{"paper_id":"2613e715-7265-4507-b945-3f88a7e1a61c","body_text":"Infertility is a disease of the reproductive system that is\ndefined as “the failure to achieve a clinical pregnancy after 12 months or more of regular unprotected sexual intercourse” ( 1 ). In the Iranian population, recent estimations\nindicated that lifetime primary infertility rates, based on\nclinical, epidemiological, and demographic definitions\nset by the World Health Organization, are respectively\n20.2, 12.8, and 9.2%, while that of secondary infertility is\n4.9% ( 2 ). One of the common disorders linked to infertility and associated with ovulation problems is polycystic\novary syndrome (PCOS). The definition of PCOS by the\nUnited States National Institutes of Health entails anovulation and hyperandrogenemia. However, the European\nSociety of Human Reproduction and Embryology/American Society for Reproductive Medicine (ESHRE/ASRM)\ndefines PCOS as polycystic ovaries diagnosed based on\nultrasound ( 3 ). Studies have reported that up to 83% of\ninfertile Iranian women have PCOS, and an infertility rate\nof 8-73% in PCOS patients was shown ( 4 ).\nSexual life of infertile women is a pivotal research area\nbecause infertility is associated with an increased risk of\nfemale sexual dysfunction (FSD) ( 5 ). Sexual function involves various domains, including sexual desire, arousal, vaginal lubrication, experiencing orgasm, coital satisfaction, and feeling of pain during intercourse ( 6 ). Infertile\ncouples are more prone to develop sexual dysfunction. A\nrecent estimation in infertile Iranian women, for instance,\nfound that 64.3% of the patients developed sexual dysfunction, with sexual desire and vaginismus having the\nhighest and lowest rates, respectively ( 7 ). Another study\nsuggested that the sexual behavior of infertile Iranian\nwomen is severely narrowed to produce pregnancy ( 8 )\nand that infertility causes Iranian women to suffer from\nserious problems in various domains, including sexuality\n( 9 ). More to the point, sexual dysfunction may considerably affect mental health as well as the sexual quality\nof life ( 10 ). Furthermore, women’s sexual problems may\neven escalate if they concurrently suffer from PCOS ( 11 ).\nThat is, the sexuality of women with PCOS may become\neven more compromised, especially as a result of obesity, hirsutism, baldness, and acne ( 12 ). Moreover, sexual\nproblems are suggested as the possible causes of discrepancies in perceptions of infertile women with and without\nPCOS towards their sexual life and function ( 13 ).\nAlthough various studies have addressed the sexual\nproblems experienced by women with PCOS ( 14 ,  15 ),\nfew studies have focused on sexual issues and their correlates when such patients simultaneously suffer from\ninfertility. Recent meta-analyses have determined similar\nsexual function between PCOS women and healthy controls ( 16 ,  17 ). However, it can be argued that further studies investigating possible effects of comorbid PCOS and\ninfertility are warranted, especially in the Iranian population. Moreover, investigating possible differences in sexual problems and their correlates between infertile PCOS\npatients and their non-PCOS counterparts may provide\nmore knowledge about the specific role that comorbid\nPCOS and infertility play in Iranian women life.\nThe present study, therefore, investigated the differences between infertile Iranian women with and without\nPCOS in terms of sexual function. It also aimed to evaluate the degree to which hormonal, anthropomorphic, and\nhyperandrogenic manifestations may be correlated with\nthe sexual function of these groups of women.\n\nThis case-control study involved infertile PCOS women\nas the case group and their infertile non-PCOS counterparts as the control group using a convenience sampling\nmethod. Patients visiting two infertility centers in Tehran, Iran were recruited. The study was introduced and\nexplained to the patients to obtain their informed consent. The questionnaires were administered using the\ninterviewer-administered method. Overall, 216 infertile\nwomen were recruited in February and March of 2018.