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  • 1. Altmäe, Signe
    et al.
    Stavreus-Evers, Anneli
    Ruiz, Jonatan R
    Laanpere, Margit
    Syvänen, Tiina
    Yngve, Agneta
    Salumets, Andres
    Nilsson, Torbjörn K
    Department of Clinical Chemistry, Örebro University Hospital.
    Variations in folate pathway genes are associated with unexplained female infertility2010In: Fertility and Sterility, ISSN 0015-0282, E-ISSN 1556-5653, Vol. 94, no 1, p. 130-137Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To investigate associations between folate-metabolizing gene variations, folate status, and unexplained female infertility.

    DESIGN: An association study.

    SETTING: Hospital-based IVF unit and university-affiliated reproductive research laboratories.

    PATIENT(S): Seventy-one female patients with unexplained infertility.

    INTERVENTION(S): Blood samples for polymorphism genotyping and homocysteine, vitamin B12, and folate measurements.

    MAIN OUTCOME MEASURE(S): Allele and genotype frequencies of the following polymorphisms: 5,10-methylenetetrahydrofolate reductase (MTHFR) 677C/T, 1298A/C, and 1793G/A, folate receptor 1 (FOLR1) 1314G/A, 1816delC, 1841G/A, and 1928C/T, transcobalamin II (TCN2) 776C/G, cystathionase (CTH) 1208G/T and solute carrier family 19, member 1 (SLC19A1) 80G/A, and concentrations of plasma homocysteine, vitamin B12, and serum folate.

    RESULT(S): MTHFR genotypes 677CT and 1793GA, as well as 1793 allele A were significantly more frequent among controls than in patients. The common MTHFR wild-type haplotype (677, 1298, 1793) CAG was less prevalent, whereas the rare haplotype CCA was more frequent in the general population than among infertility patients. The frequency of SLC19A1 80G/A genotypes differed significantly between controls and patients and the A allele was more common in the general population than in infertile women. Plasma homocysteine concentrations were influenced by CTH 1208G/T polymorphism among infertile women.

    CONCLUSION(S): Polymorphisms in folate pathway genes could be one reason for fertility complications in some women with unexplained infertility.

  • 2. Bryman, Inger
    et al.
    Sylvén, Lisskulla
    Berntorp, Kerstin
    Innala, Eva
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Bergström, Ingrid
    Hanson, Charles
    Oxholm, Marianne
    Landin-Wilhelmsen, Kerstin
    Pregnancy rate and outcome in Swedish women with Turner syndrome2011In: Fertility and Sterility, ISSN 0015-0282, E-ISSN 1556-5653, Vol. 95, no 8, p. 2507-2510Article in journal (Refereed)
    Abstract [en]

    Pregnancies occurred in 57 (12%) of 482 Swedish women with Turner syndrome with a liveborn rate of 54% in 124 pregnancies. Spontaneous pregnancies occurred in 40%, mainly in women with 45,X/46,XX mosaicism, and oocyte donation in 53% where miscarriages were less frequent, odds ratio = 0.43 (95% confidence interval 0.17-1.04).

  • 3. Cesta, Carolyn E.
    et al.
    Viktorin, Alexander
    Olsson, Henrik
    Johansson, Viktoria
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Sjölander, Arvid
    Bergh, Christina
    Skalkidou, Alikistis
    Nygren, Karl-Gösta
    Cnattingius, Sven
    Iliadou, Anastasia N.
    Depression, anxiety, and antidepressant treatment in women: association with in vitro fertilization outcome2016In: Fertility and Sterility, ISSN 0015-0282, E-ISSN 1556-5653, Vol. 105, no 6, p. 1594-1602.e3Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To investigate associations between depression, anxiety, and antidepressants before in vitro fertilization (IVF) and IVF cycle outcomes, including pregnancy, live birth, and miscarriage.

    DESIGN: Nationwide register-based cohort study.

    SETTING: Not applicable.

