Marital Quality and Depression Among Women Undergoing Artificial Insemination by Donor Due to Male Irreversible Azoospermia: A 6-Year Follow-up Study in China

Background : Infertility is a stressful situation that can lead to negative emotions such as depression. In particular, women undergoing artificial insemination by donor (AID). The quality of marriage is one of the important influencing factors of infertility treatment. This study aimed to evaluate marital quality and depression among women undergoing AID due to male irreversible azoospermia. Methods : A hospital-based cohort study was conducted at Women’ s Hospital, Zhejiang University School of Medicine from July 2016 to December 2016, with a total of 128 participants enrolled. The marital quality and mental health were measured with the Dyadic Adjustment Scale (DAS) and the Self-rating Depression Scale (SDS), respectively. Results : A DAS score of ≤ 107, indicating poor marriage quality, was found in 40.6% of the women surveyed. These women had lower education levels and higher SDS scores. Pearson correlation coefficient and multiple regression analysis showed a significant correlation between the DAS score and factors such as the duration of marriage, education level, remarriage, and SDS score. Six years after undergoing AID, the SDS score of women remained steady (26.41 ± 4.27 at the year of AID, and 26.52 ± 6.48 for the 6-year follow-up). DAS was statistically lower at the 6-year follow-up (106.19 ± 20.17) compared to that at the AID year (114.49 ± 17.65). Unexpectedly, pregnancy was not shown to improve marital quality. Conclusions : The study’s findings suggest that women undergoing AID experience poor marital quality and exhibit high levels of depression. After a 6-year follow-up, the marital adjustment for the women worsens following AID treatment. Additionally, this trend does not appear to be influenced by whether the couple bears and raises a child conceived through AID.


Introduction
Infertility is one of the most prevalent problems all over the world, defined as a couple's inability to conceive after one year of regular unprotected intercourse clinically.It affects approximately 8-12% of the reproductive-aged population [1].A contributing male factor may be identified in over half of cases, with up to 40% of those being attributed solely to secondary to male factors [2,3].Male infertility is often characterized by semen abnormality [4].Currently, assisted reproductive technology (ART) is widely used [5].While intracytoplasmic sperm injection (ICSI) revolutionized the treatment of severe male infertility in the 1990s, artificial insemination by donor (AID) remains a final recourse for individuals facing ICSI failures [6].Since it is a cost-effective and safe option for male irreversible azoospermia, AID has been adopted widely and accepted gradually, resulting in an increasing number of offspring conceived by AID [7].
In couples experiencing infertility, both men and women often report poor sleep quality and psychological issues [8][9][10].Male infertility serves as an important pre-dictor of the presence of anxiety and depression in females experiencing infertility [11].Considering the significantly higher risk of iatrogenic preterm birth in singleton pregnancies achieved after in vitro fertilization (IVF)/ICSI compared to those resulting from spontaneous conceptions, this further underscores the importance of recommending psychological counseling [12].Scaravelli et al. [13] suggested that male-related ART treatments pose risk elements that could deteriorate the psychological well-being of women.Therefore, many researchers advocate to improving the quality of life and marital quality, alongside addressing the psychological distress experienced by women with infertility and their partners [14,15].Furthermore, an infant conceived through AID has no biological relationship with the father, presenting a complex issue that cannot be overlooked, particularly considering the significant emphasis placed on blood ties in traditional Chinese culture.This is particularly pertinent given China's one-child policy in recent years [16].Furthermore, couples undergoing AID experience greater psychological pressure and more complex marital dynamics.However, to the best of our knowledge, there is limited information available regarding marital quality and depression among women undergoing AID due to male irreversible azoospermia.This study aimed to evaluate marital quality and levels of depression in Chinese women undergoing AID due to male irreversible azoospermia, explore the potential influencing factors, and investigate the relationship between pregnancy outcomes and marital quality over a 6-year follow-up period.The study seeks to provide a theoretical basis and experiential reference for individuals in similar situations.

