Does Prevalence of Female Sexual Dysfunction Differ among Infertile Patients with or without Polycystic Ovary Syndrome: A Cross-Sectional Study.

Polycystic ovarian syndrome (PCOS) is one of the most common endocrine and metabolic disorders among premenopausal women ( 1 ). It affects between 4 and 8% of women of reproductive age. Being considered a heterogeneous condition, PCOS presents with a combination of signs and symptoms linked with androgen excess and ovarian dysfunction. The underlying cause of the syndrome remains generally unknown; nevertheless, abundant evidence suggests PCOS as a complex polygenetic disorder influenced by strong epigenetic and environmental factors including dietary and lifestyle habits ( 1 , 2 ). The clinical manifestations of PCOS vary widely, ranging from menstrual disorders to clinical manifestations of hyperandrogenism and infertility. Menstrual disorders in PCOS women may present as oligomenorrhea, amenorrhea, or prolonged irregular menstrual bleeding. This is while 30% of women suffering from PCOS have normal periods. Approximately 85 to 90% of women with oligomenorrhea have PCOS; this number is as low as 30-40% in those with amenorrhea. More than 80% of PCOS women present with various symptoms of hyperandrogenism. Hirsutism, a common clinical manifestation of androgen excess, is reported in 70% of these women. More than 90% of women with normal periods who suffer from hirsutism are diagnosed with PCOS in ultrasound follow-ups ( 3 ). Acne, the other common sign of hyperandrogenism, however, is less common among PCOS women (15 to 30%) ( 4 ). PCOS is the most common cause of anovulatory infertility ( 5 ). Approximately 90 to 95% of women visiting infertility clinics with anovulation are diagnosed with PCOS. These women are reported to have normal number of primary follicles, but significantly increased secondary ones ( 6 ). The follicular growth though is disrupted in these women, limited to the diameter of 4 to 8 mm. Ovulation, therefore, never happens in these women as no dominant follicle is ever formed ( 7 ). At the same time, the evidence for intrauterine changes leading to PCOS is inconclusive. Female sexual dysfunction (FSD) is a range of psycho-sexual disorders defined as disturbed sexual desire or psychological and physiological changes in sexual relations, leading to significant tension and interpersonal issues ( 8 ). Despite the controversial link reported between FSD and PCOS, increased interest has been focused on their relationship because of their high prevalence ( 8 - 10 ). The results of studies on the relationship between PCOS and FSD are contradictory. Considering the significant impact of FSD on the quality of life of these patients, further studies are required in this field to help the public health system identify their predisposing factors and at-risk individuals. This would provide the policymakers with the required information to design and implement a screening program. Therefore, this study was designed to determine the frequency of FSD in infertile patients with PCOS and compare it with infertile patients due to other causes.

