Pharmacologic therapy to induce weight loss in women who have obesity/overweight with polycystic ovary syndrome: a systematic review and network meta-analysis.

BACKGROUND: Women with polycystic ovary syndrome (PCOS) are almost three times more likely to be obese than those without PCOS. However, we have no specific interventions to induce weight loss so far and rely on drugs used to treat other symptoms of the syndrome or obesity in the general population. OBJECTIVE: The objective of this study is to compare the effectiveness of metformin, inositol, liraglutide and orlistat to induce weight loss in women with PCOS and overweight/obesity. METHODS: A search was conducted using the MEDLINE, EMBASE, PubMed and CENTRAL databases. Individually randomized, parallel group trials that evaluated the effects of these pharmacological treatments among adults or adolescents with PCOS and overweight/obesity, compared with a placebo or metformin group, were considered eligible. Registration number: PROSPERO CRD 42017076625. RESULTS: Twenty-three trials reporting on 941 women were included in the network meta-analysis. The amount of weight lost differed significantly among the drugs (in descending order): liraglutide, orlistat and metformin. Liraglutide alone, liraglutide/metformin and metformin alone significantly reduced waist circumference, but no change was found with orlistat. Data for waist-to-hip ratio were only available for metformin, which had no significant effect. CONCLUSION: Liraglutide appears superior to the other drugs in reducing weight and waist circumference.

Pre-pregnancy weight loss in women with obesity requesting removal of their intra-uterine contraceptive device in order to conceive: a pilot study of full meal replacement.

Obesity during pregnancy is associated with increased risks of thromboembolism, gestational diabetes, pre-eclampsia, miscarriage, congenital anomaly, macrosomia and stillbirth. The current practice, directed at reducing gestational weight gain, is largely ineffective. The present pilot study was designed to assess the acceptability of a 24-week intensive weight management programme (IWMP; full meal replacement followed by partial meal replacement and weight stabilization) to achieve weight loss for women with obesity requesting removal of their intra-uterine contraceptive device in order to conceive. Twenty six (65%) of eligible participants consented to the IWMP; three received this as routine National Health Service care in the University College Hospital clinic and 14 participated in the study. The commonest reasons for not participating were dislike of milk, anxiety and lack of support from family and friends. Omitting one woman who dropped out because of problems unrelated to the intervention, the completion rate was 46.2%. Including all women who started the programme, mean body mass index decreased significantly (P = 0.005) from 37.8 to 35.3 kg/m2 . The median percentage decrease was significantly (P = 0.007) greater for women who completed the study (14.2) compared to those who dropped out (1.2). These results suggest an impressive level of weight loss in about one third of all women offered the IWMP who had to defer what they were seeking (pregnancy) while following a challenging programme that they were not seeking. However, studies of other interventions, such as partial meal replacement or commercial products, which may have higher rates of completion are still required.

An exploration of the hypothesis that testosterone is implicated in the psychological functioning of women with polycystic ovary syndrome (PCOS).

One of the diagnostic features of polycystic ovary syndrome (PCOS) is elevation of the androgen, testosterone. It is known that women with PCOS are more likely to suffer from psychological problems, especially anxiety and depression, than other women. However, little is known of how much of this is due to testosterone, and if so, what the mechanism(s) might be. This study explores the hypothesis that testosterone impacts women with PCOS both directly and indirectly, via testosterone currently in the bloodstream and through prenatal exposure. It is hypothesised that direct effects occur when testosterone acts directly upon receptors; indirect effects occur where the impact of testosterone is mediated via another variable; activational effects are ephemeral and are caused by testosterone in the bloodstream; organizational effects occur prenatally and cause permanent changes. Four pathways are hypothesised in this paper: 1/ a direct and activational pathway which improves mental rotation ability; 2/ an indirect and activational pathway, whereby distress is caused when the physiological symptoms of testosterone are experienced as embarrassing or otherwise disturbing; 3/ an indirect and organizational effect on mood, where elevated prenatal testosterone predisposes women with PCOS to low blood sugar levels and thus low mood; 4/ and finally, it is suggested that the pathway from biology to psychology can be travelled in reverse, with a direct activational effect of relaxation training on the reduction of adrenal androgens. Testing these hypotheses has important implications for our understanding of PCOS, and our ability to treat this condition more effectively.

The effect of thawing protocols on follicle conservation in human ovarian tissue cryopreservation.

