Characteristics of Retinal Image in Women with Recurrent Spontaneous Abortion

doi:10.21203/rs.3.rs-2218061/v1

Download PDF

Research Article

Characteristics of Retinal Image in Women with Recurrent Spontaneous Abortion

https://doi.org/10.21203/rs.3.rs-2218061/v1

This work is licensed under a CC BY 4.0 License

Version 1

posted

You are reading this latest preprint version

Purpose

To identify the characteristics of retinal image in women with recurrent spontaneous abortion (RSA).

Methods

A case-control study was conducted in the Shenzhen Maternity & Child Healthcare Hospital. Eighty women who were diagnosed RSA were recruited. Those women who were age matched with the RSA group and experienced a successful birth history were chosen as the control group. Retinal images were collected and characteristics were analysed. Multivariable logistic model was built to identify the characteristics of retinal image.

Results

Compared to the control group, the patients with RSA had higher CRAE (P = 0.02), Vasym(P < 0.0001) and Aasym(P = 0.002), larger Aangle(P = 0.035), BCA(P < 0.0001) and more obvious Nicking(P = 0.001) and occlusion( P = 0.001) in the retinal artery, but lower AVR(P = 0.314) in retinal characteristics. The area under the ROC curve of the multivariable logistic regression was 0.8541 (95% C.I. 0.796–0.912).

Conclusions

Compared to the Normal pregnancy women, those with RSA had special retinal characteristics, which might provide useful information for RSA identification.

retinal characteristics

recurrent spontaneous abortion

multivariable logistic regression

early clinical diagnosis

Recurrent spontaneous abortion (RSA) is defined as those women who experienced the sequential loss of two or more pregnancies before 20 weeks of pregnancy. The incidence of RSA in pregnant women in the world is about 5–20% ¹. The prevalence of RSA has been increasing in recent years. As a heterogeneous disease, RSA has a complex etiology and patients often lack specific clinical manifestations, which to some extent hinders the prediction and prevention progress of RSA ^2,3. In recent years, the occurrence of many unexplained recurrent abortions is closely related to abnormal vascular hyperplasia and insufficient blood supply of the fetus in placenta tissue ⁴, experts further found that the imbalance of vascular growth factors is related to adverse pregnancy outcomes that the imbalance of vascular growth factor is related to adverse pregnancy outcome ⁵. The latest expert consensus pointed out that a strong association between the hypercoagulable state and adverse pregnancy outcomes in recurrent miscarriage (RSA)in the past decade ⁶.

Several studies had shown that when the vascular endothelium is damaged, the release of vascular coagulation factors in the blood increases. By binding to its ligands, it can lead to adhesion and aggregation of platelets under the endothelium of damaged blood vessels and initiate a coagulation process that leads to thrombosis. Retinal vascular abnormalities are one of the most important signs of systemic diseases⁷. The observation, quantification, and monitoring of the retinal microvasculature system can be achieved in a non-invasive manner using fundus photographs and computer image analysis techniques. Our research team has done extensive research on the correlation between fundus microvascular and cardiovascular disease ^8–10. Examination of retinal microvascular abnormalities by fundus photography is currently the best non-invasive technique for evaluating hypercoagulability, which has been used to identify diseases such as hypertension, diabetes, systemic autoimmune diseases and stroke ^11–14. It has been found that retinal image analysis can be used not only for eye examinations but also as an early screening tool for cardiovascular abnormalities. However, no research has investigated the relationship between quantitative analysis of retinal characteristics and the RSA so far.

This study was conducted to identify the characteristics of fundus vessels related to RSA, which might help to diagnose the RSA at an early stage, so as to apply the intervention and treatment of the disease.

Ethical Statement

This study was approved by the ethics committee of the Shenzhen Maternity & Child Healthcare Hospital (Approval Number: SFYLS2020-005) and was performed in accordance with the guidelines of the Declaration of Helsinki (1964). All participants provided written informed consent for their participation in the study. This study was registered at the Chinese Clinical Trial Registry (registration No. ChiCTR2000029577).

