The Effect Of Progestin-primed Ovarian Stimulation (PPOS) On The Function Of Granulosa Cells

Objective:Progestin-primed ovarian stimulation(PPOS)is a new ovarian stimulation regimen by introducing progesterone as a suppression of LH surge.The clinical study found that endogenously produced progesterone in luteal phase and exogenous progesterone agents,such as medroxyprogesterone acetate(MPA)administrated in early follicular phase,could effectively block the premature LH surge.In addition,compared with the short protocol,PPOS requires higher doses of hMG,presumably because of the insensitivity of ovarian follicles to gonadotropin stimulation in the milieu of progesterone.What's more,we cannot rule out the possibility that the higher doses of hMG was associated with the impact of progesterone on the granulose cells.This study also confirmed that the MPA used in early follicular phase can effectively prevent premature LH peak.However,studies have shown that MPA suppressed estrogen production by cultured rat ovarian granulosa cells(GCs).MPA administrated in vivo had little effect on estradiol production in the rat ovaries stimulated by gonadotropins,but MPA suppressed the aromatase activity in these ovaries.Therefore,it is not clear whether the use of MPA in the PPOS program will affect the level of estrogen by inhibiting the expression of aromatase induced by FSH.Our study aimed to evaluate the ovarian response to gonadotropin stimulation under the PPOS and the effect of MPA on the GCs.Methods:This study was conducted in the Reproductive Medical Center of Shanghai Ninth People's Hospital from March 2015 to October 2015.A total of 112 patients were included,with 62 in PPOS group and 50 in short protocol group.Blood samples were collected during the ovarian stimulation and the concentrations of serum sex hormone were measured with chemiluminescence.GCs were collected from follicular fluid after oocyte retrieval by density gradient centrifugation.The aromatase,gonadotropin receptors(FSHR,LHR)and estrogen receptor ?(ER?)expression were analyzed by quantitative real-time polymerase chain reaction and western blot.Results:1.LH values gradually decreased during PPOS and no patients experienced premature LH surge.2.Serum E2 values showed a gradual increase accompanying the growth of follicles during ovarian stimulation and it was comparable between two groups.However,the FSH level was significantly higher in PPOS group than that in short protocol group(P<0.05).3.The expression of FSHR,at both the mRNA and protein levels,were significantly higher in PPOS group compared with short protocol group,the protein level of ER? were significantly higher in PPOS group than that in short protocol group.4.The expression of LHR and CYP19A1,at both the mRNA and protein levels,were comparable between PPOS group and short protocol group.Conclusions:1.MPA can effectively prevent the premature LH surge in woman undergoing controlled ovarian stimulation.PPOS may be the most appropriate ovulation stimulation protocol in combination with freeze all strategies.2.The ovarian response was not reduced in the milieu of progesterone during follicular phase.3.MPA did not have adverse effect on the expression of aromatase and the estrogen secretion by GCs.