A Comprehensive Integration of Data Regarding the Correlation of TNF-α rs1800629 Polymorphism with Susceptibility to Cervical Cancer.

BACKGROUND: Cervical cancer, globally, ranks as the runner-up among the most prevalent forms of cancer affecting women. The role of the tumor necrosis factor alpha (TNF-α) polymorphism in the susceptibility to cervical cancer has been a subject of interest. However, the current evidence regarding this association remains inconclusive. METHODS: To address this uncertainty, eligible studies were systematically searched and retrieved from various databases including Cochrane Library, EMBASE, PubMed, Web of Science, CNKI, and Wanfang database. The search was conducted until September 01, 2023. The collected literature was then subjected to independent analysis by two authors. The pooled odds ratio along with the corresponding 95% confidence interval was calculated using different genetic models. Additionally, sensitivity and cumulative analyses were performed to assess the stability of the obtained results. RESULTS: A total of 29 case-control studies involving 8850 cases and 9286 controls were included in the present analysis. The findings revealed that the TNF-α rs1800629 polymorphism increased the risk of cervical cancer under the allele genetic model (A vs. G: OR = 1.277, 95% CI = 1.104-1.477, P = 0.001) in the general population. Subgroup analysis based on ethnicity demonstrated that this polymorphism was associated with an increased risk of cervical cancer in Caucasian and African women, but not in Asians. Furthermore, subgroup analysis based on country of origin indicated a significant correlation between the TNF-α rs1800629 polymorphism and an increased risk of cervical cancer in American and Chinese women, but not in Iranian women. CONCLUSIONS: The findings from this meta-analysis suggest that the TNF-α rs1800629 polymorphism is a risk factor for cervical cancer in the general population, particularly in Caucasian and African women. However, further well-designed studies are warranted to validate these findings.

Association of the CXCL12 rs1801157 Polymorphism with Breast Cancer Risk: A Meta-Analysis.

Studies on the CXCL12 rs1801157 polymorphism show that this polymorphism is involved in development of breast cancer, but its specific relationships or effects are not consistent. The purpose of this meta-analysis was to investigate the association between CXCL12 rs1801157 polymorphism and susceptibility to breast cancer. PubMed, Scopus, Embase, the Cochrane Library, Web of Science, and CNKI were searched for eligible studies through February 01, 2023. A total of ten studies with 2093 cases and 2302 controls were included in this meta-analysis. Overall, there is a significant association between CXCL12 rs1801157 polymorphism and risk of breast cancer under the homozygote genetic model (AA vs. GG, OR= 1.350, 95% CI: 1.050-1.734, p= 0.019). Stratified by ethnicity showed a significant association in Caucasian women, but not among Asian and mixed populations. This meta-analysis confirms that CXCL12 rs1801157 polymorphism is related to breast cancer risk, especially among Caucasian women. However, well-designed large-scale studies are required to further evaluate the results.

Lack of Association between TP73 G4C14-A4T14 Polymorphism and Cervical Cancer Risk in Overall and Asian Women: A Meta-Analysis.

BACKGROUND: Growing studies revealed the association between polymorphisms in Tumor Protein TP73 (TP73) and susceptibility to cancer, especially with gynecological cancers. but, the results remained inconsistent. This meta-analysis was carried out to examine the relationship of the TP73 G4C14-to-A4T14 polymorphism (hereafter, G4C14-to-A4T14) with susceptibility to cervical cancer globally and by ethnicity. METHODS: Eligible studies were collected by retrieving PubMed, Scopus, Web of Science, Embase, Wan Fang, and CNKI published before 25 October, 2023. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of such association. RESULTS: A total of 10 case-control studies with 1804 cervical cancer cases and 2433 healthy controls were included to this study. The pooled results showed that TP73 G4C14-to-A4T14 polymorphism was not associated with cervical cancer risk in overall. in terms of stratified analyses by ethnicity, this polymorphism was not associated with risk of cervical cancer among East-Asian women. however,  there was a significant association based source of control among hospital-based studies. CONCLUSIONS: Inconsistent with previous meta-analyses, our pooled results revealed that TP73 G4C14-to-A4T14 polymorphism might not be a risk factor for development of cervical cancer globally and among East-Asian women. Moreover, further studies examining the effect of gene-gene and gene-environment interactions may eventually provide a better knowledge.