Data collection

In this case-control study, eighty women who were diagnosed RSA and 80 women who were age matched with the RSA group and experienced a successful birth history were recruited from the Shenzhen Maternity & Child Healthcare Hospital from August 1^st, 2018 to October 30^th, 2020. Women who diagnosed RSA were defined as having the sequential loss of two or more pregnancies before 20 weeks of pregnancy ¹⁵. Women who had the cardiovascular disease such as diabetes, hypertension, dyslipidemia, or inflammatory diseases which may affect the retinal blood vessels were excluded. Women were also excluded in these situations: (a) symptoms of endocrine or metabolic diseases, (b) abnormal karyotype analysis，(c) uterine abnormality. (d) pregnancy status, (e) two or more embryonic chromosomal abnormalities. The control group had no history of RSA diagnosis.

All participants were signed the informed consent before the retinal images collection. Each participant had a complete medical history. The demographic and clinical data, including age, medical history and retinal images were collected by trained doctors. Body weight (kg) and height (m) were measured and BMI (kg/m2) was calculated.

sample size

We expected to diagnose RSA by ARIS with α=0.025, power 1-β=0.9, AUC0=0.5, AUC1=0.655. Participants whit RAS or not were estimated with a 1:1 sample size. By using the PASS 15 software, 70 participants in each group were included. To estimate a 10% loss to follow-up, 156 participants were enrolled.

Retinal Characteristics

The characteristics of retinal vessels we analysis include retinal vessel characteristics, including vessel diameter, vessel branching angle and bifurcation measures, vessel tortuosity, and fractal dimensions ^16-18 (Figure 1). According to the formula developed by Knudtson et al., the retinal vessel measurements were summarized into central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE), representing the diameters of arterioles and venules respectively¹⁸. The arteriole-to-venule ratio (AVR) was calculated as the ratio of CRAE to CRVE. Vessel tortuosity provides both qualitative and quantitative information by visual grading of one fovea-centered and one disc-centered fundus image. Arteriole-venous nicking results in narrowing of the venule when crossed by an arteriole, and arteriole occlusions referred to the blockage of blood flow inside the arterioles when obstructed by an embolus. The branching pattern of retinal vessels, including bifurcation coefficient (BC), bifurcation angles (BA), and asymmetry of branches, illustrated the relationship between the trunk and the branching vessels, as the ratio of the widths of branching vessels to trunk vessels, the angles between two branching vessels, and the ratio of diameters of two branching vessels, respectively. The fractal dimension (FD) of the retinal vasculature measured the complexity of branching patterns. The analysis was performed using three sets of vessels in one retinal image. Hemorrhages and exudates were recorded as present or absent and indicated in probability (0 to 1). Retinal images were taken on the second day of hospital admission using the SmartScope Ey4 Camera (Optomed, Finland). To ensure the compatibility of the parameters, all the retinal images were scaled to 1365*1024 pixels and saved in the jpg format.

Statistical Analysis

Data like mean and standard deviation (mean± SD) for continuous variables and proportions for categorical variables were described. To analyze the clinical and retinal characteristics, two sample independent t-tests to compare the continuous data and chi-squared tests to compare the categorical data were used. The non-parametric test (Mann-Whitney test) was used, if the normality test showed rejection of the normality assumption. A P-values of less than 0.05 was considered statistically significant. A logistic regression model was used to build classification models. The sensitivity, specificity and area under the curve (AUC) of the ROC curve was evaluated. All the data were analyzed using the Statistical Package for Social Science software (Stata 15.0 (Stata Corp., College Station, TX, USA).

The flowchart of this study is shown in Figure 2. A total of 117 participants experienced RSA were included in this study, and 37 of them were excluded due to failure to meet the inclusion criteria. Then we recruited 80 participants who were age matched with the RSA group and experienced a successful birth history as the control group (Figure 2).