\nThe sample size was determined for two independent\nsamples using G*Power software V.3 ( 18 ). The estimation setting was set to a medium effect size (0.50), a significance level (α) of 0.05 (two-tailed), a power of 0.80,\nand an allocation ratio of 1. The calculation suggested\nthat a sample size of 128 participants (64 for each group)\ncould achieve the actual power of 0.803. The inclusion\ncriteria were as follows: age above 18 years and diagnosis\nof infertility for both groups, and diagnosis of PCOS for\nthe PCOS group. PCOS was diagnosed based on the international evidence-based guideline for the assessment and\nmanagement of PCOS, 2018 ( 19 ). This guideline identifies the condition in adult women if two of the three conditions of androgen excess, ovulatory dysfunction, and\npolycystic ovarian morphology are present. Ultrasound is\nrequired if either androgen excess or ovulatory dysfunction is not present. Certain disorders, including thyroid\ndisease (based on thyroid-stimulating hormone (TSH)\nlevel), hyperprolactinemia (based on prolactin level),\nand non-classic congenital adrenal hyperplasia (based on\n17-hydroxyprogesterone (17-OHP) level), were ruled out\nby clinical judgment.\nThe following exclusion criteria were considered: psychiatric disorders; severe emotional problems in the past six\nmonths; consumption of oral contraceptive pills, gonadotropin-releasing hormone (GnRH) agonists, or insulin sensitizers in the past six months; chronic cardiovascular diseases;\nprimary or secondary vaginismus and dyspareunia; pelvic\nmass; active genital infection; external vaginal anomalies;\npelvic endometriosis; and partner’s sexual dysfunction.\nA checklist was devised to survey the participants’ demographic information, including the patient’s age, occupation, and education, the spouse’s age and education,\nand the duration of their marriage. Clinical information including duration of infertility, duration of treatment, central obesity (waist-to-hip ratio), body mass index (BMI),\nand hyperandrogenic manifestations, including the presence of acne, hirsutism (Ferriman-Gallwey score), and\nbaldness (i.e. male-pattern hair loss), was also collected.\nOn the third day of the menstrual cycle (induced by\n100-200 mg progesterone in oil injection in amenorrheic patients), a baseline vaginal ultrasound examination\nwas performed, and serum follicle-stimulating hormone\n(FSH), luteinizing hormone (LH), TSH, and prolactin\nlevels were measured using immunoradiometric assays\n(Izotop, Budapest, Hungary). Dehydroepiandrosterone\nsulfate (DHEAS), 17-OHP, and total testosterone (TT)\nwere measured using enzyme immunoassays (Diagnostics Biochem Canada Inc., London, Canada).\nThe Female Sexual Function Index (FSFI) ( 20 ) was employed to assess the patients’ sexual function. This 19-item\nquestionnaire assesses six domains of sexual desire (two\nitems, domain factor 0.6), arousal (four items, domain factor 0.3), lubrication (four items, domain factor 0.3), orgasm\n(three items, domain factor 0.4), satisfaction (four items,\ndomain factor 0.4), and pain (three items, domain factor\n0.4) for a comprehensive evaluation of the female sexual\nresponse cycle. Each domain’s raw score is multiplied by its domain factor, yielding a possible score in the range of\n0 to 6, except for desire, which has a range of 1.2 to 6.\nAccording to the score which ranges 1.2-36, higher total\nscores indicate better sexual function. The questionnaire\ncan identify women who had no sexual encounters during\nthe preceding four weeks. The Persian version of the FSFI\nwas approved as a valid and reliable screening and assessment instrument, indicating a Cronbach’s alpha of 0.93 and\ntest-retest reliability of 0.83 ( 21 ). The instrument showed\na Cronbach’s alpha of 0.89 in the current dataset. The second and fifth authors administered the questionnaires using\nthe interviewer-administered method by asking patients to\nchoose the response that best described their status.\nFSD was identified based on FSFI scores. In an original\nstudy by Rosen, scores lower than 26.55 indicated a diagnosis of FSD with a specificity of 0.73 and a sensitivity\nof 0.89 ( 20 ). In addition, a raw score below 3.9 indicated\nsexual dysfunction in each domain ( 22 ).