Study Design and Participants
This study was a hospital-based cohort study conducted at Women's Hospital, Zhejiang University School of Medicine, between July 2016 and December 2016.Only women undergoing AID due to male irreversible azoospermia were enrolled in the analysis.The exclusion criteria were as follows: (1) women with a history of neurologic or psychiatric disorders; (2) those addicted to drinking or smoking; (3) individuals with female infertility; (4) those unable to read or write; (5) women who have adopted chil- A total of 644 women underwent AID at Women's Hospital, Zhejiang University School of Medicine.Out of them, 382 cases were excluded for not meeting the inclusion criteria.Among the 262 women who met the inclusion criteria, 128 agreed to participate and were enrolled in the study, resulting in an acceptance rate of 48.85%.

Measures
Marital quality was measured with the Dyadic Adjustment Scale (DAS) [17].The DAS is a 32-item tool developed to measure the quality of marriage and similar dyadic relationships.The DAS yields a global score as well as scores on four subscales: affectional expression (AE), dyadic consensus (DC), dyadic cohesion (DCh), and dyadic satisfaction (DS).A cut-off total score of 107 or lower is considered indicative of poor marital quality.
Women's mental health was assessed using the Selfrating Depression Scale (SDS) [18].The SDS comprises 20 items that rate the affective, psychological, and somatic symptoms associated with depression.Responses to items are rated on a scale of 1 to 4, with higher scores indicating more frequent symptoms.10 items are positively worded, while the remaining 10 are negatively worded.Behavior and somatic symptoms explain approximately 50% of the total possible score on the SDS.
These two scales exhibit good test-retest reliability and concurrent validity, along with satisfactory construct validity.

Procedure and Study Design
The subjects were informed of the study's purpose, and written informed consent was obtained from all participants.All couples followed standardized treatment pro-tocol for AID.Participants were requested to complete the questionnaire, which included sociodemographic and clinical information, as well as DAS and SDS, in the morning of insemination.A self-assessment of the sociodemographic questionnaire reliability was conducted using Cronbach's alpha, which yielded a score of 0.80, indicating good internal consistency and reliability.
The follow-up lasted from 2016 to 2022, a total of 6 years.46 participants declined to respond to the follow-up questionnaires, and 2 were excluded due to divorce, while 29 participants were lost to follow-up due to loss of contact.Finally, 51 subjects participated in the 6-year follow-up and completed the electronic questionnaires distributed through the hospital's follow-up system.Through statistical analysis, we aim to explore whether pregnancy is a significant factor influencing participants' marital quality and depression levels.

Statistical Analysis
Data analysis was performed using IBM Statistical Package for Social Sciences (SPSS Inc.Released 2008.SPSS Statistics for Windows, Version 17.0.Chicago, IL, USA).Continuous variables were presented as mean ± standard deviation (SD), while categorical variables were presented as frequency (percentage).Correlation between DAS and demographic characteristics was analyzed using Pearson correlation coefficient, independent samples t-test and Mann-Whitney U tests, as well as SDS and demographic characteristics.Potential factors related to the risk of marital quality were identified.Categorical variables between groups were compared using Chi-square tests.Independent t-tests were employed for normally distributed continuous outcomes, while non-normally distributed continuous outcomes were compared using Mann-Whitney U tests.A p-value of p < 0.05 was considered to be statistically significant.Two-tailed tests were used.

Results
As was shown in Table 1, 76 (59.4%) had a total DAS score of >107, while the remaining participants had a DAS score of ≤107, indicating that poor-quality marriages accounted for 40.6% of women with AID.Significant differences in education level, current employment status, duration of infertility and SDS score were found between the two groups.
In order to explore risk factors of low DAS score, we employed multiple regression analysis.DAS scores were found to be significantly correlated with the duration of marriage, education level, remarriage, and SDS score (Table 2).Stratified analyses by marriage age, educational level, and marriage status are presented in Table 3. Women with a longer duration of marriage obtained lower DAS scores in each subscale.Moreover, women with more advanced degrees had higher DAS scores, particularly in areas of AE, DC, DCh, and DS.
The females were grouped according to the pregnancy outcome after AID: the pregnant group and the nonpregnant group (Table 4).Among them, 45 cases were pregnant, resulting in a pregnancy rate of 35.16%.The mean ± SD ages of the pregnant group and non-pregnant group were 27.40 ± 3.40 and 30.64 ± 4.39, respectively, and were significantly different (p = 0.000).The age of the female was the only patient factor found to significantly affected the success of pregnancy.
Six years after AID, a follow-up regarding marital quality was initiated.A total of 51 returned questionnaires were analyzed to compare pre-versus post-intervention outcomes (Table 5).After 6 years, the SDS of women undergoing AID remained stable.However, the DAS scores were not ideal.Indeed, data revealed that the DAS score was statistically lower at the 6-year follow-up (106.19 ± 20.17) compared to the year of AID (114.49± 17.65), particularly in the areas of DCh and DS.No differences in DAS and SDS were observed between the pregnant group and the non-pregnant groups (Table 6).Pregnancy did not appear to improve marital quality.

