| In our country,2 or more than 2 times of spontaneous abortion is defined as recurrent spontaneous abortion(RSA).In addition to the clear cause of the disease,40-60% of RSA patients are clinically unexplained,which is defined as unexplained recurrent spontaneous abortion(URSA).Thyroid hormone is involved in the metabolism of various tissues and organs,and then affects the body’s growth and development process.Thyroid dysfunction during pregnancy can greatly increase the adverse consequences of pregnancy.Human chorionic gonadotrophin(HCG)is a glycoprotein hormone secreted by the fertilized egg trophoblast on the 6th day after fertilization.Its function is to maintain the growth of corpus luteum in early pregnancy and stimulate the corpus luteum to produce estrogen,thereby maintaining pregnancy and preventing abortion.Aspirin combined with low molecular weight heparin are often used clinically to treat RSA,the main purpose of combination is to prevent the occurrence of placental infarct abortion by exerting its anticoagulant effect.The positive rate of thyroid auto-antibodies is higher in URSA patients,those are more likely to have hypothyroidism.Through a thorough understanding of the pharmacological effects of aspirin and low molecular weight heparin,it is speculated that it may have the effect of improving thyroid function in URSA patients.This study intends to adminstered URSA patients with aspirin combined with low molecular weight heparin,and then through monitoring changes of thyroid hormone levels before and after administration,HCG values after pregnancy,pregnancy rates,and pregnancy maintenance rates.Further explore the role of thyroid function in pregnancy,as well as the biological mechanism of aspirin combined with low molecular weight heparin in the treatment of URSA patients.Objective: To investigate the effect of aspirin combined with low molecular weight heparin on thyroid hormones and HCG levels in pregnant women with URSA,to further clarify the biological mechanism of its therapeutic effect.Methods: From June 2016 to July 2017,in vitro fertilization and embryo transfer(IVF-ET)was performed at the Assisted Reproductive Medical Center of Shenyang Maternal and Child Hospital.Based on the consideration of ethics,it is necessary to strictly control the inclusion and exclusion criteria and ensure that there is no difference between the included patients.After fully informed consent,patients were devided in to different groups according to their wishes.Detail of groups as follows :19 patients in the conventional treatment group(A group);27 patients in the aspirin treatment group(B group);41 patients in the aspirin combined with low molecular heparin treatment group(C group).Another 48 non-pregnant healthy women of childbearing age were selected,those who had a history of one or more births as control group(Group D).Neither age nor the number of abortions has significante difference between all four groups and URSA treatment groups(P>0.05),respectively.Group A was under tocolytic treatment,meanwhile,B and C groups were administered with aspirin(100 mg/day,orally)and aspirin(100 mg/day,orally)combined with low molecular weight heparin(4100 IU/day,subcutaneous injection),respectively,on the basis of tocolytic treatment.In this study,for the same ethical point of view,group A,B,C,were given routine tocolysis treatment based on ensuring consistent treatment among all groups.Then,it can ensure that the drug effect of tocolysis treatment has no impact on comparation of aspirin and low molecular heparin.Meanwhile,in order to monitor drug safety,blood prothrombin time(PT),activated partial thromboplastin time(APTT),thrombin time(TT)and fibrinogen(FIB)were detected before administration and 12 week after pregnacy.The patients serum were collected for detecting FT3,FT4,TSH,Tg Ab,and TPOAb level before and 12 weeks after administration,and HCG values were detected on the 14 th days after embryo transfer.The same procedure were performed on group D at the same time.The pregnancy outcomes and adverse drug effect of each group were observed and recorded..Results: 1.Comparison of thyroid antibody positive rate between treatment group and control groupThe positive rates of Tg Ab,TPOAb,and ATA in the treatment group were significantly higher than those in the control group,with statistical differences.This indicates that URSA patients have a higher risk of hypothyroidism,and thyroid antibody positive is an independent risk factor of URSA.2.Comparison of thyroid hormones before and after treatmentBefore treatment,the levels of FT3 and FT4 were lower in the treatment groups than in the control group,but there was no significant difference between group A,group B,and group C.The levels of FT3 and FT4 decreased in the control group at 12 th weeks of gestation,and similar trends also observed in the treatment groups.However,the decrease in FT3 and FT4 levels during the 12 th week of gestation was greatest in the aspirin combined with low molecular weight heparin group(C group),and there was a significant difference between the conventional treatment group(A group)and the aspirin intervention group(B group).It suggests that the combination use of the two drugs has the effect on maintaining free thyroid hormone levels.The results of serum TSH level showed that the TSH levels in each treatment group were higher than those in the control group before treatment,but there was no significant difference between group A,group B,and group C.At 12 th weeks of gestation,the levels of TSH in each group decreased,comparing with group A and B,group C had the largest decrease,with significant difference.This may be related to the combination of aspirin and low molecular weight heparin that can maintain a high level of free thyroid hormone.3.Comparison of HCG values of pregnant women in each treatment groupThe β-HCG values measured in each treatment group 14 days after embryo transfer showed significantly higher in group C than in groups A and B.This indicates that aspirin combined with low molecular weight heparin can increase the blood HCG level after in vitro fertilization embryo transfer in URSA patients,which is conducive to maintaining pregnancy status.4.Comparison of pregnancy rate and pregnancy maintenance rate in each treatment groupThe pregnancy rates shown between the treatment groups ranged from low to high in group A(42.1%)<B group(51.9%)<C group(68.3%).The rate of pregnancy was significantly higher in combination administeration(Group C),and there was a statistically significant difference between the groups.That is,combination therapy can improve the success rate of URSA patients in vitro fertilization embryo transfer,and the curative effect is better than that of aspirin and conventional treatment alone.It can be seen that the maintenance rate of the patient is significantly improved,and the pregnancy outcome of the URSA patient is significantly improved.5.Adverse Drug Effect and Pregnancy Complications MonitoringCoagulation function test before and after administration showed that no coagulation abnormalities were found in all the treatment groups.A small amount of bloody vaginal secretions,vaginal bleeding,injection site defects,gastrointestinal discomfort and other adverse reactions occurred in the individual treatment groups in this study.And there were 2 cases of premature delivery and 4 cases of multiple births.No serious adverse effect and severe pregnancy complications occurred in any of the included observations.Conclusion: 1.In this study,the positive rate of thyroid antibody in patients with unexplained recurrent spontaneous abortion is significantly higher.2.In the early pregnancy,the level of free thyroid hormone decreased slightly.3.Aspirin combined with low molecular weight heparin in the treatment of URSA can decrease the reduction of free thyroid hormone levels in the early stages of pregnancy.4.After using the aspirin combined with low molecular weight heparin treatment for paitents with URSA,the success rate of pregnancy and pregnancy maintenance are significantly higher than that of aspirin monotherapy. |
PDF Full Text Request