Multifetal Pregnancy Reduction: What is Hidden Behind This Medical Term?
Abstract: Multifetal Pregnancy Reduction: What is Hidden Behind This Medical Term?
The article was designed as a retrospective overview of three basic techniques of selective multifetal pregnancy reduction. Multiple pregnancies present an excessive risk of feto–maternal morbidity and mortality, therefore selective multifetal pregnancy reduction is considered to be a perfect option to increase the chance of survival of the remaining fetuses. Factors determining the performance of selective embryo reduction were established. Additionally, special emphasis was given to complexities and risks which are in close correlation with the performance of these procedures. Comparative analysis was given to all three techniques of selective embryo reduction, including methods and statistical data of the ultimate pregnancy outcomes. Complications, interconnected with Embryo Reduction techniques were inclusively represented. The spectrum of issues including a formal comparison of the complexities and risks, which follow the multifetal selective reduction was discussed with the following concepts made. The consensus was established in almost all controversies including the basic recommendations noted for implementation into clinical practice in the conclusion. The perspectives of the further analysis were outlined.
Introduction
At present, multiple pregnancies are closely associated with Infertility Treatment outcome. The incidence of multifetal pregnancies is constantly increasing, mainly as an adverse consequence of the use of various infertility protocols. Generally outlining the issue, it should be emphasized that the number of women conceiving three or more ‘top–quality’ [morphologically perfect] fetuses with high implantation potential as increased dramatically as a result of successful infertility therapy with ovulation–inducing medications and Assisted Reproductive Technology. Despite being an efficient and widely used Treatment for infertile couples, In–Vitro Fertilization (IVF) is responsible for an increasing number of multifetal pregnancies and adverse neonatal outcomes. Indisputably, it represents an attractive option to the range of infertility treatments available at present. But, the complexities and risks should not be neglected as the negligence of the negative consequences may result into reduced fetal survival, complete fetal loss, increased neonatal mortality or irreversible morbidity.
Since such multiple gestations present an excessive risk of feto–maternal morbidity and mortality, selective Embryo Reduction during the first trimester remains one of the few reasonable options, but it should be considered that this procedure invasively prevents the multiple birth. Selective Embryo Reduction procedure has proved to be both safe and effective, and multifetal pregnancies reduced to triplets or twins proceed as if that were the number of fetuses originally conceived. There are two basic indications for the procedure’s performance: obstetric and paediatric risks. Although, this invasive procedure does have the potential to result in complete loss of the entire pregnancy and causes considerable emotional distress, it must be performed in cases if there is no alternative variant how to manage the multiplicity and to predict the outcome.
2. The overview of multifetal pregnancy reduction procedure: which techniques are used? Which complexities and risks should be considered?
2.1. Short overview of three selective embryo reduction techniques. Factors determining necessity of selective Embryo Reduction. Recommended timing for procedure performance. Following complexities.
Primarily, the performance of multifetal pregnancy reduction was done to carry out selective fetuses in cases if fetuses were affected by some malformation or genetic disorder. Later the technique was applied to the reduction of one or more fetuses in cases of multiple pregnancies [if there were three and more successfully implanted fetuses: triplets, quadruplets, quintuplets, sextuplets, septuplets, nonuplets], because of increased perinatal morbidity and mortality, as well as maternal morbidity, which complicated dramatically these pregnancies. Selective fetal reduction has been suggested as a therapeutic option for these pregnancies, to increase the chance of survival of the remaining fetuses.
The procedure is variably named: Selective Embryo Abortion, Selective Embryo Reduction, Selective Embryo Termination, but the most preferred term is now Multifetal Pregnancy Reduction (MFPR) [The ESHRE Capri Workshop Group, 2000]. Selective fetal reduction is an essential modality used to reduce both fetal and maternal risks associated with multifetal pregnancies. The procedure is usually performed under ultrasonic control at or after the ninth gestational week, by injecting 1–2 ml of KCl into the fetal heart or in its vicinity [into the pericardial region of the fetus] [Coffler et al., 1999], but nowadays this technique is improved by performance only intracardiac embryo puncture and it is possible to avoid the injection of above–mentioned toxic medications.