Discussion
Marriage is a significant life event that profoundly affects couples within society.Both physical and mental well-being are important factors within this relationship.Marital happiness tends to be impacted among infertile couples [19].Anxiety and depression levels tend to be higher for females with infertility compared to those with heart disease or undergoing AID [20].Prolonged infertility duration typically correlates with a decrease in marital satisfaction, potentially resulting in alienation of mutual affection and, in some cases divorce [21].The set of problems stemming from infertility has already become an inevitable social issue, drawing significant attention from both domestic and international scholars [22].Currently, there are no previous report in the literature of marital quality and de-pression among women undergoing AID due to male irreversible azoospermia.This study is designed to investigate the current characteristics of marital quality and depression among these women via DAS and SDS.The findings aim to establish a theoretical foundation for future psychological interventions and health education tailored to this group, employing a biopsychosocial medical model.
According to historical statistics, male infertility accounts for approximately half of infertility [23].In China, AID is primarily used in the treatment of male infertility, holding promise for male irreversible azoospermia [6].However, it raises several ethical and moral questions due to the fact that the source of the sperm is not the patient's husband.Women may have concerns about the source and quality of sperm, as well as the appearance and health of the child following conception.Additionally, they may worry about whether the child will seek out their biological father.Furthermore, these women may have concerns about the risk of child abuse and abandonment by their husbands due to the lack of a biological relationship.They may also worry about the potential for husbands to not share the workload of childcare, presenting significant challenges to traditional families as a result of this type of ART.In this study, women received AID treatment not due to their own impaired fertility but because of male irreversible azoospermia.Despite this, women bear a greater sociocultural and psychological burden, as well as experience more stress related to infertility in much of society [24,25].As a result, the women consistently experienced strong negative emotions, including depression, anxiety, and psychological pain, upon learning of their husbands' diagnosis of irreversible azoospermia, leaving them with only one option: AID.
In the present study, it was found that the level of marital adjustment was low among couples affected by male irreversible azoospermia in China, alongside a prevalence of depressive symptoms.Prior research also reported an association between marital quality and psychological issues [26].Moreover, as the duration of marriage increased, women undergoing AID obtained a significantly lower total DAS score across all subscales.Women who had been married for less than 5 years had the highest marital adjustment level.However, over time, the level of marital adjustment declined.One plausible explanation for these results is that the prolonged duration of infertility may increase the agerelated risk of treatment failure for infertility.Therefore, the chances of achieving pregnancy are also reduced.Moreover, in this study, the educational level was shown to have a positive effect on the DAS score.Individuals with higher levels of education were more likely to have access to medical healthcare services, particularly regarding infertility issues.Another interpretation could be that highly educated women exhibited more tolerance to accept a child-free life.
The success rate of pregnancy following AID was found to be satisfactory.Previous studies have identified the age of infertile women as the primary factor affecting the success rate of AID, with a finding consistent with the results of the present study [27].Cardey-Lefort et al. [28] concluded that there was a negative correlation between women's age and the live birth rate, and it seemed that the only factor with a significant effect on the pregnancy rate and live birth rate was total motile sperm count.Neuroendocrine studies suggested prolonged periods of tension, anxiety, or depression in women it may disrupt the normal functioning of neurotransmitters in the brain.This disruption can inhibit the secretion of gonadotropins and gonadal hormones, ultimately leading to ovulation failure [29].
The women in the currently study were followed up for 6 years to further investigate their marital quality.Re-grettably, only 51 valid questionnaires were returned, limiting the scope of our study.The unexpected loss of subjects during the follow-up period was primarily attributed to the reluctance of most couples were unwilling to discuss their experience with AID, often feeling ashamed or even fearful.Consequently, many of them refused to return for further visits.Moreover, some subjects were lost to follow-up due to a change in their phone number.An analysis was performed on the DAS and SDS of women undergoing AID during the 6-year follow-up.The statistical analysis showed a decline in the marriage satisfaction after 6 years.Interestingly, there were no significant differences found in DAS between the pregnancy group and  non-pregnancy group.Our hypothesis suggested that the birth of a baby would lead to an increase in women's satisfaction with marital quality.However, the presence one of a child conceived through AID or not was not associated with DAS after 6 years.The observed phenomenon seemed hard to explain within existing conceptual frameworks.Nevertheless, it is plausible that the small sample size may have limited the accuracy of the findings and affecting the representativity of the reality.
How to deal with fertility issues harmoniously, a challenge that both members of the couple must face and solve.Hence, in addition to seeking infertility treatment, targeted interventions are warranted according to the couples' psychological characteristics.Primarily, beyond congenital causes, the low quality of sperm in men can often be influenced by unhealthy lifestyle habits.Therefore, it is important to prioritize health education at this demographic, focusing on raising awareness about the detrimental impact of bad habits on conception rates.Secondly, it is crucial to respect the sense of privacy, especially considering that men with irreversible azoospermia often experience psychological distress.Moreover, it is recommended that medical personnel ensure a comfortable environment and guidance for effective communication between the man and his spouse.
The current study presents several limitations that should be acknowledge.Firstly, the main limitation lies in the small sample size, potentially restricting the generalizability of the findings.Secondly, the study was conducted at a single hospital in China, which could introduce selection bias and thereby limit the external validity of the results.Additionally, reliance on self-reported measures to assess marital quality and depression may introduce subjective biases and measurement errors.Furthermore, the study's exclusive focus on women undergoing AID may overlook the potential impact of male partners' perspectives on marital quality and mental health outcomes.Lastly, it is important to consider that cultural and societal factors unique to the Chinese context may influence the interpretation and generalizability of the findings to other cultural settings.Future research endeavors should aim to address these limitations by employing prospective designs and incorporating multi-method assessments in order to enhance the robustness and applicability of the study findings.