\nThis study was performed according to the Declaration\nof Helsinki, and the Ethics Committee of Iran University\nof Medical Sciences approved the study protocol (ID:\nIR.IUMS.FMD.REC.1396.9311290023). Informed consent was obtained from all participants.\nStatistical analysis was performed using IBM SPSS Statistics for Windows, Version 24.0 (IBM Corp., Armonk,\nNY, USA) ( 23 ). Missing data were handled using the\npairwise deletion method. Since the scores showed a nonnormal distribution, non-parametric statistics was adopted. The Mann-Whitney U test and the Chi-square test for\ncomparing the groups, as well as logistic regression for\npredicting FSD via hyperandrogenic manifestations, were\nconducted. Spearman’s Rho was also calculated to determine the correlation of patient’s age, duration of infertility, duration of treatment, BMI, central obesity, levels of\nFSH, TSH, LH, prolactin, TT, DHEAS, and 17-OHP (all\nin mcg/L), and LH/FSH ratio with the total FSFI score\nand the domains. Two-tailed P value was set at <0.05.\n\nAmong the 216 patients recruited in this study, seven\n(0.03%) patients were sexually inactive based on the FSFI\nand were excluded. Therefore, 209 infertile women, including 116 PCOS patients and 93 non-PCOS patients,\nremained in the study\nTable 1 presents the demographic and clinical characteristics of the patients. The mean age was 32.00 ±\n5.00 years, with the PCOS group being older (P<0.001).\nCentral obesity was more frequent in the PCOS group\n(P<0.01), and there was a higher degree of anovulation\nas the cause of infertility (P<0.001) in this group. Conversely, infertility in the non-PCOS group was more often\nfound to be unexplained or due to tubal causes (P<0.01).\nTable 2 presents the sexuality domains for both groups.\nArousal had the lowest score in the PCOS group (3.69 ±\n1.23) and non-PCOS group (3.67 ± 1.32). On the other\nhand, the highest mean score was related to satisfaction\nin the PCOS group (5.06 ± 1.00) and non-PCOS group\n(5.11 ± 0.95). The total FSFI for in our sample population\nwas 27.15 ± 4.30, with 26.97 ± 4.73 in the PCOS group\nand 27.38 ± 3.72 in the non-PCOS group. FSD was diagnosed in 40.2% of the participants, including 42.2% of\nthe PCOS patients and 37.6% of the non-PCOS patients.\nTable 3 presents comparisons between the PCOS and nonPCOS groups in terms of sexual function. Based on the raw\nscores for sexual function, there were no significant differences between the two groups (P=0.325 to 0.975). Also, the\ntwo groups had no significant difference in terms of FSD\n(P=0.500). Based on the categorization of sexual dysfunction in the domains (score<3.9), the two groups only showed\na significant difference in orgasm problems (P=0.035).\nAccording to Table 3, acne (51.7%), baldness (41.4%),\nand hirsutism (57.8%) were more commonly found in the\ninfertile PCOS patients (P<0.001). Acne was the sole impactful hyperandrogenic manifestation, increasing the odds\nof FSD by 1.87 [1.02, 3.43] (P=0.042) in the total sample\nand 2.18 [1.01, 4.68] (P=0.046) in the PCOS group.\nTable 4 presents the results of the hormone tests in both\ngroups. Group differences were seen in FSH, which was\nhigher in the non-PCOS group, and LH, which was higher in\nthe PCOS group (P<0.001). The LH/FSH ratio was higher in\nthe PCOS group to a statistically significant degree (P<0.001).\nIn the non-PCOS patients, there were significant relationships between LH and pain (n=87, rho=0.26, P=0.015),\nprolactin level and lubrication (n=85, rho=0.22, P=0.048),\nprolactin level and total FSFI (n=85, rho=0.22, P=0.045),\nand central obesity and arousal (n=93, rho=-0.26, P=0.013).\nIn the PCOS group, marital duration and arousal (n=103,\nrho=-0.31, P=0.001), marital duration and total FSFI\n(n=103, rho=-0.25, P=0.013), and prolactin level and orgasm (n=114, rho=-0.23, P=0.012) were correlated.\nBecause the mean ages of the two groups were statistically significantly different (P<0.001,  Table 1 ), the analyses were repeated using linear regression analysis, including the PCOS group as the dummy variable and age as\nthe covariate. There were no significant changes in the pattern of the comparisons. Additionally, controlling for\nage, partial correlations were estimated between each pair\nof hormones and sexuality domains. Consequently, the results indicated only negligible changes to the zero-order\ncorrelations. Therefore, the previously reported differences and correlations were shown to be valid.