Comparison of Sexual Function in Fertile and Infertile Women with Polycystic Ovary Syndrome (PCOS): A Comparative Cross-Sectional Study

Khadijeh Azarbayjani Department of Reproductive Health and Midwifery, Faculty of Medical Sciences, Tarbiat Modares University, Tehran. Shahideh Jahanian Sadatmahalleh (  Shahideh.Jahanian@modares.ac.ir ) Department of Reproductive Health and Midwifery, Faculty of Medical Sciences, Tarbiat Modares University, Tehran. Negin mirzaie Department of Reproductive Health and Midwifery, Faculty of Medical Sciences, Tarbiat Modares University, Tehran. Nadia Jahangiri ACECR malihe Nasiri Shahid Beheshti University of Medical Sciences Mona Zeinaloo Tehran University of Medical Sciences


Introduction
Polycystic Ovarian Syndrome (PCOS) is presented as a heterogeneous endocrine disorder that affects approximately 5-20% of reproductive aged women (1). This condition is characterized by Ovulatory Dysfunction (OD), biochemical or clinical manifestations of Hyperandrogenism (HA) such as hirsutism, acne, obesity and Polycystic Ovarian Morphology (PCOM) (2). Furthermore, infertility is de ned as the inability to conceive after a year of regular intercourses without any contraception and affects 70-80% of women with PCOS (3,4). As 71.8% of infertile women suffer from sexual dysfunction, infertility is considered a risk factor for it (5). Infertility not only has a devastating effect on patients' self-esteem, but also it imposes a lot of nancial and psychological burdens on them and consequently, infertility may affect couples' relationships and their satisfaction of sexual intercourse (6, 7). It seems that PCOS is associated with an increased risk of sexual dysfunction as follows: aesthetic factors such as hirsutism, acne and obesity change the women's attitude to their bodies, leading to diminished feminine identity, imbalance in hormonal pro le, HA and hyperinsulinemia can lead to depression and anxiety that have manifold effects on quality of life (QoL), mental health and consequently change women's sexual function (8)(9)(10)(11).
Although in many studies it is proved that infertility is strongly related to impaired sexual dysfunction, data on the association between sexual function and PCOS are limited and often contradicting (12)(13)(14)(15). Thus, in light of previous studies on the detrimental effects of infertility and PCOS on sexual function, and the synergistic effects that infertility and PCOS have on each other, infertile PCOS patients might suffer from sexual dysfunction markedly as comorbidity. Consequently, this study was designed to compare sexual function in PCOS women with and without infertility.

Methods
This prospective cross-sectional study was undertaken with the approval of Ethical Committee of Tarbiat Where, 1-β = 0.90 is power, =6 is the standard deviation of sexual function, d=.5 is accuracy of measurement, α and represent type I and II errors, respectively Consequently, for evaluation purposes, 603 eligible women with PCOS diagnosis according to the Rotterdam criteria (16) were recruited after obtaining a written consent, then they were divided into the two groups according to the presence or absence of infertility (364 in fertile group and 239 in infertile group). The infertile group included women who had referred themselves or had been referred by other physicians for diagnostic and therapeutic infertility assessments and they had a history of ≥12 month of infertility either primary or secondary infertility.
The fertile group included women who had no history of infertility, according to their own report. Inclusion criteria were as follow: married women in reproductive age (18-45years) who were sexually active for the past 4 weeks, and willing to participate in this study. The exclusion criteria to avoid possible confounding factors included: pregnancy, breastfeeding, suffering from endocrine and chronic diseases (such as diabetes, cardiovascular disease, kidney disease, benign and malignant tumors, etc.), taking any hormonal and herbal medicines in the last month as its possible impacts on sexual function and androgen levels. Finally, all participants were asked to complete questionnaires included demographic survey and Female Sexual Function Index (FSFI).
Anthropometric measurements contained weight, height, Hip Circumference (HC), and Waist Circumference (WC) were assessed by the same health-care expert. Body Mass Index (BMI) was calculated based on dividing weight in kilogram by square of height in meter for assessing the obesity (17). Additionally, WC was measured at the narrowest point between the lower rib and iliac crest in the standing position and HC at widest part of the buttocks (18).

Clinical and para-clinical features
In order to identify PCOM based on the Rotterdam PCOS criteria an ovarian volume >10 ml or containing 12 or more follicles 2-9 mm was distinguished as a positive PCOM (19).
All required laboratory tests, including Testosterone, Sex Hormone Binding Globulin (SHBG), were done on the same laboratory (ELISA method).