Association between XRCC2 Arg188His Polymorphism and Breast Cancer Susceptibility: A Systematic Review and Meta-Analysis.

Breast cancer is one of the most common cancers in the world and leading cause of cancer-related death among women. Several studies indicated that Arg188His (rs3218536) polymorphism of X-ray repair cross-complementing 2 (XRCC2) may be associated with breast cancer risk. However, this association remains ambiguous. Thus, we performed a meta-analysis to provide more precise conclusion on this issue. A comprehensive search in PubMed, Google Scholar and ISI Web of Science was performed to select all relevant studies. Odds ratios (OR) with corresponding 95% confidence intervals (CI) were applied to assess the strength of the relationships. A total of 17 studies with 5694 breast cancer cases and 6450 healthy subjects were identified. The pooled data revealed that XRCC2 Arg188His polymorphism was marginally with susceptibility to breast cancer globally under the heterozygote contrast (OR = 0.929, 95% CI = 0.873-0.987, p=0.018). Moreover, subgroup analysis by ethnicity revealed that this polymorphism was associated with breast cancer risk among Caucasians. On the whole, the present study demonstrates that the XRCC2 Arg188His polymorphism may contribute to an increased risk of breast cancer.

Comparing the IVM laboratory outcomes between stimulated IVF with unstimulated natural cycles.

Recently, more attention has been raised towards fertility preservation in women with cancer. One option is in vitro maturation (IVM) of the immature oocytes as there is not enough time for induction of an ovarian stimulation protocol. The aim was to compare the IVM laboratory outcomes between stimulated and unstimulated (natural) in vitro fertilization (IVF) cycles. In total, 234 immature oocytes collected from 15 cancer patients who underwent an IVM programme (natural IVM) and 23 IVF cycles with a controlled ovarian hyperstimulation protocol (stimulated IVM) were analyzed. The oocyte morphology, zona pellucida (ZP), and meiotic spindle presence were measured using PolScope technology. Also, the rates of oocyte maturation and fertilization were assessed in both groups. The IVM rate was higher in the stimulated cycle (P < 0.05), but the fertilization rate was insignificant in comparison with unstimulated cycles. There were no significant differences in the spindle visualization and ZP birefringence scoring between the groups (P > 0.05). The oocyte normal morphology was better in the stimulated cycle compared with the natural cycle (P < 0.05). In conclusion, IVM can be recommended for cancer patients as an alternative treatment when there is insufficient time for conventional IVF before chemotherapy initiation.

A Clinical Decision Support System for Assessing the Risk of Cervical Cancer: Development and Evaluation Study.

BACKGROUND: Cervical cancer has been recognized as a preventable type of cancer. As the assessment of all the risk factors of a disease is challenging for physicians, information technology and risk assessment models have been used to estimate the degree of risk. OBJECTIVE: The aim of this study was to develop a clinical decision support system to assess the risk of cervical cancer. METHODS: This study was conducted in 2 phases in 2021. In the first phase of the study, 20 gynecologists completed a questionnaire to determine the essential parameters for assessing the risk of cervical cancer, and the data were analyzed using descriptive statistics. In the second phase of the study, the prototype of the clinical decision support system was developed and evaluated. RESULTS: The findings revealed that the most important parameters for assessing the risk of cervical cancer consisted of general and specific parameters. In total, the 8 parameters that had the greatest impact on the risk of cervical cancer were selected. After developing the clinical decision support system, it was evaluated and the mean values of sensitivity, specificity, and accuracy were 85.81%, 93.82%, and 91.39%, respectively. CONCLUSIONS: The clinical decision support system developed in this study can facilitate the process of identifying people who are at risk of developing cervical cancer. In addition, it can help to increase the quality of health care and reduce the costs associated with the treatment of cervical cancer.

