title: The association between severe obesity and characteristics of failed fertilized oocytes.
abstract: OBJECTIVE
  Is the cytoskeletal and chromosomal organization of failed fertilized oocytes from severely obese patients (BMI ≥ 35 kg/m²) altered compared with that in patients with normal BMI (BMI 18.5-24.9 kg/m²)?
  
  
  CONCLUSIONS
  Compared with normal BMI patients, severe obesity was associated with a greater prevalence of spindle anomalies and non-aligned chromosomes in failed fertilized oocytes.
  
  
  BACKGROUND
  Obesity is associated with poor reproductive outcomes, but little is known regarding the underlying mechanisms. To address potential mechanisms, our study compared the cytoskeletal and chromosome organization in failed fertilized oocytes from severely obese and normal BMI patients.
  
  
  METHODS
  The study population was drawn from IVF patients treated in a hospital-based infertility clinic between February 2010 and July 2011. The prevalence of meiotic spindle and chromosome alignment anomalies in failed fertilized oocytes from patients with severe obesity (i.e. Class II and III; BMI 35.0-50.1 kg/m²) was compared with those from patients with normal BMI (BMI 18.5-24.9 kg/m²). Oocytes were fixed and then labeled for tubulin, actin and chromatin. Spindle number and integrity, as well as chromosome alignment, were assessed using immunofluorescence microscopy and, in some cases, confocal microscopy. Generalized estimating equations were applied, which account for the correlation among oocytes from the same patient to estimate odds ratio (OR), 95% confidence intervals (CIs) and two-sided Wald P-values. Models were adjusted for continuous age at cycle start, cycle type (IVF or ICSI) and polycystic ovarian syndrome (PCOS) a priori.
  
  
  METHODS
  University-affiliated infertility clinic. A total of 276 oocytes that failed to fertilize from 137 patients were evaluated: 105 oocytes from severely obese women (n = 47) and 171 oocytes from normal BMI patients (n = 90).
  
  
  RESULTS
  (i) Significantly more oocytes from the severely obese group exhibited two spindles compared with those from the normal BMI group (58.9 versus 35.1%; OR = 2.68, CI = 1.39-5.15, P-value = 0.003). (ii) Among oocytes with a single spindle, those from severely obese patients showed a significantly higher prevalence of disarranged spindles with non-aligned chromosomes compared with those from normal BMI patients (28.6 versus 8.6%; OR = 4.58, CI = 1.05-19.86, P-value = 0.04).
  
  
  CONCLUSIONS
  Inclusion of only failed fertilized oocytes, small sample size, unknown factors such as non-PCOS comorbidity.
  
  
  CONCLUSIONS
  For this study, by design, it is unclear whether the findings are generalizable to successfully fertilized oocytes, and whether this oocyte-level influence of obesity is generalizable to infertile women who do not undergo stimulation or, more broadly, to spontaneous conceptions in fertile women.
  
  
  BACKGROUND
  none.
  
  
  BACKGROUND
  n/a.
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Biology, Brigham & Women's Hospital and Harvard Medical School, 02115 Boston, MA, USA.
authors.forename: Ronit
authors.initials: R
authors.lastname: Machtinger
authors.forename: Catherine M H
authors.initials: CM
authors.lastname: Combelles
authors.forename: Stacey A
authors.initials: SA
authors.lastname: Missmer
authors.forename: Katharine F
authors.initials: KF
authors.lastname: Correia
authors.forename: Janis H
authors.initials: JH
authors.lastname: Fox
authors.forename: Catherine
authors.initials: C
authors.lastname: Racowsky
mesh_terms: D000293:Adolescent; D000328:Adult; D015992:Body Mass Index; D001900:Boston / Q000453:epidemiology; D015331:Cohort Studies; D003599:Cytoskeleton / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005307:Fertilization in Vitro; D006785:Hospitals, University; D006801:Humans; D021621:Imaging, Three-Dimensional; D007247:Infertility, Female / Q000150:complications* / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D008856:Microscopy, Fluorescence; D009765:Obesity / Q000150:complications*; D009767:Obesity, Morbid / Q000150:complications*; D009865:Oocytes / Q000378:metabolism / Q000473:pathology*; D010044:Outpatient Clinics, Hospital; D011247:Pregnancy; D018873:Pregnancy Rate; D008941:Spindle Apparatus / Q000378:metabolism / Q000473:pathology*; D055815:Young Adult