Two major approaches for multifetal pregnancy reduction have been developed over the past several years: transabdominal potassium chloride by injection and pelvic procedures by either transcervical aspiration or transvaginal potassium chloride injection or by an automated spring–loaded puncture device [Evans et al., 1994]. Usually, the embryos selected for reduction are those which are in the upper part of the uterus, those which have increased nuchal translucency or other ultrasonographic markers of risk [The ESHRE Capri Workshop Group, 2000]. But if it is necessary to reduce embryos implanted in other part of the uterus, the distinguishing criteria between the techniques must be followed: the transabdominal reduction tends to reduce the fundal embryos and the transcervical and transvaginal the lower ones [Evans et al., 1994].
There are three Embryo Reduction techniques: transabdominal, transcervical and transvaginal. The transabdominal technique, which is performed between the 9th and 14th weeks of pregnancy, involves injection of NaCl or KCl solution near to or inside the fetal heart, and/or amniotic fluid aspiration. The method entails a greater technical difficulty, with miscarriage rates ranging from 10.6% to 40%, and pre–term labour ranging from 20% to 64% of the cases. The transcervical technique consists of a mechanical cervical dilatation performed between the eighth and ninth weeks, followed by an embryo aspiration through the cervix using a Karman or a number 8 metallic cannula. This technique is no longer used on a practical basis due to the high complication rates, including chorioamnionitis (10%), bleeding (33%) and miscarriage (12–24.8%) [Ibérico et al., 2000].
The transvaginal technique is performed between the seventh and 11th weeks, by injecting NaCl or KCl solution into the fetal thorax. The injection of such substances into the embryo or fetal thorax is not a risk–free procedure however, and cases of anencephaly or limb amputation have been described. If the intra-embryonal injection of KCl solution accidentally reaches the amniotic fluid of the remaining embryos, this could result in a total pregnancy loss. More recently, the transvaginal technique has been performed with total or partial embryo aspiration. Single embryo tissue aspiration was compared with KCl solution injection, and showed a lower miscarriage rate (8.8% and 30% respectively). Single puncture of the intrathoracic embryo region until asystolia is verified decreases surgery time and the risks of excessive manipulation (bleeding, infection, contractions of the uterus). This is shown by our low rates of infection (1.34%), miscarriage (7.4%) and spotting (11.4%) [Ibérico et al., 2000].
2.1. Transvaginal ultrasonography–guided embryo aspiration procedure overview
Transvaginal embryo aspiration is performed in women with multifetal gestations, defined as three or more fetuses. Early transvaginal embryo aspiration is a simple and relatively safe procedure. In quadruplets or higher order gestations, this procedure is apparently safer than other methods of selective fetal reduction. First–trimester transvaginal Embryo Reduction is an effective alternative for the management of multifetal pregnancy in Assisted Reproduction. In the past the procedure performance required the injection into the Gestational Sac of chemical substances. At present, the transvaginal technique is modified by performing an intracardiac embryo puncture until asystolia is verified, without the injection of any substances. The breakthrough made possible to avoid any aspiration of embryo tissues or amniotic fluid.
The advantages of transvaginal embryo aspiration include the possibility of performing it 2–4 weeks earlier than other methods for selective fetal reduction, thus obviating the need to use KCl or other toxic substances. What is essential to consider is that selective fetal reduction should be completed in two sessions, because of technical difficulties or clinical impression that spontaneous fetal demise would follow [Coffler et al., 1999].
A routine vaginal ultrasound, confirming the number of embryos with heart activity, is performed before surgery. Under general anesthesia surgical field cleaning is carried out. The ultrasound equipped with a transvaginal transducer and puncture guide is used for selective embryo reduction procedure. The embryos are then visualized using a transvaginal ultrasound transducer to verify their number, position, size and heart activity. The uterus is scanned, and the configuration and position of each gestational sac relative to the uterine cavity and to each other is recorded. The smallest embryo and/or that located closest to the fundus of the uterus was selected for Embryo Reduction [aspiration]. This protocol reduced the technical difficulties of the procedure, and avoided the greater bleeding or infection risks resulting from the selection of a sac located near the cervix.