    PATIENT(S): Nulliparous women undergoing their first IVF cycle recorded in the Swedish Quality Register of Assisted Reproduction, January 2007 to December 2012 (n = 23,557).

    INTERVENTION(S): Not applicable.

    MAIN OUTCOME MEASURE(S): Associations between diagnoses of depression/anxiety, antidepressants, and IVF cycle outcome evaluated using logistic regression to produce adjusted odds ratios (AOR) and 95% confidence intervals (CI).

    RESULT(S): In total, 4.4% of women had been diagnosed with depression/anxiety and/or dispensed antidepressants before their IVF first cycle. The odds for pregnancy and live birth were decreased (n = 1,044; AOR = 0.86; 95% CI, 0.75-0.98; and AOR = 0.83; 95% CI, 0.72-0.96, respectively). For women with a prescription for a selective serotonin reuptake inhibitor (SSRI) only (n = 829), no statistically significant associations were found. Women with non-SSRI antidepressants (n = 52) were at reduced odds of pregnancy (AOR = 0.41; 95% CI, 0.21-0.80) and live birth (AOR = 0.27; 95% CI, 0.11-0.68). Women with a depression/anxiety diagnosis with no antidepressant (n = 164) also had reduced odds of pregnancy (AOR = 0.58; 95% CI, 0.41-0.82) and live birth (AOR = 0.60; 95% CI, 0.41-0.89). Among the women who became pregnant (39.7%), there were no statistically significant associations between exposure and miscarriage except for the women taking non-SSRI antidepressants (AOR = 3.56; 95% CI, 1.06-11.9).

    CONCLUSION(S): A diagnosis of depression/anxiety and/or treatment with antidepressants before IVF was associated with slightly reduced odds of pregnancy and live birth. Women with the presence of depression/anxiety without antidepressants had a more pronounced reduction in odds, implying that the underlying disorder is important for the observed association.

  • 4.
    Dennerstein, Lorraine
    et al.
    Department of Psychiatry, The University of Melbourne, Parkville, Victoria, Australia.
    Lehert, Philippe
    Department of Psychiatry, The University of Melbourne, Parkville, Victoria, Australia.
    Bäckström, Torbjörn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Heinemann, Klaas
    Women's Health Care, Bayer Schering Pharma, Berlin, Germany.
    The effect of premenstrual symptoms on activities of daily life2010In: Fertility and Sterility, ISSN 0015-0282, E-ISSN 1556-5653, Vol. 94, no 3, p. 1059-1064Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To assess impact of premenstrual symptoms on activities of women's daily lives (ADL). DESIGN: Cross-sectional population-based survey. SETTING: Market research company. PATIENT(S): A total of 4,085 women aged 14-50 years recruited by random telephone digit dialing in France, Germany, Hungary, Italy, Spain, the United Kingdom, Brazil, and Mexico. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): A telephone interview checklist of 23 premenstrual symptoms, sociodemographic and lifestyle variables, and ADL effects (global question and seven areas). Stepwise regression measured the effect of premenstrual symptoms and sociodemographic factors on ADL. RESULT(S): Symptoms and symptom domains (physical and mental) had similar negative effects on ADL. Activities of daily life were predominantly affected by symptom severity. Income level, age, and country also significantly affected ADL. In all, 2,638 women (64.6%) were minimally affected in ADL, 981 (24%) were moderately affected, and 454 (11.1%) were severely affected. CONCLUSION(S): Both physical and mental premenstrual symptoms have significant impact on quality of life, assessed as ADL. Up to 35% of women of reproductive age in Europe and Latin America were moderately or severely affected in ADL by cyclical premenstrual symptoms.

  • 5.
    Huber, Malin
    et al.
    Department of Obstetrics and Gynecology, Östersunds Sjukhus, Östersund, Sweden.
    Hadziosmanovic, Nermin
    Berglund, Lars
    Holte, Jan
    Using the ovarian sensitivity index to define poor, normal, and high response after controlled ovarian hyperstimulation in the long gonadotropin-releasing hormone-agonist protocol: suggestions for a new principle to solve an old problem2013In: Fertility and Sterility, ISSN 0015-0282, E-ISSN 1556-5653, Vol. 100, no 5, p. 1270-1276.e3Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To explore the utility of using the ratio between oocyte yield and total dose of FSH, i.e., the ovarian sensitivity index (OSI), to define ovarian response patterns.

