preeclampsia, and intrauterine growth retardation. The protocol of this study was registered with Open Science Framework (DOI: 10.17605/OSF.IO/B9T4E). In total, 54 randomized controlled trials (RCTs) comprising 4,957 participants were included. Low-molecular-weight heparin (LMWH) alone, aspirin plus LMWH or unfractionated heparin (UFH), aspirin plus LMWH plus intravenous immunoglobulin (IVIG), aspirin plus LMWH plus IVIG plus prednisone were found to be effective pharmacological interventions for increasing live birth rate (ORs ranging between 2.88 to 11.24). In terms of acceptability, no significant difference was found between treatments. In terms of adverse perinatal outcomes, aspirin alone was associated with a higher risk of preterm birth than aspirin plus LMWH (OR 3.92, 95% CI 1.16 to 16.44) and with lower birthweight than LMWH (SMD -808.76, 95% CI -1596.54 to -5.07). Our findings support the use of low-dose aspirin plus heparin as the first-line treatment for prevention of RM in women with APS, and support the efficacy of hydroxychloroquine, IVIG, and prednisone when added to current treatment regimens. More large-scale, high-quality RCTs are needed to confirm these findings, and new pharmacological options should be further evaluated.

The AGT Haplotype of the ESR2 Gene Containing the Polymorphisms rs2077647A, rs4986938G, and rs1256049T Increases the Susceptibility of Unexplained Recurrent Spontaneous Abortion in Women in the Chinese Hui Population.

BackgroundEstrogen has an important role in unexplained recurrent spontaneous abortion (URSA). Polymorphisms of the ESR1 gene and the ESR2 gene have been identified as risk factors for URSA, but with varied associations in Chinese populations. This study aimed to compare the role of gene polymorphisms of ESR1 and ESR2 and the risk of URSA in the Chinese Hui and Chinese Han populations.Material/MethodsChinese Hui women (n=171) and Chinese Han women (n=234) with URSA were compared with healthy controls (n=417) matched by ethnicity and age. Genotyping was performed using direct sequencing and identified three polymorphisms of the ESR1 gene (rs9340799, rs2234693, and rs3798759) and three polymorphisms of the ESR2 gene (rs207764, rs4986938, and rs1256049). The association between ESR1 and ESR2 gene polymorphisms and the risk of URSA was evaluated statistically using the odds ratio (OR) and 95% confidence interval (CI).ResultsNo association was detected between the allelic, dominant, and recessive models of ESR1 and ESR2 gene polymorphisms and the risk of URSA in Chinese Han and Hui populations (p>0.05). The distribution of the AGT haplotype containing ESR2 gene polymorphisms rs2077647A, rs4986938G, and rs1256049T was significantly reduced in patients with URSA compared with controls in the Chinese Hui population (OR, 0.29; 95% CI, 0.14–0.62; p=0.0009; padj=0.005).ConclusionsThe AGT haplotype of the ESR2 gene containing the polymorphism rs2077647A, rs4986938G, and rs1256049T (ESR2 hapAGT) was a protective factor for URSA in women in the Chinese Hui population when compared with the Chinese Han population.

Effect of occupational stress on recurrent spontaneous abortion in women of childbearing age

Objective: To investigate the influence of occupational stress on recurrent spontaneous abortion (RSA) in women of childbearing age. Methods: From January to December, 2017, 75 working women of childbearing age (25-35 years) who were admitted to a provisional hospital in Lanzhou, China and diagnosed with RSA were assigned into patient group. At a 1∶4 ratio, 300 age-matched working women who had normal first pregnancy were randomly selected as controls. A case-control study was conducted by a self-made questionnaire and the effort-reward imbalance scale. The impact of occupational stress on RSA in women of childbearing age was analyzed by evaluation of occupational harmful factors, regularity, effort-reward ratio, and sleep quality. Results: There were significant differences in the distribution of sleep, daily exercise, night shift, extrinsic-effort/low-reward score, and effort/low-reward score between the patient group and the control group (χ(2)=7.867, P<0.05; χ(2)=7.377, P<0.05; χ(2)=3.714, P<0.05; χ(2)=6.651, P<0.05; χ(2)=8.556, P<0.05) . With controlled factors such as general conditions and living habits, logistic regression analysis showed that poor sleep quality and high-effort/low-reward were risk factors for RSA (odds ratio[OR]=1.462, 95% confidence interval[CI]: 1.032~2.073; OR=3.253, 95%CI: 1.169~9.053) . A regular work was a protective factor against RSA (OR=0.644, 95%CI: 0.438-0.946) . Conclusion: In occupational stress, irregular working hours, lack of sleep, and high-effort/low-reward are risk factors for RSA. Working women of childbearing age should ensure adequate sleep, pay attention to effort-reward balance, and make a regular work schedule.

