Method for evaluating chronic endometritis of infertility patient based on hysteroscope score

Abstract

The invention discloses an infertility patient chronic endometritis assessment method based on hysteroscope scoring, and relates to the technical field of medical treatment. The method for evaluating the chronic endometritis of the infertility patient based on the hysteroscope score comprises the following steps: step 1, detecting the uterine cavity of the patient by adopting a hysteroscope examination mode; 2, judging CE specific expression of the patient under a hysteroscope; step 3, carrying out CD138 immunohistochemical detection on endometrial tissues of the patient; step 4, carrying out statistical analysis by adopting software SPSS22.0 and R4.1. 2; compared with the prior art, the CE specificity performance of a patient under the hysteroscope is examined in a hysteroscope examination mode, the hysteroscope scoring system is constructed, observation indexes in the hysteroscope scoring system can be easily mastered after learning, the hyperemia area can be divided according to the uterine cavity six-equal-division method even under the condition that no measuring tool under the hysteroscope exists, and popularization is convenient.

Description

Technical Field

[0001] The present invention relates to the field of medical technology, and in particular to a method for evaluating chronic endometritis in infertile patients based on hysteroscopic scoring. Background Art

[0002] CE is a chronic inflammation of the endometrium characterized by endometrial stromal plasma cell infiltration. Most studies have shown that CE is closely related to poor reproductive outcomes, but after antimicrobial treatment, the pregnancy rate of patients with cured CE is higher than that of patients with persistent CE. Because CE has no obvious clinical symptoms and is not easily identified by ultrasound, it is currently diagnosed through histological examination, hysteroscopy, microbiological testing, and other methods.

[0003] Hysteroscopy has the advantages of being simple, intuitive, and comprehensive. However, due to the lack of standardized diagnostic criteria, the sensitivity and specificity of hysteroscopy in diagnosing CE reported in the literature fluctuate greatly, ranging from 35.3% to 100.0% and 56.0% to 92.5%, respectively. In 2019, Cicineli et al. developed a diagnostic standard for hysteroscopy of CE, which improved the accuracy and consistency of hysteroscopy in diagnosing CE. However, the standard lacks quantitative indicators, and the doctor's subjective influence is relatively large during diagnosis. Summary of the invention

[0004] In view of the deficiencies of the prior art, the present invention provides a method for evaluating chronic endometritis in infertile patients based on hysteroscopic scoring, which solves the existing problems.

[0005] To achieve the above objectives, the present invention is implemented by the following technical scheme: a method for evaluating chronic endometritis in infertile patients based on hysteroscopic scoring, comprising the following steps:

[0006] Step 1: Use hysteroscopy to examine the patient's uterine cavity and observe the congestion area, micropolyps and interstitial edema of the patient's uterine cavity;

[0007] Step 2: Determine the patient's hysteroscopic CE-specific manifestations;

[0008] Step 3: Perform CD138 immunohistochemistry on the patient's endometrial tissue;

[0009] Step 4: SPSS22.0 and R4.1.2 software were used for statistical analysis;

[0010] Step 5: Use univariate and binary logistic regression equations to screen independent risk factors, and construct a hysteroscopic scoring system based on the screened independent risk factors.

[0011] Preferably, the hysteroscopy method comprises the following steps:

[0012] S1: routine disinfection and endoscope insertion, uterine distension with isotonic sodium chloride solution and the distension pressure is maintained at 80-110 mmHg (1 mmHg = 0.133 kPa);

[0013] S2: Observe the uterine fundus, both uterine horns and the four walls of the uterine cavity. Keep the field of vision parallel to the surface of the endometrium as much as possible. Observe the congested area, micropolyps, interstitial edema, etc.

[0014] S3: Use endoscopic forceps to grab a small amount of endometrium from the above severe areas for biopsy.

[0015] Preferably, the hysteroscopic CE-specific manifestation judgment criteria include congestion area, micropolyps, endometrial polyps and interstitial edema.

