UNASSIGNED: To investigate the mechanism of vitamin D level on the regulation of peripheral blood lymphocyte subsets and serum Th1/Th2 cytokines in patients with unexplained recurrent spontaneous abortion (URSA).
UNASSIGNED: Eighty female patients with URSA attending Sichuan Jinxin Xinan Women\'s and Children\'s Hospital from January 2020 to May 2021 were selected as the study group, and 30 age-matched women with a history of healthy deliveries were chosen as the control group, and peripheral blood lymphocyte subpopulations and serum Th1/Th2 cytokines of people with different levels of vitamin D were detected in the study group by flow cytometry, respectively. The results of immune factors before and after supplementation were analyzed in 40 of these patients with low vitamin D levels. The results of lymphoid subpopulations and Th1/Th2 cytokines in 19 patients with normal pregnancy before and after vitamin D supplementation and after normal pregnancy were also analyzed comparatively.
UNASSIGNED: (1) Serum 25(OH)D in the study group was lower than in the control group; peripheral blood Th cells, B cells and NK cells in the study group were higher than in the control group; IL-2, TNF-α, IFN-γ and IL-6 in the study group were higher than in the control group, while IL-4 and IL-10 in the study group were lower than in the control group (P < 0.05). (2) Th cells, B cells and NK cells of URSA patients in the vitamin D low level group were higher than those in the vitamin D normal group; serum cytokines IL-2, TNF-α and IFN-γ of patients in the vitamin D low level group were higher than those in the vitamin D normal group (P < 0.05); (3) Th cells, B cells and NK cells in URSA patients after vitamin D supplementation were lower than before vitamin D supplementation; serum cytokines IL-2, TNF-α and IFN-γ after vitamin D supplementation were lower than before vitamin D supplementation, IL-4 and IL-10 after vitamin D supplementation were higher than before vitamin D supplementation (P < 0.05), and there was no significant difference in IL-6 before and after vitamin D supplementation. (4) Th cells, B cells and NK cells in patients with normal pregnancy after vitamin D supplementation and after pregnancy were lower than those before vitamin D supplementation; serum cytokines IL-2, TNF-α and IFN-γ after vitamin D supplementation and after pregnancy were lower than those before vitamin D supplementation, and serum cytokines IL-4 and IL-10 after vitamin D supplementation and after pregnancy were higher than those before vitamin D supplementation, TNF -α, IFN-γ after pregnancy were lower than after vitamin D supplementation (P < 0.05), IL-6 was not significantly different before and after vitamin D supplementation and after pregnancy.
UNASSIGNED: Vitamin D deficiency rate was high in URSA patients. Th、B、NK cells and IL-2, TNF-α, IFN-γ, IL-6 cytokines were high, while IL-6 and IL-10 were low in URSA patients. IL-2, TNF-α, IFN-γ cytokines and Th, B, NK cells were increased in vitamin D deficient URSA patients, and Vitamin D deficiency may be an important cause or aggravating factor of immune dysfunction in URSA patients. Vitamin D has an immunomodulatory effect on URSA patients, promoting successful pregnancy by down-regulating peripheral blood Th, B, and NK cells and IL-2, TNF-α, and IFN-γ cytokines, while up-regulating IL-4 and IL-10.

BACKGROUND: Recent studies have linked recurrent pregnancy loss (RPL) to abnormalities in the sperm genome, specifically microdeletions in the azoospermia factor (AZF) region. This study investigated the potential association between Y chromosome microdeletions in the AZF region and RPL in Iranian couples.
METHODS: The research presents a case-control study of 240 men: 120 whose partners experienced recurrent miscarriage, and 120 who had successful pregnancies without history of miscarriage. The study used semen parameters, hormone analyses, and microdeletion analysis via multiplex PCR and the YChromStrip kit. Thus, the sequence-tagged site (STS) markers of AZFa (sY84, sY86), AZFb (sY127, sY134), and AZFc (sY254, sY255) regions were examined.
RESULTS: The variations in semen parameters and sex hormone levels between cases and controls are suggest impaired testicular function in men whose partners had recurrent miscarriages (p < 0.05). Furthermore, the study revealed a negative correlation between sperm count and follicle-stimulating hormone (FSH) level, and a positive one between sperm motility and testosterone concentration. There were no microdeletions in the control group, while the RPL group showed 20 deletions in AZFb (sY134) (16.66%) and 10 deletions each in AZFb (sY127) (8.33%) and AZFc (sY254) (8.33%).
CONCLUSIONS: Microdeletions in sY134 (AZFb) were significantly associated with RPL in Iranian men (p = 0.03). AZF microdeletion screening in couples with RPL can provide valuable information for ethnical genetic counseling and management of recurrent miscarriage. Further studies on larger populations or across various ethnic groups, conclusions and the inclusion of other factors like epigenetic changes explain the role of AZF microdeletions in RPL.