Overall, 120 women agreed to participate in the study. The mean age of the study group was lower than that of the comparison group (30.6 vs. 33.9, P=0.001). The demographic and past medical history of the two groups is shown in Table 1 . There was a significant difference in their education level (P=0.035), the presence of hirsutism (58.6 vs. 16%, P<0.001), and acne (43.1 vs. 18%, P=0.005). There were significantly more women with higher education in the comparison group, while such a difference was not reported for the education level of the spouse (P=0.235). Women in the comparison group, on the other hand, reported a higher number of previous pregnancies (41.4 vs. 24%, P=0.056). This, however, was not statistically significant. As for BMI and the duration of infertility, similarly, no significant difference was noted. Table 1 compares the FSFI score and the prevalence of FSD between the two groups. The average FSFI score was higher in the study group; though the difference was not statistically significant (28.55 vs. 28.33, P=0.730). FSD was less prevalent among the study group (43.1 vs. 52%, P=0.440). Comparison of demographic quantitative and qualitative variables and past medical history between two groups Data are presented as mean ± SD or n (%). BMI; Body mass index, PCOS; Polycystic ovary syndrome, FSFI; Female sexual function index, and FSD; Female sexual dysfunction. Table 2 illustrates the relationship between the demographic information and past medical history, and the presence of sexual dysfunction in PCOS patients. There was no significant relationship between age, BMI, duration of infertility, and sexual dysfunction. The women with FSD and their spouses were reported to have lower educational levels. The difference was only significant in the women and not among their spouses. As for the comparison group, no significant relationship was found between age and BMI, and sexual dysfunction ( Table 3 ). The average duration of infertility in women with FSD was significantly longer than that of those with no such disorder (6.7 years vs. 3.7 years, P=0.002, Fig .1 ). The relationship between demographic and past medical history with FSD in people with PCOS and Non-PCOS reasons FSD; Female sexual dysfunction, PCOS; Polycystic ovary syndrome, and BMI; Body mass index Infertility duration comparison between the two studies and comparison group. PCOS; Polycystic ovary syndrome. There was no significant difference in the education level of the non-PCOS women or their partners in the presence or absence of FSD. While hirsutism, acne, and the history of previous pregnancy were more frequently reported among those with FSD, the difference was not significant ( Fig .2 ). Comparing the level of education between patients and spouses of the two study and comparison groups. PCOS; Polycystic ovary syndrome. The frequency of sexual dysfunction in the six studied subdomains (sexual desire, psychological stimulation, vaginal moisture, peak sexual pleasure, satisfaction, and pain during intercourse) is illustrated in Table 3 . Except for "pain during intercourse", the frequency of all studied disorders was higher in the study group; none of which, however, was statistically significant. Comparison of dysfunctions in subdomains of FSD between two study and comparison groups FSD; Female sexual dysfunction and PCOS; Polycystic ovary syndrome.

The present cross-sectional study showed a significant difference in the level of education, the prevalence of hirsutism, and acne between the PCOS women and the comparison group. However, there was no significant difference in the history of previous pregnancies between these groups. The prevalence of FSD among women with and without PCOS was 35 and 29.6% according to a systematic review and meta-analysis conducted by Loh et al. ( 15 ) and 30.1% among infertile women due to PCOS aging between 18-35 ( 16 ). A systematic review and meta-analysis conducted on 3419 infertile Iranian women estimated the prevalence of FSD in this population to be about 64.3% ( 17 ). Dashti et al. ( 18 ) reported that 62.5% of women with PCOS complained of FSD symptoms, highlighting the prevalence of the condition in the general society to be between 5.5 to 11.2 percent. This is while a prevalence of as high as 46.2% was previously reported for FSD in women of reproductive age ( 19 , 20 ). According to a crosssectional study conducted in Iran, FSD is seen in 98.8% of women with PCOS, 100% of those with endometriosis, and 36.2% of fertile women ( 21 ). Similarly, a cross-sectional study conducted between 2006 and 2009 at the National Institute of Child Health and Human Development (NICHD) in China, and a case-control study conducted in 2013 in Turkey, reported FSD to be more prevalent among PCOS women (27.2 vs. 24.4% and 25 vs. 19% respectively). This is while our results revealed a lower prevalence of FSD among PCOS women ( 22 , 23 ). This is while several studies have