| BACKGROUND:The incidence of multiple pregnancies in China increased significantly,with the wide application of assisted reproductive technology.Compared with single pregnancy,multiple pregnancies bring a lot of medicine,ethics,social and economic problems,maternal complications and poor perinatal outcomes increases.All of these factors put tremendous pressure on family and social resources.At the same time,the rapid development of prenatal screening and prenatal diagnosis technology,enabling us to find more abnormal fetuses,requires us to effectively deal with abnormal fetus in multiple pregnancy.Some couples lost of early pregnancy reduction for various reasons.Multifetal pregnancy reduction(MFPR)in second trimester is an indispensable means in the management of multiple pregnancy.It is of great significance to maintain fetal number in twins and below for improving the outcome of multiple pregnancy.To decrease the incidence of miscarriage and preterm labor associated with multiple pregnancies,we adopted MFPR to selectively reduce the number of fetuses and the operation is safe and effective.Reducing the fetus in the early pregnancy is difficult to determine fetal defects,the rate of embryo retention and the risk of infection by the vagina is higher.Second trimester multifetal pregnancy reduction can also achieve selective reduction of the fetus based on the disease,which can effectively avoid the blindness of early pregnancy reduction surgery.So MFPR can effectively reduce the number of multiple pregnancy fetuses and avoid abnormal fetus birth.It can reduce maternal complications and improve the birth quality of newborns also.Second trimester MFPR includes selectively reducing high-order fetal numbers of multiple births to twin pregnancies and reduction of abnormal fetuses of multiple pregnancies in midgestation.Second trimester MFPR has been widely used in clinical practice for more than 20 years,it has also been carried out for 15 years in Shandong Provincial Hospital.The pregnancy complications of maternal and child of MC twins and multiple pregnancy are high,and 30-40%of them will led to complex twin pregnancy,so it is more difficult to deal with in clinical practice.Monochorionic(MC)twins is a special type of twin pregnancy,and a prevalence of MC twins is about 1/250 in naturally conceived pregnancies,which is 20%of all twin pregnancies.In recent years,due to the wide application of assisted reproductive technology,the incidence of single chorionic twins has been increasing year by year,which is 2～12 times more than natural pregnancy.Perinatal morbidity and mortality of MC twins were both high.The perinatal mortality was twice of dichorionic(DC)twins,and four times of singleton pregnancies with no intervention.The incidence of survival children with nervous system disorders is 4 to 5 times of DC twins and 25 to 30 times of single pregnancy.One third of the MC twins can also develop complications such as twin-to-twin transfusion syndrome(TTTS),twin reverse arterial perfusion,twin inexpressive arterial perfusion(TRAP),selective fetal uterine growth restriction(sIUGR),twin anemia polycythemia sequence(TAPS),or the abnormality and death of one of the twins and so on,which are called the complex twin pregnancy,due to unequal MC placental distribute and placental vascular anastomosis.Therefore,in some cases,it is necessary to terminate one fetus selectively to improve the survival of the remaining fetuses in the twins.However,the presence of a vascular connection creates an unacceptable risk of using intra-fetal injection as a method of selective termination.The vascular anastomosis is also associated with the final outcome of the fetus.When intrauterine death occurs in one of the twins,the risk of the other fetus dying or brain injury increased,possibly because of acute fetal blood discharge of surviving fetal through the placenta and into the pressure cycle of the underlying dead fetal.Low blood pressure and ischemia eventually lead to insufficient blood perfusion in the surviving fetus,resulting in tissue damage.This risk has been reported to be as high as 30-50%.Thus,in a complex MC pregnancy,selective termination of one of the twins can effectively improve the outcome of pregnancy.In recent years,many hospitals in China have established the Fetal Medicine Branch and have gradually started the systematic ultrasound diagnosis,vascular occlusion,vascular laser ablation and other techniques,marking the gradual introduction of perinatal medicine into the era of fetal medicine.Previous clinicians’understanding of MC twins is limited to TTTS,and they also lack effective diagnosis and treatment methods.With the