Alternative 2

RESEARCH Open Access

Prevalence and associated factors of erectile dysfunction, psychological disorders, and sexual performance in primary vs. secondary infertility men Jianxiong Ma1,2,3†, Yingying Zhang1†, Binghao Bao2†, Wangqiang Chen4, Haisong Li2* and Bin Wang2*

Abstract

Background: Many infertile couples might experience erectile dysfunction (ED) and significant changes in the quality of sexual life and psychological state though information is limited in secondary infertile men in China. To determine whether primary or secondary infertility is associated with ED, psychological disorders, and sexual performance.

Methods: This was a cross-sectional survey conducted at the Dongzhimen Hospital of Beijing University of Chinese Medicine (06/2019-01/2020). The participants completed a questionnaire including general information, sexual life, simplified International Index of Erectile Function (IIEF-5), Patient Health Questionnaire-9 (PHQ-9), and 7-item Generalized Anxiety Disorder Scale (GAD-7). Multivariable logistic regression was used to identify the factors associated with ED, depression, and anxiety.

Results: ED was more frequent in secondary vs. primary infertility (46.5 % vs. 26.7 %, P < 0.001). Compared with men with primary infertility, those with secondary infertility showed lower IIEF-5 scores (P < 0.001), higher occurrence of TOIF (P = 0.001), had a higher awareness of partner’s ovulation when having ED (P = 0.001), lower GAD-7 scores (P = 0.016), lower libido (P = 0.005), fewer intercourses per month (P = 0.001) and a lower sexual satisfaction score (P = 0.027). In the multivariate analysis, primary infertility was found to be an independent risk factor of anxiety (OR: 1.812, 95 %CI: 1.015–3.236). Some overlap is observed in factors associated with ED, psychological disorders, and sexual performance between primary and secondary infertility, but some factors are distinct.

Conclusions: The prevalence of ED in secondary infertility men was higher than that of primary infertility men, and the quality of sexual life was decreased. Primary infertility is an independent risk factor of anxiety.

Keywords: Infertility, Erectile dysfunction, Depression, Anxiety, Risk factors

© The Author(s). 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

* Correspondence: [email protected]; [email protected] †Jianxiong Ma, Yingying Zhang and Binghao Bao contributed equally to this work. 2Department of Andrology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China Full list of author information is available at the end of the article

Ma et al. Reproductive Biology and Endocrinology (2021) 19:43 https://doi.org/10.1186/s12958-021-00720-5

Introduction Infertility is the inability to conceive after 1 year of un- protected sexual intercourse [1–3]. Infertility occurs in about 15 % of reproductive-aged couples worldwide and is more common in developing countries [1]. Most re- searchers and clinicians habitually refer to those without pregnancy as primary infertility, while those with infertil- ity after a first pregnancy or for 12 months after stop- ping contraceptives as secondary infertility [4]. In 2016, the family planning policy changed from a

one-child policy to a two-child policy in China, which rekindles the need for births in many families. Still, many couples who want to have a second child may be beyond the appropriate age and be with low fertility, resulting in a large increase in the number of patients with secondary infertility. Many infertile couples will experience multiple prob-

lems, especially significant changes in the quality of sex- ual life and psychological state [5–7]. Previous studies showed that the incidence of erectile dysfunction (ED) in men with infertility is higher than that in the general population [8–10]. Infertile men also often experience depression and anxiety due to self-inflicted, couple, and social pressure [11, 12]. The negative impacts of depres- sion and anxiety on couples’ sexual life, marriage happi- ness, and quality of life are self-evident. In different studies, the reported prevalence of depression and anx- iety in infertile men ranged from 4.9 to 38 % [13–16]. In addition, there is an interaction between ED and psycho- logical condition, suggesting that these aspects have to be monitored in infertile couples [17, 18]. Nevertheless, there is limited information on the incidence and related risk factors of ED, depression, and anxiety in secondary infertile men in China. It might be beneficial to investi- gate this population and obtain relevant clinical data to assist clinicians in improving the treatment plans for in- fertile couples. Therefore, this study aimed to determine whether pri-

mary or secondary infertility is associated with ED, psy- chological disorders, and sexual performance and to investigate whether the associated factor of ED, psycho- logical disorders, and sexual performance are different between men with primary and secondary infertility. The results might help clinicians make better decisions when managing infertility.