suggested that PCOS has no significant effect on women’s sexual performance. In a case-control study conducted by Basirat et al. ( 24 ), no significant difference was revealed between the prevalence of FSD in infertile women due to PCOS and other causes. The present study revealed PCOS women to be more educated and less likely to suffer from FSD. In line with our results, a cross-sectional study conducted in Iran between 2009 and 2011 showed a significant relationship between FSD and the subjects’ education level, but not with age or BMI ( 10 ). Jaafarpour et al. ( 19 ), similarly showed the education level to have an inverse correlation with FSD. They revealed the FSD patients to be significantly older, pointing out the condition to be more common among those performing intercourse less than three times a week, having three or more children, being married for 10 years or more, or having husbands older than 40 years of age as well as being unemployed. The higher prevalence of hirsutism and acne in PCOS women is related to the nature of the underlying disease and the high incidence of hyperandrogenism in these patients; a high prevalence of hirsutism, however, is reported among those with FSD ( 25 ). This is in line with previous similar studies ( 20 , 24 ). In a study conducted by Ashrafi et al. ( 21 ), a statistically significant difference was shown between the BMI and education level of women with the most common causes of infertility. From among the studied variables, a longer period of infertility was the main risk factor linked with FSD. This could be due to the longer duration of infertility can probably contribute to additional psychological disorders such as depression ( 26 ). This was the reason behind selecting being infertile due to other reasons as the comparison group in this study with the aim of eliminating its possible confounding effect on the results. Correspondingly, a case-control study conducted by Dong et al. ( 26 ) revealed an increase in the incidence of FSD and psychological distress, especially when the infertility duration is more than 8 years. Except for "pain during intercourse," the frequency of the disorders in all sub-areas was higher, though not significantly, in the study group. In line with the study conducted by Basirat et al. ( 24 ), we failed to observe a significant difference in the FSD sub-domains between the PCOS and the comparison group. Ashrafi et al. ( 21 ), on the other hand, showed the disorders in all subdomains, except for "Orgasm" and "pain during intercourse", to be significantly higher in the PCOS group. The two exception subdomains, on the other hand, were more common in the endometriosis group. The observed differences were statistically significant. This again points out the reason behind excluding the endometriosis patients from the comparison group in the current study, as they are believed to be more prone to FSD due to the higher pain experienced during intercourse (mainly secondary to organic rather than psychological issues). PCOS, compared to other causes of infertility, appeared at a relatively younger age in our study. Despite the defined recruitment age range, the age and level of education in the comparison group were significantly higher than in the study group. This could be attributed to the fact that infertility due to PCOS is easier to treat compared with cases secondary to causes such as endometriosis, anatomical problems, and reduced ovarian reserves ( 15 , 16 ). As a result, some may suggest selecting healthy women rather than infertile ones as the comparison group to reduce the age difference between the studied groups. To our knowledge, this is the first study to compare the prevalence of FSD among PCOS and non-PCOS infertile women in Iran. The current study, however, suffered from several limitations. Firstly, due to the cross-sectional nature of this study, the assessment of the relationship between the variables as well as the longitudinal interpretations were not possible. Secondly, as the research was conducted in a tertiary center, the study population may not be representative of the entire society; therefore, conducting more studies in the future in different regions with a larger sample size can help with the generalization of its results. Due to the COVID-19 pandemic and fewer visits to the clinics, the sampling period lasted longer than the estimated time.

The present study did not reveal any significant relationship between FSD and PCOS. However, due to the contradictory nature of these results, compared with existing literature, more studies with larger sample sizes are needed. Our results however suggested that the level of education significantly influences FSD and educating women and increasing their awareness, therefore, can help improve their sexual performance. This is of great importance as it can strongly impact their quality of life and their relationship with their spouses.