BACKGROUND: Ovarian tissue cryopreservation has the potential to improve fertility preservation for a growing number of patients undergoing sterilising therapy, particularly where oocyte or embryo cryopreservation is not suitable. However, its success is limited by significant follicular apoptosis upon thawing, and there is wide variation in thawing protocols used with little evidence of efficacy. OBJECTIVE: To determine the best warming rates to maintain tissue viability. MATERIALS AND METHODS: Ovarian tissue biopsies from 11 patients were taken with informed consent and divided into four pieces, which were allocated to either fresh assessment or to one of several freeze-thaw protocols. Cryopreservation was undertaken using a Stirling cycle cryo-cooler and cryopreserved samples were exposed to different warming protocols. Tissue conservation was then assessed using a marker, neutral red, to identify viable follicles. RESULTS: The results showed greatest follicle conservation rates in fresh samples, followed by those thawed using a rapid thawing protocol (Protocol 1). Tissue thawed using an ultra fast protocol (Protocol 2) and slow warming (Protocol 3) resulted in greater follicle loss. CONCLUSION: These preliminary results indicate thawing conditions significantly affect follicle conservation in cryopreserved human ovarian tissue.

Prolactin and hostility in hospitalised patients and healthy women: A systematic review and meta-analysis.

The aim of this systematic review and meta-analysis was to assess any difference in the self-ratings of hostility in mentally healthy women with different levels of prolactin (PRL). Electronic databases (PubMed, MEDLINE, EMBASE and the Cochrane Library) were searched up to 2nd July 2012 for published literature comparing hostility levels in women with different levels of PRL. Keyword pairs ('prolactin' and 'aggression', 'prolactin' and 'hostil*', 'prolactin' and 'anger', and 'prolactin' and 'angry') were entered simultaneously. From 1065 resulting titles, and one unpublished study, 214 articles underwent full-text review by authors JB and EM. Studies were selected based on clinical relevance. Eight comparative studies consisting of 242 female patients with high PRL levels, 207 female patients with normal PRL levels and 127 healthy controls with normal PRL levels were included. Data were analysed using the inverse variance method with a random-effects model. Analysis revealed significantly higher hostility in patients with high PRL compared with that in healthy control women (Z = 1.94, p < 0.05; Hedges' g = 0.72; 95% confidence interval [CI]: -0.01-1.45), significantly higher hostility in patient controls compared with that in healthy controls (Z = 1.94, p < 0.05; Hedges' g = 0.47; 95% CI: 0.00-0.94) and non-significantly higher hostility levels in patients with high PRL compared with that in patients with normal PRL levels (Z = 1.45, p < 0.15; Hedges' g = 0.38; 95% CI: -0.13-0.89). In this meta-analysis, hostility appears to be accounted for partly by PRL levels and also partly by patient status, perhaps due to the stress of being a patient. Methodological considerations and implications for patient care are discussed.

Prolactin and aggression in women with fertility problems.

This study tested the hypothesis that women with higher prolactin feel more hostility, anger and aggression. A total of 66 women with moderate fertility problems were grouped into the 50% who had the highest and the 50% who had the lowest levels of prolactin. Levels of hostility, aggression and anger were compared. Women with higher prolactin levels did not report significantly increased hostility. After Bonferroni correction, women with lower prolactin showed non-significantly increased scores on two measures of state anger, and on a measure of trait temper. When comparing those with the highest and lowest 20% of prolactin levels, those with lower prolactin had non-significantly higher scores on trait temper and outward expression of anger, and non-significantly lower scores for control of anger. Although non-significant, these findings run counter to those of earlier studies on this topic. Implications for future research and patient care are discussed.

Visual-spatial cognition in women with polycystic ovarian syndrome: the role of androgens.