The general characteristics of the participants are summarized in Table 1. Compared to age, height, weight, and BMI index, there were no statistical differences between the RAS group and the control group（P>0.05）.

In the univariate analysis, retinal characteristics such as CRAE (P=0.020), Vasym (P=0.0000), Aasym (P=0.002), Aangle (P=0.035), BCA(P=0.0000), Nicking (P=0.001) and Aocclusion (P=0.001) were statistical significance between the two groups. (Table 2).

The multivariate logistic regression method was built to identify the retinal characteristics of RAS patients. It was shown that the larger central retinal vein equivalent (CRAE (OR: -1.3186 , 95% C.I. -2.291 – -0.346, P=0.008)), asymmetry index of venules（Vasym (OR: 53.382 , 17.697 – 89.0667, P=0.003)), asymmetry index of arterioles (Aasym (OR: 69.284 , 95% C.I. 27.593 – 110.975, P=0.001)）, bifurcation angles of arterioles（Aangle (OR:-0.255 , 95% C.I. -0.509– -0.001, P=0.049)), bifurcation coefficient of arterioles (BCA(OR: -22.712 , 95% C.I. -35.682– -9.742, P=0.001）).（Table 3 ）

The area under the ROC curve for the multivariate logistic regression with retinal characteristics alone was 0.8541 (Figure 3, 95% C.I. 0.796–0.912), the fitting degrees of classic regression models was 59.24%. (Prob> chi2 = 0.5924)

Several studies have showed light to the potential applications of retinal features in gynecological fertility. In a study of Asian retinal microcirculation, elevated blood pressure was associated with a series of changes in retinal arterioles in middle pregnant women, independent of retinal vein diameter and vascular curvature ¹⁹. During the middle trimester, the diameter of maternal retinal arterioles is narrow, and the retinal vascular network is sparse, which affects fetal growth and birth size ²⁰. Lupton, S. J., et al. proposed retinal imaging to characterize physiological vascular changes throughout pregnancy ²¹. This evidences the detection of microcirculation status through retinal vessels in pregnant women. However, these studies focused on the relationship between blood pressure and the second trimester, whereas few studies have been conducted on RSA in early pregnancy or even in prepregnancy thrombosis.

Although the etiology of RSA is complex, current data suggest that factors such as thromboembolism, alloimmunity, and autoimmunity contribute to fetal loss ^22-24. About 66% of RSA patients tend to thrombosis, which is considered an important cause of recurrent abortion ²⁵. Its mechanism is mostly due to the enhancement of coagulation function and the decrease of fibrinolysis, which leads to the formation of uterine spiral artery or villous vessel thrombosis, and decrease in endometrial receptivity and placental perfusion, leading to spontaneous abortion ²⁶. Correcting the abnormal increase in uterine artery blood flow resistance within 10 weeks of gestation can improve the pregnancy outcome ^27,28. This also suggests that to improve the adverse pregnancy outcome, we can start improving uterine artery perfusion. Additionally, early correction of the prethrombotic state in patients with recurrent abortions and increasing in uterine and placental blood supply are of great significance to ensuring the normal growth and development of embryos and reduce the abortion rate. At present, anticoagulant therapy is mainly used for recurrent abortion, which can reduce uterine thrombosis, regulate the coagulation state of the placenta, increase the blood and oxygen supply of embryonic tissue, and reduce adverse pregnancy outcomes ²⁹. At present, the clinical evaluation of RSA is often inaccurate, which leads to problems in the diagnosis of RSA ³⁰. And because the required diagnostic auxiliary tests may be time-consuming, expensive, traumatic, or unavailable in emergency situations, we should develop a simple, accurate, non-invasive and economical objective new measurement method to facilitate clinical diagnosis. To our knowledge, this is the first report to consider the value of retinal features in evaluating RSA.