The same 30 cm long ×1.6–1.8 mm outer diameter needle usually used for the ovarian follicular puncture is inserted through the puncture guide attached to the transvaginal ultrasound transducer and is advanced with a brisk movement through the vaginal fornix and the uterine wall into the most easily accessible sac. Exact alignment between the needle and the ultrasound screen guide is necessary to perform the procedure with accuracy. Alternatively, the embryo with the inappropriate smaller Crown–Rump Length (CRL) or Gestational Sac is chosen for reduction. The needle tip is positioned close to the embryo and suction is applied abruptly with a 20–ml syringe. If the uterus is mobile, assistant pushes with two hands on the hypogastrium, supporting the uterus region during the needle puncture. At this point, the surgeon starts the embryo heart puncture until asystolia is confirmed. The use of a KCl and/or NaCl solution, or injection into the sac of other chemical substances is avoided. Without aspirating embryo tissue or amniotic fluid, it is possible to visualize adequately the embryo throughout the entire procedure. This results in complete or partial aspiration of the embryo. A new needle is used each time when the needle must pass through the vaginal wall. However, when the location of the sacs permitted, the surgeon penetrates additional sacs with the same needle without reinserting it through the vaginal mucosa. All embryo reductions are carried out by the same surgeon [Coffler et al., 1999; Ibérico et al., 2000].
The average time required for the Embryo Reduction is 2.1 ± 0.5 min per sac in early gestation (sixth to ninth weeks), increasing to 5.5 ± 2.4 min per sac for later procedures, due to technical difficulties brought about by increased embryo size [Ibérico et al., 2000].
Compared to later performed procedures, transvaginal embryo aspiration is easier to accomplish. It is also possible that avoiding the burden of aborted fetuses that is left after the ‘late’ procedures is beneficial and confers the observed advantage of this procedure. In addition, this method obviates the use of KCl or other toxic substances, and the potential fetal complications that might be associated with their use. The use of intracardiac KCl in multifetal pregnancy reduction was reported as a possible risk factor for periventricular leukomalacia in premature newborns [Coffler et al., 1999].
A potential disadvantage of transvaginal aspiration at 7–8 weeks gestation would be selective fetal reduction performed too early, before the phenomenon of ‘embryo vanishing’ could occur [Coffler et al., 1999]. It was observed that during the eighth to ninth weeks of pregnancy is the optimal period to perform Embryo Reduction, as later gestational ages result in greater technical difficulties, more time–consuming surgeries, and a lower probability of spontaneous embryo reabsorption [Ibérico et al., 2000]. Ideally, Embryo Reduction should be used only when there is no chance of spontaneous embryo vanishing, which occurs in 16% to 43% of all multiple pregnancy cases. The whole pregnancy may be endangered if additional embryos were to be lost spontaneously after selective reduction to the desired number of fetuses had been completed. Moreover, if whole pregnancy losses are excluded, spontaneous fetal demise after heart activity had been documented on ultrasound was very low, as the fetus with the smaller Crown–Rump Length (CRL) or Gestational Sac has a greater chance of spontaneous demise [Coffler et al., 1999].
A considerable disadvantage of early transvaginal aspiration is the inability to identify the fetus with a structural anomaly that might be detected on ultrasound when the reduction is performed early in the second trimester. In triplet gestations, an alternative option (after appropriate counselling) is to defer selective reduction to the early second trimester, when ultrasound screening for fetal structural anomalies should be attempted. The rate of non-chromosomal structural malformations is indeed increased in multifetal pregnancies, but mainly in monozygotic gestations. Most multiple gestations occurring as a result of ovulation induction are derived from different zygotes. Ultrasonographic detection of congenital anomalies in multiple gestations may be hampered by fetal positioning and crowding, oligohydramnios and increased distance between the ultrasound transducer and the target organ. In twins, ultrasound screening for fetal anomalies is apparently as effective as in singleton gestations, but data are not available regarding the efficacy of ultrasound diagnosis of fetal structural anomalies in multiple gestations of higher order [Coffler et al., 1999].
2.2. Transcervical ultrasonography–guided embryo aspiration procedure overview
Transcervical complete aspiration of the Gestational Sac is performed under ultrasound guidance. The transcervical technique consists of a mechanical cervical dilatation performed between the eighth and ninth weeks, followed by an embryo aspiration through the cervix using a Karman or a number 8 metallic cannula. This technique is no longer used on a practical basis due to the high complication rates, including chorioamnionitis (10%), bleeding (33%) and miscarriage (12–24.8%) [Ibérico et al., 2000].
Transcervical aspiration of the Gestational Sac may be associated with an increased incidence of abortions due to infection introduced from the cervix or cervical incompetence brought about by cervical dilatation and is therefore not recommended [Dommergues et al., 1991].
2.3. Transabdominal ultrasonography–guided embryo aspiration procedure overview
The procedure is performed between 9th and 14th weeks of gestation. Before the transabdominal selective embryo abortion, an ultrasound examination is performed to know the number of embryos with cardiac activity [to detect compromised cardiac activity], to determine the chorionicity, to establish the positions of the Gestational Sacs to each other and to determine which of the fetuses are most accessible to needle insertion.
