Fertility and Sterility
Volume 94, Issue 5 , Pages 1769-1774, October 2010

A prospective evaluation of antral follicle function in women with 46,XX spontaneous primary ovarian insufficiency

  • Ziad R. Hubayter, M.D., M.P.H.

      Affiliations

    • Integrative Reproductive Medicine Unit, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland
  • ,
  • Vaishali Popat, M.D., M.P.H.

      Affiliations

    • Integrative Reproductive Medicine Unit, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland
  • ,
  • Vien H. Vanderhoof, R.N., M.H.A., C.R.N.P.

      Affiliations

    • Integrative Reproductive Medicine Unit, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland
  • ,
  • Obioma Ndubizu, M.D.

      Affiliations

    • Integrative Reproductive Medicine Unit, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland
  • ,
  • Diane Johnson, R.T., R.D.M.S.

      Affiliations

    • Clinical Center, National Institutes of Health, Bethesda, Maryland
  • ,
  • Edie Mao, M.B., R.D.M.S., R.V.T.

      Affiliations

    • Clinical Center, National Institutes of Health, Bethesda, Maryland
  • ,
  • Karim A. Calis, Pharm.D., M.P.H.

      Affiliations

    • Clinical Center, National Institutes of Health, Bethesda, Maryland
  • ,
  • James F. Troendle, Ph.D.

      Affiliations

    • Biostatistics and Bioinformatics Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland
  • ,
  • Lawrence M. Nelson, M.D.

      Affiliations

    • Integrative Reproductive Medicine Unit, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland
    • Corresponding Author InformationReprint requests: Lawrence M. Nelson, M.D., National Institutes of Health, CRC 1-3330, 10 Center Drive, MSC-1103, Bethesda, MD 20892-1103 (FAX: 301-402-0884).

Received 26 February 2009; received in revised form 13 October 2009; accepted 13 October 2009. published online 24 November 2009.

Objective

To assess ovarian follicle function in women with 46,XX spontaneous primary ovarian insufficiency.

Design

Case–control with nested prospective cohort.

Setting

Clinical Research Center, National Institutes of Health.

Patient(s)

Women with primary ovarian insufficiency without estrogen replacement for 2 weeks (N = 97) and regularly menstruating control women (N = 42).

Intervention(s)

Single injection of 300 IU hrFSH.

Main Outcome Measure(s)

Change in serum estradiol at 24 hours.

Result(s)

Antral follicles ≥3 mm were detected in 73% (69/95) of patients; both serum estradiol and progesterone levels correlated significantly with maximum follicle diameter in these women. Patients with a maximum follicle diameter ≥8 mm had significantly higher serum estradiol and progesterone levels and significantly lower FSH and LH levels compared with patients without such follicles. In controls estradiol levels increased significantly after FSH administration, but in patients this was not the case despite the presence of an antral follicle ≥8 mm.

Conclusion(s)

Most women with 46,XX spontaneous primary ovarian insufficiency have antral follicles detectable by ultrasound, suggesting that down-regulation of FSH receptors is not the predominant mechanism of follicle dysfunction. Evidence of progesterone secretion by antral follicles ≥8 mm in these patients is consistent with prior histologic evidence that follicle luteinization is the predominant mechanism of follicle dysfunction in this condition. Prospective controlled investigation designed to improve ovulatory function and fertility in these women is indicated.

Key Words: Primary ovarian insufficiency, hypergonadotropic hypogonadism, premature ovarian failure, premature menopause, lutienized Graafian follicle

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 Z.R.H. had nothing to disclose. V.P. has nothing to disclose. V.H.V. has nothing to disclose. O.N. has nothing to disclose. D.J. has nothing to disclose. E.M. has nothing to disclose. K.A.C. has nothing to disclose. J.F.T. has nothing to disclose. L.M.N. has nothing to disclose.

 Supported by the Intramural Research Program of the National Institute of Child Health and Human Development, National Institutes of Health. Vien H. Vanderhoof and Lawrence M. Nelson are Commissioned Officers in the United States Public Health Service.

PII: S0015-0282(09)03885-0

doi:10.1016/j.fertnstert.2009.10.023

Fertility and Sterility
Volume 94, Issue 5 , Pages 1769-1774, October 2010