We envision that certain inflammatory factors or deposited immune complexes present in women with RSA will impair the early pregnancy process, while also damaging the tiny blood vessels in the fundus, thus triggering changes in the retinal blood vessels. Our study preliminarily showed that more changes in retinal arterioles occur in RSA patients than in healthy women. First, our study confirms significant differences in retinal features between patients with RSA and healthy women. These parameters provide the functional characteristics of RSA. Among them, CRVE, Vasym, Aasym, Aangle and BCA performed well in distinguishing the status of RSA vessels from that of normal small vessels and could be regarded as high-risk factors of RSA (P < 0.05).The fundus artery diameter in the RSA group was slightly larger than that in the healthy group, but the arteriovenous ratio was not different, which may be related to the adaptation of the individual to the overall circulatory state..Second, we found that the largest difference in fundus microarteries between groups resulted from arteriolar asymmetry and bifurcation, and resulted from clear BCA differences, indicating morphological changes in the arterioles. Furthermore, the risk of the narrowing of the venule at the crossing point of arteriole and arterial occlusionde was higher in the RSA group than in the healthy group. This all indicates elevated fundus minimal arterial resistance in the patient, reflecting poor arterial perfusion in patients with RSA. At the same time, we found that the protective factors: CRAE, Aangle, and BCA, in which BCA was more significantly different in the two groups, which may be the result of hypercoagulation and compensatory action in RSA patients. Retinal features provide more information than clinical features. Retinal characteristic models can better distinguish between those at risk of miscarriage and those who are healthy. It is conceivable that fundus feature images have potential as imaging biomarkers in the non-invasive diagnosis of RSA. In clinical practice, some special women, such as patients with endometriosis, often with abnormal coagulation indicators after pregnancy, and even reach the drug indication, so the coagulation test after pregnancy is also very necessary. Fundus features examination is to identify patients with potential abortion risk as soon as possible, and get timely intervention and anticoagulant treatment, which may improve the embryo survival rate of these patients, prevent pregnancy complications and improve pregnancy outcome. Of course, whether this model can be used as a basis for detecting the risk of abortion or pre-thrombotic state in pregnant women and IVF-ET patients requires us to collect further evidence and expand the scope of the study ³¹. This is what we are working for the future.

Our research has several limitations. Foremost, due to the relatively small sample size, we did not separate the data for model validation, which needs to be solved in future research. Secondly, because there many factors affect RSA, we not only consider the main influencing factors of retinal characteristics such as thrombotic factors (pregnancy, BIM>30, antiphospholipid syndrome, homocysteine) but also consider some interactive influencing factors (NK, ANA, blocking antibody, anti-SM, HS-DIME). Clinical factors can screen out the influencing factors and build the model with retinal characteristics to improve the ability of the model. Therefore, it is necessary to incorporate the retinal image information and clinical features into the risk assessment model to improve its ability to identify specific events. Finally, this is an observational study, the results can only reveal the potential relationship. Therefore, a prospective cohort is required to determine future relationships.

Our study identified the RSA patients by retinal characteristics without clinical data dimension training. The results show that CRAE, Vasym, Aasym, Aangle and BCA were the retinal characteristics of the RSA patients. This provides the possibility for us to identify RSA earlier.

This study has some limitations. All participants in the study were recruited from the same hospital, which may lead to potential selection bias. Therefore, multicenter clinical studies are necessary in further research. In addition, cross-sectional design resulted in difficulties in causal inference. A larger sample size is needed in further research.

Data Availability

The EXCEL data used to support the findings of this study are available from the corresponding author upon request.

Ethical Approval

This study was approved by the Ethics Committee of the Maternity & Child Healthcare Hospital, Southern Medical University and carried out in accordance with the guidelines of the Declaration of Helsinki (Approval number: SFYLS2020-005).

Consent for publication

All patients provided written informed consent prior to participation in any study-related procedures.

Conflicts of Interest

the authors declare that there are no conflicts of interest regarding the publication of this paper.