The procedure was performed under local anesthesia, a 22.5–gauge needle under ultrasound guidance is transabdominally inserted through the uterus wall, then into the amniotic cavity, and finally pushes into the fetal thorax at a level above the diaphragm. Then, potassium chloride solution (amount ranging from 0.5 to 5 ml) is injected slowly so as not to dislodge the needle tip, leading to the cessation of the heartbeat. Asystole is usually seen within 1–2 min of injection of potassium chloride and total procedural time is typically less than five minutes. Additional fetuses could be reduced with the same needle puncture or, more commonly, with a separate needle stick. The fetus (fetuses) reduced are those that are most easily accessible, usually those closest to the anterior uterine wall and/or the fundus while those above the cervix were avoided [Abdel Baset F. Mohammed et al., 2015].
In a multichorionic pregnancy, the fetus (fetuses) reduced are those that are most easily accessible, usually those closest to the anterior uterine wall and/or the fundus. The fetus above the cervix is avoided whenever possible because of a hypothetical increased risk for infection or uterine irritability if that fetus was reduced. However, if a fetus has a lagging crown rump length, a significantly smaller sac, markers of aneuploidy, or an obvious anomaly, then that fetus is preferentially reduced since these findings are associated with adverse pregnancy outcome (miscarriage, fetal aneuploidy) [Abdel Baset F. Mohammed et al., 2015].
The determination of fetal status as part of the decision process must be a priority to reduction [by transabdominal cardiac puncture injection], which includes more than just nuchal translucency ultrasound, detection of the cardiac activity and position of the fetuses into uterus.
Conclusion
Multiple pregnancy has a higher probability of obstetric complications, perinatal morbidity and mortality, especially when more than two fetuses are present. Performance of selective Embryo Reduction in multifetal gestations are inevitable since it has been established that the obstetric outcome for triplets or a higher number of fetuses is significantly worse than that for singletons or twins. Despite first trimester Multifetal Pregnancy Reduction (MFPR) reduces extreme prematurity before 32 weeks and improves fetal growth without excessive fetal loss, the exact number of fetuses that should be left in the uterus is highly polemized theme. Although singletons have longer gestations and lower neonatal morbidity compared to twin gestations, the latter are more feasible for most of multifetal pregnancy reductions. Taken together these emerging concepts suggest that infertility specialists should focus their practical skills almost exclusively on the prevention of the multiple pregnancies through the improvement of multiphasic clinical procedures. Prevention of the multifetal pregnancies should primary be an imperative of the clinical approaches. The spectrum of issues concerning the prevention methods should be discussed in every single case with the following concepts made: cancelling superovulation cycles should be included as necessary and Embryo Transfer techniques in IVF/ICSI cycles should be improved.
Performing multifetal pregnancy reduction in women with four or more successfully implanted and developing fetuses [quadruplets, quintuplets, sextuplets, septuplets, nonuplets] seems well–established, but this is less true for women with three fetuses [for triplets]. Selective fetal reduction has been suggested as a therapeutic option for these pregnancies, in order to increase the chance of survival of the remaining fetuses. Therefore, before taking the decision to perform embryo reduction in cases of triplets there should be considered all possible versions of the consequences, including the risk of delivering extremely prematurely in case if the couple would decide to have triplets. The consensus should be established in almost all controversies through the inclusive dialogue between the experienced fertility experts, embryologists and the couple. Understanding the principles of performing multifetal pregnancy reduction in appropriate circumstances, for instance, when the ability to carry the pregnancy to viability is very small is ethically justified because it meets the criterion of least harm and most potential good, as multifetal pregnancy reduction increasing the chance of survival of the remaining fetuses [in critical situations] is an unsurpassable and unparalleled opportunity for the successful management of such pregnancies.
Additionally, it is necessary to emphasize one extremely vital concept for the successful pregnancy outcome: any kind of multiple pregnancy, even the one, which does not have any complications and seems to be ‘perfect’ needs to be guided and monitored by the experienced clinicians in order to prevent or limit the possibilities of the negative consequences’ occurrence. The management of multifetal pregnancy is difficult. While fetal reduction is a possible management option, it should not be an absolute determinant of absolute safety of this procedure as the results can be controversial to expectations and still there are no established inclusive exclusive criteria for its performance.
References:
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