A Large-Scale Prospective Cohort Study on the Association of Environmental Exposures and Behavioral Factors With Infertility and Assisted Reproductive Technology (ART) Success Rates
Conditions: Environmental Exposure, Assisted Reproductive Technology, Prospective Study
Sponsor: The Third Xiangya Hospital of Central South University

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A large-scale, prospective cohort study 
to investigate the association between 
environmental exposures and behavioral 
factors and infertility (success rate of 
assisted reproductive technology) 
 
 
 
 
Sponsor: Xiangya Third Hospital, Central South University 
 
 
Funding source: None available 
 
Research Institution: Xiangya Third Hospital, Central South 
University 
 
Research Leader: Peng 
Ena 
Research contact person: Zhao Xingping (13327215012) 
 
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Version date: 2024.7.1 
 
 
 
 
 
 
Table of contents 
 
Research Proposal Summary  .........................................................................................................................3 
Research Text  .....................................................................................................................................................6 
1. Research Background  ................................................................................................................................6 
2. Research Objectives  ................................................................................................................................7 
3. Research Design  .........................................................................................................................................8 
4. Research Content  .......................................................................................................................................9 
5. Data completeness and quality assurance  .............................................................................. 18 
6. Ethical Statement .................................................................................................................................. 18 
Reference  ........................................................................................................................................................... 19 
 
 
 

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Research Proposal Summary 
Trial Title: A Large-Scale, Prospective Cohort Study Exploring the 
Association Between Environmental Exposure and Behavioral Factors 
and Infertility (Success Rate of Assisted Reproductive Technology)  
Research Objective: This study aims to clarify the reasons for the 
failure of assisted reproductive technology (ART) in infertile 
patients in Hunan Province, to achieve early identification and 
prediction of risk factors, and thus improve the success rate of 
ART. 
 
Experimental Design: 
is a prospective cohort study, aiming to collect data from 5,000 
participants (male to female ratio 1:1) . 
Experimental procedure: 
1. To establish a large-scale, prospective cohort of infertile 
patients to provide basic data for studying the association between 
environmental, biological, and social factors and ART success rates. 
2. Analyze the association between exposure to environmental factors 
(such as environmental pollutants related to plastic products) 
(internal exposure) and infertility ( ART success rate) to provide 
a scientific basis for formulating environmental protection 
policies. 
3. To explore the impact of lifestyle and social factors on the 
success rate of ART in infertile patients, and to provide guidance 
for improving public reproductive health literacy. 
4. To construct a predictive model for adverse pregnancy outcomes 
in infertile couples undergoing ART, providing new insights for 
improving the success rate of ART in infertile patients.   
 

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Selection criteria: 
(1) A. Women aged 18 to 46 who use their own eggs or men aged 18 to 
55 who use their own sperm; B. Patients who meet the diagnostic 
criteria for infertility; C. Patients with a clear history of 
persistent infertility; D. Patients who voluntarily participate in 
the program and sign an informed consent form; 
Exclusion criteria: 
(1)  
A. Individuals undergoing artificial insemination with any of 
the following contraindications to ARTs : a. Impaired sperm-egg 
fertilization due to fallopian tube factors in the woman. b. The 
woman has an acute infection of the reproductive or urinary system 
or a sexually transmitted disease. c. The woman has a genetic disease, 
a serious physical illness, or a mental or psychological disorder. 
d. A history of birth defects in infants confirmed to be caused by 
female factors. e. The woman has been exposed to teratogenic doses 
of radiation, toxins, or drugs and is currently under the influence 
of these factors. f. The woman has a history of alcoholism, drug 
abuse, or other unhealthy habits. B. Individuals undergoing first-
generation or second-generation IVF with any of the following 
contraindications to ARTs: a. Either the donor of gametes has an 
acute infection of the reproductive or urinary system or a sexually 
transmitted disease, or has a history of alcoholism, drug abuse, or 
other unhealthy habits. b. Either the donor of gametes has been 
exposed to teratogenic doses of radiation, toxins, or drugs and is 
currently under the influence of these factors. c. The woman 
receiving donated embryos/eggs suffers from an acute infection of 
the reproductive or urinary system or a sexually transmitted disease, 
or has a history of alcoholism, drug abuse, or other unhealthy habits. 
d. The woman's uterus is not capable of carrying a pregnancy or she 

