OBJECTIVE: PGT-A to deselect aneuploid embryos in ART cycles may hold promise by augmenting pregnancy rates per transfer and reducing pregnancy loss rates for patients with unexplained recurrent pregnancy loss.
OBJECTIVE: To explore effectiveness of PGT-A in managing unexplained recurrent pregnancy loss by evaluating several key aspects: (i) the likelihood of a live birth in a subsequent spontaneous pregnancy, (ii) whether women with unexplained recurrent pregnancy loss have higher rate of aneuploidy, (iii) whether euploid blastocysts offer comparable live birth rate in patients with unexplained recurrent pregnancy loss, (iv) whether the endometrium is less selective in unexplained recurrent pregnancy loss, and (v) whether PGT-A increases live birth rate or reduces pregnancy losses until delivery.
METHODS: PubMed and Cochrane Library databases were searched from inception until June 2024.
UNASSIGNED: Studies involving patients with ≥2 unexplained recurrent pregnancy loss, who underwent ART with or without PGT-A, or expectant management were included.
METHODS: The primary outcome measure was the live birth rate. Secondary outcome measures were aneuploidy rate, clinical pregnancy rate, and clinical pregnancy loss rate.
RESULTS: Whether couples with unexplained recurrent pregnancy loss have higher embryo aneuploidy rates remains equivocal. Euploid blastocyst transfers yielded comparable clinical pregnancy loss rate (OR:1.10, 95%CI:0.57-2.13), and live birth rate (OR:1.04, 95%CI: 0.74-1.44) in patients with and without unexplained recurrent pregnancy loss. Comprehensive chromosome analysis of products of conception shows similar aneuploidy rates between patients with and without recurrent pregnancy loss and does not support less selective endometrium hypothesis. PGT-A decreased clinical pregnancy loss rate (OR: 0.42, 95% CI: 0.27-0.67) and enhanced live birth rate per transfer (OR: 2.17, 95% CI: 1.77-2.65) and live birth rate per patient (OR: 1.85, 95% CI: 1.18-2.91) in unexplained recurrent pregnancy loss patients.
CONCLUSIONS: Current low-quality evidence suggests that PGT-A enhances live birth rate per transfer and per patient in unexplained recurrent pregnancy loss. Well-designed randomized controlled trials comparing ART with-PGT-A versus expectant management for unexplained recurrent pregnancy loss are warranted.

UNASSIGNED: The research combined different bibliometric techniques to analyze systematically recurrent pregnancy loss (RPL) documents from 1970 to 2023.
UNASSIGNED: Overall, 1287 documents from the Web of Science database associated with recurrent pregnancy loss between 1970 and 2023 were identified for more than 300 journals. The data were analyzed with VOSviewer software.
UNASSIGNED: The trend of paying attention to the topic of RPL can be divided into three periods. The number of publications on RPL increased significantly after 2010. Most of the papers were published in Obstetrics and Gynecology and Reproductive Biology areas. Utilizing co-occurrence and co-citation analysis, our study found that the most influential documents mapped the knowledge structure, and projected future research directions. The co-occurrence analysis showed five clusters even though the co-citation analysis designates four.
UNASSIGNED: RPL has increased in recent years exponentially and some areas were explained carefully, therefore these results could be used as a research agenda for the future direction by a range of interested beneficiaries.

UNASSIGNED: Inherited thrombophilia, mainly the Factor V Leiden (FVL) and Prothrombin mutation (PTM) are the most risk factors for venous thrombosis especially during pregnancy and was strongly associated with recurrent pregnancy loss (RPL), a devastating reproductive problem that affects more than 1% of couples who are trying to conceive. The frequencies also the correlation among these polymorphisms and RPL have been reported controversially in various populations.
UNASSIGNED: In this study we evaluated the presence inherited thrombophilia amongst 35 Tunisian women with more than 2 miscarriages, referred to our genetic counseling.
UNASSIGNED: DNA was extracted from peripheral blood samples and PCR-RFLP was performed for the molecular diagnosis of mutation.
UNASSIGNED: FVL and PTM were detected in 5.7 % and 2.9% respectively; in women with a particular history of early fetal loss and thrombotic events.
UNASSIGNED: This study emphasizes the importance of testing for FVL and FIIM in women with RPL; mainly in the context of thrombotic events. Multi-center collaboration is necessary to clarify the real impact of thrombotic molecular defects on the pregnancy outcome, to ascertain the effect of inherited thrombophilia on recurrent pregnancy loss and then to evaluate the appropriate therapeutic approach.

