Abstract
Luteal phase deficiency (LPD) is a consequence of the corpus luteum (CL) inability to produce and preserve adequate levels of progesterone. This is clinically manifested by short menstrual cycles and infertility. Abnormal follicular development, defects in neo-angiogenesis or inadequate steroidogenesis in the lutein cells of the CL have been implicated in CL dysfunction and LPD. LPD and polycystic ovary syndrome (PCOS) are independent disorders sharing common pathophysiological profiles. Factors such as hyperinsulinemia, AMH excess, and defects in angiogenesis of CL are at the origin of both LPD and PCOS. In PCOS ovulatory cycles, infertility could result from dysfunctional CL. The aim of this review was to investigate common mechanisms of infertility in CL dysfunction and PCOS.
Similar content being viewed by others
References
G.E. Jones, Some newer aspects of management of infertility. J. Am. Med. Assoc. 141, 1123–1129 (1949)
W. Wuttke, L. Pitzel, D. Seidlova-Wuttke, B. Hinney, LH pulses and the corpus luteum: the luteal phase deficiency. Vitam. Horm. 63, 131–158 (2001)
E. Diamanti-Kandarakis, C.R. Kouli, A.T. Bergiele, F.A. Filandra, T.C. Tsianateli, G.G. Spina, E.D. Zapanti, M.I. Bartzis, A survey of the polycystic ovary syndrome in the Greek island of Lesbos: hormonal and metabolic profile. J. Clin. Endocrinol. Metab. 84, 4006–4011 (1999)
Rotterdam ESHRE/ASRM-Sponsored PCOS consensus workshop group, Revised 2003 consensus on diagnostic criteria and long‐term health risks related to polycystic ovary syndrome (PCOS). Hum. Reprod. 19, 41–47 (2004)
S.F. Witchel, S.E. Recabarren, F. González, E. Diamanti-Kandarakis, K.I. Cheang, A.J. Duleba, R.S. Legro, R. Homburg, R. Pasquali, R.A. Lobo, C.C. Zouboulis, F. Kelestimur, F. Fruzzetti, W. Futterweit, R.J. Norman, D.H. Abbott, Emerging concepts about prenatal genesis, aberrant metabolism and treatment paradigms in polycystic ovary syndrome. Endocrine (2012). doi:10.1007/s12020-012-9701-4
M.J. De Souza, B.E. Miller, A.B. Loucks, A.A. Luciano, L.S. Pescatello, C.G. Campbell, B.L. Lasley, High frequency of luteal phase deficiency and anovulation in recreational women runners: blunted elevation in follicle-stimulating hormone observed during luteal-follicular transition. J. Clin. Endocrinol. Metab. 83, 4220–4232 (1998)
P. Miller, M. Soules, Luteal phase deficiency: pathophysiology, diagnosis and treatment. Global libr. Women’s Med. (2009). doi:10.3843/GLOWM.10327
E. Diamanti-Kandarakis, C. Christakou, E. Marinakis, Phenotypes and environmental factors: their influence in PCOS. Curr. Pharm. Des. 18, 270–282 (2012)
J.E. Nestler, Metformin for the treatment of the polycystic ovary syndrome. N. Engl. J. Med. 358, 47–54 (2008)
R. Tsutsumi, N.J. Webster, GnRH pulsatility, the pituitary response and reproductive dysfunction. Endocr. J. 56, 729–737 (2009)
R. Joseph-Horne, H. Mason, S. Batty, D. White, S. Hillier, M. Urquhart, S. Franks, Luteal phase progesterone excretion in ovulatory women with polycystic ovaries. Hum. Reprod. 17, 1459–1463 (2002)
G.F. Erickson, D.A. Magoffin, V.G. Garzo, A.P. Cheung, R.J. Chang, Granulosa cells of polycystic ovaries: are they normal or abnormal? Hum. Reprod. 7, 293–299 (1992)
P. Fedorcsak, R. Storeng, P.O. Dale, T. Tanbo, T. Abyholm, Impaired insulin action on granulosa-lutein cells in women with polycystic ovary syndrome and insulin resistance. Gynecol. Endocrinol. 14, 327–336 (2000)
S. Rice, N. Christoforidis, C. Gadd, D. Nikolaou, L. Seyani, A. Donaldson, R. Margara, K. Hardy, S. Franks, Impaired insulin-dependent glucose metabolism in granulosa-lutein cells from anovulatory women with polycystic ovaries. Hum. Reprod. 20, 373–381 (2005)
J.M. Weiss, S. Polack, K. Diedrich, O. Ortmann, Effects of insulin on luteinizing hormone and prolactin secretion and calcium signaling in female rat pituitary cells. Arch. Gynecol. Obstet. 269, 45–50 (2003)