development of fetal medical technology,the diagnosis and treatment of MC twins is obviously improved.There are a variety of block technique can be used in the selective termination of single chorionic MC twin pregnancy,including radiofrequency ablation technology(RFA),umbilical cord bipolar electric coagulation(BCC),umbilical cord ligation and etc.We implemented the first second-trimester RFA reduction in July 2011,and carried out 99 cases until June 2017,including TTTS,sIUGR,TRAP,MC triple pregnancies,DC triple pregnancies and MC quadruplet pregnancies.Though it can reduce the incidence of multiple pregnancy complications of multiple pregnancy,but there may be some complications during the MFPR operation.In order to better understand for the best way and number of reduction,avoid the happening of complications,this study collected the 738 cases of pregnancy women in Shandong Provincial Hospital between January 2005 and December 2015,conducted MFPR using potassium chloride heart injection.We mainly analyzed the number of patients each year,the fetus number of pregnancy,way of conceiving and pregnancy outcomes of patients.We also analyzed the pregnancy outcomes of reduction group compare with the group of normal twin pregnancies,and compared the incidence of gestational diabetes mellitus(GDM)and hypertensive disorder complicating pregnancy(HDCP)in two groups.In addition,we also analyzed the effects of different puncture times on pregnancy outcome,GDM and HDCP,and analyzed the related factors of complications.In July,2011,we carried out the first case of the RFA reduction,and 99 cases were conducted until June 2017.In order to deepen the understanding of the diagnosis and treatment of MC twin pregnancy,provide a better treatment plan for the complex twin pregnancy,we analyzed the basic status of these patients,including the timing of reduction,final pregnancy outcomes,complications and the related factors,so as to further improve the safety and success rate of the surgery.METHODS:In this study,we mainly use two surgical methods to carry out MFPR:using transabdominal ultrasound-guided injection of potassium chloride to fetal heart in the second trimester and mid-trimester radiofrequency ablation reduction surgery.MFPR of fetal heart injection of potassium chloride:23G PTC needle quickly puncture the heart of aimed fetus under ultrasound guided.After blood was drawn back,then inject 10%potassium chloride solution 2～5ml into fetal heart.After the heartbeat stopped,unplug the puncture needle and observe the fetal heart using ultrasound for more than 15min to confirm the cardiac arrest.Selections for the reduced fetus:Preoperative ultrasound was used to assess fetal size,morphology and the thickness of the nuchal translucency(NT)layer.If an abnormal fetus was found,the fetus should be reduced.If no abnormal is found,a smaller fetus,with less amniotic fluid or a fetus at the bottom of the uterus is selected.MFPR of radiofrequency ablation technique:After the 1%lidocaine local anesthetization,using the RITA 1500X RF needle,avoid the placenta or choose the thinnest part of placenta under ultrasound guidance,quickly penetrates the fetal abdominal wall of the umbilical cord insertion portion as measured in advance of the direction and angle.And color doppler flow is used to determine the correct position of the needle.If it is in the correct position,then push the RF needle tail so that the anchor electrode popping from the tip of the needle like an "umbrella",scanning again using color doppler blood flow to determine the location of the electrode.The setting radio frequency temperature is 100-110 ℃,energy is 150 W(25-45W actually).It lasts 3 min for a complete cycle and cold for 1min after each heating cycle.During the process color doppler continuously monitors the blood flow.After the blood flow is completely stopped,the radiofrequency ablation is completed,the anchor electrode is retracted,the needle track is ablated and the RF needle is pulled out.The whole process of surgery was completed under ultrasonic monitoring,and the fetal heartbeat was observed 30～60 min after operation.24 hours after surgery,sonography was performed on reductive fetuses and survivors,and the umbilical cord blood flow of survivors was measured.For those pregnancies more than 20 weeks at four weeks after the surgery and less than 20 weeks of pregnancy at 24 weeks of pregnancy,MRI assessment are used to evaluate whether there is hypotensive brain injury.We mainly analyzed the basic information such as the number of patients visiting the hospital during 2005-2015,the number of fetuses in pregnancy and the way of conceiving.And we also calculated