Questionnaires
A socio demographic questionnaire emphasizing on assessing past medical history, menstrual dating and regularity, gynecological history, medications, and family history was completed.
To assess sexual function, all participants were asked to ll out FSFI questionnaire included 19 questions to measure women's sexual performance in six areas: desire, arousal, lubrication, orgasm, sexual satisfaction and sexual pain through the Likert scale. Total score was obtained by summing the six domain scores. A higher score is associated with a lower degree of sexual dysfunction and total score of 23 the optimal cut score for differentiating women with and without sexual dysfunction (20). The reliability and validity of this questionnaire have been con rmed in Iran (21).

Statistical method
All analyses were carried out using SPSS software (ver. 25.0) (SPSS, Chicago, IL, USA). Normality was assessed by Kolmogorov-Smirnov test and data presented as Mean+SD for quantitative data which were compared using the Mann-Whitney's U test (MW). Also two groups were compared in terms of qualitative variables through the chi-square test and data were presented as number and percentage. P 0.05 was considered to be statistically significant.

Results
Overall, 25 of the 646 eligible women who were asked to complete the surveys declined to participate in the study due to the length of time required to complete it and the sexual-related content of questionnaire. A total of 603 women were participated in the trial, 18 were excluded due to sexual inactivity (n=7), and unwillingness to complete questionnaires (n=11) (Figure 1). The mean age of fertile women was 30.75±5.22 years, and infertile women was 30.76±5.56. Table 1 shows an overview of some of the main characteristics of the two groups. The mean duration of infertility in infertile women was 4.1±3.06 years and a signi cant proportion of infertile women had primary infertility (64.8%). Although there was no signi cant difference in mean level of testosterone between fertile and infertile groups (P>0.05), SHBG level was signi cantly different between these groups (P <0.05). As can be seen from the table 2 there was no signi cant difference in terms of age and BMI (P>0.05), however WC and HC were signi cantly higher in the infertile group (P <0.05). Two groups had signi cant differences in terms of occupation status and education level and the level of education in the fertile group was higher than the infertile group (P <0.05). ** Values are given as number/percent by using chi-square test Table 3 provides evaluation of the two groups with regard to FSFI. It reveals that no signi cant differences were evidenced in terms of total score, desire, arousal, lubrication, and satisfaction scores (P>0.05), however pain scores were signi cantly higher in the fertile women (P<0.05). Discussion PCOS as a common hormonal disorder can affects various aspects of women's life. The results of previous studies revealed that women diagnosed with PCOS suffer from sexual dysfunction (12). As mentioned earlier hormonal imbalances, HA and its related clinical features such as obesity, acne, hirsutism, and alopecia lead to physical and psychological changes that reduce women's sexual satisfaction (22). Infertility and its treatment as common complications that PCOS women are faced with can affect the women's sexual function (23,24). In addition, some studies have suggested that infertility is a risk factor for sexual dysfunction in women diagnosed with infertility; however, the results of previous researches were controversial (24,25). This outcome is contrary to that of luk et al. (32) who found that infertility can affect psychological wellbeing, marital relationships, sexual relationships, and QoL of couples' lives. Furthermore, Moghaddam et al. (33) not only reported signi cant reduction in infertile women's sexual function compared with fertile women, but also found an inverse relationship between desire and infertility. Coskuner et al. (34) argued that although sexual function was signi cantly different between fertile and infertile women, sexual QoL was same between these groups.
There are various explanations for the inconsistency of the association between infertility and sexual function. For instance, although previous researches have shown strong association between the level of androgens and sexual function, no signi cant difference was observed between fertile and infertile women in terms of testosterone level in our study, (35). It seems that the results of comparing sexual function between these groups may be affected by this association. study, they also reported that there was no signi cant association between serum SHBG levels and female sexual function. Different results of the studies mentioned above imply that the relationship between infertility and sexual function is a complex process, which might be in uenced by multiple factors, including age, economic status, duration of marriage, type of marriage, duration of infertility's treatment and marriage satisfaction (39).
As a matter of fact, the longer duration of infertility they face, the more sexual dysfunction they suffer (40). Moreover, Hassanin et al. (41) stated that infertility is one of the most important cause of sexual dysfunction in four to six years after infertility diagnosis. In other words, increasing the duration of infertility and unsuccessful treatment reduces the hope of having children and can have adverse effects on sexual function. In our study the mean duration of infertility in infertile group was 4.1± 3.60 and the effects of infertility on women's sexual function may be displayed over a longer period of time.
