Association between domain-specific physical activity and mental health status after embryo transfer in IVF-ET-assisted pregnancy patients

Physical activity has been shown to impact mental health in in vitro fertilization-embryo transfer (IVF-ET) patients, but the relationship between domain-specific physical activity and mental health in this population remains unclear. In a cross-sectional observational study, 208 patients undergoing IVF-ET with long-term ovulation induction cycles were recruited from a reproductive center. The International Physical Activity Questionnaire and the symptom checklist 90 (SCL-90) were used to assess physical activity levels and mental health status, respectively. Analyses of variance and linear regression analyses were conducted to identify the relationship between physical activity and mental health. There were differences between different physical activity level in times of transfers, years of infertility, and times of abortions. Patients with high levels of physical activity had fewer symptoms than those with low levels of physical activity. Occupation, transport and household physical activity had significant negative correlations with the respective SCL-90 factor scores. Linear regression analysis revealed that occupation physical activity was associated with lower depression and anxiety, and transport physical activity and household physical activity were associated with lower obsessive–compulsive, interpersonal sensitivity, depression, anxiety, and psychoticism scores. The study indicates that increased engagement in physical activity, specifically activities related to occupation, transportation, and household, may be associated with improved mental health among IVF-ET patients.


Research subjects
The cross-sectional observational study was undertaken by the reproductive center of Qilu Hospital of Shandong University.Between June 2015 and June 2017, a total of 302 women with IVF-ET long-term ovulation induction cycles were recruited; 37 refused to participate and 57 were screened but deemed ineligible based on criteria.In total, 208 patients were enrolled in the current study.They all had no limitations on physical activity.In ovulation induction, a long gonadotropin-releasing hormone agonist regimen and recombinant human FSH were applied.The maturation of oocytes was stimulated with human chorionic gonadotropin.Intramuscular administration occurs when the anterior guiding follicle reaches an average diameter of 20 mm with two bristles > 16 mm.Oocyte retrieval was conducted after 36 h.Intracytoplasmic sperm injection was conducted according to routine protocols.Women with a positive pregnancy test continue to use vaginal progesterone gels until week 12 of pregnancy.
Inclusion criteria: (1) Patients who received IVF-ET treatment; (2) Who were able to sign an informed consent and were able to cooperate with researchers to complete relevant scale surveys; (3) Revisited Qilu Hospital on time, without treatment by other medical units; (4) Age: < 35 years old; (5) Regular menstrual cycle (27-32 days); (6) IVF-ET treatment using a GnRH-a long COH protocol; (7) The indication of IVF-ET is a tubal factor, and patients with apparent uterine, endocrine and immune infertility are excluded, and male partners are excluded.Exclusion criteria: (1) Patients who have received psychological counselling; (2) Comorbid with other diseases that affect daily activities, such as limb disability, stroke, cardiac insufficiency, etc. (3) Occupations that require high-intensity physical activity, such as food delivery, construction workers, harvest farmers, etc.

Data collection
A self-compiled general questionnaire was used to collect information about the general information of IVF-ET patients.General information includes age, times of oocyte retrievals, number of pregnancies, number of embryos transferred, number of transfers, years of infertility, times of births, times of abortions, etc.Data were collected by questionnaire.On the day of embryo transfer, prior to providing written informed consent, the patient was thoroughly briefed about the purpose, significance, and content of the questionnaire.Subsequently, on the 7th day following embryo transfer, study participants completed the general questionnaire (e.g.age, education levels, times of oocyte retrievals, number of pregnancies, number of embryos transferred, times of transfers, years of infertility, times of abortions, times of births), IPAQ questionnaire and SCL-90 scale.Following the completion of the questionnaires, statistical analyses were conducted.