\nDemographic and clinical information of the study sample\nData are presented as mean ± SD or n (%). IUI; Intrauterine insemination, IVF;  In vitro \nfertilization, ICSI; Intrauterine insemination, PCOS: Polycystic ovary syndrome,\nBMI; Body mass index,  a  ; Mann-Whitney U (Asymp. P),  b ;\nPearson’s Chi-square test (2-sided), and  c  ; Anovulation and tubal\ncategories are not mutually exclusive. The bolded P indicates a significant\ndifference.\nComparisons of sexual function\nPCOS; Polycystic ovary syndrome, M; Mean, SD; Standard deviation, Min; Minimum, Max;\nMaximum, FSFI; Female sexual function index, FSD; Female sexual dysfunction (FSFI\nbelow 26.55 for global FSD and below 3.9 for domain FSD),  a  ;\nMann-Whitney U (Asymp. P) on the raw scores, and  b ; Pearson’s\nChi-square test (2-sided) on the FSD categorizations. The bolded P indicates a\nsignificant difference.\nPredicting FSD based on hyperandrogenic manifestations\nFSFI; Female sexual function index, FSD; Female sexual dysfunction (FSFI below 26.55),\nPCOS; Polycystic ovary syndrome, CI; Confidence interval,  a  ; The\nunadjusted models included each hyperandrogenic manifestation as an independent\nvariable and FSD as a dependent variable, and  b ; The models were\nadjusted for age. Bolded results indicate significant (P<0.05)\nComparisons of laboratory results\nPCOS; Polycystic ovary syndrome, M; Mean, SD; Standard deviation, Min; Minimum, Max;\nMaximum, FSH; Follicle-stimulating hormone, TSH; Thyroid-stimulating hormone, LH;\nLuteinizing hormone, DHEAS; Dehydroepiandrosterone sulfate and 17-OHP:\n17-hydroxyprogesterone,  a  ; All values are in microgram per liter, and\n b ; Mann-Whitney U (Asymp. P). Bolded results indicate a significant\ndifference.\n\nThe aim of this study was to evaluate sexual function\nand its correlates among infertile patients with and without\nPCOS. The findings suggest that infertile women with and\nwithout PCOS considerably suffered from diminished\nsexual function. A recent meta-analysis reported domains\nof lubrication, orgasm, and satisfaction to be the sources\nof difference between infertile and fertile women ( 24 ),\nwhile these three domains were proportionately better in\nthe two groups evaluated in the current study\nIt should be noted that domain-specific FSD was\ndetermined by a relatively higher cut-off point (< 3.9),\nwhich was originally applied to infertile women ( 25 );\nhowever, some other studies employing slightly lower\ncut-off points, reported a relatively higher degree of\ndomain-specific FSD in healthy Iranian women ( 26 ).\nNevertheless, similar to the aforementioned study ( 26 ),\ndesire and arousal problems not only showed a marked\nprevalence but were also the most problematic sexual\ndomains in the current study\nIn addition, the literature suggests that women with\nand without PCOS in the general population ( 16 ,  17 ) and\ninfertile Iranian women with and without PCOS ( 27 ) do\nnot differ in terms of sexual function. Although PCOS\nwomen compared with their healthy counterparts, may\nmainly have dissatisfaction with their sex life, rather than\nwith sexual activity ( 28 ), the current study indicated a\ndiminished level of sexual function in both groups, with\nthe orgasm domain being a specific source of difference.\nThis indicates a crucial need for further attention paid to\nthe sexuality of infertile PCOS women.\nFurthermore, while some studies could not determine\nthe effects of hyperandrogenic manifestations on sexual\nfunction ( 29 ), others indicated that acne-related concerns\ncould reduce sexual satisfaction in both PCOS women and\ntheir spouses ( 30 ). Also, in our study, although infertile\nPCOS patients featured higher levels of LH and FSH, as\nwell as an elevated LH/FSH ratio, it was the non-PCOS\ngroup that showed a significant association between LH\nand pain. In addition, an earlier study found no association\nbetween LH and quality of life of PCOS patients ( 31 ).