oskayet al. (42) in their study with the aim of evaluation sexual function in Turkish infertile women argued that simply having the purpose of achieving pregnancy through sexual intercourse and the frequency of sexual intercourse per week can affect sexual function in infertile women. They reported that by the increasing frequency of intercourse per week sexual function in all domain increase. Also another important factors that can affect sexual function in infertile women is the cause of infertility. Infertile women that have been diagnosed with mixed factor compared to women with unknown cause are more likely to have sexual dysfunction. From this it is conclude that in women diagnosed with infertility the effect of infertility on sexual function can vary depending on the cause and severity of infertility and the importance of having children in couples.
Furthermore, Pakpour et al. (43) reported that older age, self-reported depression, secondary infertility, lower educational level and higher partner education as the further risk factors for female sexual dysfunction in infertile couples.
In our study, the level of education in the fertile group was higher than infertile group. Based on the results of some previous studies, it was expected that an increase in education level would be associated with an increase in sexual satisfaction (44). Also in the study of samimi et al (45). The quality of women's sexual life with increasing educations level has shown a statistically signi cant increase .However, the nding that higher levels of education raise women's sexual satisfaction and improve sexual performance has been rejected by some recent studies (46, 47).
Another important factor that may affect the quality of life and consequently the quality of sexual life is an individual's occupation. Based on the result of study by Nikbina et al.(44), the type of occupation had a statistically signi cant relationship with the scores of different areas of female sexual function. Contrary to these results, in the study of Alizadeh et al. (48)., there was no statistically signi cant difference between the sexual performance of employed and housewives women. Although employment might lead to being independence and expression of women in society, it has not been affected in being satis ed from married life.
Women's sexual function is related to their mental health status (49). Depression signi cantly affects the quality of women's sexual life (50). Kim et al. (51) showed strong relationship between depression and taking infertility treatment in infertile women. Possible explanation for this association can include experiencing abortion after pregnancy with infertility treatments, anxiety of high risk pregnancy, burden of pregnancy and importance of having child.
Different cultural conditions may explain this inconsistency between the results. Hence, in eastern societies, fertility and motherhood ability are considered as the important social and family values, infertility impose psychological burden to individuals (52,53). What can be deduced from the results of various studies is that although infertility can in uence sexual function through various ways, the other manifestations and complications of PCOS and other concurrent factor are more in uential factors in patients' sexual dysfunction.
The results of our study showed that the pain score was signi cantly higher in the fertile group. Factors that can affects sexual pain in women includes younger age, lower BMI, less emotional intimacy with a sexual partner, vaginal infections, especially fungal infections, and severe depression (54). In our study, there were no signi cant different between two group in terms of age and BMI, but accurate information on other factors that may affect sexual pain was not available. Consequently, for the best comparison of sexual function between fertile and infertile women with PCOS, evaluation of many factors is required.
The main weakness of this study was the paucity of adequate information about women's mental health status such as depression, anxiety, cause and severity of infertility, sexual problem in partner and burden of infertility which could affect their sexual function. Further studies, which take these variables into account, will need to be undertaken.

Conclusion
The present study was designed to evaluate the simultaneous effects of infertility and PCOS on female sexual function. One of the more signi cant ndings to emerge from this study is that infertility merely is not a risk factor for sexual dysfunction without considering other factors. What can be deduced from the results of the present study and several other similar studies in this eld is that infertility can affect women's sexual function but this effect varies depending on various factor that can affect women's sexual function which was discussed earlier . In fact, in addition to various individual socio-cultural variables that affect women's sexual function, the effect of factors such as the cause, severity and duration of infertility as well as the attitudes of women's to their problem can be different on sexual function. In order to improve the quality of life of infertile women, interventions should be designed and presented by women's health professionals according to the circumstances of each person and taking into account these differences. .211) approved the study protocol. All procedures were in accordance with the ethical standards of the Regional Research Committee and with the Declaration of Helsinki 1964 and its later amendments. After explaining the study's purposes, a written consent and a verbal assent were collected from all participants. They were informed that their participation was voluntary, con dential and anonymous, and that they had the right to withdraw from the research at any time.

Consent for publication
Not applicable.
Availability of data and materials The data sets used and analyzed for the current study are available upon reasonable request.

Competing interests
The authors declare no con icts of interest.  Flowchart of the participants included in the study