K.J. Meenakumari, S. Agarwal, A. Krishna, L.K. Pandey, Effects of metformin treatment on luteal phase progesterone concentration in polycystic ovary syndrome. Braz. J. Med. Biol. Res. 37, 1637–1644 (2004)
A. La Marca, F.J. Broekmans, A. Volpe, B.C. Fauser, N.S. Macklon, Anti-Müllerian hormone (AMH): what do we still need to know? Hum. Reprod. 24, 2264–2275 (2009)
A. Munsterberg, R. Lovell-Badge, Expression of the mouse anti-mullerian hormone gene suggests a role in both male and female sexual differentiation. Development 113, 613–624 (1991)
A.P.N. Themmen, Anti-Müllerian hormone: its role in follicular growth initiation and survival and as an ovarian reserve marker. J. Natl. Cancer Inst. Monogr. 34, 18–21 (2005)
S.A. Stubbs, K. Hardy, P. Da Silva-Buttkus, J. Stark, L.J. Webber, A.M. Flanagan, A.P. Themmen, J.A. Visser, N.P. Groome, S. Franks, Anti-Müllerian hormone protein expression is reduced during the initial stages of follicle development in human polycystic ovaries. J. Clin. Endocrinol. Metab. 90, 5536–5543 (2005)
P. Pigny, E. Merlen, Y. Robert, C. Cortet-Rudelli, C. Decanter, S. Jonard, D. Dewailly, Elevated serum level of anti-mullerian hormone in patients with polycystic ovary syndrome: relationship to the ovarian follicle excess and to the follicular arrest. J. Clin. Endocrinol. Metab. 88, 5957–5962 (2003)
D.S. Wachs, M.S. Coffler, P.J. Malcom, R.J. Chang, Serum anti-mullerian hormone concentrations are not altered by acute administration of follicle stimulating hormone in polycystic ovary syndrome and normal women. J. Clin. Endocrinol. Metab. 92, 1871–1874 (2007)
J.H. Kim, M.M. Seibel, D.T. MacLaughlin, P.K. Donahoe, B.J. Ransil, P.A. Hametz, C.J. Richards, The inhibitory effects of müllerian-inhibiting substance on epidermal growth factor induced proliferation and progesterone production of human granulosa-luteal cells. J. Clin. Endocrinol. Metab. 75, 911–917 (1992)
L. Pellatt, S. Rice, H.D. Mason, Anti-Müllerian hormone and polycystic ovary syndrome: a mountain too high? Reproduction 139, 825–833 (2010)
M.P. Grossman, S.T. Nakajima, M.E. Fallat, Y. Siow, Müllerian-inhibiting substance inhibits cytochrome P450 aromatase activity in human granulosa lutein cell culture. Fertil. Steril. 89, 1364–1370 (2008)
L.P. Reynolds, A.T. Grazul-Bilska, D.A. Redmer, Angiogenesis in the corpus luteum. Endocrine 12, 1–9 (2001)
H.M. Fraser, C. Wulff, Angiogenesis in the corpus luteum. Reprod. Biol. Endocrinol. 1, 88 (2003)
N. Ferrara, G. Frantz, J. LeCouter, L. Dillard-Telm, T. Pham, A. Draksharapu, T. Giordano, F. Peale, Differential expression of the angiogenic factor genes vascular endothelial growth factor (VEGF) and endocrine gland-derived VEGF in normal and polycystic human ovaries. Am. J. Pathol. 162, 1881–1893 (2003)
A. Galvao, S. Henriques, D. Pestka, K. Lukasik, D. Skarzynski, L.M. Mateus, G.M. Ferreira-Dias, Equine luteal function regulation may depend on the interaction between cytokines and vascular endothelial growth factor: an in vitro study. Biol. Reprod. 86, 1–9 (2012)
M.B. Stanek, S.M. Borman, T.A. Molskness, J.M. Larson, R.L. Stouffer, P.E. Patton, Insulin and insulin-like growth factor stimulation of vascular endothelial growth factor production by luteinized granulosa cells: comparison between polycystic ovarian syndrome (PCOS) and non-PCOS women. J. Clin. Endocrinol. Metab. 92, 2726–2733 (2007)
Conflict of interest
The authors declare that they have no competing interests.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Boutzios, G., Karalaki, M. & Zapanti, E. Common pathophysiological mechanisms involved in luteal phase deficiency and polycystic ovary syndrome. Impact on fertility. Endocrine 43, 314–317 (2013). https://doi.org/10.1007/s12020-012-9778-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12020-012-9778-9