Methods Study design and participants This was a cross-sectional survey conducted at the an- drology clinic of Dongzhimen Hospital of Beijing Uni- versity of Chinese Medicine from June 2019 to January 2020. The study was approved by the medical ethics committee of Dongzhimen Hospital of Beijing University

of Chinese Medicine. Written informed consent was ob- tained from each participant. The inclusion criteria were: (1) the male partner of a

married couple with pregnancy plans; (2) settled down and living with his wife; (3) regular intercourse with wife and without contraception for at least one year [19]; (4) sought medical help because his wife could not conceive; and (5) agreed to participate in the survey and signed the informed consent form. The exclusion criteria were: (1) obvious genital malformation; (2) severe cardiovascu- lar or cerebrovascular disease; (3) liver, kidney, or mental disease; or (4) hypertension, diabetes mellitus, or chronic obstructive pulmonary disease.

Questionnaires The participants were surveyed using an anonymous questionnaire that included general information (age, height, weight, education level, marriage duration, and couple’s relationship), fertility assessment (primary or secondary infertility, cause of infertility, and history of semen collection for assisted reproductive technology), International Index of Erectile Function (IIEF-5), sexual life (awareness of partner’s ovulation period, timely ovu- latory intercourse failure [TOIF], self-reported sexual de- sire, intercourse frequency, intra-vaginal ejaculation latency time [IELT], and sexual satisfaction), Patient Health Questionnaire-9 (PHQ-9), and 7-item General- ized Anxiety Disorder Scale (GAD-7). Each participant filled out a paper questionnaire and

recorded their sexual activity six months before the sur- vey. It took about 5–10 min to complete the question- naire. Andrology physicians or medical interns with uniform training guided the participants to complete the questionnaire independently and explained the items to those with reading or understanding problems. The IIEF-5 was used to assess the occurrence and se-

verity of erectile dysfunction (ED). The IIEF-5 score ranges from 5 to 25, with 22–25 indicating no ED, 12– 21 indicating mild ED, 8–11 indicating moderate ED, and 5–7 indicating severe ED [20]. The Chinese version of IIEF-5 has been validated [21]. TOIF was defined as the inability to have an erection or maintaining an erec- tion for satisfactory ejaculation during intercourse with the female partner during the ovulation period. Sexual satisfaction was assessed using a Likert-7 scale, with 1 to 7 reflecting very dissatisfied to very satisfied. The PHQ-9 [22] was used for the screening of depression and the as- sessment of symptom severity. It consists of nine items, each scored 0 to 3. PHQ-9 scores of 0–4 indicated no depressive symptom, 5–9 indicated mild depressive state, and ≥ 10 indicated confirmed depression, and its sensi- tivity and specificity are above 90 % [23]. The PHQ-9 has been validated in Chinese [24]. GAD-7 [25] was used for the screening of generalized anxiety and the

Ma et al. Reproductive Biology and Endocrinology (2021) 19:43 Page 2 of 10

assessment of symptom severity. It consists of seven items, each scored 0 to 3. The GAD-7 score was 0–4 for no anxiety symptom, 5–7 for mild anxiety state, ≥ 8 for confirmed anxiety, and its sensitivity and specificity were above 90 % [26]. The GAD-7 has been validated in Chin- ese [27].

Statistical analysis Data were analyzed using SPSS 21.0 (IBM, Armonk, NY, USA). Continuous variables were expressed as means ± standard deviations. Continuous data with a normal distribution were analyzed using Student’s t- test, while data with a skewed distribution were ana- lyzed using the Mann-Whitney U-test. Categorical variables were expressed as frequencies (percentages) and analyzed using the chi-square test. Variables with P < 0.20 in the univariable logistic regression analyses were included in the multivariable stepwise logistic regression analysis to analyze the independent factors associated with ED, depression, and anxiety. The odds

ratios (ORs) and 95 % confidence intervals (CIs) were calculated. P-values < 0.05 were considered statistically significant.

Results Characteristics of the participants This study enrolled 387 married men who met the study inclusion criteria. The participants were divided into the primary (n = 258) and secondary (n = 129) infertility groups according to whether they already had children. The patient characteristics are summarized in Table 1. Compared with the patients who had primary infertility, those with secondary infertility were older (38.8 ± 5.7 vs. 31.4 ± 3.8 years, P < 0.001), had a higher body mass index (BMI) (24.9 ± 3.4 vs. 24.3 ± 3.1 kg/m2, P = 0.05), had a higher monthly income (P = 0.001), had a lower educa- tion level (P = 0.003), had a longer marriage (6.8 ± 5.8 vs. 3.2 ± 2.1 years, P < 0.001), and showed a higher propor- tion of infertility caused by both male and female factors (P < 0.001).

