Comparation of magnetic resonance hysterosalpingography and hysterosalpingosonography for the assessment of fallopian tubal occlusion of female infertility: A protocol for systematic review and meta-analysis.

OBJECTIVE: To evaluate the diagnostic performance of magnetic resonance hysterosalpingography (MR-HSG) for fallopian tubal occlusion in the context of female infertility when compared to the diagnostic performance of hysterosalpingosonography in evaluation of fallopian tubal occlusion of female infertility.
METHODS: We will search PubMed, Web of Science, Cochrane Library, and Chinese biomedical databases from their inceptions to the October 31, 2021, without language restrictions. Two authors will independently carry out searching literature records, scanning titles and abstracts, full texts, collecting data, and assessing risk of bias. Review Manager 5.2 and Stata14.0 software will be used for data analysis.
RESULTS: This systematic review will investigate whether MR-HSG has more diagnostic value than hysterosalpingosonography in evaluation of fallopian tubal occlusion of female infertility.
CONCLUSION: Our meta-analysis indicated MR-HSG may serve as an alternative for further evaluation of fallopian tubal occlusion of female infertility. SYSTEMATIC REVIEW REGISTRATION: INPLASY2021110050.

Introduction

In recent years, the incidence of infertility has been on the rise, and tubal subfertility or infertility is credited with up to 30% of the etiology of infertility.[ The main factors that cause fallopian tubal infertility include pelvic inflammation, endometriosis, mycoplasma infection, history of pelvic and abdominal surgery, and congenital anatomical abnormalities.[ An assessment of fallopian tube patency is an important part of infertility. Laparoscopic examination and conventional X-ray hysterosalpingography (X-HSG) are accepted as the gold standard for that purpose. Laparoscopic examination can achieve the purpose of diagnosis of fallopian tubal occlusion. However, it is still invasive and expensive, which is not easy to be accepted by patients.[ X-HSG is the most commonly used in the clinic to diagnose fallopian tubal occlusion. However, the main disadvantages of this technique are the exposure of the human body to ionizing radiation and adverse reactions to iodine and meanwhile has a low sensitivity for the diagnosis of pelvic adhesions, which is why it cannot replace laparoscopy. In addition, many doctors do not recommend the use of this method because patients are unable to have sex for 3 months after the examination and there is a risk of pulmonary embolism.[

Magnetic resonance hysterosalpingography (MR-HSG) is a novel technique used in evaluating tubal patency with very few pioneering studies at both national and international levels, which is less invasive and avoids exposure of ovaries to ionizing radiation. Having the inherent advantage of magnetic resonance in imaging the pelvis, MR-HSG is an innovative tool for female infertility evaluation and may be used as a one-stop investigation tool in detecting uterine, ovarian, and tubal pathologies.[ Jagannathan D et al had assessed that the diagnostic accuracies of MR-HSG and conventional X-ray HSG (X-HSG) in identifying tubal patency in women with infertility. They concluded that pelvic MRI is an inevitable tool in infertility evaluation, and MR-HSG can be used in addition as it avoids exposure of the reproductive organs to radiation and has the same efficacy as X-HSG.[ Li YZ et al had studied that Compared with the conditional X-HSG (the imaging gold standard), the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio and the area under the curve of MR-HSG for tubal occlusion were 0.91 (95% CI: 0.48–0.99), 1.00 (95% CI: 0.87–1.00), 230.47 (95% CI: 6.79–7824.72), 0.09 (95% CI: 0.01–0.80), 2676.10 (95% CI: 61.35–120000), and 1.00 (95% CI: 0.99–1.00), respectively. Subgroup analyses revealed that viscosity of contrast agent (P = .024) and test order (P = .036) affected the accuracy of MR-HSG to evaluate tubal occlusion. They concluded that the study indicated MR-HSG may serve as an alternative for further evaluation of fallopian tubal occlusion of female infertility. However, MR-HSG is not commonly used in the clinic to evaluate the tubal occlusion in the context of female infertility, and the diagnostic accuracy of MR-HSG is not convincing due to the relatively small number of patients who have been assessed.[