BACKGROUND: We conducted this systematic review and meta-analysis to better understand the association between rs1799762 PAI-1 gene polymorphism and the risk of RPL.
METHODS: A systematic search for studies that assessed the association between PAI-1 4G/5G polymorphism and RPL risk published in search sources, PubMed/Medline, ISI Web of Knowledge, Scopus, and Google Scholar till January 2024 was conducted.
RESULTS: There were 23 case-control studies in total, with a high degree of statistical heterogeneity among them which indicated the need for subgroup analysis. We found a significant positive association between the risk of RPL and 4G/4G PAI-1 (OR: 2.57; 95% CI: 1.69-3.90), likewise 4G/5G (OR: 2/02 95% CI: 1.39-2.92) and mixed genotype (4G/4G+4G/5G) (OR: 2.31 95% CI: 1.81-2.93). Considering the ethnicity, the 4G/4G polymorphism is significantly associated with Asian descent (OR: 2.10; CI: 1.65-2.69) while the strong association (OR: 6.47; CI: 3.23-12.97) observed in the Greater Middle East descent is not statistically significant (P=0.16). PAI-1 4G/5G polymorphism association with RPL was only significant in Greater Middle East descent (OR: 2.93; CI: 2.41-3.56), and mixed genotype was significantly associated with RPL in Asian (OR: 2.37; CI: 1.55-3.61), Greater Middle East (OR: 3.01; CI: 2.16-4.19), and European populations (OR: 1.38; CI: 0.91-2.10). The association between RPL and PAI-1 4G/4G was significant for RPLs both under 12 weeks (OR: 1.82; 95% CI: 1.34-2.47), and under 24 weeks (OR: 1.46; 95% CI: 1.11-1.92), while considering heterozygote form the association was only significant for RPLs under 24 weeks (OR: 1.91; 95% CI: 1.58-2.31). Regarding the mixed genotype, there is a significant positive association between PAI-1 and RPL for RPLs under 12 weeks (OR: 2.09; 95% CI: 1.49-2.93), and under 24 weeks (OR: 2.10; 95% CI: 1.52-2.92).
CONCLUSIONS: Our findings indicate a significant association between the rs1799762 PAI-1 polymorphism and the risk of RPL.

Cytokines are a type of protein that play an important role in the immune response and can also affect many physiological processes in the body. Cytokine polymorphisms refer to genetic variations or mutations that occur within the genes that code for cytokines, which may affect the level of cytokine production and function. Some cytokine polymorphisms have been associated with an increased risk of developing certain diseases, while others may be protective or have no significant effect on health. In recent years, the role of cytokine polymorphisms in the development of recurrent pregnancy loss (RPL) has been studied. RPL or miscarriage is defined as the occurrence of two or more consecutive pregnancy losses before the 20th week of gestation. There are diverse causes leading to RPL, including genetic, anatomical, hormonal, and immunological factors. With regard to cytokine polymorphisms, a few of them have been found to be associated with an increased risk of RPL, for instance, variations in the genes that code for interleukin-6, tumor necrosis factor-alpha, and interleukin-10. The exact mechanisms by which cytokine polymorphisms affect the risk of recurrent miscarriage are still being studied, and further research is essential to fully understand this complex condition. This brief review aims to summarize the recent literature on the association between cytokine polymorphisms and RPL.

OBJECTIVE: This systematic review and meta-analysis aimed to evaluate the diagnostic value of the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in women with a history of abortion (missed and threatened) and recurrent pregnancy loss (RPL) in comparison with healthy pregnancies.
METHODS: Electronic databases including MEDLINE, Scopus, Web of Science, Embase, and Cochrane Library were searched for NLR and PLR in women who experienced early pregnancy loss up to January 1, 2023 with a combination of proper keywords. Meta-analysis was done for comparison with three or more studies and summary estimates were measured.
RESULTS: A total of 390 citations were retrieved initially, and after screening, 16 articles were deemed eligible for the final review. Among these, 14 studies underwent meta-analysis. The meta-analysis revealed that the standard mean of the NLR was significantly higher in abortion cases compared to the control group. However, there was no significant difference in the PLR between the pregnancy loss group and the control group.
CONCLUSIONS: NLR was significantly higher among RPL patients compared to the control group, according to these data, NLR may be capable of being used in the diagnosis of RPL as an easy, cheap, and accessible modality. Further studies, which take these variables into account, will need to be undertaken to determine the diagnostic value of NLR and PLR in early pregnancy loss.