the pregnancy outcomes,GDM and HDCP in the reductive group and the normal group.And we also respectively compared reducing one fetus in triple pregnancies and two fetuses in quadruplet pregnancies with control group.In addition,we calculated the number of puncture times on pregnancy outcome,GDM and HDCP,and analyzed the related factors of complications.Intrauterine infection after reduction is the most serious complication of MFPR,we analyzed the factors of infection may be related,including way of conceiving,the number of puncture times,the number of fetus and the number of reductive fetus.The research of mid-trimester radiofrequency ablation reduction technique mainly analyzed the statistics of patients conducted radiofrequency ablation reduction from 2011 to 2017.We divided them to two groups according to the number of fetus,MC twins group and triple and quadruplet pregnancies group.Basic information of pregnant women,including age,way of conceiving,fetal gestational age,the rate of miscarriage,premature birth rate,the gestational age of delivery and fetal birth weight were analyzed.Then the MC twins group were divided into four groups:sIUGR,TTTS,deformity and TRAP,respectively,and the failure rate,miscarriage rate,preterm birth rate and the gestational age of delivery,fetal birth weight were analyzed.In addition,we compared the failure cases with not failure cases,analyzed the reduction gestational age,radiofrequency ablation,cycle number,melting time,heart disappear time(to exclude the TRAP cases),compared the miscarriage cases with the corresponding control group,analyzed the reduction gestational age,radiofrequency ablation,cycle number,melting time,heart disappear time(to exclude the TRAP cases),in order to find whether these factors have any effect on the surgical complications and pregnancy outcomes.All data were analyzed using SPSS 20.0 statistical software,and P<0.05 was considered to have significant statistical difference.RESULTS:MFPR of fetal heart injection of potassium chloride:Based on the overall data survey,we found that the number of patients who came to the hospital during the 11 years between 2005 and 2015 is on the rise.For the number of fetuses in pregnancy,we found that the proportion of multiple pregnancies with a five and above birth rate decreased from 2005 to 2015,from 13.33%of the total number of pregnancies in 2006 to 2.42%in 2015.Moreover,we divided the 11 years into two groups(group A:2005-2010;group B 2011-2015),the statistics on the number of fetuses in different stages showed that the percentage of twin pregnancies increased from 17.02%(32/188)in group A to 27.09%(149/550)in group B.The number of triple pregnancies,quadruplet pregnancies and quintuplet pregnancies or above were all decreased in group B.Taken together,the number of fetuses in pregnancy in group B is significantly different from group A(χ2=8.183,P= 0.042,<0.05).Based on the age of’ 738 patients from 2005 to 2015 and the gestational age at the time of reduction,we found that their average age of pregnant women was 29.38 ±4.21 years old,and the average age of pregnant women in group A was 29.94 ± 4.59 years old.The average age of pregnant women in 2011-2015group B was 29.18 ±4.05 years old,which was significantly lower than before(t/χ2 = 2.00,P = 0.046,<0.05).The mean gestational age of fetal reduction was 15.13 ± 3.52 weeks.The mean gestational age for pregnant women in group A was 14.91 ± 2.69 weeks.The average gestational ages of fetal surgery in group B was 15.20 ± 3.76 weeks.There was no significant difference between the two periods(t=-1.14,P = 0.257,>0.05).The way they conceive can mainly be divided into in vitro fertilization embryo transfer(IVF-ET),natural pregnancy,ovulation induction,traditional Chinese medicine treatment and other assisted reproductive technology.The rate of patients who underwent 1VF-ET was 34.01%(251/738),46.75%(345/738)in ovulation induction therapy,13.69%(101/738)in spontaneous conception,and 2.30%(17/738)in patients receiving traditional Chinese medicine and 3.25%(24/738)of those who underwent other assisted reproductive technologies.We can see that the majority of the patients are conceived by assisted reproductive technology.According to the different time periods,the results showed that in group B,the proportion of patients with IVF-ET decreased from 39.36%(74/188)to 32.18%(177/550),the proportion of ovulation induction increased from 39.89%(75/188)to 49.09%(270/550),and the proportion of spontaneous conception increased from 10.64%(20/188)to 14.73%(80/550),while the proportion of patients who conceived through traditional Chinese medicine was 3.72%(7/188)to 1.82%(10/550).The