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has a serious physical illness that prevents her from conceiving. C. 
No embryo transfer was performed after egg retrieval; D. More than 
180 days have passed since frozen embryo transfer was performed after 
egg retrieval; 
Statistical methods: Lasso regression was used, and a penalty 
function was constructed. Variables were selected based on the lambda 
value that minimized the error, achieving subset shrinkage and 
avoiding overfitting. ART failure in infertile patients was used as 
the outcome indicator, and the selected indicators were used as 
predictors. Algorithms such as Cox proportional hazards regression, 
random forest (RF), extreme gradient boosting ( XGBoost ), and Naive 
Bayes (NB) were employed to construct a risk prediction model. 
 
 

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Research Text 
1. Research Background 
Along with economic progress, a series of problems, such as the use of many 
chemical products, excessive destruction of the ecological environment, various 
chemical (biological) pollution of human living environment, use of various 
genetically modified food technologies, large doses of pesticide residues in food, 
and abuse of antibiotics, seriously threaten human fertility. Infertility is becoming 
increasingly serious. It is estimated that the infertility rate of Chinese women is as 
high as 15-20% (400,000-500,000) and the infertility rate of men is as high as 10-
12% (450,000) 
[1] . The incidence of infertility is rising year by year worldwide, 
bringing heavy psychological and economic burdens to many families. As a result, 
human assisted reproductive technology ( ART ) has emerged, which can make 
up for the regret of couples who cannot have offspring in the traditional way, and 
at the same time make a certain contribution to the genetic improvement of 
genetic diseases. This has a profound impact on the entire human society. 
In vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) are the 
main ART methods for fertilizing eggs. With the advancement and widespread 
application of ART, the proportion of ART-born babies is increasing. Currently, 
the number of ART babies born globally each year has exceeded 350,000, and the 
cumulative number of IVF babies has reached 5 million. The proportion of ART 
newborns in Europe is 0.2%-3.9%. According to statistics, as of 2011, the proportion 
of ART newborns in China has reached 1.013% 
[2] . However, the success rate of 
ART in most reproductive centers hovers around 40%, and the delivery rate is still 
only 20%-30% 
[3] . Among them, the high rate of spontaneous abortion is one of 
the key reasons affecting the live birth rate. The causes of spontaneous abortion 
are extremely complex. Even after comprehensive medical examination, the 
causes of many spontaneous abortions remain unknown. Therefore, it is necessary 
to comprehensively explore the possible risk factors for early spontaneous 

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abortion 
[4] . Most of the attention in the past has been focused on the impact of 
clinical factors on infertility and antiretroviral therapy, rather than environmental 
factors such as ambient air pollutants and new environmental pollutants. Previous 
studies have analyzed air pollutants exposed to by ART participants and found 
harmful associations between pregnancy failure and particulate matter 
[5, 6] and 
nitrogen dioxide 
[7, 8] in ambient air pollutants. With the widespread use of new 
materials, new environmental problems have also emerged. Studies have 
suggested that parental exposure to new pollutants, such as phthalates , 
phthalates, and nanoplastic particles, is associated with adverse pregnancy 
outcomes 
[9-11] . In addition, a US study suggests that improving lifestyle and social 
factors, including diet, can effectively improve ART success rates 
[12] . 
However, China has not yet conducted comprehensive and in-depth 
research on the impact of environmental factors, lifestyles, and social factors on 
infertility ( ART success rate). Therefore, we plan to conduct a large-scale, 
prospective cohort study to explore the association between environmental 
exposures and behavioral factors and infertility. 
 