OBJECTIVE: To evaluate the correlation between the antiannexin A5 antibodies (aAnxA5) multiples of median (MOM) and subsequent pregnancy outcomes in women with recurrent miscarriage (RM).
METHODS: Totally, 310 RM women were included in this study and grouped into tertiles according to their MOM of preconception aAnxA5 circulating levels determined by ELISA. The effect of aAnxA5 on the pregnancy outcomes was performed using multiple logistic regression. The outcomes included early miscarriage (before 10 weeks of gestation), late miscarriage (between 10 and 24 weeks), ongoing pregnancy (beyond 10 weeks), and live birth (after 24 weeks) characterized by pregnancy with fetal heartbeat.
RESULTS: For each unit increase in aAnxA5 MOM, the odds of live birth after 24 weeks and ongoing pregnancy were reduced by 40.2% (OR = .598; 95%CI 0.406-0.882, P = .010) and 38.1% (OR = .619; 95%CI 0.424-0.904, P = .013), respectively, after adjusting for demographic and clinical characteristics. The rise in aAnxA5 MOM was associated with an increased risk of early miscarriage (OR = 1.616; 95%CI 1.106-2.361, P = .013) and miscarriage (early + late miscarriage) (OR = 1.671; 95%CI 1.134-2.464, P = .010). Further subgroup analyses showed a decreased risk of live birth rates after 24 weeks of gestation in the two subgroups: maternal age ≥35 years (OR = .131; 95%CI 0.026-0.652), and previous pregnancy loss ≥ 3 (OR = .381; 95%CI 0.173-0.837).
CONCLUSIONS: Higher preconception aAnxA5 MOM levels in women with RM may be linked with a decreased risk of live birth after 24 weeks and an increased risk of early miscarriage, especially in individuals aged ≥35 years or with previous pregnancy losses ≥3.

Recurrent miscarriage (RM) is a condition defined as having three or more consecutive pregnancy losses before the 20 weeks of pregnancy. The present study was undertaken to investigate association of Interleukin-17A (IL-17A) rs2275913 polymorphism with RM. To this end, we searched the international databases (Web of Science, PubMed, Embase, and Scopus) and extracted studies investigating the association of IL-17A rs2275913 polymorphism with RM using the appropriate keywords. The collected data were analyzed with the random-effects model and STATA (version 14). A total of five studies met the eligibility criteria, and total sample size was 998 subjects. Mean age of the cases and controls were 31.41 ± 4.16 and 30.56 ± 3.5 years, respectively. Our results disclosed a significant relationship of the IL-17A rs2275913 AA genotype [odds ratio (OR)=1.68; 95% confidence interval (CI)=1.16- 2.43; I2=19; P=0.294) with RM. There was no statistically significant correlation between IL-17Ars2275913 GG genotype (OR=1.04; 95% CI=0.64-1.7; I2=59.5; P=0.042) and GA genotype (OR=0.85; 95% CI=0.65-1.12; I2=19.1; P=0.293) with RM. Our findings revealed that the IL-17A rs2275913 polymorphism is associated with RM, and the AA genotype of this polymorphism increased possibility of being involved in RM.