Funding: This work was supported by the Sanming Project of Medicine in Shenzhen (No. SZSM201612046); the Shenzhen Science, Technology and Innovation Committee (Natural Science Foundation) (No. JCYJ20210324130001004); the Shenzhen Science, Technology and Innovation Committee (Natural Science Foundation) (No. JCYJ20210324130012031); the Shenzhen Science, Technology and Innovation Committee (Natural Science Foundation) (No. JCYJ20210324130013033); the funders had no role in the study design; data collection, analysis, and interpretation; decision to publish; or preparation of the manuscript.

Supplementary Materials

These are the retinal images of 160 participants recruited in the study. Supplementary for univariate analysis.

Acknowledgment: We thank the Institute of Maternity & Child Healthcare of Shenzhen Maternity & Child Healthcare Hospital for its supervision and support for the implementation of the pilot scheme and safety control. We also thank Shenzhen Maternity & Child Healthcare hospital, Shenzhen Hospital of Traditional Chinese medicine and Guangzhou University of Traditional Chinese medicine for their help and cooperation.

Author contributions: Wu JM and Zhuo YY conceived of the presented idea and planned the experiments. Zhuo YY, Ma F and Ning Y conducted the experiments. Zhuo YY and Ma F designed the computational framework and analyzed the data. Wu JM, LJ and Lin YT wrote the manuscript. All authors discussed the results and contributed to the final manuscript.