Association between Fetal MTHFR A1298C (rs1801131) Polymorphism and Neural Tube Defects Risk: A Systematic Review and Meta-Analysis.

BACKGROUND: The association of the fetal MTHFR A1298C (rs1801131) polymorphism and neural tube defects (NTDs) susceptibility has been widely demonstrated, but the results remain inconclusive. Thus, we performed a meta-analysis to investigate the association between fetal MTHFR A1298C polymorphism and NTDs risk. METHODS: An electronic search of PubMed, web of science, SciELO, CNKI database for studies on the fetal MTHFR A1298C polymorphism and NTDs risk was performed up to March 30, 2020. RESULTS: A total of 22 case-control studies with 3,224 fetuses with NTDs and 3,295 controls were selected. Overall, pooled data showed that the fetal MTHFR A1298C polymorphism was not significantly associated with risk an increased risk of NTDs in the global population. When stratified analysis by ethnicity, country of origin and NTDs type, still no statistically significant association was found. CONCLUSIONS: Our pooled data emerged no evidence for significant association between fetal MTHFR A1298C polymorphism and NTDs risk.

Association of Fetal MTHFR C677T Polymorphism with Susceptibility to Neural Tube Defects: A Systematic Review and Update Meta-Analysis.

Background MTHFR gene may be a key epigenetic regulation-related factor crucial during embryogenesis. We performed a meta-analysis to determine the association of fetal MTHFR C677T polymorphism with neural tube defects (NTDs).Methods A comprehensive literature search of the PubMed, Embase, and CNKI database was performed up to April 10, 2020.Results A total of 19 case-control studies with 2,228 NTDs cases and 4,220 controls were identified. Pooled data revealed that the fetal MTHFR C677T polymorphism was significantly highly correlated with development of NTDs in the overall population. Stratified analysis showed a significant association among Caucasians and Asians, but not in mixed populations. There was a significant association between the MTHFR C677T polymorphism and spina bifida risk. No publication bias was found under any genetic model.Conclusions Our pooled data support the fetal MTHFR C677T polymorphism association with risk of NTDs, especially among Caucasians and Asians.

Advantages and disadvantages of using Carbon Nanostructures in Reproductive Medicine: two sides of the same coin.

Carbon nanostructures are important nanomaterial with interesting physical and chemical properties. These nanostructures have been assessed for application in different fields of medicine, such as cancer detection and treatment, Parkinson disease, reproductive medicine, etc. This nanomaterial can be used in reproductive medicine as a drug delivery system, antifungal, antiviral, and antibacterial agent, condom-coating agent, enhancer of sperm fertilizing ability, ectopic pregnancy treatment, trophoblastic diseases, endometriosis, uterine fibroids, and Assisted Reproduction Techniques (ART) improvement. The other side of this coin involves various side effects of carbon nanostructures, especially negative effects on reproductive systems. All carbon nanostructures showed toxicity on the reproductive system by producing reactive oxygen species and oxidative stress. Less attention has been given to the unique properties of carbon nanostructures, except for their practical attractiveness, the other side of this coin, namely the risks and side effects of these compounds - especially in the case of a reproductive system that supports the survival and health of future generations. Therefore, we suggest paying particular attention to the negative aspects of the increasing use of carbon nanostructures.

A Meta-Analysis for Association of XRCC3 rs861539, MTHFR rs1801133, IL-6 rs1800795, IL-12B rs3212227, TNF-α rs1800629, and TLR9 rs352140 Polymorphisms with Susceptibility to Cervical Carcinoma.