OBJECTIVE: To investigate whether women with unexplained recurrent pregnancy loss have impaired arterial vascular health compared with controls, and to evaluate whether this is modifiable by exercise.
METHODS: Experimental case-control pilot study.
METHODS: University medical centre in the Netherlands.
METHODS: Twelve women with unexplained recurrent pregnancy loss, 11 nulliparous women and 19 primiparous women with a history of uncomplicated pregnancies.
METHODS: In all three groups we measured baseline characteristics, metabolic components and arterial vascular health, and repeated this in women with unexplained recurrent pregnancy loss after 1 month of protocolled and supervised cycle training.
METHODS: Differences in arterial vascular health between women with unexplained recurrent pregnancy loss and controls, and the effect of exercise on arterial vascular health in women with unexplained recurrent pregnancy loss.
RESULTS: Women with unexplained recurrent pregnancy loss have a significantly increased carotid intima media thickness in comparison with both controls (both P < 0.01), a significantly decreased brachial endothelial dependent flow-mediated vasodilation in comparison with both controls (nulliparous: P < 0.01; primiparous: P = 0.05) and a significantly decreased femoral endothelial dependent flow-mediated vasodilation in comparison with primiparous women (P = 0.01). The endothelium independent glyceryl trinitrate response was similar in all groups. With 1 month of exercise, the carotid intima media thickness decreased significantly by 7% (P = 0.05) and the femoral FMD increased significantly by 10% (P = 0.01) in women with unexplained recurrent pregnancy loss.
CONCLUSIONS: Women with unexplained recurrent pregnancy loss have an impaired vascular health in comparison with controls. This impaired arterial vascular health can be improved by exercise.

To evaluate the prevalence of abnormal endocrine dysfunction for recurrent pregnancy loss (RPL) amongst patients with two versus three or more pregnancy losses.
This cross-sectional study retrospectively collected pre-pregnancy data of 537 women diagnosed with RPL in Shengjing Hospital of China Medical University from 2017 to 2022, including the baseline data of patients and the test results of endocrine factors. Several endocrine dysfunction included in this study were: thyroid dysfunction, obesity, hyperprolactinemia, polycystic ovary syndrome and blood glucose abnormality. Furthermore, vitamin D level were collected to study its relationship with endocrine dysfunction. Finally, we subdivided the patients according to the number of previous pregnancy loss and compared the prevalence of endocrine dysfunction between subgroups.
Among 537 RPL patients, 278 (51.8%) patients had abnormal endocrine test results. The highest incidence of endocrine dysfunction was thyroid dysfunction (24.39%, 131/537), followed by hyperprolactinemia (17.34%, 85/490), obesity (10.8%, 58/537), polycystic ovary syndrome (10.50%, 56/533), and abnormal blood glucose (5.29%, 27/510). Only 2.47%(13/527) of patients have vitamin D level that reach the standard. After subdividing the population according to the number of pregnancy loss, we did not find that the incidence of endocrine dysfunction (P=0.813), thyroid dysfunction (P=0.905), hyperprolactinemia (P=0.265), polycystic ovary syndrome (P=0.638), blood glucose abnormality (P=0.616) and vitamin D deficiency (P=0.908) were different among patients with two versus three or more pregnancy losses. However, obesity (P=0.003) was found more frequently observed in patients with more times of pregnancy loss.
The prevalence of endocrine dysfunction in RPL population is high. There is no difference in the prevalence of endocrine dysfunction, except for obesity, among patients with two or more pregnancy losses, which may suggest investigations of endocrine dysfunction when patients have two pregnancy losses.

BACKGROUND: Recurrent miscarriage (RM) is defined as the loss of two or more consecutive pregnancies. A functional SNP, -238G>A in the promoter region of TNF-α, affects the gene transcription activity with implications on human pregnancy. Previous limited studies, linking the TNF-α -238 G>A to the risk of recurrent miscarriage have been inconclusive.
METHODS: The PCR-RLFP technique was used to evaluate this polymorphism in 199 RM cases and 215 control women from Amritsar, Punjab. For a meta-analysis, a total of 13 eligible studies (including the present study) comprising 2947 cases and 2933 controls were included. To evaluate the association among different genetic models, odds ratio with a 95% confidence interval (CI) and chi-square were used.
RESULTS: Genotype and allelic frequency did not differ significantly between both groups (p = .07 and p = .24, respectively). In the present meta-analysis, a significant association was found with the recessive model (OR-1.78 CI:1.24-2.55, p = .002).
CONCLUSIONS: Although, TNF-α -238 G>A polymorphism did not provide any risk in the case-control study but provided risk towards the development of RM with the recessive genetic model in the pooled analysis.