\nHowever, LH was previously shown to be connected with\norgasm problems in healthy, postmenopausal women\n( 32 ) and with sexual function in PCOS patients in the\ngeneral population ( 33 ). LH contributes to the circulation\nof reproductive hormones, including androgens and\nestrogens ( 34 ), and it is suggested to make women apt\nto love and intimacy ( 35 ). In addition, studies in which\nsignificant hormonal correlations were seen with LH in\nPCOS patients, emphasized the multifactorial nature of\nhuman sexual function which can be influenced by a\nvariety of psychosocial and cultural factors ( 33 ). Thus,\nmore studies are needed to provide supports for the results\nobserved in the current study.\nThe current study revealed a significant contrast between\nthe two groups in the relationship between prolactin level\nand sexual function. Other studies have also reported\nthat among various relevant hormones, there was only a\nnegative association between prolactin level and function\nof orgasm in PCOS women ( 36 ). Elevated prolactin levels\nwere found to be associated with sexual problems in the\ngeneral population ( 37 ). Also, women with PCOS can have\nmildly elevated levels of prolactin ( 38 ). Thus, the current\nresults in line with the previous findings ( 36 ), indicated\nthe diminished function of orgasm to be associated with\nhigher prolactin levels in infertile PCOS women.\nContrary to expectations, higher central obesity which is\nmarked in PCOS women ( 11 ,  12 ), indicated lower sexual\narousal in infertile non-PCOS women only. Additionally,\nalthough some studies reported that the age of infertile\nwomen had a negative association with sexual function\n( 39 ), the current findings instead, suggest the negative\nimpact of marital duration on sexual arousal and total\nFSFI in infertile PCOS women. Thus, the current results\nindicate that obesity and marital characteristics could\nalso be sources of difference in sexual function between\ninfertile PCOS women and those without PCOS.\nUltimately, the distinctions raised in the current study\nsuggest that infertile PCOS and non-PCOS women\nmay need more well-tailored research on their specific\nbiological, hormonal, and psychological dimensions. It is\nsuggested that future studies include spouses assessments\nto further examine the relational nature of sexual desire\nand arousal in patients. More importantly, some studies\nhave suggested implementing educational interventions to\nenhance the sexual function of infertile women ( 40 ). The\ncurrent study, which indicates the exclusively negative\neffect of prolactin level, acne, and marital duration on\nthe sexual function of infertile PCOS women, implies\nthat interventions may need to be modified accordingly\nto educate patients on how to manage their specific\nproblems. Last but not least, policymakers concerned\nwith the family structure and sexual health of the Iranian\npopulation, should focus on and facilitate particular needs\nand problems of the patients in order to maintain their\nmarriage as socially stable and psychologically fruitful as\nthe wider population does.\nThis study lacked a control group of fertile women.\nTherefore, it failed to find any possible differences\nbetween fertile and infertile women, especially those who\nmay seek professional help for their sexual problems.\nMoreover, since this study had a cross-sectional design,\ncaution needs to be taken in making any generalizations\nor considering causal implications.\n\nThis study demonstrated diminished sexual function in\ninfertile Iranian women, especially in terms of the desire\nand arousal domains. The PCOS and non-PCOS groups\nwere not significantly different in terms of sexual function,\nwhile orgasm dysfunction was higher in the PCOS\nwomen. In addition, acne increased sexual dysfunction\nin the PCOS women. The infertile non-PCOS women\nwith higher levels of prolactin had lower dyspareunia and\nthose with higher LH had lower total FSFI and lubrication\nproblems, while the higher the central obesity the higher\ntheir arousal problems. However, infertile PCOS women\nmainly showed orgasm dysfunction as a result of lower\nlevels of prolactin, and lower total FSFI and arousal as a\nresult of marital duration.","source_license":"CC-BY-4.0","license_restricted":false}