BACKGROUND: In spite of substantial declines in both incidence and mortality rates in the past 50 years, cervical cancer remains one of the leading causes of cancer associated mortality among women globally. We performed this meta-analysis to explore the role of XRCC3 rs861539, MTHFR rs1801133, IL-6 rs1800795, IL-12B rs3212227, TNF-α rs1800629 and TLR9 rs352140 polymorphism with susceptibility to cervical carcinoma. METHODS: The search databases include PubMed, SciELO, MedRxiv, Web of Science, Scopus, Cochrane Library, China National Knowledge Infrastructure, and China Biology Medicine disc up to 30 June 2021. The language is limited to English and Chinese. The comparison between the polymorphisms and cervical cancer was assessed using pooled odds ratio (OR) and 95% confidence interval (CI). The data are statistically analyzed by Comprehensive Meta-Analysis (CMA) 2.0 software. RESULTS: A total of 59 studies including seven studies with 1,112 cases and 1,233 controls on XRCC3 rs861539, 14 studies with 2,694 cases and 3349 controls MTHFR rs1801133, four studies with 1,121 cases and 1,109 controls on IL-12B rs3212227, seven studies with 1,452 cases and 2,186 controls on IL-6 rs1800795, 20 studies with 4,781 cases and 4909 controls on TNF-α rs1800629, and seven studies with 1743 cases and 2292 controls on TLR9 rs352140 were included. There was a significant association between XRCC3 RS861539, TNF-α rs1800629, and IL-6 rs1800795 polymorphisms and an increased risk of cervical carcinoma in overall population. However, the MTHFR rs1801133, IL-12B rs3212227 and TLR9 rs352140 polymorphisms were not associated. CONCLUSION: The pooled analysis showed that XRCC3 RS861539, TNF-α rs1800629, and IL-6 rs1800795 were associated with cervical carcinoma susceptibility, but not MTHFR rs1801133, IL-12B rs3212227 and TLR9 rs352140 polymorphisms.

Proliferating cell nuclear antigen presentation, as a marker of folliculogenesis, in the transplanted ovarian tissue.

AIM: One of the most important ways to understand the ovarian biology is studding the initiation of primordial follicle development and subsequent folliculogenesis control. In this study, proliferating cell nuclear antigen (PCNA) presentation was used as a marker of follicular development in the thawed ovarian tissue (OT) following transplantation onto chick embryo chorioallantoic membrane (CAM) using two methods of freezing of slow freezing and vitrification. METHODS: Samples of OT from 10 patients were subjected to slow freezing and vitrification. After warming, CAM transplantation was done and PCNA proliferation index (PI; percent of PCNA-positive granulosa cells) was calculated for each follicle stage. Image J software was used to determine the mean staining intensity. RESULTS: PCNA was positive for granulosa cells and oocytes nuclei, but negative for ooplasm. There were no remarkable PCNA staining in the granulosa cells of primordial follicles, but increased significantly as follicle progression (p < 0.05). Proliferation rate was also insignificantly higher in the vitrified than slow freezing group, before and after transplantation (p < 0.05). Lower PCNA presentation index was observed after CAM transplantation (p < 0.05). The earliest stage of follicular recruitment took place in the transitional follicles, before squamous cells transform to cuboidal cells. CONCLUSION: PCNA showed that follicles had proliferation power after cryopreservation. Higher presentation after vitrification may indicate accelerated folliculogenesis in the thawed OT.

Association of IL-6 -174G>C and -572G>C Polymorphisms with Susceptibility to Cervical Cancer and Ovarian Cancer.

