The Effect Of Growth Hormone On Pregnancy Outcomes Of Patients With Thin Endometrium And The Mechanism Involved

Objective:Thin endometrium has a strong impact on pregnancy outcomes in ART.Some studies showed positive correlation between endometrium thickness on the day of HCG administration and pregnancy rates.There have been few therapeutic methods universally acknowledged.In our clinical practice,we found that GH could improve endometrial thickness and pregnancy outcomes of patients with thin endometrium.It is indicated that GHR was found expressed in glandular cells of the human endometrium from the mid to late luteal phases,revealing a key role of GH in implantation.So,we hypothesize that GH could improve endometrial cell proliferation,stromal angiogenesis and endometrial receptivity.A retrospective analysis was performed and cell culture was used to confirm our hypothesis.Methods : Ninety-three patients with previous thin endometrium were included.Forty of them have administrated GH additionally.Primary and secondary outcomes were endometrial thickness,implantation rate and clinical pregnancy rate of GH group and control group.The endometrial thickness was also compared between before and after GH administration within GH group.The RL95-2,a human endometrial carcinoma cell line,was used in our study.RL95-2 cell proliferation was examined by CCK-8 assay and flow cytometry was used to test cell cycle.Expression of eight receptivity-related genes in RL95-2 cells was analyzed by real-time PCR and western blot.Results:1.Endometrial thickness,implantation rate and clinical pregnancy rate were significantly improved in GH group compared with control group.2.Endometrial thickness was significantly improved after GH administration compared with the precious cycles within GH group.3.GH had an effect on endometrial cell proliferation,making the G1 phase reduced and the S phase increased.4.Real-time PCR showed that VEGF,ItgB3 and IGF-I mRNA were up-regulated significantly after GH exposed.5.Western blot showed that expression of VEGF,ItgB3 and IGF-I protein were up-regulated significantly after GH exposed.6.AG490,an inhibitor of JAK2 enzyme,had an inhibitory impact on GH.7.GH has no impact on the expression of ItgAV,LIF,EGF,HOXA10 and SPP1.Conclusions : Our results indicated that GH supplement may improve pregnancy outcomes of patients with thin endometrium who undergoing FET.The mechanism might be that GH can act on human endometrial cell to promote proliferation,vascularization and to up-regulate receptivity-related molecules expression.And JAK/STAT may be the pathway involved.