Correlation of single nucleotide polymorphisms in the promoter region of the ANXA5 (annexin A5) gene with recurrent miscarriages in women of Greek origin

Background: Recent findings show that a number of single nucleotide polymorphisms (SNPs) within the promoter region of the annexin A5-gene (ANXA5) reduce the expression of the reporter gene and so they display a significant association with recurrent pregnancy loss (RPL).Objective: The objective of the present study aimed to address the contribution of ANXA5 M2 haplotype consisting of four minor alleles: (SNP1: (−)467G > A, SNP2: (−)448A > C, SNP3: (−)422T > C, and SNP4: (−)373G > A) in the occurrence of recurrent pregnancy losses in the Greek population, and the role of further two minor alleles: SNP5: (−)302 T > G and SNP6: (−)1C > T as independent risk factors for RPL.Methods: A 752-bp genomic region of ANXA5 promoter was amplified by PCR using specific primers. Genotypic analysis by Sanger sequencing was performed for these six SNPs (minor alleles) in the promoter region of ANXA5 gene, in 100 (100) Greek women with recurrent miscarriages (median =3) and 70 (70) fertile controls. Statistical analysis was done using the SAS 9.3 for Windows (SAS Institute Inc, NC, USA) and SPSS packages for Windows (C.DiMaggio 2013, SAS Institute 2014).Results: This case-control study revealed that there is no significantly increased risk of RPL among the M2/ANXA5 haplotype carriers in the Greek population, as there were no statistical differences between the patients with recurrent pregnancy losses and the fertile controls (11.5% in RPL cases versus 9.29% in controls, p-value: .6364). There was no difference in SNP5 and SNP6 minor carriership between the two groups. In particular, carriers of SNP5 and SNP6 had an increased risk for RPL state with odds ratio: 1.2472 and 1.3846 respectively, however without statistically significant importance.Conclusion: The M2/ANXA5 haplotype does not differ between RPL patients and controls in the Greek population. Also, it is the first time that SNP5 and SNP6 minor alleles were evaluated extensively in women of European origin with recurrent pregnancy losses (RPL), and they do not seem to be independent risk factors in the occurrence of RPL in the Greek population. Though, this has to be confirmed in further and larger clinical trials with women of European origin.

Acetylsalicylic acid does not prevent first‐trimester unexplained recurrent pregnancy loss: A randomized controlled trial

Recurrent pregnancy loss occurs in about 1% of fertile couples. Without proper evidence for an effect, different treatments have been used when no etiological factor has been detected. The present trial is the first randomized trial to compare 75mg acetylsalicylic acid with placebo for women with recurrent pregnancy loss. This randomized, double-blind, placebo-controlled trial was conducted at a single center between 2008 and 2015. Recurrent pregnancy loss was defined as at least 3 consecutive first-trimester miscarriages within the couple. Women <40years old with a body mass index <35kg/m2 were eligible if the workup was negative. Randomization was through a third party, who manufactured and delivered the study drugs, and occurred when fetal heartbeat was detected, to either 75mg acetylsalicylic acid or placebo; 200 women in each group. Group allocation was concealed until all the study participants had a pregnancy outcome registered. All women attended the same control program. Primary outcome was live birth. Statistical analyses were according to intention-to-treat. All 400 women completed the follow up. Live birth rate was 83.0% (n=166) and 85.5% (n=171) for the acetylsalicylic acid and placebo groups, respectively (P=0.58). The difference was -2.5% (95% CI -10.1% to 5.1%). The risk ratio was 0.97 (95% CI 0.89-1.06). Treatment with acetylsalicylic acid did not prevent recurrent miscarriage in women with at least three consecutive miscarriages in the first trimester, of unknown reasons and in the same relationship. The fertility prognosis is very good, the live birth rate being >80% with or without acetylsalicylic acid.