[0016] Preferably, the congestion area is determined as follows: the uterine cavity area is divided into six equal parts, that is, the uterine cavity is divided into two parts along the coronal plane of the uterus using the line connecting the openings of the bilateral fallopian tubes; with the midpoint of the line as the starting point and the internal cervical os as the end point, the two parts of the uterine cavity are radially divided into three equal parts along the uterine wall, for a total of six parts, regardless of whether it is point-like congestion, lamellar congestion or mixed congestion, one-sixth of the uterine cavity area is used as a reference to calculate the proportion of the total congestion area to the uterine cavity area, and a congestion area equal to 0 is level 0, 0 to <1 / 6 is level 1, 1 / 6 to <1 / 3 is level 2, 1 / 3 to <1 / 2 is level 3, and ≥1 / 2 is level 4.

[0017] Preferably, the micropolyp is judged as having a diameter less than 1 mm and having a distinct vascular axis.

[0018] Preferably, the endometrial polyp is judged as a cone-shaped or finger-shaped growth, and endometrial stroma, glands and thick blood vessels can be seen under a pathological examination microscope.

[0019] Preferably, the interstitial edema is judged as: pale and thick intima (proliferative stage).

[0020] Preferably, the method of CD138 immunohistochemical detection is:

[0021] 1) Rinse the blood stains on the surface of the endometrium, fix it with 10% neutral formaldehyde solution, dehydrate it, make it transparent, embed it in paraffin, and slice it;

[0022] 2) CD138 immunohistochemical staining;

[0023] 3) Randomly observe 30 high-power fields in the area with the strongest staining intensity;

[0024] 4) CE was diagnosed when 5 or more typical plasma cells were observed in the endometrial stroma in at least one high-power field.

[0025] Beneficial Effects

[0026] The present invention provides a method for evaluating chronic endometritis in infertile patients based on hysteroscopic scoring.

[0027] Compared with the prior art, it has the following beneficial effects:

[0028] 1. This method for evaluating chronic endometritis in infertile patients based on hysteroscopic scoring examines the patient's hysteroscopic CE-specific manifestations through hysteroscopic examination and constructs a hysteroscopic scoring system. The observation indicators in the hysteroscopic scoring system can be easily mastered after learning. Even in the absence of hysteroscopic measurement tools, the congested area can be divided according to the six-equal division of the uterine cavity, which is easy to promote.

[0029] 2. This method for evaluating chronic endometritis in infertile patients based on hysteroscopic scoring has improved the diagnostic criteria for hysteroscopic CE by establishing a hysteroscopic scoring system. It is a powerful supplement to the current diagnosis of CE based on histological CD138 positivity, indicating that the scoring system has good stability. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] Figure 1 It is a schematic diagram of the method flow of the present invention. DETAILED DESCRIPTION

[0031] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0032] See Figure 1 , the present invention provides the following four technical solutions:

[0033] The first embodiment: a method for evaluating chronic endometritis in infertile patients based on hysteroscopic scoring, comprising the following steps:

[0034] Step 1: Use hysteroscopy to examine the patient's uterine cavity and observe the congestion area, micropolyps and interstitial edema of the patient's uterine cavity;

[0035] Step 2: Determine the patient's hysteroscopic CE-specific manifestations;

[0036] Step 3: Perform CD138 immunohistochemistry on the patient's endometrial tissue;

[0037] Step 4: SPSS22.0 and R4.1.2 software were used for statistical analysis. After the data normal distribution test, the measurement data were all non-normally distributed and expressed as median (upper and lower quartiles) [M(Q1, Q3)]. Non-parametric tests were used for inter-group comparisons. Count data were expressed as number of cases (percentage) [n(%)]. Pearson chi-square test, continuity correction or Fisher's exact test were used for inter-group comparisons.

[0038] Step 5: Use univariate and binary logistic regression equations to screen independent risk factors, and construct a hysteroscopic scoring system based on the screened independent risk factors.

[0039] Second embodiment: the method of hysteroscopy

[0040] Preoperative preparation

[0041] ① All patients underwent hysteroscopy during the endometrial hyperplasia phase (3-7 days after menstruation);

[0042] ②Sign the informed consent form for laparoscopy;

[0043] ③Exclude sexual intercourse, fever, and acute inflammation;

[0044] ④Urine pregnancy test is negative.