Survey tools
International Physical Activity Questionnaire (IPAQ) was used to evaluate patients' physical activity after embryo transfer 10,11 .It is recognized as one of the most established and widely used physical activity level questionnaires for adults (15-69 years old) globally, with sufficient validity and reliability [12][13][14]  www.nature.com/scientificreports/ in the IVF patients 15 .The questionnaire consists of five parts: daily work, housework, transportation, sports and leisure, and sleep.The data collected regarding physical activity included the activity's intensity, duration, frequency, and surrounding environment.The amount of activity was recorded separately, and each physical activity could be converted into the metabolic equivalent.IPAQ calculation method 16 : data cleansing and truncation were performed according to the principle of abnormal value elimination.The total amount of weekly physical activity was calculated in (metabolic equivalent) MET-min from the following formula: a particular activity energy expenditure (MET-mins) = the metabolic equivalent value of the activity (MET level) × average daily activity time (mins) × number of weekly activities.The metabolic equivalents of each activity are shown in Table S1, and the MET-min/week was used for the analysis.According to the following principles based on previous study 17 , the total activity level is divided into three levels (high, medium, and low) determined by the intensity of four specific types of activities.High-level physical activity was classified if either of the following two criteria is met: (1) total high-intensity physical activity ≥ 3 days and a total weekly activity level ≥ 1500 MET-min/w; (2) total physical activity ≥ 7 days and a total weekly activity level ≥ 3000 MET-min.Medium-level physical activity was defined as meeting any of the following three criteria: (1) at least 20 min per day of any high-intensity physical activity, total ≥ 3 days; (2) at least 30 min per day of any moderate-intensity physical activity and/or walking activities, total ≥ 5 days; (3) total physical activity ≥ 5 days and a total weekly activity level > 600 MET-min/w.Finally, low-level physical activity was defined by either of the following two criteria: (1) no activity reported; (2) some activity reported but not meeting the above-mentioned medium or high grouping criteria.
The symptom checklist 90 (SCL-90) was compiled by Derogatis et al. of the United States in 1975 18 .It has demonstrated an excellent capability to distinguish people who may be on the verge of psychological disorders.Each item is scored on a 5-point scale (from 1 to 5).There are two leading statistical indicators of SCL-90: (1)  Factor score: The scale includes 90 items on a total of 10 factors.Each factor reflects a certain aspect of the subject: somatization, obsessive-compulsive symptoms, interpersonal sensitivity, depression, anxiety, hostility, phobic anxiety, paranoia, psychoticism, and others (reflects sleeping and eating).( 2) Global severity index (GSI): Higher GSI scores imply more severe psychopathologic symptoms since they are derived from the mean of all 90 questions in the SCL-90, which is the "global" measure of psychological symptoms.
The stress score was calculated based on previous studies 19,20 , the total score was the sum of the numbers of embryos were transferred, times of transfers, years of infertility, and times of abortions.The higher scores mean more perceived stress in the process of assistant reproductive technology.

Statistical analysis
The sample size was determined via a priori power analysis using G*Power version 3.1.9.619 21 , and followed the power calculations proposed by Cohen 22 : for a medium regression coefficient (β = 0.2) with a significance level (α) set at 0.05 and a desired statistical power of 80%, the calculated required sample size was 184.Similarly, for a moderate bivariate correlation (r = 0.3) with the same significance level and desired statistical power, the required sample size was 84.Additionally, for an ANOVA with a medium effect size (f = 0.25), the significance level set at 0.05, and a desired statistical power of 80%, the calculated required sample size was 159.For the Chi-square analysis, considering an effect size (f = 0.25), an α error probability of 0.05, power (β error probability) of 0.8, and degrees of freedom equal to 6, the calculated required sample size was 143.Consequently, the sample size in our study should adequately achieve statistical power for our strategy intervention.
All statistical analyses were performed using SPSS software v26.0.Levene's test was used to assess the homogeneity of variances, and Shapiro-Wilk test was used to evaluated the homogeneity of variances and normality conversion was conducted when needed.Analyses of variance (ANOVA) and Chi-square were conducted to compare clinical data and scores of each factor and GSI of SCL-90 scale among patients with the three levels of physical activity, and the Tukey test was used for post hoc analysis.Pearson's correlation was used to explore associations between scores of each factor of SCL-90 scale and different intensity and domains of physical activity.Linear regression analysis was performed to investigate the relationship between physical activity and mental health, initially without adjustments and subsequently accounting for covariates.Age, stress scores, and education were identified as potential confounding variables.Covariates associated with mental health, as determined through ANOVA or Pearson's correlation, were included in the adjusted model.Results are given as standardized coefficients (B) with 95% CI.For all tests, two-sided p < 0.05 was considered statically significant.