    DESIGN: Retrospective cross-sectional study.

    SETTING: University-affiliated private center.

    PATIENT(S): The entire unselected cohort of 7,520 IVF/intracytoplasmic sperm injection treatments (oocyte pick-ups [OPUs]) during an 8-year period (long GnRH agonist-recombinant FSH protocol).

    INTERVENTION(S): None.

    MAIN OUTCOME MEASURE(S): The distribution of the OSI (oocytes recovered × 1,000/total dose of FSH), the cutoff levels for poor and high response, set at ±1 SD, and the relationship between OSI and treatment outcome.

    RESULT(S): OSI showed a log-normal distribution with cutoff levels for poor and high response at 1.697/IU and 10.07/IU, respectively. A nomogram is presented. Live-birth rates per OPU were 10.5 ± 0.1%, 26.9 ± 0.6%, and 36.0 ± 1.4% for poor, normal, and high response treatments, respectively. The predictive power (C-statistic) for OSI to predict live birth was superior to that of oocyte yield.

    CONCLUSION(S): The OSI improves the definition of ovarian response patterns because it takes into account the degree of stimulation. The nomogram presents evidence-based cutoff levels for poor, normal, and high response and could be used for unifying study designs involving ovarian response patterns.

  • 6. Isaksson, Stina
    et al.
    Sydsjö, Gunilla
    Skoog Svanberg, Agneta
    Lampic, Claudia
    Department of Neurobiology, Care Sciences, and Society, Karolinska Institutet, Huddinge, Sweden.
    Preferences and needs regarding future contact with donation offspring among identity-release gamete donors: results from the Swedish Study on Gamete Donation2014In: Fertility and Sterility, ISSN 0015-0282, E-ISSN 1556-5653, Vol. 102, no 4, p. 1160-1166Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To investigate the attitudes and preferences regarding future contact with donation offspring among identity-release donors of oocytes or sperm.

    DESIGN: Longitudinal cohort study.

    SETTING: University-based fertility clinics in Sweden.

    PATIENT(S): A total of 210 women and men were questioned 5-8 years after their donation of oocytes or sperm.

    INTERVENTION(S): Questionnaires given to donors prior to their donation and 5-8 years after donation.

    MAIN OUTCOME MEASURE(S): Donors' attitudes and preferences regarding future contact with their donation offspring.

    RESULT(S): A majority of identity-release oocyte (65%) and sperm (70%) donors were positive toward being contacted by an offspring of mature age. More than half wanted to be notified by the clinic when an offspring requested information about them, but about a third were negative toward receiving this information. One in four reported a need for counseling regarding future contact with an offspring.

    CONCLUSION(S): Several years after donation, a majority of identity-release oocyte and sperm donors show positive attitudes toward future contact with their offspring. Donors appear to have different preferences for information and support regarding such contact. Fertility clinics and health-care services should provide counseling regarding contact with an offspring to the donors who express a need for this.

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  • 7. Jung, Seungyoun
    et al.
    Allen, Naomi
    Arslan, Alan A.
    Baglietto, Laura
    Brinton, Louise A.
    Egleston, Brian L.
    Falk, Roni
    Fortner, Renee T.
    Helzlsouer, Kathy J.
    Idahl, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology.
    Kaaks, Rudolph
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Merritt, Melissa
    Onland-Moret, Charlotte
    Rinaldi, Sabina
    Sanchez, Maria-Jose
    Sieri, Sabina
    Schock, Helena
    Shu, Xiao-Ou
    Sluss, Patrick M.
    Staats, Paul N.
    Travis, Ruth C.
    Tjonneland, Anne
    Trichopoulou, Antonia
    Tworoger, Shelley
    Visvanathan, Kala
    Krogh, Vittorio
    Weiderpass, Elisabete
    Zeleniuch-Jacquotte, Anne
    Zheng, Wei
    Dorgan, Joanne F.
    Demographic, lifestyle, and other factors in relation to antimullerian hormone levels in mostly late premenopausal women2017In: Fertility and Sterility, ISSN 0015-0282, E-ISSN 1556-5653, Vol. 107, no 4Article in journal (Refereed)
    Abstract [en]