BACKGROUND: During the past decades, the expansion of molecular development has had a key role in understanding the basis of gynecological cancer. Interleukin-6 (IL-6) is known to be involved in the pathogenesis of different cancers. Here, we evaluated the association of IL-6 -174G>C and -572 G>C polymorphisms with susceptibility to cervical and ovarian cancers in an Iranian population. METHODS: A total of 131 cases with ovarian cancer, 124 cases with cervical cancer and 140 healthy subjects were enrolled to the study. DNA was extracted from peripheral blood cells of subjects to genotype the IL-6 -174G>C and -572 G>C polymorphisms by amplification refractory mutation system (RFLP) polymerase chain reaction (PCR). RESULTS: There was a significant association of IL-6 -174G>C CC genotype (OR= 3.231, 95% CI: 1.130-9.239, p=0.029) and C allele (OR = 1.915; 95%CI: 1.266-2.896, p=0.002) with an increased risk of ovarian cancer. Moreover, the IL-6 -174G>C CC genotype (OR= 3.162, 95% CI: 1.094-9.141, p=0.034) and C allele (OR = 1.724; 95%CI: 1.129-2.633, p=0.012) was associated with increased risk of cervical cancer. CONCLUSIONS: This study showed that the IL-6 -174G>C polymorphism was associated with ovarian cancer and cervical cancer risk. However, IL-6 -572 G>C polymorphism was not associated.

Ovarian Tissue Reservation and Risk of Reimplantation in a Young Girl with Acute Lymphocytic Leukemia after 6-Month Chemotherapy: A Case Report.

In the fertility preservation programs, ovarian cryopreservation is usually offered when the risk of premature ovarian failure is high (>30-50%) while the risk of ovarian metastasis is low. According to the guidelines, it must be done before the patient receives chemotherapy. A 22-year-old girl with acute lymphocytic leukemia was a candidate for ovarian cryopreservation after 6 months of chemotherapy. Despite chemotherapy, the anti-Mullerian hormone survey was within normal range. Ovarian tissue cryopreservation was done. In the histology survey, follicular density was 7.48. This case shows that only having a history of chemotherapy does not exclude the patient from the fertility preservation program. Regarding referring the patients for fertility preservation, cumulative factors such as a history of gonadotoxic treatment, age, and treatment protocol should be considered. In addition, the case was negative for assessing of CD45 marker. New data may challenge previous strict criteria, and extend the indications of this effective method in preserving fertility among cancer patients.

A meta-analysis for the risk and prevalence of preeclampsia among pregnant women with COVID-19

Preeclampsia and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection are both life-threatening disorders when they occur during pregnancy. They are similarly characterized by systemic immune activation and have a deleterious effect on maternal endothelial cells. During the coronavirus disease-2019 (COVID-19) pandemic, there were reports of preeclampsia or a preeclampsia-like syndrome occurring in pregnant women with SARS-CoV-2 infection. We performed a meta-analysis to estimate the risk and prevalence of preeclampsia and SARS-CoV-2 infection in pregnant women. A comprehensive literature search was conducted in PubMed, Web of Science, Scopus, and China National Knowledge Infrastructure to identify all relevant studies published up to February 29, 2020. All studies that reported the prevalence of preeclampsia in pregnant women with SARS-CoV-2 infection were selected. A total of 10 case-control studies and 15 case series met our inclusion criteria. Pooled data revealed no significant difference between infected pregnant women and uninfected pregnant women for the risk of preeclampsia [odds ratio (OR)=1.676, 95% confidence interval (CI) 0.679-4.139, p=0.236]. The stratified analysis revealed significant risk in the infected Asian pregnant women (OR=2.637, 95% CI 1.030-6.747, p=0.043), but not Caucasian. The prevalence of preeclampsia was 8.2% (95% CI 0.057-0.117) in infected pregnant women with COVID-19 in the overall population. Its prevalence was highest in North America (10.7%), followed by Asian (7.9%), Caucasian (6.7%), European (4.9%), and West Asian (2.6%) infected pregnant women. Our pooled data showed that the prevalence of preeclampsia in pregnant women with SARS-CoV-2 infection was 8.2%. However, there was no increased risk of occurrence of preeclampsia among pregnant women with SARS-CoV-2 infection.

