Aging-related premature luteinization of granulosa cells is avoided by early oocyte retrieval

    1. Norbert Gleicher1,2,6
    1. 1The Center for Human Reproduction (CHR), 21 East 69th Street, New York, New York 10021, USA
      2Foundation for Reproductive Medicine, New York, New York 10021, USA
      3Department of Obstetrics and Gynecology, Albert Einstein College of Medicine, Bronx, New York 10461, USA
      4Department of Obstetrics and Gynecology, Wake Forest University, Winston Salem, North Carolina 27106, USA
      5Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, Kansas 66160, USA
      6Stem Cell Biology and Molecular Embryology Laboratory, The Rockefeller University, New York, New York 10065, USA
    1. Correspondence should be addressed to Y-G Wu; Email: ywu{at}


    Why IVF pregnancy rates decline sharply after age 43 is unknown. In this study, we compared granulosa cell (GC) function in young oocyte donors (n=31, ages 21–29), middle-aged (n=64, ages 30–37) and older infertile patients (n=41, ages 43–47). Gene expressions related to gonadotropin activity, steroidogenesis, apoptosis and luteinization were examined by real-time PCR and western blot in GCs collected from follicular fluid. FSH receptor (FSHR), aromatase (CYP19A1) and 17β-hydroxysteroid dehydrogenase (HSD17B) expression were found down regulated with advancing age, while LH receptor (LHCGR), P450scc (CYP11A1) and progesterone receptor (PGR) were up regulated. Upon in vitro culture, GCs were found to exhibit lower proliferation and increased apoptosis with aging. While FSH supplementation stimulated GCs growth and prevented luteinization in vitro. These observations demonstrate age-related functional declines in GCs, consistent with premature luteinization. To avoid premature luteinization in women above age 43, we advanced oocyte retrieval by administering human chorionic gonadotropin at maximal leading follicle size of 16 mm (routine 19–21 mm). Compared to normal cycles in women of similar age, earlier retrieved patients demonstrated only a marginal increase in oocyte prematurity, yet exhibited improved embryo numbers as well as quality and respectable clinical pregnancy rates. Premature follicular luteinization appears to contribute to rapidly declining IVF pregnancy chances after age 43, and can be avoided by earlier oocyte retrieval.

    • Received in final form 29 June 2015
    • Accepted 8 July 2015
    • Made available online as an Accepted Preprint 11 August 2015
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