percentage of pregnancies that were assisted by other assisted reproductive techniques dropped from 6.38%(12/188)to 2.18%(12/550),so we found that the pattern of conception during two periods was significantly different(χ2 = 16.183,P = 0.003,<0.01).In addition,we further analyzed the reason of the reduction,the results show that 76.56%(565/738)of the patients were due to the number of fetuses,while only 23.44%(173/738)were due to fetal abnormalities.Separate statistics for different time periods showed that a decrease in the patients due to number of fetuses in group B compared with group A,which was reduced from 82.45%(155/188)to 74.55%(410/550),the percentage due to fetal abnormalities was increased from 17.55%(33/188)to 25.45%(140/550),indicating a significant change in the causes of reduction(χ2= 4.874,P = 0.027,<0.05).The average number of puncture times per fetus was 1.49 + 0.80.Compared with the average penetration of 1.93 + 0.99 times in group A,the average number of puncture times in group B has decreased significantly to 1.33 + 0.66(t=7.66,P<0.001).We also analyzed the incidence of various complications of conduction.The results showed that post-operative complications occurred in 3.53%(26/738)of the total patients,of which post-operative complications in group A was 4.26%(8/188)and 3.64%(20/550)in group B.There was no significant difference between the two periods(χ2 = 0.147,P= 0.701,>0.05).As for the pregnancy outcomes,GDM and HDCP statistics,we found that the incidence of full-term pregnancy was 81.74%(591/723),the incidence of abortion was 11.62%(84/723),and the incidence of preterm birth less than 37 weeks was 6.64%(48/723).There was no significant difference in pregnancy outcomes between different time points(x2=0.957,P=0.620,>0.05).The incidence of GDM was 2.21%(16/723),with no significant difference between the two periods(χ 2=1.901,P=0.096,>0.05).The incidence of HDCP was 5.26%(38/723),which decreased from 8.06%(16/186)in group A to 4.10%(22/537)in group B and had statistical significance(x2=5.631,P=0.018,<0.05).And we also respectively compared the pregnancy outcomes of reducing one fetus in 310 triple pregnancies(group 1)and reducing two fetuses in 102 quadruplet pregnancies(group 2)with 150 normal twins pregnant women(control group),the incidence of abortion was 9.03%(28/310)and 19.61%(20/102),the incidence rate of premature birth was 6.45%(20/310)and 6.86%(7/102),the incidence of full-term delivery was 84.52%(262/310),73.53%(75/102).The incidence of GDM was 2.58%(8/310)and 0 respectively,the incidence of HDCP was 6.13%(19/310)and 11.76%(12/102)respectively.Compared with the control group,the results show that the group 2 and control group have significant differences in pregnancy outcomes(χ2= 10.92,P = 0.013,<0.05),the group 1 and the control group have no significant differences in pregnancy outcomes(χ2= 5.47,P = 0.195,>0.05),the group 1 and group 2 have significant differences in pregnancy outcomes(χ2 = 8.52,P = 0.042,<0.05).We divided group 1 to three little groups according to the puncture times.In the patients with one puncture,the incidence of miscarriage was 8.38%(16/191)and the incidence of premature birth was 6.28%,the incidence of full-term birth was 85.34%(163/191).In the patients with two punctures,the incidence of miscarriage was 8.45%(6/71),the rate of premature birth was 7.04%(5/71),and the incidence of full-term birth was 84.51%(60/71).In the patients with three or more punctures,the incidence of abortion was 12.77%(6/47)and the preterm birth was 6.38%(3/47),the incidence of full-term birth was 80.85%(38/47).But compared with the control group,the number of puncture times did not affect pregnancy outcomes(χ2 = 6.48,P = 0.372,>0.05).Intrauterine infection is a severe complication of the MFPR operation.We analyzed several factors may be related to the infection,including the way they conceive(P = 0.739,>0.05),the number of puncture times(P = 0.638,>0.05),the number of the fetus(P = 0.079,>0.05),and the number of reduced fetus(P = 0.652,>0.05),there was no significant relationship,but because of the insufficient of infection cases,this result needs further data accumulation.MFPR of radiofrequency ablation technique:a total of 99 pregnant women performed radiofrequency ablation in our hospital from July 2011 to June 2017.Surgical success criteria:the blood flow of the umbilical cord was completely stopped,and we observed subsequent cardiac arrest and survival of the other MC fetus in 24 hours.Postoperative complications.were monitored:after 24h and 6 weeks of the surgery,the patients were examined for B ultrasound,and the related complications of radiofrequency ablation