    Objective: To identify reproductive, lifestyle, hormonal, and other correlates of circulating antimullerian hormone (AMH) concentrations in mostly late premenopausal women. Design: Cross-sectional study. Setting: Not applicable. Patient(s): A total of 671 premenopausal women not known to have cancer. Intervention(s): None. Main Outcome Measure(s): Concentrations of AMH were measured in a single laboratory using the picoAMH ELISA. Multivariable-adjusted median (and interquartile range) AMH concentrations were calculated using quantile regression for several potential correlates. Result(s): Older women had significantly lower AMH concentrations (>= 40 [n = 444] vs. < 35 years [n = 64], multivariable-adjusted median 0.73 ng/mL vs. 2.52 ng/mL). Concentrations of AMH were also significantly lower among women with earlier age at menarche (< 12 [n = 96] vs. >= 14 years [n = 200]: 0.90 ng/mL vs. 1.12 ng/mL) and among current users of oral contraceptives (n = 27) compared with never or former users (n = 468) (0.36 ng/mL vs. 1.15 ng/mL). Race, body mass index, education, height, smoking status, parity, and menstrual cycle phase were not significantly associated with AMH concentrations. There were no significant associations between AMH concentrations and androgen or sex hormone-binding globulin concentrations or with factors related to blood collection (e.g., sample type, time, season, and year of blood collection). Conclusion(s): Among premenopausal women, lower AMH concentrations are associated with older age, a younger age at menarche, and currently using oral contraceptives, suggesting these factors are related to a lower number or decreased secretory activity of ovarian follicles.

  • 8. Lindahl, Magnus S
    et al.
    Olovsson, Matts
    Nyberg, Sigrid
    Umeå University Hospital, Umeå, Sweden.
    Thorsen, Kim
    Olsson, Tommy
    Umeå University Hospital, Umeå, Sweden.
    Sundström Poromaa, Inger
    Increased cortisol responsivity to adrenocorticotropic hormone and low plasma levels of interleukin-1 receptor antagonist in women with functional hypothalamic amenorrhea2007In: Fertility and Sterility, ISSN 0015-0282, E-ISSN 1556-5653, Vol. 87, no 1, p. 136-142Article in journal (Refereed)
    Abstract [en]

    Objective: To assess the hypothalamic-pituitary-adrenal (HPA) axis at all levels, to determine the origin of the previously reported hypercortisolism in patients with functional hypothalamic amenorrhea. A secondary aim was to evaluate factors outside the central nervous system which are known to affect the HPA axis, i.e., circulating levels of interleukin-6 (IL-6), interleukin-1 receptor antagonist (IL-1Ra), and fat mass-adjusted leptin levels, in patients with functional hypothalamic amenorrhea and healthy controls.

    Design: Cross-sectional study.

    Setting: Umeå University Hospital, Umeå, Sweden.

    Patients: Fifteen subjects with hypothalamic amenorrhea, and 14 age- and weight-matched controls.

    Interventions: None.

    Main Outcome Measures: We collected blood samples four times during a 24-hour interval for analysis of cortisol, leptin, IL-1Ra, and IL-6 levels. We performed a low-dose oral dexamethasone test and a low-dose ACTH test. We measured body-fat percentage using a dual-energy X-ray absorptiometer.