[0045] Surgical method

[0046] ① Anesthesia method: Patients voluntarily choose painless hysteroscopy or hysteroscopy without anesthesia, and the anesthesia method is intravenous propofol anesthesia.

[0047] ② Uterine distension and perfusion: The distension fluid is 5% mannitol or 0.9% saline, and the distension pressure is 80-110 mmHg.

[0048] ③Surgical steps: The patient takes the lithotomy position, routinely disinfects the vulva and vagina with iodine cotton balls, spreads a sterile drape, inserts a vaginal speculum, cleans the external cervical opening again, connects the hysteroscope system, and the hysteroscope to perform an orderly exploration of the uterine cavity for the first time, first exploring the cervical canal, then entering the uterine cavity to explore the bilateral uterine horns, and then exploring the uterine fundus and the left and right anterior and posterior walls. During the hysteroscopic examination, the anterior and posterior walls of the uterus are thoroughly examined along the surface of the endometrium to obtain a field of view parallel to the surface of the endometrium, so that irregularities on the surface of the endometrium can be easily discovered. At the same time, the uterine cavity performance under hysteroscopy is recorded, and the hysteroscopic examination pictures are saved.

[0049] ④ Observation contents: endometrial congestion or bleeding spots, glandular vascular thickening or spider-web dilatation, endometrial micropolyps, endometrial hyperplasia, and intrauterine mucus. The sensitivity and specificity of hysteroscopy were evaluated with pathological diagnosis as the gold standard.

[0050] Diffuse endometrial congestion: Diffuse endometrial congestion, the area is greater than 50% of the uterine cavity area;

[0051] Focal endometrial hyperemia: Focal endometrial hyperemia with an area less than 50% of the uterine cavity area and a diameter greater than 2 cm;

[0052] Endometrial vascular enlargement: endometrial vascular axonal vessels or spider web-like capillary dilation;

[0053] Endometrial punctate hyperemia: The endometrium is punctately hyperemic, with more than 5 hyperemic spots under the microscope;

[0054] Intrauterine mucus: viscous fluid in the uterine cavity that is difficult to flush out of the uterine cavity by uterine distension fluid.

[0055] ⑤ Laparoscopic video analysis is performed by two hysteroscopists (associate chief physician / attending physician + resident physician) to jointly complete the hysteroscopic diagnosis, and the one with the highest professional title determines the score.

[0056] ⑥ Acquisition and preservation of endometrial tissue: For those suspected of endometritis or endometrial thickening after hysteroscopy, scrape the diseased tissue with a curette or biopsy forceps, fix the endometrial specimen with formalin, and send it for pathological examination for hematoxylin-eosin staining and CD138 immunohistochemical staining. The gold standard for the diagnosis of endometritis is pathological diagnosis. The diagnosis of chronic endometritis is related to the detection of the number of plasma cells in the endometrial stroma, as well as changes in secondary characteristics such as neutrophilia and lymphocytosis in the endometrium and glandular cavity. Transmembrane heparin sulfate proteoglycan synthase-1 (syndecan.1, CD138) is a special marker for plasma cells, which can improve the diagnostic rate of chronic endometritis compared with conventional hematoxylin-eosin staining.

[0057] ⑦ Postoperative treatment and precautions: Oral antibiotics (clarithromycin 500 mg) were given at the end of the examination, and bathing and sexual intercourse were prohibited for 2 weeks.

[0058] ⑧Adverse events observed included uterine perforation, bleeding, infection, water intoxication, and induced abortion syndrome.

[0059] Endometritis diagnosis method

[0060] After hysteroscopy, all patients underwent endometrial biopsy with a curette, and the removed endometrial tissue was stained with HE and immunohistochemistry for CD138. Endometrial pathology is considered the gold standard for diagnosing endometrial lesions.

[0061] IIE staining diagnostic criteria:

[0062] ①1① Diagnosis of CE: Typical plasma cells are seen in the endometrial stroma, with basophilic cytoplasm, nuclei biased to one side, dark nuclear staining, and wheel-shaped nuclei under high magnification;

[0063] ② Suspected diagnosis of CE: no typical plasma cells were found in the endometrial hematoxylin and eosin red staining, the endometrial stromal cells were spindle-shaped, similar to fibrosis, and lymphocytes were concentrated in the endometrial stromal cells;

[0064] ② 2② Non-CE, none of the above situations were observed.