Table 1 Characteristics of the patients

Characteristics Total (n = 387)

Primary infertility (n = 258)

Secondary infertility (n = 129)

P

Age (years), mean ± SD 33.9 ± 5.7 31.4 ± 3.8 38.8 ± 5.7 < 0.001

BMI (kg/m2), mean ± SD 24.5 ± 3.2 24.3 ± 3.1 24.9 ± 3.4 0.05

Monthly income (RMB), n (%) 0.001

0-5000 10 (2.6) 9 (3.5) 1 (0.8)

5001-10,000 44 (11.4) 30 (11.6) 14 (10.9)

10,001–15,000 114 (29.5) 85 (32.9) 29 (22.5)

15,001–20,000 131 (33.9) 89 (34.5) 42 (32.6)

> 20,000 88 (22.7) 45 (17.4) 43 (33.3)

Education level, n (%) 0.003

Junior high school and lower 10 (2.6) 3 (1.2) 7 (5.4)

High school 62 (16.0) 32 (12.4) 30 (23.3)

University 228 (58.9) 160 (62.0) 68 (52.7)

Above university 87 (22.5) 63 (24.4 %) 24 (18.6)

Marriage duration (years), mean ± SD 4.4 ± 4.1 3.2 ± 2.1 6.8 ± 5.8 < 0.001

Couple’s relationship, n (%) 0.194

Average 40 (10.3) 23 (8.9) 17 (13.2)

Good 347 (89.7) 235 (91.1) 112 (86.8)

ART semen collection, n (%) 0.743

No 286 (73.9) 192 (74.4) 94 (72.9)

Yes 10 1(26.1) 66 (25.6) 35 (27.1)

Cause of infertility, n (%) < 0.001

Male factors 181 (46.8) 128 (49.6) 53 (41.1)

Female factors 47 (12.1) 33 (12.8) 14 (10.9)

Both factors 100 (25.8) 49 (19.0) 51 (39.5)

Unknown 59 (15.2) 48 (18.6) 11 (8.5)

SD standard deviation, BMI body mass index, ART assisted reproduction technology

Ma et al. Reproductive Biology and Endocrinology (2021) 19:43 Page 3 of 10

Erectile dysfunction, psychological disorders, and quality of sexual life among infertile men Table 2 shows that there are significant differences in ED (including prevalence, IIEF-5 score and TOIF), GAD score and sexual life (including sexual life satisfaction score and frequency) between primary and secondary infertile men.

Indeed, compared with men with primary infertility, those with secondary infertility showed a higher frequency of ED (46.5 % vs. 26.7 %, P < 0.001). This difference is sup- ported by a lower IIEF-5 scores in men with secondary in- fertility (20.0 ± 4.6 vs. 21.7 ± 3.5, P < 0.001). In addition, a

Table 2 Erectile dysfunction, psychological disorders, and quality of sexual life among infertile men

Total (n = 387)

Primary infertility (n = 258)

Secondary infertility (n = 129)

P

Erectile dysfunction

Severity of ED, n (%) < 0.001

Without ED 258 (66.7) 189 (73.3) 69 (53.5)

Mild 115 (29.7) 65 (25.2) 50 (38.8)

Moderate 11 (2.8) 3 (1.2) 8 (6.2)

Severe 3 (0.8) 1 (0.4) 2 (1.6)

IIEF-5 score, mean ± SD 21.2±3.9 21.7 ± 3.5 20.0 ± 4.6 < 0.001

TOIF, n (%) 0.001

Never appeared 270 (69.8) 191 (79.6) 79 (62.7)

< 50 % 70 (18.1) 38 (15.8) 32 (25.4)

≥ 50 % 26 (6.7) 11 (4.6) 15 (11.9)

Partner ovulation, n (%) 0.570

Known 366 (94.6) 240 (93.0) 126 (97.7)

Unknown 21 (5.4) 18 (7.0) 3 (2.3)

People who know partner’s ovulation, n (%) 0.001

Without ED 270 (74.0) 191 (79.6) 79 (62.7)