 
2. Research Objectives 
    This study aims to clarify the reasons for the failure of 
assisted reproductive technology ( ART ) in infertile patients in Hunan Province , 
to achieve early identification and prediction of risk factors , and thus improve the 
success rate of ART . 
2.1 . Establish a large-scale, prospective cohort of infertile patients to provide 
basic data for studying the association between environmental, biological, and 
social factors and ART success rates . 
2.2 . Analyze the association between exposure to environmental factors ( such as 

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environmental pollutants related to plastic products ) (internal exposure) and 
infertility (ART success rate) to provide a scientific basis for the formulation of 
environmental protection policies. 
2. 3. To explore the impact of lifestyle and social factors on the success rate of 
ART in infertile patients , and to provide guidance for improving public 
reproductive health literacy. 
2.4 . To construct a predictive model for adverse pregnancy outcomes in infertile 
couples undergoing ART , providing new insights for improving the success rate 
of ART in infertile patients . 
 
3. Research Design 
3.1 . Research on the Construction of an Infertility Cohort in Hunan Province 
This study aims to establish a cohort of infertile patients in Hunan Province, 
including those who visited Xiangya Third Hospital in Changsha, Hunan Province 
from December 2024 to December 2034. Study participants will be selected based 
on clearly defined inclusion and exclusion criteria. Baseline data collection will 
cover multiple dimensions, including sociodemographic characteristics, lifestyle 
behaviors, basic health status, physiological and biochemical indicators, and 
internal exposure measurements to environmental factors. Follow-up will be 
conducted from the start of the study through reproductive care, pregnancy, 
delivery, and childbirth to observe the ART live birth rate of infertile patients. This 
will provide data support for research on the identification, early prediction, 
intervention, and prevention of ART risk factors in infertile patients. 
3.2 . Research on risk factors for ART failure in infertile patients 
Based on the infertility cohort and database established in Content 1 of Hunan 
Province, this study uses a multivariate analysis method to explore the association 
between relevant environmental, lifestyle, and social risk factors and ART success 
rate, thereby identifying risk factors for ART failure and comparing the differences 
among different risk factors. This provides an evidence basis for effective 

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interventions such as early prediction , reduction, or elimination of non-clinical 
factors leading to ART failure rate. 
3.3 . Research on the Construction and Evaluation of Predictive Models for 
ART Failure in Infertile Patients 
Building upon Contents 1 and 2, this study uses ART failure in infertile patients as 
the outcome indicator and sociodemographic characteristics, basic health status, 
environmental exposure, lifestyle behaviors, and physiological and biochemical 
indicators as potential predictive factors. It combines traditional regression 
analysis and machine learning algorithms to construct a risk prediction model for 
ART failure in infertile patients . The model is then validated internally and 
externally, and its performance is evaluated based on discrimination, calibration, 
and predictive ability. 
 
4. Research Content 
4.1 . A cohort study of infertility in Hunan Province 
4.1.1 . Baseline Survey 
4.1.1.1 . The research units selected were Xiangya Third Hospital and the 
Department of Health Toxicology, School of Public Health, Central South 
University. The above-mentioned hospitals are provincial key clinical specialties in 
the field of ART for infertility. The Department of Health Toxicology, School of 
Public Health, Central South University has a foundation for research on exposure 
to relevant environmental risk factors and related populations, and has a good 
foundation for cooperation, which is conducive to the development of the 
infertility cohort. 
4.1.1.2 . Inclusion criteria for study subjects: 
(1) Infertility cohort 

