The Effect Of Tamoxifen On Thin Endometrium In Patients Undergoing Frozen-thawed Embryo Transfer

BackgroundSuccessful implantation depends on favorable uterus receptivity,as evaluated by endometrial thickness(EMT),endometrial pattern,and the(sub)endometrial blood flow.Of these factors,EMT is particularly important given the association of thin endometrium with poor pregnancy outcomes in assisted reproductive technology treatment(ART).Thus,thin endometrium is a ticklish problem in assisted reproductive technology(ART).Multiple protocols have been proposed to increase the thickness of thin endometrium in frozen-thawed embryo transfer(FET)cycles.These protocols include hormonal replacement with estrogen,intrauterine infusion of granulocyte colony-stimulating factor,endometrial somatic stem cells,or bone marrow mesenchymal stem cells;and other protocols using aspirin,vitamin E plus pentoxifylline,L-arginine,or sildenafil.However,all the protocols showed controversy and none of them is standardized.Meanwhile,the known causes for thin endometrium are varied,such as repeated uterine curettage(UC),chronic pelvic inflammation,endocrine factors,and idiopathic thin endometrium.Methods to increase EMT suitable for different causes remain to be explored.Frozen-thawed embyo transfer is an important method in ART,it can provide endometrium with good receptivity for implantation and improve pregnancy outcomes.ObjectiveTo examine the effect of tamoxifen in patients with a thin endometrium in FET,and compare the improvement in endometrial thickness and pregnancy outcomes stratified by different etiologies of thin endometrium.MethodsRetrospective analysis of 267 patients with thin endometrium undergoing FET from Reproductive Hospital Affiliated to Shandong University who were enrolled between January 2012 and August 2015.These 267 women were recruited for a new tamoxifen protocol;all had an EMT of less than 7.5 mm in previous cycles,including natural cycle(NC),hormone replacement treatment(HRT),and ovulation induction(OI)cycles.Comparing the endometrium thickness between each previous cycle and tamoxifen cycle.Further dividing the 267 patients into 4 groups on the basis of different causes of thin endometrium:(1)history of intrauterine adhesions(IUA)diagnosed by hysteroscopy(n=34),(2)?2 times of UC(n=104);(3)bilateral tubal occlusion(n=78);(4)polycystic ovary syndrome(PCOS)(n=51),the endometrium thickness and the pregnancy outcomes of four groups were compared for analysis.ResultsCompared with the previous treatments,the new tamoxifen protocol improved EMT significantly:from 6.04±0.83mm to 7.81 ±1.49mm in the NC group,from 6.22±1.06mm to 8.12±1.63 mm in the HRT group,and from 6.31 ±0.97mm to 7.96±1.46 mm in the OI group(all P<0.001).However,no significant difference was found in endometrium pattern between previous cycles and tamoxifen treatment(P=0.298,0.500,0.494 respectively).Sixty three patients(182 FET cycles)had endometrial blood flow data both in previous cycles and in TAM cycles,and the difference of blood flow was not significant as well(P=0.254).Among patients stratified by different etiologies,patients with PCOS had the thickest endometria(9.24mm in PCOS vs.8.13mm in UC vs.7.83mm in BTO vs.7.13mm in IUA).Cycle cancellation rates(45.24%in IUA,28.24%in UC,39.81%in BTO and 14.04%in PCOS,respectively),biochemical pregnancy rates(43.48%in IUA,48.94%in UC,44.07%in BTO and 71.43%in PCOS,respectively),clinical pregnancy rates(43.48%in IUA,32.98%in UC,38.98%in BTO and 63.27%in PCOS,respectively)and live birth rates per cycle(30.43%in IUA,32.98%in UC,18.64%in BTO and 53.06%in PCOS,respectively)were significantly different among four groups(all P<0.05).The PCOS group had better pregnancy outcome compared with other three groups.Multivariable regression analysis showed that EMT was related to live birth(odds ratio:1.501,95%confidence interval:1.441-1.564).Conclusions1.Tamoxifen can improve the EMT of patients with thin endometrial significantly after NC,HRT,and OI cycles during FET.2.Tamoxifen has no effect in endometrial pattern or endometrial blood flow.3.Age,EMT and the number of transferred embryo were related to live birth during FET.4.Compared with patients with IUA,UC or BTO,patients with PCOS show the most benefit from tamoxifen and achieve better pregnancy outcomes.