    Results: Patients with hypothalamic amenorrhea had increased diurnal cortisol levels (P<.001). The cortisol response to intravenous low-dose ACTH was increased in functional hypothalamic amenorrhea patients compared to control subjects (P<.01), but they had similar rates of dexamethasone suppression. Patients with hypothalamic amenorrhea also had decreased diurnal leptin (P<.05), and decreased diurnal IL-1Ra levels (P<.05), compared to controls. Body-fat percentage was the main predictor of leptin levels.

    Conclusion: The present study suggests novel links for the development of functional hypothalamic amenorrhea, including increased adrenal responsiveness and impairments in proinflammatory cytokine pathways.

  • 9.
    Ottander, Ulrika
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Solensten, Nils Gunnar
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Olofsson, Jan I
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Intraovarian blood flow measured with color doppler ultrasonography inversely correlates with vascular density in the human corpus luteum of the menstrual cycle2004In: Fertility and Sterility, ISSN 0015-0282, E-ISSN 1556-5653, Vol. 81, no 1, p. 154-159Article in journal (Refereed)
    Abstract [en]

    Objective

    To evaluate the morphologic characteristics underlying the ultrasonographic appearance and blood flow dynamics in the human corpus luteum (CL) of the menstrual cycle.

    Design

    Cross-sectional study.

    Setting

    Umeå University Hospital, Umeå, Sweden.

    Patient(s)

    Twenty-six otherwise healthy women with proven fertility and a history of regular menstrual cycles, scheduled for elective hysterectomy or tubal sterilization.

    Intervention(s)

    An ovulatory LH rise in urine was established and the CL age was determined according to the day after the LH rise. Before surgery, a standardized ultrasonographic examination of the CL, including B-mode and color Doppler ultrasonography measurements, was performed. Upon commencing the minilaparotomy, the CL was excised and measured using a digital slide-caliper. The volume density (percentage of CL volume occupied by blood vessels) of factor VIII–related antigen immunostained endothelial cells was determined.

    Main outcome measure(s)

    Pulsatility index obtained from intraovarian blood vessels supplying the CL and volume density of blood vessels in CL tissue. The CL maximal and minimal outer and inner dimensions were measured in vivo by ultrasonography and ex vivo by a digital slide caliper.

    Result(s)

    A statistically significant decrease of blood vessel density and an increased resistance to blood flow, as indicated by pulsatility index, was established during the course of corpus luteum development. An inverse correlation between pulsatility index and volume density of blood vessels was found. A high degree of agreement between ultrasonographic and anatomic measurements of surgically removed CL was found.

    Conclusion(s)

    Transvaginal ultrasonography in combination with intraovarian color Doppler flow measurements is a simple and reliable method to evaluate the size and vascularization of the human CL.

  • 10.
    Persson, Sofia
    et al.
    Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden; Department of Obstetrics and Gynecology, Sundsvall County Hospital, Sundsvall, Sweden.
    Elenis, Evangelia
    Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.
    Turkmen, Sahruh
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology. Department of Obstetrics and Gynecology, Sundsvall County Hospital, Sundsvall, Sweden.
    Kramer, Michael S.
    Departments of Epidemiology, Biostatistics and Occupational Health and of Pediatrics, McGill University Faculty of Medicine, QC, Montreal, Canada; Department of Obstetrics and Gynaecology, National University Hospital, National University of Singapore, Singapore.
    Yong, Eu-Leong
    Department of Obstetrics and Gynaecology, National University Hospital, National University of Singapore, Singapore.
    Sundström Poromaa, Inger
    Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.
    Higher risk of type 2 diabetes in women with hyperandrogenic polycystic ovary syndrome2021In: Fertility and Sterility, ISSN 0015-0282, E-ISSN 1556-5653, Vol. 116, no 3, p. 862-871Article in journal (Refereed)
    Abstract [en]

    Objective: To assess the risk of type 2 diabetes (T2D) in women with polycystic ovary syndrome (PCOS) in relation to body mass index (BMI) and the hyperandrogenic (HA) PCOS phenotype.

    Design: Population-based cohort study.

    Setting: Data from six Swedish national registers, with participants being followed for a maximum of 19 years.