With ED 95 (26.0) 38 (15.8) 32 (25.4)

Psychological disorder

PHQ-9 score, mean ± SD 5.5 ± 4.1 5.5 ± 4.2 5.5 ± 3.9 0.685

Severity of depression, n (%) 0.621

None 185 (47.8) 127 (49.2) 58 (45.0)

Mild 144 (37.2) 91 (35.3) 53 (41.1)

Confirmed diagnosis 58 (15.0) 40 (15.5) 18 (14.0)

GAD-7 score, mean ± SD 6.2 ± 3.8 6.8 ± 4.2 6.2 ± 3.8 0.016

Severity of anxiety, n (%) 0.075

None 152 (39.3) 96 (37.2) 56 (43.4)

Mild 100 (25.8) 63 (24.4) 37 (28.7)

Confirmed diagnosis 135 (34.9) 99 (38.4) 36 (27.9)

Sexual life

Sexual desire, n (%) 0.005

Normal 229 (59.1) 167 (65.0) 62 (48.4)

General 110 (28.4) 66 (25.7) 44 (34.4)

Low 46 (38.7) 24 (9.3) 22 (17.2)

Intercourse frequency per month, mean ± SD 5.3 ± 2.1 5.6 ± 2.1 4.8 ± 2.0 0.001

IELT (min), mean ± SD 5.9 ± 3.6 6.0 ± 3.5 5.7 ± 3.6 0.299

Sexual satisfaction score, mean ± SD 5 (4–6) 6 (4–6) 5 (3–6) 0.027

SD standard deviation, ED erectile dysfunction, IIEF-5 simplified International Index of Erectile Function, TOIF timely ovulation intercourse failure, IELT intra-vaginal ejaculation latency time, PHQ-9 Patient Health Questionnaire-9, GAD-7 7-item Generalized Anxiety Disorder Scale

Ma et al. Reproductive Biology and Endocrinology (2021) 19:43 Page 4 of 10

higher occurrence of TOIF was found in the secondary fertile group (37.3 % vs. 20.4 %, P = 0.001). Table 2 also shows that the severity of anxiety and depression and the PHQ-9 score were not significantly different between the two groups, but the GAD-7 scores was lower in the sec- ondary infertility group (P = 0.016), suggesting that anxiety symptoms were more severe in the secondary infertility group than in the primary infertility group. Regarding sex- ual life, the men with secondary fertility had lower libido (P = 0.005), fewer intercourses per month (P = 0.001), and a lower sexual satisfaction score (P = 0.027) than the men with primary infertility. Figure 1 shows that the prevalence of ED and sexual life

satisfaction score were significantly different by age in pri- mary infertile men but not secondary infertile men. In- deed, the prevalence of ED was higher among men with primary infertility > 35 years of age compared with those ≤ 35 years of age (P = 0.002). The sexual satisfaction was lower among men with primary infertility > 35 years of age compared with those ≤ 35 years of age (P = 0.020). Inter- course frequency was lower in men > 35 years of age com- pared with those < 35 years of age, both in primary (P = 0.006) and secondary (P = 0.024) infertility.

Multivariable logistic regression analysis of ED, depression, and anxiety risk factors in all patients Table 3 shows that primary infertility is an independent risk factor of anxiety. Indeed, IIEF-5 score (OR = 0.87, 95 %CI: 0.81–0.93, P < 0.001), primary infertility (OR = 0.55, 95 %CI: 0.31–0.99, P = 0.044), ART semen collec- tion (OR = 3.25, 95 %CI: 1.84–5.73, P < 0.001), female factor (OR = 0.16, 95 %CI: 0.06–0.42, P < 0.001), both male and female factor infertility (OR = 0.17, 95 %CI: 0.09–0.33, P < 0.001), and unknown cause of infertility

(OR = 0.26, 95 %CI: 0.12–0.59, P = 0.001) were independ- ently associated with anxiety (Table 3). Table 3 also shows that other factors are independ-

ently associated with ED, psychological disorders, and sexual performance. Among all patients, marriage dur- ation (OR = 1.09, 95 %CI: 1.01–1.17, P = 0.019), inter- course frequency (PR = 0.74, 95 %CI: 0.64–0.87, P < 0.001), TOIF (OR = 7.25, 95 %CI: 3.87–13.56, P < 0.001), and IELT (OR = 0.80, 95 %CI: 0.72–0.89, P < 0.001) were independently associated with ED (Table 3). Low libido (OR = 3.51, 95 %CI: 1.11–8.99, P = 0.031), sexual satisfac- tion score (OR = 0.61, 95 %CI: 0.46–0.80, P = 0.001), assisted reproductive technology (ART) semen collection (OR = 3.39, 95 %CI: 1.69–6.82, P < 0.001), both male and female factor infertility (OR = 0.37, 95 %CI: 0.16–0.89, P = 0.024), and unknown cause of infertility (OR = 0.12, 95 %CI: 0.02–0.99, P = 0.048) were independently associ- ated with depression (Table 3).