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①Inclusion criteria : A. Women aged 18 to 46 using their own eggs or men 
aged 18 to 55 using their own sperm; B. Patients meeting the diagnostic criteria 
for infertility; C. A clear history of persistent infertility ; D. Willingness to participate 
in the program and signing an informed consent form; E.... 
② Exclusion Criteria: A. Individuals undergoing artificial insemination with any of 
the following contraindications to ARTs: a . Female partner has impaired sperm-
egg fertilization due to fallopian tube factors. b. Female partner suffers from acute 
infection of the reproductive or urinary system or sexually transmitted diseases. c. 
Female partner suffers from genetic diseases, serious physical illnesses, or mental 
or psychological disorders. d. History of birth of an infant with congenital defects 
confirmed to be caused by female factors. e. Female partner has been exposed to 
teratogenic doses of radiation, toxins, or drugs and is currently within the period 
of their effects. f. Female partner has a history of alcoholism, drug abuse, or other 
unhealthy habits. B. Individuals undergoing first-generation or second-
generation IVF with any of the following contraindications to ARTs: a. Either 
partner donating gametes suffers from acute infection of the reproductive or 
urinary system or sexually transmitted diseases, or has a history of alcoholism, 
drug abuse, or other unhealthy habits. b. Either partner donating gametes has 
been exposed to teratogenic doses of radiation, toxins, or drugs and is currently 
within the period of their effects. c. The woman receiving the donated 
embryo/egg suffers from an acute infection of the reproductive or urinary system, 
a sexually transmitted disease, or has a history of alcoholism, drug abuse, or other 
unhealthy habits. d. The woman's uterus is not capable of carrying a pregnancy, 
or she has a serious physical illness that prevents her from conceiving. C. No 
embryo transfer was performed after egg retrieval ; D. More than 180 days after 
egg retrieval, frozen embryos were transferred. 
( 2 ) Diagnostic criteria for infertility: 
① Infertility: Couples who have been having regular unprotected sexual 
intercourse for at least one year and have not conceived. 

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② Primary female infertility: women who have never had a history of 
pregnancy and have never become pregnant despite not using contraception. 
③ Secondary infertility in women : women who have a history of pregnancy 
but have not conceived for 12 consecutive months without using 
contraception. 
④ Male primary infertility: The male has never impregnated a woman. 
⑤ Secondary male infertility: Infertility that occurs after a man has previously 
impregnated a woman. 
⑥ Unexplained infertility: Infertility where the cause cannot be found using 
standard infertility assessment methods. 
⑦ Diagnostic criteria for azoospermia: No sperm was found in the semen 
after centrifugation and microscopic examination three or more times, while 
excluding those who do not ejaculate and those who ejaculate retrogradely. 
⑧ Diagnostic criteria for oligospermia: sperm concentration in semen 
analysis is less than 15 × 10⁶ 
/ ml. 
⑨ Diagnostic criteria for asthenospermia: The percentage of progressively 
motile sperm in semen analysis is less than 32%. 
⑩ Diagnostic criteria for teratospermia : The percentage of sperm with 
normal morphology in semen analysis is less than 4%. 
⑪ Polycystic ovary syndrome (PCOS): The most commonly used diagnostic 
criteria are the Rotterdam criteria proposed in 2003 by the European Society 
for Reproductive and Embryological Medicine and the American Society for 
Reproductive Medicine: A. Infrequent ovulation or anovulation; B. Clinical 
manifestations of hyperandrogenism and/or hyperandrogenemia; C. 
Polycystic ovarian changes: ultrasound shows ≥12 follicles with a diameter 
of 2-9 mm in one or both ovaries , and/or ovarian volume ≥10 ml; D. 
Meeting 2 of the 3 criteria and excluding other causes of hyperandrogenism, 
such as congenital adrenal hyperplasia, Cushing's syndrome , and androgen-
secreting tumors. 

