LPD with high AMH

 

Anti Mullerian hormone in LPD and PCOS

AMH is a member of the transforming growth  factor B superfamily and is a protein produced by fetal Sertoli cells  in order to promote the Mullerian duct regression during  testicular  differentiation in the male  fetus.

In the ovaries AMH is expressed by  the granulosa cells of primordial follicles  and seems to  inhibit  the recruitment of follicles  from the resting pool to growing phase . It is well established that serum  AMH  levels are higher  in women with PCOS compared to healthy controls AMH can negatively affect the function  of granulose lutein cells. It has been   shown to inhibit in culture the proliferation  and the progesterone production of human  granulosa derived lutein  cells  and also reduced the expression of LH  receptors  as well as the activity of aromatase in cultured human  granulosa derived lutein cells  therefore   increased levels of AMH  in PCOS can be responsible for CL dysfunction and LPD  although  further investigations are required to support this.

Angiogenesis in LPD and PCOS

Angiogenesis is crucial for the formation and function of CL as the newly  formed blood vessels provide   the CL with nutrients and low density lipoproteins required for steroidogenesis   . Under this perspective alterations in concentrations and/ or expression patterns of angiogenic factors  may lead to luteal  dysfunction

In fact inhibition of vascular endothelial growth  factor during  the luteal phase  leads to impaired angiogenesis  in the CL  and has been associated with reduced progesterone  production and secretion Therefore  decreased  VEGF  levels can eventually led to LPD  but further studies are required to support this . In contrast VEGF  levels are increased  in PCOS and also  temporally and spatially different in compared  to normal    controls a recent animal study suggests  a novel auto/ paracrine action of cytokines  specifically  tumor necrosis factor alpha on  the up regulation of VEGF  for angiogenesis stimulation in equine early CL. Possibly this is a result of increased sensitivity   of lutein granulosa cells  of polycystic ovaries to insulin which  leads to increased VEGF production in compared to normal   ovaries Although controversy exists it is possible that impaired angiogenesis   may be a cause  of LPD in PCOS oteh angiogenic factors such as angiopoietins epidermal   growth factors insulin like growth   factors fibroblast  growth  factor 1 and 2 also participate in luteal  angiogenesis  but it is not known  whether these  factors  are involved in the pathogenesis of LPD.

Treatment  of LPD should  target  to normalize menstrual   abnormalities and improve  pregnancy rates. As LPd is a multifactorial  disorder  individualized approach of the patient is necessary. Administration of progesterone   or human chorionic gonadotropin  is the most common treatement  LPD Ovulation  can be induced by clomiphene citrate and/or gonadotropin.

Conclusion

Many factors associated with PCOS such as hyperinsulinemia elevated AMH  levels  and impaired angiogenesis are also involved in the pathophysiology of LPD. Given the importance of CL function for the achievement and maintenance of pregnancy  we speculate   that LPD  could be another  possible  factor involved  in infertility observed in women  with PCOS. The identification of new angiogenic   factors  in LPD  eventually could open routes to new therapeutic approaches for the treatment  of patients with PCOS, Further  investigations are needed to understand  the exact pathophysiological  mechanisms.