STUDY QUESTION: Are women with polycystic ovary syndrome (PCOS) better at three-dimensional mental rotation than other women? SUMMARY ANSWER: Women with PCOS scored significantly higher on a mental rotation task than a female control group. WHAT IS KNOWN ALREADY: PCOS is a condition characterized by elevated testosterone levels. Some researches have found that three-dimensional mental rotation task performance is positively correlated with testosterone levels. STUDY DESIGN, SIZE, DURATION: This cross-sectional study was conducted between June 2006 and January 2009. The participants were 69 women with PCOS and 41 controls recruited from five gynaecology clinics in London. The control group consisted of non-PCOS women of comparable subfertility to PCOS group. These groups sizes gave roughly 80% power to detect moderate effect sizes for the main statistical test. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants were recruited at London gynaecology clinics. The women were aged between 18 and 43. PCOS was diagnosed based on the Rotterdam criteria. Controls were women who experienced some degree of subfertility. Blood samples from participants were frozen for up to 4 months until being assayed by direct electrochemiluminescence. The mental rotation task was undertaken electronically. Some questionnaires and other tasks were completed as control measures. MAIN RESULTS AND THE ROLE OF CHANCE: Women with PCOS scored significantly higher than controls: median (range) 3.00 (0-9) and 2.00 (0-8), respectively (U = 1147.500, N1 = 69, N2 = 41, P < 0.047). Within the PCOS group, circulating levels of testosterone were significantly positively correlated with three-dimensional scoring (rs = 0.376, n = 56, P < 0.002), whereas estradiol was significantly negatively correlated with three-dimensional scoring (rs = -0.473, n = 29, P < 0.010). In the control group, the relationship between sex hormones and mental rotation was non-significant. Other factors, including general intelligence and social class, did not account for these findings. A subgroup analysis comparing hyperandrogenic PCOS cases, non-hyperandrogenic PCOS cases and controls, in which age and body mass index were controlled for using ANCOVA, found a non-significant difference in three-dimensional scoring between the three groups (F = 1.062, d.f. = 1, 73, P < 0.351). LIMITATIONS, REASONS FOR CAUTION: The small number of women in the control group meant that correlations were underpowered in this group. WIDER IMPLICATIONS OF THE FINDINGS: This study is the first to find a benefit of PCOS in visuospatial cognition, and the first to find a link between visuospatial cognition and sex hormones in PCOS. The fact that the correlations went in the opposite direction in the PCOS group compared with the controls might suggest the influence of increased prenatal exposure to androgen in PCOS. STUDY FUNDING/COMPETING INTEREST(S): The assays for this study were funded by the Department of Psychology, City University London. All authors report no conflicts of interest.

Meta-analysis of sex difference in testosterone levels in umbilical cord blood.

This meta-analysis reviewed published literature comparing human male and female umbilical cord total testosterone (T) levels. A total of 18 studies using 1,229 samples from 602 male and 627 female newborns were analysed using the RevMan 5 statistical package. Analysis using the inverse variance method based on a random-effects model revealed significantly higher cord T in boys than girls at a moderate effect size (Hedges' g = 0.57). There was significant heterogeneity between the 18 studies, although the five studies using direct assays showed no heterogeneity. For studies using extraction and chromatography, those that combined T from arterial and venous cord blood found a larger sex difference than those using only cord venous samples (Hedges' g = 0.94 vs 0.32); this suggests umbilical cord venous T is of maternal/placental origin and arterial T is of fetal origin. The wide range of T values between studies suggests high cross-reactivity in the assay methods reviewed.

Anxiety and depression in polycystic ovary syndrome: a systematic review and meta-analysis.

BACKGROUND: Our aim was to assess differences in anxiety and depression between women with and without (controls) polycystic ovary syndrome (PCOS). METHODS: We conducted a systematic review and meta-analysis of published literature comparing women with PCOS to control groups on anxiety and depression. Electronic databases were searched up to 17 December 2010. The inverse variance method based, as appropriate, on a random- or fixed-effects model in Review Manager, Version 5 was used to analyse the data. RESULTS: Twelve comparative studies were included; all studies assessed depression (910 women with PCOS and 1347 controls) and six also assessed anxiety (208 women with PCOS and 169 controls). Analysis revealed higher depression (Z = 17.92, P < 0.00001; Hedges' g = 0.82; 95% CI 0.73-0.92) and anxiety (Z = 5.03, P < 0.00001; Hedges' g = 0.54; 95% CI 0.33-0.75) scores in the participants with, than without, PCOS. Studies controlling for BMI showed a smaller difference between women with PCOS and controls on anxiety and depression scores than studies not controlling for BMI. CONCLUSIONS: Women with PCOS on average tend to experience mildly elevated anxiety and depression, significantly more than women without PCOS. Women with PCOS with lower BMI tended to have slightly lower anxiety and depression scores, suggesting that having a lower BMI reduces anxiety and depression. Future studies might consider (i) controlling for BMI, (ii) stratifying by medication use in order to control for any anti-androgenic effects of medication and (iii) excluding women with polycystic ovaries from control groups.