OBJECTIVE: Estrogen and progesterone play key roles in the maintenance of pregnancy, and their function is mediated via estrogen receptor 1 (ESR1)/estrogen receptor 2 (ESR2) and progesterone receptor (PGR), respectively. It has been suggested the genetic variations in ESR1, ESR2, and PGR may contribute to recurrent pregnancy loss (RPL); however, the available evidence remains controversial. This meta-analysis aimed to explore the relation of various polymorphisms in ESR1, ESR2, and PGR genes to the risk of RPL.
METHODS: A systematic literature search was conducted using PubMed and Scopus up to August 2023 to obtain relevant studies. The odds ratios (ORs) with 95% confidence intervals (95% CIs) were computed and pooled with the use of random-effects models to test the associations.
RESULTS: A total of 31 studies with 12 different polymorphisms, including 5 polymorphisms for ESR1, 3 polymorphisms for ESR2, and 4 polymorphisms for PGR, were analyzed in this meta-analysis. Overall, no significant relationship was found between various polymorphisms of ESR1 and ESR2 with RPL in any of the genetic analysis models. PGR rs590688 (C > G) polymorphism was significantly related to the elevated risk of RPL under the dominant (OR = 1.67; 95 %CI: 1.15-2.44), allelic (OR = 1.55; 95 %CI: 1.13-2.12), and GC vs. CC (OR = 1.55; 95 %CI: 1.07-2.23) models. No significant association was identified for other variants of PGR gene.
CONCLUSIONS: Unlike estrogen receptors, variations in PGR rs590688 (C > G) may be linked to the increased risk of RPL. More studies are required to confirm this finding.

UNASSIGNED: Recurrent reproductive failure (RRF) is a common pregnancy complication, imposing great physical, emotional and financial burden for the suffered couples. The leading cause of RRF is believed to be aneuploid embryo, which could be solved by preimplantation genetic testing for aneuploidy (PGT-A) in theory. With molecular genetic development, PGT-A based on comprehensive chromosomal screening (CCS) procedures and blastocyst biopsy is widely applied in clinical practice. However, its effects in RRF were not defined yet.
UNASSIGNED: A systematic bibliographical search was conducted without temporal limits up to June, 2023. Studies about the effects of PGT-A based on CCS procedures and blastocyst biopsy in RRF were included.
UNASSIGNED: Twenty studies about the effects of PGT-A based on CCS procedures and blastocyst biopsy in RRF were included. It revealed that PGT-A could optimise the reproductive outcomes of RRF sufferers, especially in those with advanced age. However, in patients with multiple occurrences of pregnancy losses, the benefits of PGT-A were limited.
UNASSIGNED: More randomized controlled trials with large sample size are required to evaluate the benefits of PGT-A in RRF sufferers and identify which population would benefit the most.

UNASSIGNED: Aside from embryonic factors, various factors can intricately interfere with embryo implantation and maintenance of pregnancy, causing recurrent implantation failure (RIF) or recurrent pregnancy loss (RPL). This review focuses the optimization of thyroid function, thrombophilia, immunity, and uterine milieu (OPTIMUM) treatment strategy on RIF and RPL.
UNASSIGNED: Three studies employing the OPTIMUM treatment strategy for patients with RIF and/or RPL were reviewed.
UNASSIGNED: The OPTIMUM improved pregnancy rates in women with RIF aged <40 years. Among advanced age women, however, no significant differences in pregnancy rates were observed between the control, OPTIMUM, and preimplantation genetic testing for aneuploidy (PGT-A) groups, although pregnancy rates were highest after OPTIMUM + PGT-A. The OPTIMUM reduced miscarriage rates in women with RPL aged <40 years. Among advanced age women, PGT-A, but not the OPTIMUM, contributed to miscarriage prevention. Factors predicting pregnancy success in women with RIF who received the OPTIMUM included thrombophilia and young age. Risk factors for an unsuccessful live birth among women with RPL who received the OPTIMUM included advanced age, infertility, diminished ovarian reserve, and non-ART treatment.
UNASSIGNED: The OPTIMUM can improve pregnancy outcomes in women with RIF/RPL, except for advanced age women with embryonic factor-induced reproductive failure.

UNASSIGNED: Recurrent miscarriage is defined as 2 or more failed clinical pregnancies, typically known as repeated pregnancy loss, occurring before 20 gestational weeks, and further categorized into primary and secondary types. It represents a common and distressing condition to deal with in the field of reproductive medicine, usually affecting <5% of couples, with up to 50% of cases lacking a clearly defined aetiology. The epidemiology also varies depending on maternal age. Remarkably, the situation significantly afflicts expecting parents, whereas maternal factors, such as age and previous pregnancy loss rate, are commonly reported as risk factors. Although previously underestimated, existing evidence suggests the male factor is a possible cause of recurrent pregnancy loss.
UNASSIGNED: A non-systematic literature review was conducted in the PubMed and Scopus databases for articles written in English investigating the possible association of the male factor in recurrent pregnancy loss. The eligible studies were synthesized in a narrative review format upon discussion and consensus among the authors after being previously independently assessed and selected.
UNASSIGNED: Lifestyle, obesity, genetic predisposition, chromosomal anomalies, endocrine dysfunction, anatomical abnormalities, immunological factors, infections, and oxidative stress can result in poor embryo development and recurrent miscarriage. Although professional organizations currently recognize male gender as a possible risk factor, specific recommendations on the diagnostic and therapeutic field are still lacking, and the condition necessitates a high level of suspicion and case-by-case management.
UNASSIGNED: In this review, we delve deeper into the contribution of the male factor in the concept of recurrent miscarriage.