Recurrent pregnancy loss (RPL) or recurrent miscarriage is the failure of pregnancy before 20-24 weeks that influences around 2-5% of couples. Several genetic, immunological, environmental and physical factors may influence RPL. Although various traditional methods have been used to treat post-implantation failures, identifying the mechanisms underlying RPL may improve an effective treatment. Recent evidence suggested that gene expression alterations presented essential roles in the occurrence of RPL. It has been found that long non-coding RNAs (lncRNAs) play functional roles in pregnancy pathologies, such as recurrent miscarriage. lncRNAs can function as dynamic scaffolds, modulate chromatin function, guide and bind to microRNAs (miRNAs) or transcription factors. lncRNAs, by targeting various miRNAs and mRNAs, play essential roles in the progression or suppression of RPL. Therefore, targeting lncRNAs and their downstream targets might be a suitable strategy for diagnosis and treatment of RPL. In this review, we summarized emerging roles of several lncRNAs in stimulation or suppression of RPL.

Unexpected and repeated miscarriages in a woman\'s life cycle can be a mental and physical burden and lead to post-traumatic stress disorder. However, women may also experience inner growth with such experiences.
This study was qualitative descriptive research examining the experiences of South Korean women who had recurrent miscarriages three or more times.
The average age of the participants was 34.6 years, and the average number of recurrent miscarriages was 3.87. Additionally, five themes were identified as follows: (1) Confusing as if in muddy water, (2) Self-examination of past daily life, (3) Empathy and comfort in homogeneous groups, (4) Religious beliefs that include the lost fetus, and (5) Transforming for internal growth.
Based on the results of this study, intervention strategies need to be implemented to support the inner growth of women who have experienced recurrent miscarriages.

BACKGROUND: Maternity services underwent much change during the COVID-19 pandemic. Research on the impact on miscarriage care and experiences during this time is sparse. Within a national evaluation of recurrent miscarriage care, we qualitatively explored stakeholder views and experiences of recurrent miscarriage services in Ireland. This study describes the impact of the COVID-19 pandemic on those experiences and perceptions of care.
METHODS: People with professional and lived experience of recurrent miscarriage and service engagement were actively involved in this qualitative study from idea generation to analysis and reporting. We recruited women and men with two or more consecutive first-trimester miscarriages, and people involved in the management/delivery of recurrent miscarriage services and supports. We used purposive sampling to ensure that perspectives across disciplinary or lived experience, geographical, and health service administrative areas, were included. We conducted semi-structured interviews, virtually all due to COVID-19 restrictions, between June 2020 and February 2021. These were audio-recorded, and data were transcribed, and subsequently analyzed using reflexive thematic analysis.
RESULTS: We interviewed 42 service providers and 13 women and 7 men with experience of recurrent miscarriage. We actively generated two central themes during data analysis. The first-\'Disconnected\'-describes how many women navigated miscarriage diagnosis and management and care in subsequent pregnancies alone; many felt that this resulted in increased trauma. At the same time, men struggled with not being present to support their partners and described feeling disconnected. The second theme highlighted \'The perceived dispensability of recurrent miscarriage services and supports\'. Some service providers felt that service reduction and redeployment demonstrated a lack of value in the service. Virtual clinics facilitated access to services, but a preference for in-person care was highlighted.
CONCLUSIONS: Our analysis provides rich insights into the significant impacts that the COVID-19 pandemic has had on the way recurrent miscarriage care is provided and experienced, with important implications for early pregnancy, miscarriage and recurrent miscarriage care. Services have undergone significant changes and, while these may be temporary, how services should be delivered in the future requires consideration, particularly given the deficits in care and care experiences highlighted prepandemic.
UNASSIGNED: Members of the multidisciplinary RE:CURRENT Project Research Advisory Group (including four parent advocates, two of whom are co-authors on this article) were actively involved throughout the study, including the generation of topic guides and the refining of themes.