were observed.Among them,there were 5 cases of surgical failure,1 case of intrauterine infection after operation,13 cases of miscarriage and 31 premature births,5 cases of fetal dysplasia induced labor,44 cases of full-term pregnancy,and the total survival rate is 79.79%.According to the number of pregnancy fetus,these women were divided into twins group(74 cases)and triplet and more group(25 cases),analyzing the age of pregnant women and gestational age when the RFA reduction was conducted.Results suggest that the pregnant women in twins group with an average age of 30.40±4.93 years old,that in triplet and more group was 31.72±4.81 years old,t= 1.17,P =0.247,>0.05,there was no statistical difference.The average reduction gestational age of twins group was 21.64±5.71 weeks,and that of triplet and more group was 16.57±2.14 weeks,Z value is 5.66,P<0.001.The difference was statistically significant,show that the average reduction gestational age of triplet and more pregnancy was much smaller than that of twins.This is affected by the cause of the reduction,triplet and more pregnant women mainly to reduce the number of fetuses,MFPR can be conducted in early gestational age,and pregnant women of complicated twin pregnancies including SIUGR,TTTS,fetal abnormalities,TRAP and so on,all needs to wait until the detection of the problems.The methods of conception were analyzed separately.The fertility rate of IVF-ET was 5(6.76%)in the twins group,the population under ovulation induction therapy was 0 and the number of spontaneous conception was 69(93.24%).And 13(52.00%)cases were conceived by IVF-ET in triplet and more pregnancy group,that of ovulation induction procreation was 2(8.00%),spontaneous conception was 10(40.00%).There was a significant statistical difference between them,P<0.001.This result indicating that multiple pregnancies with more than three babies were mostly caused by the application of assisted reproduction techniques.Besides these,the failure rate was 5.41%in twins group,the failure rate was 4.00%in triplet and more pregnancy group and P= 1.000.The abortion rate was 17.57%and 17.57%in two groups.With 21 cases of premature delivery,28.38%of premature births,10 cases of triplets and more pregnancy group,40.00%of preterm births,and P=0.279.There was no significant difference between the two groups.The average delivery gestational age of the twins group was 37.64±3.29 weeks,and the average delivery gestational age was 37.00±3.86 weeks,and t=-1.32,P=0.186.The average weight of the fetuses in the twins group was 2950.00±970.00g,and the average weight of the fetuses of the triplets and more group was 2475.00±600.00g,t=-2.41,P=0.008,and there was a significant statistical difference.The twins group was divided into sIUGR(11 cases),TTTS(26 cases),fetal malformation(26 cases)and TRAP(5 cases)according to the reduction reason,excluded 5 patients with fetal dysplasia after the RFA procedure.Then we analyzed the fetal gestational age of operation,delivery gestational age,failure rate,miscarriage rate,premature delivery(less than 37 weeks of gestational age at delivery)and average fetal weight.The fetal gestational age of reduction in sIUGR group was 22.13±2.80 weeks,in TTTS group was 21.70±2.96 weeks,in fetal malformation group was 21.35±3.59 weeks,and in TRAP group was 23.54±3.50 weeks,F = 0.69,P = 0.559,no significant difference had been found.The delivery gestational age in sIUGR group was 38.09±1.41 weeks,the TTTS group was 34.34±3.84 weeks,the fetal malformation group was 37.61 ±2.67 weeks,and the TRAP group was 35.66±4.42 weeks,F=4.09,P=0.012,there was a significant difference.The average fetal weight of SIUGR group was 3328.33±409.90g,the TTTS group was 2290.28±809.21g,the fetal malformation group was 2835.10±603,25g,and the TRAP group was 2516.67±1086.66g,F=3.92,P= 0.015,with a significant difference.The failure rate of the TTTS group was 7.69%(2/26),the failure rate of fetal malformation group was 7.69%(2/26),and the other two groups had no failure cases,P=1.000,no significant difference had been found.The abortion rate of sIUGR group was 45.45%(5/11),the TTTS group was 7.69%(2/26),the fetal malformation group was 15.38%(4/26),and the TRAP group was 20.00%(1/5),P=0.061,there was no significant difference between them.The premature birth rate in sIUGR group was 9.09%(1/11),the TTTS group was 46.15%(12/26),the fetal malformation group was 26.92%(7/26),and the TRAP group was 20.00%(1/5),P=0.137,there was no significant difference.Post-operative abortion was the main adverse pregnancy outcome of RFA,we analyzed the data of miscarriage cases and the corresponding premature birth and term birth group,including