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⑫ Ovarian insufficiency refers to a serum follicle-stimulating hormone (FSH) 
level greater than 10 U/L or a total of fewer than 5 follicles in both ovaries 
during the early follicular phase. It can further develop into premature ovarian 
failure. 
⑬ Pelvic and fallopian tube factors are caused by previous infections, surgical 
procedures, etc., resulting in pelvic adhesions, fallopian tube blockage, 
hydrosalpinx, and impaired egg-picking function of the fimbriae of the 
fallopian tubes. 
⑭ Endometriosis refers to the growth of uterine glands and stroma outside 
the endometrium and myometrium of the uterine cavity, causing lesions. 
4.1.1.3 . Survey Content: The baseline survey includes questionnaires, clinical 
physical examination and physiological and biochemical indicators, scale 
assessments , and the specific type of ART technology ultimately received . Details 
are as follows: 
(1) Questionnaire survey: covering sociodemographic characteristics , baseline 
health status, lifestyle, environmental factors and medical history, etc., and 
collecting general information and medical history of both spouses on site. 
① Sociodemographic characteristics include gender, age, occupation, education 
level, and socioeconomic status; 
② Baseline health includes: (including age at first attempt to conceive, use of oral 
contraceptives, and presence of sexual dysfunction) 
A. Female: 
a. Self-assessment of health status; 
b. The woman's menstrual and reproductive history (including age of menarche, 
regularity of menstruation, and whether menstruation is infrequent (infrequent 
menstruation generally refers to a menstrual cycle that is longer than 35 days). 
c. Contraceptive history (method, frequency); 
d. Medical history, medication history, family history, etc.; 
e. Obstetric history; 

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B. Male: 
a. Self-assessment of health status: Date of onset of puberty; whether any sexual 
problems have occurred (including difficulty maintaining an erection, premature 
ejaculation, or inability to ejaculate). 
b. Contraceptive history (method, frequency); 
c. Medical history, medication history, family history, etc.; 
History of cryptorchidism (undescended testis); whether the patient has 
undergone vasectomy or other abdominal, pelvic, or scrotal surgery; use of 
antibiotics or other over-the-counter medications (dosage, frequency); use of 
illicit drugs such as marijuana, cocaine, or anabolic steroids. 
③ Lifestyle behaviors include: 
a. Diet and Nutrition: Food frequency questionnaire + whether you have a habit 
of eating food in plastic bags + use of disposable tableware; frequency of eating 
fruit peels and vegetables; consumption of canned food; frequency of drinking 
milk tea; amount of tea and coffee consumed; use of dietary supplements 
(vitamins); smoking and alcohol consumption (dosage and frequency). 
b. Daily routine: Exercise (frequency, duration); daily use of electronic devices; 
sleep quality (start and end times); nap habits (duration of naps); 
c. Work environment: Are there any conditions that are unfavorable to fertility, 
such as prolonged sitting , high temperature, environmental pollution, radiation, 
chemical reagents, etc.? 
d. Living environment: Exposure to chemicals, pesticides, radiation, or toxins such 
as lead, especially frequent exposure; exposure to kitchen fumes; whether you 
have recently lived in a house with new furniture or renovations; whether the 
surrounding area is close to garbage stations or transportation hubs; 
e. Personal care: Use of skincare and cosmetic products (frequency, type of 
products used); frequency of perming, dyeing, and manicures per year) 
④ Environmental factors include: 
A. Traditional air pollutants: Data on six traditional air pollutants (PM 2.5 , PM 10 , SO 