Meta-analysis of the frequency of intrauterine growth restriction and preterm premature rupture of the membranes in pregnant women with COVID-19

The impact of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in pregnancy has yet to be determined. Some studies indicate that SARSCoV- 2 infection may be associated with a higher risk of adverse outcomes in pregnant women. Here, we performed a meta-analysis to estimate the frequency of intrauterine growth restriction (IUGR) and preterm premature rupture of the membranes (PPROM) in pregnant women with Coronavirus disease-2019 (COVID-19). A comprehensive search was performed in various databases, such as PubMed, Scopus, SciELO, MedRxiv, and Web of Science, to find all relevant studies published before 10 February 2021. Cross-sectional and consecutive case series reporting the pregnancy outcomes of COVID-19 were included. A total of 24 studies, including 8 studies on IUGR and 16 studies on PPROM, were selected. Pooled data showed that the frequencies of IUGR and PPROM in pregnant women with COVID-19 were 2.6% and 9.9%, respectively. Analyses stratified by ethnicity showed that the frequencies of IUGR in Asian and Caucasian COVID-19-infected pregnant women were 2.9% and 2.0%, respectively. Moreover, the frequencies of PPROM in Asian and Caucasian COVID-19-infected pregnant women were 10.2% and 5.8%, respectively. This meta-analysis showed that the frequencies of IUGR and PPROM in COVID-19-infected pregnant women were 2.6% and 9.9%, respectively. However, well-designed, large-scale and multicenter clinical studies are required to improve and validate these results.

A meta-analysis for association of eNOS VNTR 4b/a, - 786 T > C and + 894G > T polymorphisms with risk of recurrent pregnancy loss.

BACKGROUND: The association of polymorphisms at nitric oxide synthases (eNOS) gene with recurrent pregnancy loss (RPL) susceptibility has been the focus of attention in several studies. However, the conclusions have been divergent and controversial. Therefore, we performed this study to precisely evaluate the association of eNOS polymorphisms with the risk of RPL. METHODS: A universal search in PubMed, Web of Knowledge, SciELO, MedRxiv, Scopus and web of Science was performed to identify relevant studies up to January 25, 2020. RESULTS: A total of 39 eligible studies including 15 studies with 2274 cases and 1933 controls on VNTR 4b/a, nine studies with 1640 cases and 1268 controls on -786C > T, and 15 studies with 2660 cases and 2557 controls on + 894G > T polymorphism were selected. Pooled data revealed that eNOS VNTR 4b/a (dominant model: OR = 1.174, 95% CI 1.021-1.350, p = 0.025) and + 894G > T (allele model: OR = 1.278, 95% CI 1.024-1.595, p = 0.030; homozygote model: OR = 1.442, 95% CI 1.084-1.917, p = 0.012; dominant model: OR = 1.305, 95% CI 1.006-1.693, p = 0.045; and recessive model: OR = 1.378, 95% CI 1.045-1.817, p = 0.023) polymorphisms were significantly associated with an increased risk of RPL, but not - 786 T > C. Stratified analysis by ethnicity revealed that the eNOS + 894G > T was associated with RPL risk in Asians. CONCLUSIONS: To sum up, our results indicated that the eNOS VNTR 4b/a and + 894G > T polymorphisms might be contributing to RPL development, but not the - 786C > T polymorphism.

Association of PON1, LEP and LEPR Polymorphisms with Susceptibility to Breast Cancer: A Meta-Analysis.

OBJECTIVE: Breast cancer is the most common cancer in American women, except for skin cancers. In this meta-analysis, the associations of polymorphisms within paraoxonase 1 (PON1), leptin (LEP) and leptin receptor (LEPR) genes with susceptibility to breast cancer were comprehensively evaluated. METHODS: A universal search in PubMed, Scopus, CNKI, SID, Web of Knowledge and Google Scholar was performed to identify relevant studies up to 01 May, 2021. The strength of the associations was estimated by Odds ratios (ORs) with 95% confidence intervals (95% CIs). RESULTS: A total of 39 case-control studies including 7 studies with 2005 cases and 2748 controls were on PON1 rs662, 6 studies with 2,031 cases and 1,973 controls on PON1 rs854560, 12 studies with 3,444 cases and 3,583 controls on LEP rs7799039, and 14 studies with 5,330 cases and 6,188 controls on LEPR rs1137101 were selected. Pooled data showed that PON1 rs662 and rs854560 polymorphisms were associated with risk of breast cancer in overall population, but not LEP rs7799039 and LEPR rs1137101. CONCLUSIONS: Our pooled data revealed that the PON1 rs662 and rs854560 polymorphisms were significantly associated with an increased risk of breast cancer in the overall population. However, LEP rs7799039 and LEPR rs1137101 polymorphisms were not associated.