fetal gestational age and the number of radiofrequency ablation cycle,melting time and disappearing time of fetal heartbeat(to exclude the TRAP cases).The results show that the twins after reduction,including 13 cases of abortion and 40 cases of premature birth and term delivery.The MFPR gestational age of abortion group was 22.28±2.28 weeks,that of the premature birth and term delivery group was 20.35±5.57 weeks,t=1.034,P=0.301.In the abortion group,the cases with 1 cycle of RFA were 10(76.92%),2 cycles were 2(15.38%),3 cycles were 1(7.69%),in premature birth and term delivery group,the cases with 1 cycle were 36(90.00%),2 cycles were 4(10.00%),3 cycles was 0,P=0.172.The ablation time in abortion group was 5.90±1.00 minutes,and in the premature birth and term delivery group was 5.90±1.15 minutes,Z=0.073,P=0.942.The disappearing time of fetal heartbeat of abortion group was 31.00±32.50 minutes,and the premature birth and term delivery group was 30.00±10.00 minutes,Z=0.770,P=0.441,and the difference was not significant.After the RFA reduction,we regarded the heartbeat of reserved fetus disappeared in 24 hours as failure.As a serious complication after surgery,we compared the operative gestational age,radiofrequency ablation cycles,ablation time,and the disappearing time of fetal heartbeat(excluding TRAP cases)between failed cases and successful cases.The results show that the failure rate was 5.05%(5/99),the reduction gestational age of failure group was 20.14±4.81 weeks,that of successful group was 20.59±3.50 weeks,t=0.28,P= 0.780.In the failure group,the cases with 1 cycle of RFA were 3(60.00%),2 cycles was 1(20.00%),3 cycles was 1(20.00%),in the successful group,the cases with 1 RFA cycle were 74(79.57%),2 cycles were 17(18.28%),3 cycles were 2(2.15%),P = 0.126.The ablation time of failure group was 7.00±7.10 minutes,and that of the successful group was 6.00±1.30 minutes,Z=0.769,P=0.442.All the differences were not significant.The disappearing time of fetal heartbeat in failure group was 10.00±11.00 minutes,the successful group was 30.00± 12.00 minutes,Z=-2.33,P=0.020,and the difference was significant.CONCLUSIONS:1.In the 11 years between 2005-2015,the number of patients undergoing fetus reduction in our hospital showed an upward trend.The number of fetuses of multiple pregnancy was decreased.The results show that the proportion of IVF-ET patients decreased,while the proportion of ovulation induction and naturally conceived patients increased,which were due to the normative application of ART.The reason for the reduction of the fetus was mainly to reduce the number of fetuses.According to the result of the different time periods statistics,the proportion of fetal reductions due to fetal number was decreased,and the proportion of fetal reductions due to abnormal fetus was significantly increased,significant changes have taken place in the causes of reduction.2.The greater the initial number of fetuses,the higher the incidence of miscarriage.The number of different puncture times did not affect the pregnancy outcome.3.There was no significant relationship between intrauterine infection and the cause of reduction,the way of conception,the number of puncture times,the number of fetus and the number of reduced fetus.4.The overall survival rate of radiofrequency ablation in our hospital was 79.79%,of which the complicated twin pregnancy was 75%,and the triplets and the above pregnancies was 96%.The pregnancy outcomes were different for different reduction reasons.5.The average reduction gestational age of triplet and more pregnancy was much smaller than that of twins.The average weight of the newborn in the twins group was heavier than that of the fetuses of the triplets and the above group.In the twins group,the majority way of conception was spontaneous conception,and the majority way of conception was IVF-ET in triplet and more pregnancy group.This result indicating that multiple pregnancies with more than three babies were mostly caused by the application of assisted reproduction techniques.6.RFA reduction patients with TTTS still have higher incidence of preterm birth and low birth weight after the operation.7.There was no significant relationship were observed between miscarriage with gestational age,the number of radiofrequency ablation cycle,melting time and disappearing time of fetal heartbeat(to exclude the TRAP cases).8.Our results show that the failure rate was 5.05%(5/99),the disappearing time of fetal heartbeat in failure group was lower than that of the successful group.The rapid disappearance of fetal heartbeat after ablation indicates that the surgery may ultimately fail. |
PDF Full Text Request