    Patient(s): All women with an International Statistical Classification of Diseases and Related Health Problems, version 10, diagnosis of PCOS, androgen excess, or anovulatory infertility born between 1950 and 1999 (n = 52,535) were identified in the Patient Register. The HA PCOS phenotype was defined by two filled prescriptions for anti-androgenic drugs. For each woman with PCOS, five control women (n = 254,624) were randomly chosen from the Total Population Register, matched for age and geographic area.

    Intervention(s): No interventions were performed.

    Main Outcome Measure(s): International Statistical Classification of Diseases and Related Health Problems, version 10, diagnosis of T2D or prescription of antidiabetic treatment other than metformin.

    Result(s): The cumulative incidence rates of T2D were 1.3%, 4.4%, and 14.2% in controls (non-PCOS women) and women with normoandrogenic (NA) and HA PCOS, respectively. After adjustment for BMI, women with PCOS had a twofold higher rate of T2D than non-PCOS women (adjusted hazard ratio, 2.52 [95% confidence interval, 2.15–2.96]). Women with HA PCOS had a higher rate of T2D than those with NA PCOS (adjusted hazard ratio, 3.86 [95% confidence interval, 3.16–4.72]).

    Conclusion(s): Polycystic ovary syndrome is an independent risk factor for T2D, even after adjustment for BMI. Women with the HA PCOS phenotype face an even higher risk of T2D than those with the NA PCOS phenotype.

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  • 11. Stener-Victorin, Elisabet
    et al.
    Baghaei, Fariba
    Holm, Göran
    Janson, Per Olof
    Olivecrona, Gunilla
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Lönn, Malin
    Mannerås-Holm, Louise
    Effects of acupuncture and exercise on insulin sensitivity, adipose tissue characteristics, and markers of coagulation and fibrinolysis in women with polycystic ovary syndrome: secondary analyses of a randomized controlled trial2012In: Fertility and Sterility, ISSN 0015-0282, E-ISSN 1556-5653, Vol. 97, no 2, p. 501-508Article in journal (Refereed)
    Abstract [en]

    Objective: To investigate the possible effects of low-frequency electroacupuncture (EA) and physical exercise on markers of coagulation and fibrinolysis, insulin sensitivity, and adipose tissue characteristics in women with polycystic ovary syndrome (PCOS). Design: Secondary analyses of a prospective, randomized controlled clinical trial. Setting: Department of Physiology and Department of Obstetrics and Gynecology, University of Gothenburg. Patient(s): Eighty-four women with PCOS were randomized. Intervention(s): Women with PCOS were randomized to 16 weeks of low-frequency EA (14 treatments), physical exercise (at least 3 times/wk), or no intervention. Main Outcome Measure(s): Anthropometrics, circulating coagulation and fibrinolytic markers, insulin sensitivity (euglycemic hyperinsulinemic clamp), hemodynamics, and adipose tissue morphology/function recorded at baseline, after 16 weeks of intervention, and after a 16-week follow-up. Result(s): In the low-frequency EA group, circulating plasminogen activator inhibitor 1 activity decreased by 21.8% after 16 weeks of intervention and by 31.1% at the 16-week follow-up and differed from the physical exercise and the no intervention groups. The EA group had decreases in circulating fibrinogen and tissue plasminogen activator (t-PA), sagittal diameter, and diastolic blood pressure after treatment, and fibrinogen remained lower at the 16-week follow-up. In the physical exercise group, lipoprotein lipase activity increased and diastolic blood pressure decreased after treatment, and both diastolic and systolic blood pressure were lower at follow-up. No other variables were affected. Conclusion(s): Low-frequency EA counteracted a possible prothrombotic state in women with PCOS, as reflected by a decrease in plasminogen activator inhibitor 1 activity. Despite within-group improvements, there were no between-group differences in anthropometric, metabolic, or hemodynamic variables after 16 weeks of EA or physical exercise at the dose/intensity studied. (Fertil Steril(R) 2012;97:501-8. (C) 2012 by American Society for Reproductive Medicine.)

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