Henrik Leonhardt

Adipose Tissue Has Aberrant Morphology and Function in PCOS: Enlarged Adipocytes and Low Serum Adiponectin, But Not Circulating Sex Steroids, Are Strongly Associated with Insulin Resistance

CONTEXT Comprehensive characterization of the adipose tissue in women with polycystic ovary syndrome (PCOS), over a wide range of body mass indices (BMIs), is lacking. Mechanisms behind insulin resistance in PCOS are unclear. OBJECTIVE To characterize the adipose tissue of women with PCOS and controls matched pair-wise for age and BMI, and to identify factors, among adipose tissue characteristics and serum sex steroids, that are associated with insulin sensitivity in PCOS. DESIGN/OUTCOME MEASURES Seventy-four PCOS women and 31 controls were included. BMI was 18-47 (PCOS) and 19-41 kg/m(2) (controls). Anthropometric variables, volumes of subcutaneous/visceral adipose tissue (magnetic resonance imaging; MRI), and insulin sensitivity (clamp) were investigated. Adipose tissue biopsies were obtained to determine adipocyte size, lipoprotein lipase (LPL) activity, and macrophage density. Circulating testosterone, free testosterone, free 17β-estradiol, SHBG, glycerol, adiponectin, and serum amyloid A were measured/calculated. RESULTS Comparison of 31 pairs revealed lower insulin sensitivity, hyperandrogenemia, and higher free 17β-estradiol in PCOS. Abdominal adipose tissue volumes/distribution did not differ in the groups, but PCOS women had higher waist-to-hip ratio, enlarged adipocytes, reduced adiponectin, and lower LPL activity. In regression analysis, adipocyte size, adiponectin, and waist circumference were the factors most strongly associated with insulin sensitivity in PCOS (R(2)=0.681, P < 0.001). CONCLUSIONS In PCOS, adipose tissue has aberrant morphology/function. Increased waist-to-hip ratio indicates abdominal/visceral fat accumulation, but this is not supported by MRI. Enlarged adipocytes and reduced serum adiponectin, together with a large waistline, rather than androgen excess, may be central factors in the pathogenesis/maintenance of insulin resistance in PCOS.

Vascular pedicle lengths after hysterectomy: toward future human uterus transplantation.

OBJECTIVE: To estimate uterine vessel lengths and diameters recovered at radical hysterectomy to assess prospects for direct vascular anastomosis bilaterally to the external iliacs in uterus transplantation, and thereby the feasibility of live uterus donation as a future treatment of absolute uterine factor infertility. METHODS: Patients (n=19; study group) undergoing radical hysterectomy for gynecologic malignancy participated. Preoperative magnetic resonance imaging (MRI) was performed in four patients to evaluate the usefulness in estimation of vessel lengths. At hysterectomy, the uterine arteries and veins were dissected separately from the anterior divisions of the internal iliacs to their attachments to the uterine cervix. The lengths of the free vascular pedicles were measured bilaterally and the distal vessel diameters were recorded. The inter-external iliac artery distance, corresponding to distance between proposed bilateral anastomosis sites, was measured. Perioperative and postoperative outcomes were compared with 76 patients (control group) undergoing standard radical hysterectomy without particular uterine vessel dissection. RESULTS: The MRI showed uterine artery lengths of 55–100 mm. The duration of surgery was slightly longer in the study group (median 297 minutes) compared with the control group (262 minutes), but with no differences in perioperative and postoperative morbidity. The lengths (median) of the free portions of the left uterine artery and vein were 68 mm and 55 mm, and the right uterine artery and vein were 65 mm and 50 mm, respectively. The inter-external iliac artery distance (median) was 90 mm. CONCLUSION: This study demonstrates that long vascular pedicles can be obtained after selective dissections of the uterine arteries and veins without compromising postoperative recovery in a live uterine donor situation. LEVEL OF EVIDENCE: II

Ovarian morphology assessed by magnetic resonance imaging in women with and without polycystic ovary syndrome and associations with antimüllerian hormone, free testosterone, and glucose disposal rate