Ethics approval and consent to participate
This study was approved by the Ethics Committees of Qilu Hospital of Shandong University (KYLL-2016-331).All participants obtained written informed consent after the procedure was fully explained and before participating in the trial.All procedures contributing to this work follow the ethical standards of the Declaration of Helsinki of 1975, as revised in 2008.

Association between physical activity and mental health in IVF-ET-assisted pregnancy patients.
As shown in Table 1, there were 33 (15.8%)IVF-ET-assisted pregnancy patients in the low physical activity level group, 100 (48.1%) in the medium physical activity level group, and 75 (36.1%) in the high physical activity level group.There were differences between different physical activity level in times of transfers, years of infertility, and times of abortions.Comparisons of SCL-90 scores among the three groups of physical activity levels are shown in Table 2.The SCL-90 factor scores such as somatization (p = 0.025), obsessive-compulsive (p < 0.001), interpersonal sensitivity (p = 0.046), depression (p < 0.001), anxiety (p < 0.001), hostility (p < 0.001), phobia anxiety www.nature.com/scientificreports/(p = 0.014), paranoid ideation (p = 0.038), and psychoticism (p = 0.005) in the low physical activity level groups were significantly higher than those in the high physical activity level group, and the obsessive-compulsive (p = 0.005), interpersonal sensitivity (p = 0.008), depression (p = 0.002), anxiety (p = 0.013), hostility (p = 0.032) in medium physical activity level groups were significantly higher than those in the high physical activity level group.

Discussion
At present, the reproductive center of the hospital uses the IVF-ET long program to stimulate the ovulation cycle to help infertile patients be pregnant.At the same time, bed rest after embryo transfer is still routine practice in some reproductive centers, and it is believed that reducing postoperative activity can help improve pregnancy outcomes.Walker et al. believe that, in most cases, physical activity during pregnancy is beneficial to both mother and fetus 23 ; it is also applicable to patients who are pregnant after IVF-ET.So far, there is still a lack of quantitative data on relationship between physical activity and mental health after an embryo transfer in IVF-ET patients.
The previous study has shown that there were elevated symptoms of anxiety and depression among pregnant individuals 24 , which may have long-term impacts on their children 25 .In addition, exercise during pregnancy could reduce the rate of occurrence of antenatal depression and depressive symptoms 26,27 .What's more, high levels of physical activity during pregnancy decreased the odds of developing prenatal depression and anxiety 28 .Consistent with the previous study, the present study found that there were statistically significant associations of different physical activity levels with mental health in IVF-ET patients.In addition, patients with high levels of activity demonstrated significantly greater differences mental health compared to their counterparts with low  The relationship between mental health and physical activity is inconsistent across different life domains, and it is critical to explore the context that may influence the relationship between physical activity and mental health.The previous meta-analysis showed that leisure-time physical activity and transport physical activity were positively associated with mental health 9 .However, it should be noted that even if the amount of activity is "high" in this study, there is no too strenuous exercise, let alone those who do physical exercise.In this study, 21.63% of patients continued working following embryo transfer, and only 7.21% underwent work-related heavy physical activity, such as going up and down stairs every day.There were 12.72% of patients who were engaged in heavy physical housework daily, such as mopping the floor in a short period.However, 15.87% of patients with lowlevel activity did not engage in any housework and activities, instead, they were basically in a recumbent state.It is notable from the present study that IVF-ET patients may perform a limited number of physical activities, therefore, it is imperative for more related propaganda and education during the assisted reproductive process.