In recent years, hysterosalpingosonography (Sono-HSG) has been increasingly employed. This technique is well tolerated and easily performed and it may not only assess tubal patency but also detect uterine cavity anomalies. In addition, the technique allows simultaneous observation of the ovary and myometrium, avoiding ionizing radiation. Two-dimensional hysterosalpingo-contrast-sonography (2D-HyCoSy) and three/four-dimensional hysterosalpingo-contrast-sonography (3D/4D-HyCoSy) have been applied in fallopian tubal occlusion in women with infertility.[ Alcázar JL et al showed pooled estimated sensitivity and specificity of 2D-HyCoSy were 86 (95% CI = 80%–91%) and 94% (95% CI = 90%–96%), respectively. The corresponding figures for 3D/4D-HyCoSy were 95% (95% CI = 89%–98%) and 89% (95% CI = 82%–94%). High heterogeneity was found for both sensitivity and specificity. No statistically significant differences were found between the methods (P = .13). So that they concluded that 2D-HyCoSy has a similar diagnostic performance to 3D/4D-HyCoSy. However, the main limitation of Sono-HSG is that the accuracy of inspection results is largely related to the operator's experience, which means that it has certain subjective factors and is largely dependent on the level of the operators.[

High-quality Meta-analysis has been increasingly regarded as one of the key tools for achieving evidence. Therefore, the present meta-analysis aims to evaluate whether MR-HSG is more effective than Sono-HSG in the diagnosis of female infertility with fallopian tubal obstruction.

Materials and methods

This study was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta Analyses) guidelines and the protocol was registered in the INPLASY (INPLASY2021110050).

Eligibility criteria

Type of study

This study will only include high quality clinical cohort or case control studies that evaluate the diagnostic performance of MR-HSG when compared to Sono-HSG in evaluation of fallopian tubal occlusion of female infertility.

Type of patients

The patients should be those who had undergone fallopian tubal occlusion of female infertility.

Intervention and comparison

Fallopian tubal occlusion of female infertility of all patients were assessed with Laparoscopic examination or conventional X-HSG.

Type of outcomes

The primary outcomes include a semi-quantitative scoring system, through which fallopian tubal occlusion of female infertility was graded by means of both MR-HSG and Sono-HSG.

Search methods

PubMed, Web of Science, Cochrane Library, and Chinese biomedical databases will be searched from their inceptions to the October 31, 2021, without language restrictions. The search strategy for PubMed is shown in Table 1. Other online databases will be used in the same strategy.

Table 1

Search strategy sample of PubMed.

Number	Search terms
1	Fallopian tubal occlusion of female infertility or female infertility
2	Hysterosalpingography or HSG
3	Magnetic resonance Hysterosalpingography or MR-HSG
4	Hysterosalpingosonography or Sono-HSG or hysterosalpingo-contrast-sonography or HyCoSy
5	and 1–4

Data extraction and quality assessment

Two authors will independently select the trials according to the inclusion criteria, and import into Endnote X9. Then remove duplicated or ineligible studies. Screen the titles, abstracts, and full texts of all literature to identify eligible studies. All essential data will be extracted using previously created data collection sheet by 2 independent authors. Discrepancies in data collection between 2 authors will be settled down through discussion with the help of another author. The following data will be extracted from each included research: year of article, first author's surname, sample size, number of every grade. The quality of selected studies will be independently evaluated according to a tool for the quality assessment of methodological index for non-randomized studies (MINORS). The MINORS criteria included 12 assessment items. Each of these items is scored as “yes” (2), “no” (0), or “unclear” (1). MINORS score ranged from 0 to 24; and score ≥17 indicate a good quality. Any disagreements between 2 investigators will be solved through discussion or consultation by a 3rd investigator.

Statistical analysis

The STATA version 15.1 software (Stata Corporation, College Station, TX, USA) will be used for meta-analysis. We calculated the pooled summary odds ratio (OR) and its 95% confidence interval (CI). The Cochran's Q-statistic and I2 test will be used to evaluate potential heterogeneity between studies.[ If the Q-test shows a P < .05 or I2 test exhibits >50%, indicating significant heterogeneity, and the random effect model will be employed or if heterogeneity is not significant, the fixed-effects model was used. If it is possible, we will perform meta-analysis to analyze the pooled outcome data when acceptable homogeneity has been identified. Otherwise, we will conduct subgroup analysis to investigate potential causes for substantial heterogeneity among eligible studies. Sensitivity analysis will be performed to evaluate the influence of a single study on the overall estimate. We will use Begger's funnel plots and Egger's linear regression test to investigate publication bias.[