Multivariable logistic regression analysis of ED, depression, and anxiety risk factors according to the type of infertility Table 4 shows that the associated factors of primary and secondary infertile men are different. Indeed, TOIF was independently associated with ED in primary (OR = 6.09, 95 %CI: 2.55–14.52, P < 0.001) and secondary infertility (OR = 9.23, 95 %CI: 2.73–31.20, P < 0.001). The sexual satisfaction scores were independently associated with ED in primary (OR = 0.33, 95 %CI: 0.23–0.47, P < 0.001) and secondary infertility (OR = 0.23, 95 %CI: 0.14–0.40, P < 0.001) (Table 4). Low libido (OR = 5.50, 95 %CI: 1.34–22.69, P = 0.018), sex-

ual satisfaction scores (OR = 0.57, 95 %CI: 0.40–0.82, P = 0.002), and unknown cause of infertility (OR = 0.10, 95 %CI:

Fig. 1 Erectile dysfunction, psychological disorders, and quality of sexual life by age among patients with different infertile type. a Prevalence of erectile dysfunction among patients with different infertility type and by age. Comparisons of age groups, by infertility type, for (b) PHQ-9, c GAD- 7 score, d sexual satisfaction, e intercourse frequency, and f intra-vaginal ejaculation latency time (IELT). ** represents P < 0.05

Ma et al. Reproductive Biology and Endocrinology (2021) 19:43 Page 5 of 10

0.01–0.90, P = 0.040) were independently associated with de- pression in primary infertility, but not in secondary infertility. ART semen collection was independently associated with de- pression both in primary (OR = 4.29, 95 %CI: 1.72–10.71, P = 0.002) and secondary (OR = 3.62, 95 %CI: 1.12–11.76, P = 0.032) infertility. IIEF-5 scores were associated with de- pression in secondary infertility (OR = 0.82, 95 %CI: 0.73– 0.92, P = 0.001) (Table 4). TOIF (OR = 4.00, 95 %CI: 1.80–8.90, P = 0.001), female

factor infertility (OR = 0.20, 95 %CI: 0.07–0.57, P = 0.0.003), and unknown factor infertility (OR = 0.28, 95 %CI: 0.12–0.69, P = 0.006) were independently associ- ated with anxiety in primary infertility. BMI (OR = 0.78, 95 %CI: 0.65–0.92, P = 0.004), IIEF-5 scores (OR = 0.72, 95 %CI: 0.59–0.87, P = 0.001), IELT (OR = 0.73, 95 %CI: 0.56–0.95, P = 0.019), and sexual satisfaction scores (OR = 2.86, 95 %CI: 1.44–5.71, P = 0.003) were

independently associated with anxiety in secondary in- fertility. Finally, ART semen collection (primary: OR = 3.44, 95 %CI: 1.65–7.17, P = 0.001; secondary: OR = 3.26, 95 %CI: 1.10–9.67, P = 0.034) and both male and female factor infertility (primary: OR = 0.10, 95 %CI: 0.04–0.26, P < 0.001; secondary: OR = 0.17, 95 %CI: 0.05–0.54, P = 0.003) were associated with the two types of infertility (Table 4).