Symmetric dimethylarginine (SDMA) is raised in women with polycystic ovary syndrome: a pilot study.

Polycystic ovary syndrome (PCOS) is associated with endothelial dysfunction, which may be caused by elevated levels of asymmetric dimethylarginine (ADMA). ADMA reduces nitric oxide production in diabetes mellitus, hypertension and renal failure. Symmetric dimethylarginine (SDMA) is a stereoisomer produced alongside ADMA, and has recently been described as a risk factor for cardiovascular events. In this cross-sectional study based in a teaching hospital, 16 women with PCOS were recruited alongside 15 healthy controls, and fasting venous blood samples were obtained. Renal function was measured, and ADMA and SDMA were analysed using a high-performance liquid chromatography method. After controlling for BMI, mean ADMA and SDMA levels in women with PCOS were higher than in controls (p = 0.036 and p = 0.030, respectively). Renal function was not different between the two groups (p = 0.152). Women with PCOS have raised levels of SDMA, a molecule implicated in endothelial dysfunction and long-term cardiovascular risk.

Umbilical vein testosterone in female infants born to mothers with polycystic ovary syndrome is elevated to male levels.

The aetiology of polycystic ovary syndrome (PCOS) is poorly understood, but an intrauterine hyperandrogenic environment has been implicated. This study was designed to assess whether the female offspring of mothers with PCOS are exposed to raised levels of testosterone (T) in utero. In this case-control study, three groups of pregnant women were recruited from the labour ward: PCOS women with a female baby (n = 10, PCOS girls); control women with a female baby (n = 20, control girls) and control women with a male baby (n = 10, control boys). Maternal and umbilical vein (UV) blood was assayed for T levels. UV T in PCOS girls was significantly raised, compared with control girls (p < 0.012). The difference in UV T between PCOS girls and control boys was not significant (p < 0.254). This is the first demonstration of a hyperandrogenic in utero environment in PCOS pregnancies; UV T in female infants is raised to male levels.

Ovulation-stimulation drugs and cancer risks: a long-term follow-up of a British cohort.

To assess long-term health effects of ovarian-stimulation drugs we followed-up for over 20 years a British cohort of 7355 women with ovulatory disorders, 43% of whom were prescribed ovarian-stimulation drugs, and identified a total of 274 deaths and 367 incident cancers. Relative to the general population, the cohort experienced lower mortality from most causes, including from all neoplasms combined, and lower incidence of cervical cancer, but higher incidence of cancers of the breast (relative risk: 1.13; 95% CI 0.97, 1.30) and corpus uteri (2.02; 1.37, 2.87). There were, however, no significant differences in the risk of cancers of the breast, corpus uteri, ovary, or of any other site, between women who had been prescribed ovarian-stimulation drugs and those who had not. Further analyses by type of drug and dose revealed a dose-response gradient in the risk of cancer of the corpus uteri (P for linear trend=0.03), with women given >or=2250 mg of clomiphene having a 2.6-fold (2.62; 0.94, 6.82) increase in risk relative to those who were not treated. These findings do not support strong associations between ovulation-stimulation drugs and cancer risks, but they indicate the need for continued monitoring to establish whether risks are elevated in certain subgroups of users.

Could epithelial ovarian cancer be associated with chlamydial infection?

PURPOSE OF INVESTIGATION: Epithelial ovarian cancer (EOC) is the leading cause of death from gynaecological malignancy in the UK. The pathogenesis of this disease is poorly understood. Our hypothesis was that chlamydial infection might play a role in the pathogenesis of EOC. METHODS: 122 serum samples of patients undergoing surgery for benign or malignant gynaecological conditions were analysed. There was a total of 41 patients with EOC (33.6%), 27 with benign cystadenomas (22.1%) and 54 with normal ovaries (44.3%). RESULTS: There was a higher incidence of IgA seropositivity and lower incidence of IgG seropositivity in the EOC group compared with the other groups; however, this was not statistically significant. There was no statistical difference in the serum IgM antibodies to chlamydia in the three different groups. CONCLUSION: Although chronic infection and persistent inflammation may contribute to the pathogenesis of EOC, and chlamydia is a common genital tract pathogen, our study did not find an association between chlamydia and EOC.