[0065] CD138 immunohistochemistry diagnostic criteria:

[0066] ① To diagnose CE, 5 or more typical plasma cells were observed in the endometrial stroma under 400x high-power microscope;

[0067] ② For non-CE, 30 high-power fields were randomly observed in the area with the strongest staining intensity in the endometrial CD138 immunohistochemical staining specimens. If less than 5 plasma cells or no typical plasma cells were found, the sensitivity, specificity, positive predictive value and negative predictive value of hysteroscopy for diagnosing chronic endometritis were calculated based on the pathology report.

[0068] The third implementation method: clinical pathological factors and hysteroscopic manifestations related to CE

[0069] The results of univariate analysis showed that there were no significant differences in clinical pathological factors such as baseline hormone levels, history of ectopic pregnancy, and history of miscarriage between the CE group and the non-CE group (all P>0.05); however, there were significant differences in the grade of congestion area and micropolyps under hysteroscopy between the CE group and the non-CE group (all P<0.01).

[0070] Ectopic pregnancy itself is a high-risk pregnancy condition, not a "high-risk factor" for a certain disease or condition in the traditional sense. However, there are some high-risk factors for ectopic pregnancy, and ectopic pregnancy itself also brings many high-risk risk conditions. Inflammation can cause adhesion of the fallopian tube mucosa, stenosis of the lumen, and damage to the cilia, resulting in obstruction of the fertilized egg's movement in the fallopian tube and implantation in the fallopian tube, increasing the risk of ectopic pregnancy. Whether ectopic pregnancy is treated conservatively or surgically, it may cause certain damage to the reproductive organs and affect reproductive function.

[0071] Combined with clinical data, the history of ectopic pregnancy, grade of congestion area, and micropolyps were included in the binary logistic regression analysis. The results showed that they were all independently associated with CE (all P<0.05). Therefore, the history of ectopic pregnancy, grade of congestion area, and micropolyps were included in the hysteroscopic evaluation system.

[0072] A hysteroscopic scoring system was constructed with congestion area grade, micropolyps, and history of ectopic pregnancy as independent variables, and a hysteroscopic scoring model was obtained. A calibration curve was drawn based on the probability of CE predicted by the hysteroscopic scoring system and the actual probability of CE. The results showed that the calibration curve and the ideal curve had a good fit, indicating that the model has good prediction accuracy.

[0073] The results of ROC curve analysis showed that the AUC value of the above hysteroscopic scoring model for diagnosing CE was 0.801 (95% CI: 0.742-0.861), the optimal threshold was -0.93, the sensitivity was 74.0%, the specificity was 73.9%, and the model's predictive ability was moderate.

[0074] A calibration curve was drawn based on the probability of CE predicted by the hysteroscopic scoring system and the actual probability of CE. The results showed that the calibration curve and the ideal curve had a good fit, indicating that the model has good predictive accuracy.

[0075] The fourth implementation method:

[0076] Methods: A case-control study was conducted in 238 infertile patients who underwent hysteroscopy and endometrial biopsy in the Reproductive Center of Shijiazhuang Maternity and Childbirth Hospital from October 1 to December 31, 2019. They were divided into CE group (73 cases) and non-CE group (165 cases) according to the results of CD138 immunohistochemistry staining. Univariate and binary logistic regression were used to screen the independent risk factors affecting CE, and a hysteroscopy scoring system was established.

[0077] Results: The results of univariate and binary logistic regression analysis showed that congestion area of ​​grade 2 or above, micropolyps, and history of ectopic pregnancy were independent risk factors for CE (all P<0.05).

[0078] Conclusion: The hysteroscopic scoring system consisting of congestion area, micropolyps, and history of ectopic pregnancy can effectively, simply, and intuitively predict the occurrence of CE in infertile patients, which is helpful to improve the diagnostic criteria of hysteroscopic CE and effectively make up for the shortcomings of histological diagnosis.

[0079] Meanwhile, the contents not described in detail in this specification belong to the prior art known to those skilled in the art, and the model parameters of each electrical appliance are not specifically limited, and conventional equipment can be used.

