Mitochondrial Activity of Cumulus Cells From the Cumulus-oocyte Complex and Oocyte Competence
Condition: Infertility
MeSH terms: Infertility
Study type: Observational

Summary: 
      The need for non-invasive biomarkers of oocyte competency has become urgent as women
      increasingly delay attempts at childbearing. The aging process is complex and includes
      impaired mitochondrial dysfunction, oxidative stress, diminished metabolic activity, and
      activity of several cell-signaling systems. Cumulus cells form an intimate association with
      the oocyte in the follicle, and they can have a significant impact on oocyte meiotic and
      developmental competence. In the IVF lab, the clump of cumulus cells is typically cut away
      from the oocyte immediately after an oocyte retrieval procedure, and then the cumulus cells
      are discarded. Measuring the mitochondrial respiratory activity of cumulus cells may serve as
      a non-invasive biomarker for oocyte competency and a predictor of reproductive success in IVF
      patients in the future.
    

Detailed description: 
      Background The number of couples undergoing in vitro fertilization (IVF) is rapidly growing
      worldwide. However, only approximately 5% of aspirated human oocytes have the competence to
      implant and develop into a child (Ziebe, 2013). Reasons for this low percentage of competence
      include genetic abnormalities and metabolic problems.

      Moreover, this oocyte developmental competence decreases as a woman ages, and therefore
      maternal age is the single best predictor of reproductive outcome in women (Keefe et al,
      2015). In general, the aging process is complex and includes impaired mitochondrial
      dysfunction, oxidative stress, diminished metabolic activity, and activity of several
      cell-signaling systems (Bentov, 2011).

      Oocyte Competency is the Key to Embryo Potential The oocyte is the major determinant of
      embryo developmental competence in women. The oocyte transmits not only the mother's nuclear
      but also her mitochondrial genome to the embryo. The maternal and paternal genomes are
      neither symmetrical nor equal in their contributions to embryo fate.

      Oxygen Consumption and Oocyte/Embryo Competence Clinically useful biomarkers of oocyte
      competency are needed (Keefe et al, 2015). Oxygen consumption is a quality marker for human
      oocyte competence conditioned by ovarian stimulation regimens (Tejera et al., 2011).
      Furthermore, oxygen consumption rates of embryos have been found to be associated with
      successful implantation and can be used to select the embryo with the best developmental
      potential (Tejera et al., 2012).

      Rationale of Studying Cumulus Cells Ovarian follicles are highly specialized structures that
      support the growth and development of oocytes during controlled ovarian stimulation for IVF.
      Cumulus cells are somatic cells that form an intimate association with the oocyte in the
      follicle. Cumulus cells possess specialized cytoplasmic projections that penetrate through
      the zona pellucida [shell] and form gap junctions at their tips with the oocyte, generating
      an elaborate structure called the cumulus-oocyte complex (COC) (Albertini et al., 2001;
      Gilchrist et al., 2008). Cumulus cells metabolize the bulk of the glucose consumed by the COC
      to supply metabolic intermediates to the oocyte, and COC glucose metabolism is pivotal in
      determining oocyte developmental competence (Sutton-McDowall et al., 2010). It is well known
      that cumulus cells support oocyte development through the provision of essential nutrients,
      information molecules, metabolic precursors and signaling molecules (Hutt et al., 2007).
      Because of the metabolic and communication link between the cumulus and the oocyte, glucose
      availability and metabolism within the cumulus can have a significant impact on oocyte
      meiotic and developmental competence (Thompson JG, 2007).

      If the coordinated somatic cell-oocyte interactions are perturbed by metabolic disease and/or
      maternal aging, molecular damage of the oocyte can alter macromolecules, induce mitochondrial
      mutations, all of which can harm the oocyte (Dumesic et al, 2015). For example, in 2015 Hsu
      et al. reported that endometriosis may be associated with mitochondrial dysfunction in pooled
      cumulus cells, and subjects with endometriosis may have a defect in cumulus cell
      mitochondrial function, which may contribute to decreased fertilization and implantation
      rates (Barnhart et al., 2002). The purpose of this study is to determine if the mitochondrial
      respiratory activity of cumulus cells is associated with maternal age and reproductive
      outcomes (oocyte competence).
    

Intervention name(s): Age
Intervention type(s): Other
Intervention description(s): Maternal Age
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Patients undergoing in vitro fertilization
      
Biospecimen description: 
      Cumulus Cells
    
Keywords: IVF; In vitro fertilization; Cumulus Cells; Oocyte; Embryo; Fertility