The association between polycystic ovaries and endometrial cancer.

BACKGROUND: Women with polycystic ovary syndrome (PCOS) are assumed to be at increased risk of endometrial cancer (EC), albeit of a more differentiated type with better prognosis than in normal women. This study was designed to test these assumptions, as evidence for them is lacking. METHODS: The prevalence of polycystic ovaries (PCO), as a marker of PCOS, was investigated in ovarian sections from 128 women with EC and 83 with benign gynaecological conditions. The expression of the prognostic markers p53, Ki67, Bcl2 and cyclin D1 was also investigated by immunohistochemistry in endometrial tumours from 11 women with PCO and 16 with normal ovaries. RESULTS: Overall, PCO were similarly prevalent in women with EC (8.6%) and benign controls (8.4%); however, in women aged <50 years, PCO were more prevalent in women with EC (62.5 versus 27.3%, P = 0.033). Cyclin D1-expressing endometrial tumours tended to be more prevalent in women with PCO compared to normal ovaries (36.4 versus 6.25%, respectively, P = 0.071). Bcl2-, p53- and Ki67-expressing tumours were similarly prevalent. CONCLUSIONS: The association between PCOS and EC appears confined to premenopausal women. The tendency for cyclin D1-expressing endometrial tumours to be more prevalent in women with PCO challenges the assumption that EC prognosis is improved in women with PCOS.

Microvascular dysfunction in women with polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is associated with multiple cardiovascular risk factors and an increased prevalence of arterial dysfunction. However, microvascular dysfunction in PCOS has not been assessed. METHODS: Subjects comprised 12 women with PCOS and 12 age-matched controls with normal ovaries. Microvascular function was assessed by observing forearm skin microvascular erythrocyte flux responses, to cumulative iontophoretic doses of 1% (w/v) acetylcholine (ACh) and 1% (w/v) sodium nitroprusside (SNP), using laser Doppler imaging. RESULTS: Basal microvascular perfusion was comparable in PCOS and controls. The increase in skin microvascular perfusion in response to ACh was however generally blunted in PCOS women (P = 0.018). Peak ACh-induced erythrocyte flux was also less (p < 0.04) in PCOS women (125.1 +/- 21.7, i.e. 5.3-fold basal flux) than in controls (200.8 +/- 28.5, i.e. 8.3-fold basal flux). Analysis of covariance indicated this effect was unrelated to differences in body mass index or serum testosterone but serum insulin may be a weak confounder. No differences were noted between the PCOS and control groups in their response to SNP. CONCLUSION: Despite its limited sample size studied, this is the first demonstration that women with PCOS exhibit microvascular endothelial dysfunction, indicated by an inhibited vasodilatory response to ACh.

Cell cycle and apoptotic proteins in relation to ovarian epithelial morphology.

OBJECTIVE: To assess the relationship between the expression of cell cycle and apoptotic proteins and the morphological appearance of the surface epithelium in non-neoplastic ovaries. METHODS: The subjects for this study were 79 women who had undergone oophorectomy for benign conditions at the North Middlesex Hospital, London, and Royal Free Hospital, London, and whose ovaries had been reported on routine histology as entirely normal or containing physiological cysts or endometriosis. The epithelial morphology was reassessed on haematoxylin and eosin-stained paraffin wax sections using nine cytological and architectural parameters associated with premalignant intraepithelial changes. A 'score' was obtained for each ovary. Expression of p53, Ki67, cyclin D1 and Bcl-2 in the surface, cystic and endometriotic epithelium was assessed in corresponding sections using standard immunohistochemistry. RESULTS: The median score for the morphological changes was significantly higher in the sections, which expressed p53 compared to those which did not. This difference remained significant in a subanalysis of the sections, which did not contain endometriosis. No relationship was identified between the morphological score and the expression of Ki67, Bcl-2 and cyclin D1. CONCLUSION: Increased intraepithelial abnormality as assessed by an epithelial morphological score of ovarian sections is associated with expression of the p53 cell cycle protein. This lends credence to the hypothesis that the ovarian surface or cystic epithelium goes through an identifiable precursor or "premalignant" phase before the development of invasive disease. Further work is required to characterise the changes that take place before the development of malignancy in ovarian epithelium.

Polycystic ovary syndrome, diabetes and cardiovascular disease: risks and risk factors.