[0080] It should be noted that, in this article, relational terms such as first and second, etc. are only used to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Moreover, the terms "include", "comprise" or any other variants thereof are intended to cover non-exclusive inclusion, so that a process, method, article or device including a series of elements includes not only those elements, but also other elements not explicitly listed, or also includes elements inherent to such process, method, article or device.

[0081] Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions and variations may be made to the embodiments without departing from the principles and spirit of the present invention, and that the scope of the present invention is defined by the appended claims and their equivalents.

Claims

1. A method for evaluating chronic endometritis in infertile patients based on hysteroscopic scoring, characterized in that: The following steps are involved: Step 1: Use hysteroscopy to examine the patient's uterine cavity and observe the congestion area, micropolyps and interstitial edema of the patient's uterine cavity; Step 2: Determine the patient's hysteroscopic CE-specific manifestations; Step 3: Perform CD138 immunohistochemistry on the patient's endometrial tissue; Step 4: SPSS22.0 and R4.1.2 software were used for statistical analysis; Step 5: Use univariate and binary logistic regression equations to screen independent risk factors, and construct a hysteroscopic scoring system based on the screened independent risk factors.

2. The method for evaluating chronic endometritis in infertile patients based on hysteroscopic scoring according to claim 1, characterized in that: The method of hysteroscopy comprises the following steps: S1: routine disinfection and endoscope insertion, uterine distension with isotonic sodium chloride solution and the distension pressure is maintained at 80-110 mmHg; S2: Observe the uterine fundus, both uterine horns and the four walls of the uterine cavity. Keep the field of vision parallel to the surface of the endometrium as much as possible. Observe the congested area, micropolyps, interstitial edema, etc. S3: Use endoscopic forceps to grab a small amount of endometrium from the above severe areas for biopsy.

3. The method for evaluating chronic endometritis in infertile patients based on hysteroscopic scoring according to claim 1, characterized in that: The criteria for judging the specific manifestations of CE under hysteroscopy include congestion area, micropolyps and interstitial edema.

4. The method for evaluating chronic endometritis in infertile patients based on hysteroscopic scoring according to claim 3, characterized in that: The congestion area is determined as follows: the uterine cavity area is divided into six equal parts, that is, the uterine cavity is divided into two parts along the coronal plane of the uterus using the line connecting the openings of the bilateral fallopian tubes; with the midpoint of the line as the starting point and the internal cervical os as the end point, the two parts of the uterine cavity are radially divided into three equal parts along the uterine wall, for a total of six parts. Regardless of whether it is point-like congestion, lamellar congestion or mixed congestion, one-sixth of the uterine cavity area is used as a reference to calculate the proportion of the total congestion area to the uterine cavity area. A congestion area equal to 0 is grade 0, 0 to <1 / 6 is grade 1, 1 / 6 to <1 / 3 is grade 2, 1 / 3 to <1 / 2 is grade 3, and ≥1 / 2 is grade 4.

5. The method for evaluating chronic endometritis in infertile patients based on hysteroscopic scoring according to claim 3, characterized in that: The micropolyp is judged as having a diameter less than 1 mm and a clear vascular axis.

6. The method for evaluating chronic endometritis in infertile patients based on hysteroscopic scoring according to claim 3, characterized in that: The endometrial polyp is judged as a cone-shaped or finger-shaped growth, and under the pathological examination microscope, endometrial stroma, glands and thick blood vessels can be seen.

7. The method for evaluating chronic endometritis in infertile patients based on hysteroscopic scoring according to claim 3, characterized in that: The judgment of the interstitial edema is: the intima is pale and feels heavy.

8. The method for evaluating chronic endometritis in infertile patients based on hysteroscopic scoring according to claim 1, characterized in that: The method of CD138 immunohistochemical detection is: 1) Rinse the blood stains on the surface of the endometrium, fix it with 10% neutral formaldehyde solution, dehydrate it, make it transparent, embed it in paraffin, and slice it; 2) CD138 immunohistochemical staining; 3) Randomly observe 30 high-power fields in the area with the strongest staining intensity; 4) CE was diagnosed when 5 or more typical plasma cells were observed in the endometrial stroma in at least one high-power field.

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