Discussion

A patient should present with failure to achieve a successful pregnancy after 12 months or more of regular unprotected intercourse in a woman under the age of 35 years and 6 months without success in a woman 35 or older in order to suspect infertility.[ WHO estimated that infertility affects 50 to 80 million women worldwide and 11.3% of married women with only 35% of these presenting for medical assistance.[ The anatomy of the fallopian tube is complex starting from its embryological development and continuing with its vascular supply and ciliated microstructure, that is the key to the process of egg transport to the site of fertilization. There are many strongly documented causes of tubal infertility: infections (Chlamydia Trachomatis, Gonorrhea, and genital tuberculosis), intrauterine contraceptive devices, endometriosis, and complications after abdominal surgery, etc[ As a result, the meta-analysis is devoted to evaluating the diagnostic performance of MR-HSG compared to the Sono-HSG in evaluation of fallopian tubal occlusion of female infertility.

Some authors have studied MR-HSG for the evaluation of the uterine cavity, tubal shape, tubal occlusion and other pelvic causes of female infertility. The first MR-HSG trial dates back to 1996 when Fred et al evaluated its efficacy in 18 rabbit uterine horns. Five of the fallopian tubes were lit and 11 were left unaltered. MR-HSG showed concurrent results in 14 of the 16 cases. Sensitivity and specificity of MR-HSG were 95.5% and 70%, respectively, for tubal blocks. The use of MR-HSG in pelvic magnetic resonance in cases of infertility protocols has a great way in the future.[ It can replace X-HSG and can be the one-stop investigation method for identifying uterine lesions, structural abnormalities, tubal status, and ovaries in female infertility workup. In addition, it also has the added advantage of avoidance of radiation exposure to the potential reproductive organs and use of highly diluted contrast.[ Sono-HSG has been advocated as the initial step for assessing tubal patency in women presenting with infertility. The technology is free of ionizing radiation as well as has real-time dynamic imaging and, so it is commendably tolerated by patients and widely used in clinical practice. There are multiple modes to choose from. We can use 2D real-time ultrasound, 3D static ultrasound or 4D real-time ultrasound for diagnosis. Some scholars (Dreyer et al, 2014; Hamed et al, 2009) have demonstrated that its diagnostic performance is similar to X -HSG. After two-dimensional ultrasound scanning, the observed area was reconstructed in a certain spatial and temporal order, so that the morphology in the fallopian tube lumen could be clearly, continuously and dynamically displayed, and the false image caused by fallopian tube spasm or peristalsis could be avoided. In addition, the method is also helpful for doctors to observe the diffusion of contrast agent in pelvic cavity, increase the richness of diagnostic information, and improve the efficiency of diagnosis.[

From what has been discussed above, the results of these studies have been contradictory. Just to clarify, in this study, we will perform a systematic review to summarize high-quality studies. The desired meta-analysis should include all current relevant, high-quality, homogenous studies, without publication bias, and use appropriate models and correct statistical methods. After the completion of the system review, it is also necessary to constantly improve practical work, including:

acceptance of clinical practice test and evaluation of clinicians;

accept the cost-benefit evaluation;

Pay attention to the emerging clinical studies, and reevaluate the systematic evaluation in time. Only when clinicians master the method of systematic evaluation, can they provide evidence for various clinical problems in their specialty, and evidence-based medicine can develop smoothly.[

Acknowledgments

We would like to thank all our colleagues working in the First Affiliated Hospital to Dalian Medical University.

Author contributions

Conceptualization: Cong Wang.

Data curation: Jili Zhang.

Formal analysis: Jili Zhang.

Funding acquisition: Cong Wang.

Investigation: Jinyi Bian, Xiaopeng Zhang.

Methodology: Cong Wang.

Project administration: Cong Wang.

Resources: Jinyi Bian, Xiaopeng Zhang.

Software: Jili Zhang, Jinyi Bian, Xiaopeng Zhang.

Supervision: Jili Zhang, Jinyi Bian.

Validation: Jili Zhang, Jinyi Bian.

Visualization: Cong Wang.

Writing – original draft: Jili Zhang.

Writing – review & editing: Jili Zhang, Xiaopeng Zhang.