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2 , CO, NO 2 , and O 3 ) were used. The observation exposure period was divided 
into seven periods according to the IVF treatment process (i.e., 85 days before 
oocyte retrieval to the day of oocyte retrieval, Gn initiation to the day of oocyte 
retrieval, oocyte retrieval to the day of embryo transfer, 30 days before frozen-
thawed embryo transfer to the day of embryo transfer, embryo transfer to the day 
of HCG pregnancy test , 85 days before oocyte retrieval to the day of HCG test in 
fresh cycles, and 30 days before embryo transfer to the day of HCG test in frozen-
thawed cycles). Data from the air monitoring station closest to the patient's 
residence was used as approximate exposure. 
B. Environmental pollutants related to plastic products : 
Plastic raw materials: Different types of plastic monomers (polyethylene (PE), 
polypropylene (PP), polyvinyl chloride (PVC), polystyrene (PS), polyethylene 
terephthalate (PET), polycarbonate (PC), polyamide (PA), polymethyl methacrylate 
(PMMA), epoxy resin (EP), polyurethane (PU), polyphenylene sulfide (PPS), 
polyetheretherketone (PEEK), polytetrafluoroethylene (PTFE), ethylene-vinyl 
acetate copolymer (EVA) and different particle sizes) 
plastic. 
Plastic additives : plasticizers, flame retardants, antioxidants, colorants, 
lubricants, fillers and foaming agents (see Appendix 2 for details). 
on factors such as whether the living environment is adjacent to a street or main 
road, the renovation status of the residence or workplace (historical renovations, 
new furniture), and whether there are petrochemical plants or waste incineration 
plants nearby. 
(2) Clinical physical examination: 
① Physical examination for female patients: routine gynecological examination, 
vaginal secretion examination, transvaginal ultrasound, ultrasound-guided tubal 
patency test, sex hormone testing, and detection of antisperm antibodies, anti-
endometrial antibodies, anticardiolipin antibodies, and anti-ovarian antibodies. 
For patients whose cause cannot be determined through other examinations, 

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hysteroscopy and laparoscopy may be performed. (Follicular fluid, urine, and 
blood samples should be collected.) 
② Physical examination for male patients: Specialized andrological examination, 
routine semen analysis, sperm morphology 
examination, mycoplasma 
examination, chlamydia examination, gonorrhea examination, and antisperm 
antibody testing. Routine semen analysis: Patients abstain from ejaculation for 2-
7 days, collect semen via masturbation, and use a semen analysis system. The 
analysis report includes semen volume, color, liquefaction time, motility, sperm 
density, and sperm morphology. (Semen, urine, and blood samples are collected.) 
(3) Sample collection and preservation 
Sampling containers: Blood, urine, semen, and follicular fluid are collected 
using glass sampling containers .  
Sampling time: a total of 4 times, namely: the first admission physical 
examination, the day of surgery, the 14th-16th day after surgery, and the 30th 
day after surgery. 
Samples collected: blood, urine, semen (seminal plasma without sperm), 
follicular fluid, vaginal/ cervical secretions. 
Preservation method: Blood is divided into two parts: whole blood is frozen 
at -80℃ and the supernatant is frozen after centrifugation ; urine, follicular fluid 
and semen are frozen directly at -80℃ . 
( 4 ) Scale assessment: 
The Hospital Anxiety and Depression Scale (HADS) , the Social Support Rating 
Scale , and the Perceived Stress Scale (PSS) were used . 
(5) Record the type of ART technology finally accepted. 
4.1.2 Follow-up 
Participants registered individually or as couples and were followed up from 
the start of the study through reproductive care, pregnancy, delivery, and 
childbirth . Follow-up was conducted every three months during the assisted 
reproductive treatment phase, pregnancy, and the first six months postpartum, 

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and every two years postpartum . Specific follow-up content and methods are as 
follows: 
(1) Success in the field of ART refers to live birth , which can be obtained through 
doctor diagnosis or access to medical system records, while recording whether 
adverse pregnancy outcomes and their types (miscarriage, stillbirth, premature 
birth, low birth weight infant, macrosomia, congenital abnormalities, stillbirth, 
neonatal death). 
(2) Variable factors such as lifestyle in the baseline indicators: The specific content 
is the same as in 1.1.3. 
1.3 Data Management 
A database of infertility cohorts in Hunan Province will be established, and 
baseline survey information and follow-up information will be managed in a 
standardized and electronic manner through a project-specific software system. 
At the same time, original data and relevant biological samples will be retained 
for verification. 
1.4 Quality Control 
Establish a standardized survey manual to clearly define survey items and 
methods. Provide standardized training to surveyors to ensure they use consistent 
and standardized methods to collect questionnaire information. 
4.2 . Research on risk factors for ART failure in infertile patients 
To identify risk factors for ART failure in infertile patients , based on previously 
established data from an infertile cohort in Hunan Province, participants were 
grouped according to different lifestyle behaviors, health conditions, 
environmental factors, and other potential risk factors (e.g., if smoking was a 
potential risk factor, participants were divided into smoking and non-smoking 
groups). A multivariate Cox proportional hazards model was used to adjust for 
confounding factors, and differences in pregnancy outcomes were compared 
between the groups , calculating the risk factor (HR) and 95% confidence interval 
(CI). An HR > 1 was considered a risk factor, while an HR < 1 was considered a 

