Effect Of Dehydroepiandrosterone Pretreatment On In Vitro Fertilization And Embryo Transfer In Patients With Diminished Ovarian Reserve

Obejective:To investigate the effect of dehydroepiandrosterone(DHEA)supplementation on treatment of in vitro Fertilization and embryo transfer(IVF-ET)cycle outcomes in women with Diminished ovarian reserve(DOR).Methods:This is a retrospective case-controlled study include two parts.Totally 300 women with Diminished ovarian reserve(DOR)were enrolled to this study with 345 controlled ovarian hyperstimulation(COH)cycles from December 2013 to December 2016.Part ?:Self-control study involving 45 patients who had one IVF cycles before and after DHEA treatment,they all had experienced a prior IVF cycle and failed to conceive.Of these 45 cycles were given DHEA supplementation(25 mg t.i.d.)for at least 60 days(max.91 days,average 81.87±16.21 days)prior to this IVF cycle makes to post-treatment group.Another cycle without DHEA of the same patient makes to pre-treatment group.In all enrolled COH cycles,GnRH agonist with gonadotropin(Gn)protocol was used,each case used the same COH protocol before and after DHEA treatment.Basic features,all data concerning COH,laboratory and clinical outcomes were then compared.Part ?:255 patients were enrolled with 255 COH cycles and divided into two groups according to the pretreatment with DHEA supplementation or not,patients receiving DHEA 25mg three times a day for at least 60 days(max.93 days,average 81.07±7.06 days)were taken as the study group,including196 cycles,while those without DHEA pretreatment were taken as the control group,including 59 cycles.Ovarian response markers included serum FSH levels,and antral follicle count(AFC),basic hormonal profiles as well as patients general condition were measured and separately compared between the pre-and post-treatment group,study and control group.The dosage and duration of Gn,estradiol levels,luteinizing hormone levels and progesterone levels on the day of HCG administration(trigger day,or HCG day),and the thickness of endometrium(Em)on trigger day were measured and separately compared between the pre-and post-treatment group,study and control group.The number of oocytes retrieved,the number of metaphase ?oocytes,the cleavage rate,the fertilization rate,the number of high-quality embryo were compared between two groups,separately.And the clinical pregnancy of the patients was observed in self-control group.The outcome of IVF-ET treatment(including clinical pregnancy rate,implant rate,early abortion rate and cycle cancellation rate)were compared in the study group and control group.Results:(1)No differences were found between the pre-and post-treatment groups in BMI,AFC and day 3 features.No differences were found between the two groups in the total amount of gonadotrophins used as well as in the duration of the stimulation.No differences were found between the two groups in the levels of E2,LH on HCG days as well as the thickness of Em on HCG days.The levels of progesterone on HCG days in the post-treatment group was significantly higher than that of the pre-treatment group(P<0.05).The number of Oocytes retrieved and M? Oocytes were statistically significant higher in the post-treatment group(P<0.05).No differences between the two groups were found in fertilization rate,number of high-quality embryo,total fertilization rate,cleavage rate and high-quality embryo rate.(2)There was no significant difference in the ratio of infertility type and the ratio of COH protocol between the study group and control group.(3)There were no differences between study group and control group in patients general condition including age,duration of infertility,as well as BMI,AFC,and basic hormonal profiles.No differences were found between the two groups in the total amount of gonadotrophins used as well as in the duration of the stimulation.No differences were found between the two groups in the levels of E2,LH on HCG days as well as the thickness of Em on HCG days.The levels of progesterone on HCG days in the study group was significantly higher than that of the control group(P<0.05).The number of Oocytes retrieved and M?Oocytes,as well as fertilization rate,number of high-quality embryo,total fertilization rate and cleavage rate.But the high-quality embryo rate was statistically significant higher in the study group.While there were no difference between two groups in clinical pregnancy rate,the number of embryos transferred,implant rate,early abortion rate and cycle cancellation rate.Conclusions:(1)As it increased retrieved oocytes and M? oocyte numbers on the same person's different COH cycle,we conclude that DHEA supplementation can improve ovarian response in women with DOR,but the application of DHEA pretreatment comparative study showed that it did not increase the number of oocytes and mature oocytes in different patients.(2)The high-quality embryo rate was statistically significant higher in the study group compared to the control group,and DHEA supplementation increased retrieved oocytes and M? oocyte numbers in self-control group,while there were no difference in clinical pregnancy rate.(3)Elevated levels of P on HCG days in post-treatment group and study group were observed,which should cause clinical attention because that elevated P has a negative effect on endometrium-embryo asynchrony.How to deal with it?It is recommended to stop taking DHEA when entering the COH cycle,or to cancel the fresh transplantation with DHEA supplementation cycle,make the embryo cryopreservation,then treat with Frozen-thawed Embryo Transfer(FET)after the completion of the endometrial preparation.Whether DHEA pretreatment can improve the pregnancy outcome on treatment of IVF-ET remains to be further studied.