Polycystic ovary syndrome is one of the most common endocrine disorders in the human, affecting approximately 10% of women of reproductive age. Although originally considered a gynaecological disorder, the syndrome is associated with a wide range of endocrine and metabolic abnormalities, including insulin resistance. Affected women are at an increased risk of developing gestational and non-insulin dependent diabetes and there is an association with cardiovascular risk factors including obesity, hypertension, dyslipidaemia, hyperhomocysteinaemia, increased intima media thickness and impaired vascular elasticity. The effect on cardiovascular mortality is currently unclear. However, in view of the proven links with diabetes and the cardiovascular risk markers, this condition should be considered within the province of physicians as well as gynaecologists.

Antioxidants and reactive oxygen species in follicular fluid of women undergoing IVF: relationship to outcome.

BACKGROUND: The role of free radicals and reactive oxygen species (ROS) in female reproductive function is still unclear. The present study was designed to investigate their relationship with ovulation, fertilization and conception. METHODS: Follicular aspirates obtained from women undergoing IVF following controlled ovarian stimulation were evaluated using the ferric reducing antioxidant power (FRAP) assay for baseline total antioxidant capacity (TAC). Both the baseline TAC and the decline in TAC over 72 h (two-point assay) were used as markers of oxygen radical activity. RESULTS: A total of 303 follicular aspirates from 63 women were analysed. Two hundred and eighteen (71.9%) yielded oocytes, 169 (77.5%) of these fertilized and 134 (79.3%) of these embryos survived until the time of embryo transfer. Baseline TAC was no different in follicular fluid whether the follicle contained an oocyte or not, but was significantly higher in fluid from follicles whose oocyte successfully fertilized and significantly lower in fluid from follicles where the resultant embryo survived to transfer. The decline in TAC was lower when the oocytes fertilized and higher in association with embryo viability, but the differences were not statistically significant. CONCLUSIONS: These results provide further evidence that ROS play a role in female reproductive function.

Polycystic ovaries.

Transvaginal ultrasound is currently the gold standard for diagnosing polycystic ovaries. The results of studies using ultrasound suggest a prevalence in young women of at least 20%. Between 5% and 10% of these women with polycystic ovaries shown on ultrasound will have the classical symptoms of polycystic ovary syndrome such as infertility, amenorrhoea or signs of hirsutism and obesity, as originally described by Stein and Leventhal in 1935. However, the significance of polycystic ovaries in asymptomatic women is still under investigation, as is the role of Doppler (pulsed and colour) and three-dimensional ultrasound. Ultrasound has also contributed to our understanding of the local and systemic haemodynamic changes associated with polycystic ovaries, although the relationship of these changes to morbidity and mortality is unknown.

Ovarian epithelial dysplasia in relation to ovulation induction and nulliparity.

OBJECTIVE: The goal of this study was to assess the relationship between ovulation induction, nulliparity, and ovarian epithelial dysplasia. METHODS: This retrospective cohort study was performed in one teaching and one district general hospital in London. The subjects, 83 women who had undergone hysterectomy and bilateral oophorectomy and whose ovaries were reported as "normal," were divided into three groups: ovulation induction (13), nulliparity (20), and fertile controls (50). These ovaries were independently reviewed by two pathologists who assigned a score of 0, 1, or 2 to nine epithelial cytological and architectural features. The main outcome measure was the total dysplasia score, which was used to quantify the degree of ovarian epithelial abnormality in the three groups. RESULTS: The mean dysplasia score was significantly higher in the women who had undergone ovulation induction than in the fertile controls (7.92 vs 5.70, P = 0.012). The magnitude of the difference between the ovulation induction group and controls remained similar after adjusting for age, parity, and duration of oral contraceptive use (2.17, 95% CI: -0.11-4.44). However, the statistical significance of this difference was reduced (P = 0.062). We did not find any evidence of a difference in dysplasia score between nulliparous women and controls, neither before (P = 0.85) nor after adjusting for age and duration of oral contraceptive use (P = 0.87). CONCLUSIONS: These results suggest a possible association between ovarian epithelial dysplasia and ovulation induction therapy, in accord with previous reports of increased risk of ovarian cancer in women with a history of fertility treatment. The higher dysplasia score could be attributable to the drugs used to induce ovulation or to a genetic susceptibility to ovarian cancer.