Somatization
Previous studies have indicated that anxiety and depression in women with infertility are affected by multiple factors such as family habitation 29 , smoking and drinking status of their partners 30 , family economic status 31 , and their age 32 and educational level 33 .The present results did not observe a relationship between age and perceived stress with mental health, which may be because of the status of the investigated groups of IVF-ET patients who have relatively good mental health.However, the results showed that total activity especially occupation, transport, and household activities correlated with variables of SCL-90.Transport positively associated with mental health possibly supported this phenomenon that those who walk or bike to work experienced enjoyment 9 .Although the previous study has indicated that household activity had no relationship with mental health or mental disorders 9 , the present study found the results opposite with previous.In fact, physical activity in home isolation during the epidemic helped improve adults' depression, and anxiety, and increased sleep duration 34 .Sedentary behaviors such as television time have been connected with psychological anguish 35 , whereas lowering television viewing may contribute to reduced psychological distress, particularly in women 36 .Increasing activity during labor is not likely to be worthwhile in reducing the prevalence of mental disorders, which indicated the work-related physical activity was positively associated with mental ill-health 9,37 , as individuals with occupations that involve higher amounts of physical activity are more likely to experience more work and stress.The present study found the occupational physical activity was positive with mental health, which may related the nature of work, access to greenspace, job satisfaction 37 .In addition, no correlation between the leisure physical activity could due to the women in the study may just have done little PA during leisure time within the past 7 days.Diverse domains of physical activity exhibit distinct correlations with post-exercise mood.Consequently, forthcoming research endeavors should delve into the nuanced, long-term relationships between domain-specific physical activity and mental health outcomes.
This study has significant theoretical value for clarifying the correlation between physical activity and mental health in IVF patients, which provides the basis for improving mental health in the IVF-ET process.On the other hand, this study has limitations as well, including a relatively small sample size and limited data collected at baseline.As the present was cross-sectional observational study, there was no criteria and data determined regarding the type of physical activity prior to the start of the study.Furthermore, the study was cross-sectional and could not establish a causal relationship.In addition, the relevant confounding variables were not collected in present study, which may have resulted in erroneous associations between physical activity and these variables, which could affect the generalizability of the conclusion.Furthermore, the use of the IPAQ which assesses physical activity over the past 7 days, introduces a potential overlap with laboratory visits, possibly not fully capturing participants' habitual or typical physical activity patterns.

Conclusion
This study showed that total and domains-specific physical activity after embryo transfer may be associated with mental health in IVF patients.In particular, appropriate occupation activity, transport activity and household activity could be implemented for IVF-ET patients which may beneficial for their mental health.The stakeholder should think highly of the domain-specific physical activity of the IVF patients in developing interventions, and treatment programs in the future.

Table 1 .
Comparison of sociodemographic factors and clinical data between different groups of physical activity levels.Quantitative data is expressed in mean ± standard error of mean, and qualitative data is expressed in n.

Table 2 .
Comparison of scores of each factor and GSI of SCL-90 scale among the different groups of physical activity levels.GSI global severity index, ANOVA and turkey post hoc was used in data.M ± SEM: mean ± standard error of mean.*p < 0.05, **p < 0.01, ***p < 0.001 vs. low physical activity level; # p < 0.05, ## p < 0.01 vs. medium physical activity level.The scores of each factor range from 0 to 5 points.

Table 3 .
Correlation among scores of each factor and GSI of SCL-90 scale and total and different domains of physical activity.GSI global severity index.
*p < 0.05, *p < 0.01, ***p < 0.001 of the Pearson correlation coefficient.The MET-min/week of physical activity was used for the analysis.
levels of activity, in contrast, the distinctions between those with moderate-level activity and low-level activity were less prominent.Extra bed rest may cause excessive psychological stress and adversely affect pregnancy outcomes.While our study findings suggest a positive association between physical activity and the mental health of IVF-ET patients, future prospective studies incorporating interventions are warranted to further explore the potential benefits of physical activity on the mental health outcomes in IVF-ET patients.

Table 4 .
Associations between total physical activity and factor scores of SCL-90 in IVF patients.CI confidence interval.The MET-min/week of physical activity was used for the analysis.