Definitions of infertility and recurrent pregnancy loss: a committee opinion. Fertil Steril 2020; 113(3): 533-5."http://doi.org/10.1016/j.fertnstert.2019.11.025"
Diejomaoh M, Jirous J, Al-Azemi M, Baig S, Gupta M, Tallat A. The relationship of recurrent spontaneous miscarriage with reproductive failure. Med Princ Pract 2003; 12(2): 107-11."http://doi.org/10.1159/000069122"
Kaser D. The Status of Genetic Screening in Recurrent Pregnancy Loss. Obstet Gynecol Clin North Am 2018; 45(1): 143-54."http://doi.org/10.1016/j.ogc.2017.10.007"
Vidyadhari M, Sujatha M, Krupa P, Nallari P, Venkateshwari A. Association of genetic polymorphism of vascular endothelial growth factor in the etiology of recurrent pregnancy loss: a triad study. Journal of assisted reproduction and genetics 2019; 36(5): 979-88."http://doi.org/10.1007/s10815-019-01431-y"
Turpin CA, Sakyi SA, Owiredu WK, Ephraim RK, Anto EO. Association between adverse pregnancy outcome and imbalance in angiogenic regulators and oxidative stress biomarkers in gestational hypertension and preeclampsia. BMC Pregnancy Childbirth 2015; 15: 189."http://doi.org/10.1186/s12884-015-0624-y"
Dixon SG, Bruce CT, Glueck CJ, et al. Retinal vascular occlusion: a window to diagnosis of familial and acquired thrombophilia and hypofibrinolysis, with important ramifications for pregnancy outcomes. Clinical ophthalmology (Auckland, NZ) 2016; 10: 1479-86."http://doi.org/10.2147/opth.S106969"
Shoughy SS, Tabbara KF. Ocular findings in systemic lupus erythematosus. Saudi J Ophthalmol 2016; 30(2): 117-21."http://doi.org/10.1016/j.sjopt.2016.02.001"
Yuanyuan Z, Jiaman W, Yimin Q, Haibo Y, Weiqu Y, Zhuoxin Y. Comparison of Prediction Models based on Risk Factors and Retinal Characteristics Associated with Recurrence One Year after Ischemic Stroke. J Stroke Cerebrovasc Dis 2020; 29(4): 104581."http://doi.org/10.1016/j.jstrokecerebrovasdis.2019.104581"
Zhuo Y, Wu J, Qu Y, et al. Clinical risk factors associated with recurrence of ischemic stroke within two years: A cohort study. Medicine 2020; 99(26): e20830."http://doi.org/10.1097/md.0000000000020830"
Zhuo YY, Wu JM, Kuang L, et al. The Discriminative Efficacy of Retinal Characteristics on Two Traditional Chinese Syndromes in Association with Ischemic Stroke. Evid Based Complement Alternat Med 2020; 2020: 6051831."http://doi.org/10.1155/2020/6051831"
Li M, Wang G, Xia H, Feng Z, Xiao P, Yuan J. Retinal vascular geometry detection as a biomarker in diabetes mellitus. European journal of ophthalmology 2022; 32(3): 1710-9."http://doi.org/10.1177/11206721211033488"
Betzler BK, Sabanayagam C, Tham YC, et al. Retinal vascular profile in predicting incident cardiometabolic diseases among individuals with diabetes. Microcirculation (New York, NY : 1994) 2022; 29(4-5): e12772."http://doi.org/10.1111/micc.12772"
Huang KK, Huang S, Yun WW, Zhang ZX, Jia YW, Zhang M. [Correlation between total cerebral small vessel disease score and retinal vessel diameters in patients with mild stroke]. Zhonghua yi xue za zhi 2021; 101(1): 62-7."http://doi.org/10.3760/cma.j.cn112137-20200405-01088"
Gao R, Zeng X, Qin L. Systemic autoimmune diseases and recurrent pregnancy loss: research progress in diagnosis and treatment. Chinese medical journal 2021; 134(17): 2140-2."http://doi.org/10.1097/cm9.0000000000001691"
Evaluation and treatment of recurrent pregnancy loss: a committee opinion. Fertility and sterility 2012; 98(5): 1103-11."http://doi.org/10.1016/j.fertnstert.2012.06.048"
Yatsuya H, Folsom AR, Wong TY, Klein R, Klein BE, Sharrett AR. Retinal microvascular abnormalities and risk of lacunar stroke: Atherosclerosis Risk in Communities Study. Stroke 2010; 41(7): 1349-55."http://doi.org/10.1161/strokeaha.110.580837"
Patton N, Aslam T, Macgillivray T, Pattie A, Deary IJ, Dhillon B. Retinal vascular image analysis as a potential screening tool for cerebrovascular disease: a rationale based on homology between cerebral and retinal microvasculatures. J Anat 2005; 206(4): 319-48."http://doi.org/10.1111/j.1469-7580.2005.00395.x"
Knudtson MD, Lee KE, Hubbard LD, Wong TY, Klein R, Klein BE. Revised formulas for summarizing retinal vessel diameters. Curr Eye Res 2003; 27(3): 143-9."http://doi.org/10.1076/ceyr.27.3.143.16049"
Li LJ, Cheung CY, Ikram MK, et al. Blood pressure and retinal microvascular characteristics during pregnancy: Growing Up in Singapore Towards Healthy Outcomes (GUSTO) Study. Hypertension (Dallas, Tex : 1979) 2012; 60(1): 223-30."http://doi.org/10.1161/hypertensionaha.112.195404"
Li LJ, Aris I, Su LL, et al. Associations of maternal retinal vasculature with subsequent fetal growth and birth size. PloS one 2015; 10(4): e0118250."http://doi.org/10.1371/journal.pone.0118250"
Lupton SJ, Tooher J, Hodgson LA, et al. OS010. Use of retinal imaging to characterise physiological vascularchanges throughout pregnancy. Pregnancy hypertension 2012; 2(3): 179-80."http://doi.org/10.1016/j.preghy.2012.04.011"
Rajagopal R, Apte RS. Seeing through thick and through thin: Retinal manifestations of thrombophilic and hyperviscosity syndromes. Survey of ophthalmology 2016; 61(2): 236-47."http://doi.org/10.1016/j.survophthal.2015.10.006"
Li J, Fong S, Sung Y, Cho K, Wong R, Wong KKL. Adaptive swarm cluster-based dynamic multi-objective synthetic minority oversampling technique algorithm for tackling binary imbalanced datasets in biomedical data classification. BioData Min 2016; 9: 37."http://doi.org/10.1186/s13040-016-0117-1"
Lattová V, Dostál J, Pešková M, Sobek A, Jr., Procházka M. [Recurrent implantation failure and thrombophilia]. Ceska gynekologie 2015; 80(1): 5-10
Pandey MK, Thakur S, Agrawal S. Lymphocyte immunotherapy and its probable mechanism in the maintenance of pregnancy in women with recurrent spontaneous abortion. Arch Gynecol Obstet 2004; 269(3): 161-72."http://doi.org/10.1007/s00404-003-0560-3"
Tessier DR, Yockell-Lelièvre J, Gruslin A. Uterine Spiral Artery Remodeling: The Role of Uterine Natural Killer Cells and Extravillous Trophoblasts in Normal and High-Risk Human Pregnancies. Am J Reprod Immunol 2015; 74(1): 1-11."http://doi.org/10.1111/aji.12345"
Janiak E, Fulcher IR, Cottrill AA, et al. Massachusetts' Parental Consent Law and Procedural Timing Among Adolescents Undergoing Abortion. Obstet Gynecol 2019; 133(5): 978-86."http://doi.org/10.1097/aog.0000000000003190"
Campbell S, Black RS, Lees CC, Armstrong V, Peacock JL. Doppler ultrasound of the maternal uterine arteries: disappearance of abnormal waveforms and relation to birthweight and pregnancy outcome. Acta Obstet Gynecol Scand 2000; 79(8): 631-4
Maged AM, Abdelhafiz A, Mostafa WA, et al. The role of prophylactic use of low dose aspirin and calheparin in patients with unexplained recurrent abortion. Gynecol Endocrinol 2016; 32(12): 970-2."http://doi.org/10.1080/09513590.2016.1203408"
Pereza N, Ostojić S, Kapović M, Peterlin B. Systematic review and meta-analysis of genetic association studies in idiopathic recurrent spontaneous abortion. Fertil Steril 2017; 107(1): 150-9.e2."http://doi.org/10.1016/j.fertnstert.2016.10.007"
Cahen-Peretz A, Haas J, Hadi E, Carp H, Hershko Klement A. Cancer diagnosis among women with recurrent pregnancy loss: a retrospective cohort study. Reproductive biomedicine online 2021; 43(6): 1057-62."http://doi.org/10.1016/j.rbmo.2021.08.001"