This cross-sectional study compares the frequency of sexual dysfunction as the primary outcome in a group of infertile PCOS women and those suffering from infertility due to other causes. The secondary objective was to identify the characteristics in PCOS women associated with a higher prevalence of FSD. The two mentioned groups were recruited from those visiting the infertility clinic of Arash Women’s Hospital, Tehran, Iran between the beginning of December 2018 and the end of November 2019. The participants were married women between the ages of 20 to 40 years. PCOS was diagnosed based on the Rotterdam criteria, which requires at least two of three findings, chronic anovulation, clinical or biochemical symptoms of hyperandrogenism, and the presence of polycystic ovaries in the ultrasound imaging ( 11 ). In some cases, the diagnosis was made after ruling out other disorders mimicking PCOS [thyroid disease, hyperprolactinemia, and nonclassical congenital adrenal hyperplasia (mainly 21-hydroxylase deficiency characterized by serum 17-hydroxyprogesterone)]. In certain women with amenorrhea or more severe phenotypes of PCOS, further extensive evaluations were performed to rule out other possible causes such as pregnancy and Asherman syndrome ( 12 ). Accordingly, the diagnosis was made based on the existence of clinical or biochemical evidence of hyperandrogenism (after excluding other pathologies) along with persistent oligomenorrhea. The comparison group included infertile patients due to reasons other than PCOS. Those with a history of psychiatric disorders or taking psychiatric medication, with a history of hospitalization in the past month, or taking oral contraceptive pills in the last two months were excluded. Subjects diagnosed with endometriosis were also excluded as the condition is accompanied by problems, including pain due to organic issues, interfering with the study objectives. Hirsutism was assessed using a modified Ferriman-Gallwey scoring system. This tool assesses hair growth in seven areas: upper lip, chin, chest, back, abdomen, arms, and thighs. A score of zero suggests the absence of terminal hair growth and four suggests extensive growth. A total score of eight or more indicates hirsutism. A questionnaire containing a personal and past medical history of the women was completed by a reliable observer. The participants and their spouses were divided into five groups based on their education level into illiterate, below diploma, diploma, bachelor's degree and less, and master's degree and higher. A translated version of the female sexual function index (FSFI) questionnaire was completed for each subject. Over the past 20 years, the FSFI has been considered as the standard questionnaire for the assessment of sexual performance among women. The reliability of the Persian version of this questionnaire has already been proven in earlier studies ( 13 ). The questionnaire contains 19 questions on sexual performance during the past four weeks in 6 areas, including sexual desire, psychological arousal, vaginal moisture, peak sexual pleasure, satisfaction, and pain during intercourse. A score between 0 and 5 can be given for each question. The scores for each field are then calculated by adding that of all the questions in each section and then multiplying the result by a certain factorial number, recommended by the developer ( 14 ). This number aims to balance the weight of different fields based on the number of questions in each section. The total score is, finally, calculated by adding the scores of the six sections. The maximum score for each section is six and thus 36 for the whole questionnaire. A higher total score indicates better sexual performance. The cut-off point for the whole questionnaire is 28 and for each subscale is sexual desire at 3.3, psychological stimulation at 3.4, vaginal moisture at 3.4, peak sexual pleasure at 3.4, satisfaction at 3.8, and pain during the relationship at 3.8. In other words, scores higher than the cut-off point indicate good performance and lower ones show sexual dysfunction. A score of zero indicates no sexual activity during the past four weeks. The sample size was calculated based on the data gathered in previous studies [expected FSD prevalence of 60% ( 10 )], and a power of 95%. Fifteen percent was added to compensate for possible data loss, resulting in a sample size of 120 patients. The data were analyzed using SPSS 25 (IBM Corp., Armonk, New York, USA). In addition to the frequency of sexual dysfunction and its subdomains in the two studied groups, the relationship between FSD and age, the history of pregnancy, the literacy level of the patient and her spouse, (BMI) profile, the duration of infertility, hirsutism, and acne were assessed. Mann-Whitney U test was used to assess the non-parametric variables (age and duration of infertility) as well as to compare the education level of the patients and their spouses between the two groups. The chi-square test helped to assess the relationship between the qualitative variables and FSD, whereas the independent t test illustrated the correlation between the quantitative variables and sexual dysfunction. Fisher’s exact test was applied to compare the sexual function subdomains in the two groups, due to the small number of cases. As for pain during intercourse, however, chi-square was applied due to the higher number of cases affected by the problem. The purpose, optionality, and confidentiality of the study were explained separately to each patient and written consent was obtained from those who agreed to enter the study. The study was approved by the Ethics Committee of Tehran University of Medical Sciences (IR.TUMS.MEDICINE.REC.1398.585).