Association of AXIN2 s2240308 C>T, rs1133683 C>T, rs7224837 A>G Polymorphisms with Susceptibility to Breast Cancer.

BACKGROUND: The association of genetic polymorphisms at Axis inhibition protein 2 (AXIN2) gene and susceptibility to different cancer has attracted much interest. The present study aimed to evaluate the association between AXIN2 rs2240308 C>T, rs1133683 C>T, rs7224837 A>G polymorphisms with susceptibility to breast cancer. METHODS: A polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay was designed to genotype the AXIN2 rs2240308 C>T, rs1133683 C>T, rs7224837 A>G polymorphisms among 150 breast cancer patients and 150 healthy subjects. RESULTS: The frequencies of these genetic variants were in agreement with Hardy-Weinberg equilibrium in healthy controls (p>0.05). The frequencies of AXIN2 rs2240308 C>T, rs1133683 C>T, rs7224837 A>G genotypes were similar in breast cancer patients and controls. There was no a significant association between the AXIN2 SNP and risk of breast cancer. CONCLUSION: The impact of AXIN2 polymorphisms in the breast cancer development remains unclear. Our results indicated that AXIN2 rs2240308, rs7224837 and rs1133683 polymorphisms did not contribute to increased risk of breast cancer. More studies with larger sample sizes and diverse ethnicities are warranted to verify our finding.

A meta-analysis of the association of the ACE I/D and PAI-1 4G/5G polymorphisms with recurrent pregnancy loss in Iranian women: Are the investigations adequate?

The associations of ACE I/D and PAI-1 4G/5G polymorphisms with recurrent pregnancy loss (RPL) in Iranian women have yielded controversial results. Thus, we conducted a meta-analysis to obtain more certain results. A comprehensive literature search was performed in the PubMed, Web of Sciences, Scopus, MedRxiv, SID, and CNKI databases up to January 1st, 2021, using the appropriate terms. All case-control studies were included. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the strength of associations. A total of 14 studies including eight studies with 783 patients and 761 healthy subjects on ACE I/D and six studies with 1.155 patients and 699 healthy subjects on PAI-1 4G/5G were included. Combined data revealed that ACE I/D polymorphism was significantly associated with RPL risk in Iranian women under three models i.e., allele [OR=0.744, 95% CI: (0.640-0.864); p≤0.001], dominant [OR=0.774, 95% CI: (0.601-0.996); p=0.047], and recessive [OR=0.767, 95% CI: (0.611-0.963); p=0.022]. Moreover, the pooled data showed a significant association between the PAI-1 4G/5G polymorphism and RPL risk under all five models i.e., allele [OR=2.352, 95% CI: (1.623-3.408); p≤0.001], heterozygote [OR=8.364, 95% CI: (4.744-14.756); p≤0.001), homozygote [OR=2.192, 95% CI: (1.093-4.394); p=0.027), dominant [OR=2.354, 95% CI: (1.309-4.235); p=0.004], and recessive [OR=5.208, 95% CI: (3.005-9.025); p≤0.001]. Stratification analysis revealed that these polymorphisms were associated with RPL risk by the number of miscarriages. Our pooled data indicated that ACE I/D and PAI-1 4G/5G polymorphisms were significantly associated with an increased risk of RPL in Iranian women. These significant findings showed that the investigation might be adequate for ACE I/D and PAI-1 4G/5G polymorphisms in the Iranian population.