OBJECTIVE To characterize ovarian morphology and perfusion by magnetic resonance imaging (MRI) in women with and without polycystic ovary syndrome (PCOS) and to investigate associations with antimüllerian hormone (AMH), free T, and glucose disposal rate (GDR). DESIGN Explorative cross-sectional study. SETTING University hospital. PATIENT(S) Fifty-eight women with PCOS and 31 controls from the general population. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Antral follicle count (AFC), ovarian/stromal volume, perfusion, AMH, free T, and GDR. RESULT(S) Antral follicles of 1-3 and 4-6 mm, but not 7-9 mm, were more numerous, and total AFC (1-9 mm) was higher in women with PCOS. Ovarian volume was larger in women with PCOS. AMH and free T were higher and GDR was lower in women with PCOS. All values were more deranged in classic compared with nonclassic PCOS. There was a positive correlation between AMH and AFC, 1-3 mm (r = 0.81), and between AMH and total AFC (r = 0.87). In receiver operating characteristic analyses, the area under the curve was 0.89 for total AFC, 0.86 for AMH, and 0.90 for free T. PCOS was independently associated with AFC and free T but not with AMH or GDR when adjusted for age and body mass index. CONCLUSION(S) Counting antral follicles down to 1 mm in size by MRI yielded higher AFCs than previously reported. AFC, AMH, and free T discriminated with high accuracy between women with PCOS and controls, but AMH was not independently associated with PCOS. CLINICAL TRIAL REGISTRATION NUMBER NCT00484705.

Ovarian volume and antral follicle count assessed by MRI and transvaginal ultrasonography: a methodological study

Background Ultrasonographic measurements of ovarian volume and antral follicle count are of clinical importance as diagnostic features of polycystic ovarian syndrome (PCOS), and as a parameter in estimation of ovarian follicular reserve in infertility care. Purpose To compare two-dimensional (2D)/three-dimensional (3D) transvaginal ultrasonography (TVUS) and magnetic resonance imaging (MRI) for estimation of ovarian volume and antral follicle count, and to assess reproducibility and inter-observer agreement of MRI measurements. Material and Methods Volumes of 172 ovaries in 99 women aged 21–37 years were calculated (length x width x height x 0.523) with conventional 2D TVUS and 2D MRI. Semi-automatic estimates of ovarian volumes were obtained by 3D MRI. Antral follicles were counted manually on 2D MRI and automatically by 3D TVUS (SonoAVC), and stratified according to follicle size. Results Mean ovarian volume assessed by 2D TVUS (13.1 ± 6.4 mL) was larger than assessed by 2D MRI (9.6 ± 4.1) and 3D MRI (11.4 ± 4.5) (P < 0.001). Total follicle count was higher by 2D MRI than by 3D TVUS, mean difference 14.3 ± 16.2 follicles (P < 0.001). In the smallest size interval of 1–3 mm the mean difference was 22.2 ± 17.6 (P < 0.001). Intra- and inter-observer absolute agreement assessment for MRI measurements of ovarian volume and total follicle count showed ICC coefficients >0.77. Conclusion 2D MRI reveals more antral follicles, especially of small size, than 3D TVUS. Ovarian volume estimation by MRI provides smaller volumes than by the reference standard 2D TVUS. Ovarian volume estimation by 3D MRI, allowing independence of non-ellipsoid ovarian shape measurement errors, provides volumes closer to 2D TVUS values than does 2D MRI. Reproducibility and inter-observer agreement of 2D MRI measurements of ovarian volume and total follicle count are good.

Uterine morphology and peristalsis in women with polycystic ovary syndrome.

Background Polycystic ovary syndrome (PCOS) is associated with chronic oligo-anovulation and high circulating sex hormone levels. Women with PCOS have an increased risk of developing endometrial cancer. In anovulatory women with PCOS a positive relationship between endometrial thickness and endometrial hyperplasia has been observed. Uterine peristalsis, which has been suggested to be of importance for female fertility, has not previously been studied in PCOS. Purpose To assess whether women with PCOS have altered endometrial thickness, uterine wall morphology, and peristalsis. Material and Methods In this prospective case-control study 55 women with PCOS (mean age, 29.5 years+4.5 SD) and 28 controls (27.6+3.2) were examined using magnetic resonance imaging (MRI), assessing thickness of endometrium, junctional zone (JZ), and myometrium, and evaluating the occurrence, frequency (waves/min), strength (amplitude), pattern, and direction of peristalsis. Uterine morphology was also assessed by transvaginal ultrasonography (TVUS). Results The endometrium was thinner in PCOS with oligo-amenorrhea compared to controls, also after adjustments for age and BMI (adjusted P = 0.043). There was no difference in thickness of the JZ or the myometrium in cases versus controls. Uterine peristalsis was less commonly observed in women with PCOS than in controls (adjusted P = 0.014). Conclusion There were no differences in myometrial morphology between PCOS and controls, but the endometrium was thinner in PCOS with oligo-amenorrhea. Based on cine MRI, uterine peristalsis was less common in PCOS than in controls.

Serum anti-Müllerian hormone and ovarian morphology assessed by magnetic resonance imaging in response to acupuncture and exercise in women with polycystic ovary syndrome: secondary analyses of a randomized controlled trial

To investigate whether electro‐acupuncture or physical exercise influence serum anti‐Müllerian hormone (AMH), antral follicle count (AFC) or ovarian volume in women with polycystic ovary syndrome (PCOS).