Discussion Secondary infertility is a particular type of infertility and mainly refers to couples that have offspring but cannot successfully conceive again. In China, there are many couples with secondary infertility, and the number has surged in recent years due to the change in the family planning policies. Although these couples have a strong wish for pregnancy, most of them are older than the op- timal reproductive age, with difficulties in conceiving naturally [28, 29]. The purpose of this study was to determine whether

primary or secondary infertility is associated with ED, psychological disorders, and sexual performance, and to investigate whether the associated factor of ED, psycho- logical disorders, and sexual performance are different between men with primary vs. secondary infertility. The results suggest that the frequency of ED in men of Chin- ese couples with secondary infertility was higher than that of men in the primary infertility group (46.5 % vs. 26.7 %), and the quality of sexual life was lower. Some overlap is observed in factors associated with ED, psy- chological disorders, and sexual performance between primary and secondary infertility, but some factors are distinct. A previous study showed that the frequency of sexual

life during pregnancy attempts is increased compared to usual, and the median monthly intercourse frequency is 7 [30], which seems to require male partners to maintain better sexual function to satisfy the couple’s sexual life. On the other hand, the present study showed that the male partners in the secondary infertility group showed worse sexual function and significantly lower quality of sexual life compared with the males in the primary infer- tility group. About 17.2 % of the men had a long period of low sexual desire, the median monthly sexual fre- quency was 4.5, and 46.5 % vs. 26.7 % of the male part- ners with secondary and primary infertility, respectively, reported ED. Although the incidence of ED was lower than the 57.8 % observed in another Chinese study [31], this frequency was still higher than 40.6 % among men aged > 40 years in China [32]. In addition to factors such as age, marriage duration, and couple’s relationship, it should be considered that unresolved infertility might play a role in worsening ED. Therefore, male partners in secondary infertile couples have low levels of overall

Table 3 Multivariable logistic regression analysis of ED, depression, and anxiety risk factors

Variables OR 95 % CI P

Erectile dysfunction

Marriage duration (years) 1.088 1.014–1.168 0.019

Intercourse frequency per month 0.744 0.639–0.867 < 0.001

TOIF 7.247 3.872–13.564 < 0.001

IELT (min) 0.797 0.715–0.887 < 0.001

Depression

Sexual desire

Normal Reference

General 0.954 0.391–2.328 0.917

Low 3.514 1.107–8.987 0.031

Sexual satisfaction score 0.605 0.456–0.803 0.001

ART semen collection 3.391 1.686–6.818 < 0.001

Cause of infertility

Male factors Reference

Female factors 0.000 0 0.997

Both factors 0.373 0.159–0.887 0.024

Unknown 0.124 0.016–0.985 0.048

Anxiety

IIEF-5 score 0.870 0.812–0.931 < 0.001

Primary infertility 1.812 1.015–3.236 0.044

ART semen collection 3.247 1.839–5.734 < 0.001

Cause of infertility

Male factors Reference

Female factors 0.162 0.063–0.418 < 0.001

Both factors 0.169 0.087–0.327 < 0.001

Unknown 0.260 0.115–0.589 0.001

OR odds ratio, CI confidence interval, IIEF-5 simplified International Index of Erectile Function, TOIF timely ovulation intercourse failure, IELT intra-vaginal ejaculation latency time, ART assisted reproduction technology

Ma et al. Reproductive Biology and Endocrinology (2021) 19:43 Page 6 of 10

sexual satisfaction. Although the multivariable analysis indicated that the factors affecting ED were the same be- tween primary and secondary infertility, the magnitude of their contribution was different. TOIF frequently occurs in couples with childbearing

needs. It is defined as a failure of ovulation and inter- course coordination, which is a type of situational ED. The occurrence of TOIF is often related to low libido caused by forced sexual intercourse, and it af- fects the chance of natural conception. Therefore, male reproductive function and sexual function need to be considered as a whole [30]. In the present study, TOIF was found in the two groups of partici- pants, and both groups showed high awareness rates

of ovulation of their female partners, which was higher than in a previous study [31]. Nevertheless, the frequency of TOIF in the secondary infertility group was significantly higher than that in the primary in- fertility group, which indicates that clinically, couples with secondary infertility should pay special attention to their intercourse efficiency. Of course, the fre- quency of intercourse failure in males with ED signifi- cantly increased during ovulation. This situation was observed in both the secondary and primary infertility groups, indicating that if there is a previous history of ED, it might be necessary to consider giving erectile dysfunction drugs that could increase the success rate of timely sexual intercourse during ovulation.