Conclusions
In conclusion, women undergoing AID due to male irreversible azoospermia exhibit poor marital quality and elevated levels of depression.Marital adjustment in women undergoing AID is associated with the duration of marriage, education level, remarriage, and SDS score.The findings of this study underscore the importance of providing psychosocial support to these women.Clinicians should prior-itize addressing the emotional well-being and marital quality of these women throughout the AID process, offering tailored counseling services to meet their specific needs.

Table 1 . Sociodemographic and clinical characteristics of women undergoing AID.
Note: Values are n (%) or mean ± SD. * indicates p < 0.05.SDS and age were tested for normal distribution using the t-test.The duration of infertility, remarriage, educational level, current employment status, yearly household income, and financial support were tested using the Chi-square test.AID, artificial insemination by donor; DAS, Dyadic Adjustment Scale; SDS, Self-rating Depression Scale; SD, standard deviation.

Table 2 . Multiple regression analysis of DAS score and variables in women undergoing AID.
dren.Ethical approval for this study was obtained from the Institutional Review Board of Women's Hospital, Zhejiang University School of Medicine (Approval No. 20150010).

Table 4 . The characteristics in women undergoing AID between pregnant group and non-pregnant group.
The duration of infertility, remarriage, educational level, current employment status, yearly household income, and financial support were tested using the Chi-square test.AID, artificial insemination by donor; DAS, Dyadic Adjustment Scale; SDS, Self-rating Depression Scale; SD, standard deviation.
Note: Values are n (%) or mean ± SD. * indicates p < 0.05.DAS, SDS, and age were tested for normal distribution using the t-test.

Table 6 . The DAS and SDS in women undergoing AID between pregnant group and non-pregnant group at 6-year follow-up.
Note: Values are mean ± SD.Quantitative data were tested for normal distribution using the t-test.AID, artificial insemination by donor; DAS, Dyadic Adjustment Scale; AE, affectional expression; DC, dyadic consensus; DCh, dyadic cohesion; DS, dyadic satisfaction; SDS, Self-rating Depression Scale; SD, standard deviation.