Tables 1 to 3 are available in the Supplementary Files section.

Table1.pdf
Table 1 RSA, recurrent Spontaneous Abortion; BMI, body mass index; Normal distribution data are represented by (mean ± standard deviation), and non-normal distribution data are represented by median (third quartile, first quartile)
Table2.pdf
Table 2 Note: Nicking, the narrowing of venule at the crossing point of the arteriole; Aocclusion, arteriole occlusion; Tortuosity, tortuosity; Aasym, asymmetry index of arterioles; Vasym, asymmetry index of venules; BCV, bifurcation coefficient of venule; BCA, bifurcation coefficient of arterioles; Vangle, bifurcation angles of venule; Aangle, bifurcation angles of arterioles; CRAE, central retinal artery equivalent; CRVE, central retinal vein equivalent. AVR, CRAE to CRVE ratio; FDv, the fractal dimension of the retinal vasculature; arterioles FDa, the fractal dimension of the retinal arterioles. The p-value with a * represents nonparametric test of matched pair data (Wilcoxon Signed-Rank Test), others use paired t-test. ****represents P＜0.000,**represents P＜0.01,*represents P＜0.05.
Table3.pdf
Table 3 Note: The p-value with a * represents nonparametric test of matched pair data (Wilcoxon Signed-Rank Test), others use paired t-test. **represents P＜0.01,*represents P＜0.05.

Download PDF

Version 1

posted

You are reading this latest preprint version

Characteristics of Retinal Image in Women with Recurrent Spontaneous Abortion

Status:

Version 1

Abstract

Purpose

Methods

Results

Conclusions

Figures

Introduction

Material And Methods

Results

Discussion

Conclusion

Limitations

Declarations

References

Tables

Supplementary Files

Status:

Version 1