Table 4 Multivariable logistic regression analysis of ED, depression, and anxiety risk factors among primary and secondary infertile men

Variable Primary infertile men Secondary infertile men

OR 95%CI P OR 95%CI P

Erectile dysfunction

TOIF 6.091 2.549-14.522 <0.001 9.226 2.728-31.199 <0.001

Sexual satisfaction score 0.326 0.226-0.470 <0.001 0.232 0.135-0.398 <0.001

Depression

Sexual desire

Normal Reference

General 0.813 0.280-2.355 0.702 - - -

Low 5.501 1.340-22.693 0.018 - - -

Sexual satisfaction score 0.570 0.397-0.819 0.002 - - -

ART semen collection 4.292 1.720-10.711 0.002 3.621 1.115-11.763 0.032

Cause of infertility

Male factors Reference - - -

Female factors 0 0 0.998 - - -

Both factors 0.304 0.086-1.073 0.064 - - -

Unknown 0.101 0.011-0.898 0.040 - - -

IIEF-5 score - - - 0.821 0.732-0.922 0.001

Anxiety

BMI - - - 0.776 0.654-0.921 0.004

TOIF 3.998 1.796-8.897 0.001 - - -

ART semen collection 3.437 1.647-7.173 0.001 3.255 1.095-9.672 0.034

Cause of infertility

Male factors Reference Reference

Female factors 0.196 0.067-0.571 0.003 0.117 0.011-1.212 0.072

Both factors 0.097 0.036-0.259 <0.001 0.171 0.054-0.544 0.003

Unknown 0.283 0.116-0.693 0.006 0.083 0.006-1.133 0.062

IIEF-5 score - - - 0.716 0.588-0.870 0.001

IELT (min) - - - 0.726 0.556-0.948 0.019

Sexual satisfaction score - - - 2.861 1.435-5.705 0.003

OR odds ratio, CI confidence interval, IIEF-5 simplified International Index of Erectile Function, TOIF timely ovulation intercourse failure, IELT intra-vaginal ejaculation latency time, ART assisted reproduction technology

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The occurrence of ED is often affected by a variety of factors, mainly divided into psychological, organic, and mixed types [8, 33, 34]. With the increase of age, the erectile function of men will gradually decline, and the degree of depression is more likely to affect the patient’s sexual desire and affect the erectile function [8, 33, 34]. In this study, sexual satisfaction in general was associ- ated with ED in men with secondary infertility, suggest- ing that older couples preparing for pregnancy should improve the quality of their sexual life from both emo- tional and physiological aspects, and the low frequency of intercourse can also predict the status of ED. It is worth noting that low sexual satisfaction was also an in- dependent risk factor for the occurrence of ED in male partners of couples with primary infertility. We believe that this is related to the fact that young men are more dependent on high expectations to induce erections. This is supported by the subgroup analysis that showed differences in ED and sexual satisfaction between youn- ger and older men. The degree of sexual desire in pa- tients with ED in the primary infertility group was not different from that of the secondary infertility group. The TOIF frequency of nearly 20 % of men in the pri- mary infertility group could explain this problem. Andrological diseases are mostly caused by physical and

mental disorders [8, 33, 34]. Many patients with androlo- gical diseases have different degrees of mental and psycho- logical problems. The incidence of depression and anxiety disorders in patients with andrological diseases is signifi- cantly higher than that in the general population [17, 35, 36]. Psychological factors are often important factors in- fluencing disease outcomes and communication between physicians and patients, especially for patients with andro- logical diseases [37]. The long time to prepare for preg- nancy and the uncertainty of the fertility outcome increase the stress of the husband and wife. This increas- ing pressure may not only bring negative emotions but may also affect male sexual and reproductive functions. A study analyzed the effects of psychological stress on male hormones and sperm quality of male partners, noting that psychological stress first reduces serum total testosterone levels and secondly increases serum luteinizing hormone and follicle-stimulating hormone levels, suggesting that stress management might be required to improve male fertility [38]. We included only male partners from infer- tile couples in our study and found that the incidence of depression in the men in the primary and secondary infer- tility groups was 15.5 % and 14.0 %, respectively, while the incidence of anxiety was 38.4 % and 27.9 %, without sig- nificant difference in the frequency of anxiety, but with a significantly higher GAD-7 anxiety scale score in primary infertility, indicating that men who are preparing for preg- nancy for the first time are more likely to have anxiety in the face of unpredictable fertility outcomes.