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protective factor. Further comparisons were made regarding the differences in risk 
factors for ART failure among infertile patients. 
4.3 . Research on the Construction and Evaluation of Predictive Models for ART 
Failure in Infertile Patients 
4.3.1 . Screening of candidate predictors 
4. 3.1.1. The risk factors for ART failure in infertile patients identified in the above 
studies were used as candidate predictors, including sociodemographic 
characteristics, basic health status, lifestyle, physiological and biochemical 
indicators, and environmental factors. 
4. 3.1.2. Screening candidate predictors based on Lasso regression: Given the 
large number of candidate predictors, direct modeling can easily lead to high 
complexity. Therefore, the Lasso regression method is adopted. By constructing a 
penalty function, the lambda value with the smallest error is used as the standard 
to screen variables, thereby achieving the purpose of subset shrinkage and 
avoiding overfitting. 
4.3.2 . Construction of Risk Prediction Model 
Using ART failure in infertile patients as the outcome indicator and selected 
indicators as predictive factors, a risk prediction model was constructed using 
algorithms such as Cox proportional hazards regression , random forest (RF), 
extreme gradient boosting ( XGBoost ), and Naive Bayes (NB). 
4.3.3 . Evaluation and Validation of Risk Prediction Model 
4.3.3.1 . Validation Methods: Internal and external validations were performed to 
evaluate the model's internal and external effectiveness. Internal validation 
employed a 10-fold cross-validation method, dividing the data into 10 mutually 
exclusive subsets. Nine subsets were selected as the training set and one subset 
as the validation set in each iteration, repeated 10 times, and the average value 
was used as the model performance evaluation result. External validation involved 
applying the risk prediction model built for this region to other regions to evaluate 
its performance. 

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4.3.3.2 . Evaluation Indicators: The predictive model is evaluated based on three 
aspects: discrimination, calibration, and predictive ability. The discrimination of the 
model is assessed by calculating the area under the receiver operating 
characteristic curve (AUC); the calibration curve is plotted to assess the calibration 
of the model; and the predictive ability of the model is evaluated from multiple 
aspects, including error rate, sensitivity, and specificity. 
4.3.3.3 . Optimal Model Selection: Based on the model discrimination and 
calibration map results, the optimal prediction model is selected, and finally a 
prediction model for the risk of ART failure in infertile patients is formed. 
4.3.4 Visualization of Risk Prediction Model 
By presenting and reporting risk prediction models in the form of scorecards, 
nomograms, web calculators, or applications, the models can be visualized, 
thereby forming a simple, convenient, efficient, and easy-to-promote risk 
prediction system and promoting its application in practice. 
5. Data integrity and quality assurance 
Researchers should ensure that data is authentic, accurate, 
complete, and traceable, and should ensure the integrity of basic 
clinical research documents during retention, avoiding intentional or 
unintentional alteration or loss. 
6. Ethical Statement 
The clinical research will adhere to the relevant regulations of 
the World Medical Association's Declaration of Helsinki and the Ethical 
Review Guidelines for Biomedical Research Involving Human Subjects. 
The research protocol will be approved by the ethics committee before 
the clinical research can commence. The privacy of research 
participants and the confidentiality of data will be protected 
throughout the research process. 

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