In this study, the multivariable logistic regression analyses showed that poor erectile function was inde- pendently associated with marriage duration, intercourse frequency, TOIF, and IELT. The higher TOIF frequency might explain why the prevalence of ED is higher in sec- ondary infertile men. Furthermore, sexual desire, sexual satisfaction, ART semen collection, and cause of infertil- ity were independently associated with depression, and IIEF-5 score, secondary infertility, ART semen collec- tion, and cause of infertility were independently associ- ated with anxiety. For men in the primary infertility group, TOIF and sexual desire were independently asso- ciated with ED, sexual desire, sexual satisfaction, ART semen collection, and cause of infertility were independ- ently associated with depression, and TOIF, ART semen collection, and cause of infertility were independently as- sociated with anxiety. In secondary infertility, TOIF and sexual satisfaction were independently associated with ED, ART semen collection, and IIED-5 scores were inde- pendently associated with depression, and body mass index (BMI), ART semen collection, cause of infertility, IIEF-5 score, IELT, and sexual satisfaction were inde- pendently associated with anxiety. Although TOIF ap- pears less frequently than men in the secondary infertility group, the psychological effects of TOIF ap- pear to be greater in men in the primary infertility group. Chinese men with infertility are prone to psycho- logical disorders [5, 6], and this should be considered in the management of such patients. This study has limitations. First, other scales of androlo-

gical issues (such as International-Prostatic Symptom Score and the National Institutes of Health Chronic Pros- tatitis Symptom Index) were not used, thus failing to re- fine the factors that could be associated with ED. Second, the study population was from specialized clinics and might not represent all men with infertility issues. In addition, the sample size of the present cross-sectional study was small. Third, the difference in age between the two fertility types is a confounding factor. Therefore, we conducted multivariable analyses and subgroup analyses. In the multivariable analysis, we found that primary infer- tility was an independent risk factor for anxiety. The de- sire and pursuit of an offspring might cause anxiety in the primary infertile population, while secondary infertile pa- tients might have less pressure on bearing a child since they already have a child. This is supported by the litera- ture [39]. Nevertheless, the results could help the clini- cians quickly and effectively identifying patients with ED, depression, and anxiety and propose management methods. In addition, it suggests that clinicians should pay close attention to the role of psychological factors when making a diagnosis or treatment in those patients. Of course, the study should also include female partners’ sex- ual function and psychological status, and evaluate male

Ma et al. Reproductive Biology and Endocrinology (2021) 19:43 Page 8 of 10

and female factors together, which will be supplemented in our subsequent studies.

Conclusions This study provides evidence that although primary vs. secondary infertility was not independently associated with ED, the prevalence of ED in male partners of cou- ples with secondary infertility in China was higher than that of the males in the primary infertility group and that they had decreased sexual quality of life. TOIF oc- curs more frequently in men with secondary infertility and might be one of the factors for male fertility disor- ders. Moreover, primary infertility is an independent risk factor for anxiety. The study suggests that when a male partner of a secondary infertile couple seeks medical help, clinicians should pay attention to combining sexual dysfunction and psychological treatment based on repro- ductive abnormalities.

Abbreviations ED: Erectile dysfunction; IIEF-5: International Index of Erectile Function; PHQ- 9: Patient Health Questionnaire-9; GAD-7: 7-item Generalized Anxiety Disorder Scale; TOIF: Timely ovulation intercourse failure; WHO: World Health Organization; ORs: Odds ratios; CIs: Confidence intervals

Authors’ contributions JM and WC carried out the studies, participated in collecting data, and drafted the manuscript. YZ and BB performed the statistical analysis and participated in its design. HL and BW participated in the acquisition, analysis, or interpretation of data and drafted the manuscript. All authors read and approved the final manuscript.

Funding This study was financially supported by the National Natural Sciences Foundation of China (#81804092 and 81704086), the Natural Science Foundation of Zhejiang Province, China (#LY19H270012 and GF20H270004), and the Hangzhou Health Science and Technology Plan Project (#2018A38). The funders played no roles in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.

Availability of data and materials The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Ethics approval and consent to participate The study was approved by the medical ethics committee of Dongzhimen Hospital of Beijing University of Chinese Medicine. Written informed consent was obtained from each participant.

Consent for publication Not Applicable.

Competing interests The authors declare no conflict of interest.

Author details 1The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China. 2Department of Andrology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China. 3Key Laboratory of Integrative Chinese and Western Medicine for Prevention and Treatment of Sexual Dysfunction of Zhejiang Province, Hangzhou, China. 4Department of Reproductive Medicine, Zhejiang Provincial Integrated Chinese and Western Medicine Hospital, Hangzhou, China.

Received: 5 August 2020 Accepted: 17 February 2021

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