Vanishing Twin Syndrome

Etiology

In the majority of cases, the cause of vanishing twin remains unknown, but certain etiological factors are considered to be associated with the loss of the embryo, which includes:[2][3]

• Advanced maternal age (usually more than 30 years) [4]
• Chromosomal abnormalities in the deceased twin
• Use of assisted reproductive techniques (ART) such as; in vitro fertilization (IVF) [5]
• Increase the incidence of multiple gestations
• Small placenta or other anatomical abnormalities of the placenta may be associated with early twin loss
• Genetic and teratogenic factors [6]

Epidemiology

Before the advent of ultrasound, little was known about the phenomenon of vanishing twin syndrome (VTS). It was disclosed in 1945 by Stoeckel that the rate of multiple gestations is greater than the rate of their birth, i.e., a twin or even multiple can be lost during multi-fetus pregnancy before the mother is even aware of the loss or the fact that she was carrying multiple fetuses. Since ultrasonography and transvaginal sonography in early pregnancy, vanishing twin syndrome is more frequently diagnosed. Vanishing twin syndrome is evaluated to happen in 36% of twin pregnancies and in half of the pregnancies that begins with at least three or more gestational sacs.

With respect to assisted reproductive techniques (ART), it is assessed to occur in 20-30% pregnancies. This phenomenon is progressively predominant with the utilization of the assisted conceptive methods, as more than one embryo is transferred to the uterus; the rate of multiple gestations also increases.[7][3] The vanishing twine syndrome was seen to be associated with very low birth weight (VLBV) and low APGAR scores.[8]

Pathophysiology

Abnormalities that brings about the vanishing of the fetus are usually present from right off the early development as opposed to happening from an intense acute insult.[3] A study including 30 patients performed by Robinson and Caines demonstrated the fetal surface of the placenta as an empty and flattened sac, as pathological evidence of the disappearing twin. Another study conducted by Finberg and Birnholz found a small area containing 30 ml of dark brown blood in the pathological specimen of abortion; this observation was followed by the appearance of a hemorrhagic second sac seen on ultrasonography, which made the patient opt for elective abortion. As per Finberg and Birnholz, if the pregnancy ends in abortion, the results are that the product of conception is commonly fragmented. On the contrary, if the pregnancy continues to term, the subsequent sac may have been removed or expelled, resorbed or fragmented, or may persevere as a little atretic section neglected considerably even after careful examination of the placenta and the membranes.[9]

The vanishing twin may have the following physiologic outcomes:

• Resorption: Even though resorption is the most likely physiologic explanation for the vanishing of the specific proportion of the gestational sac, the valid incidence of resorption is still unknown. Different study results show that resorption can be observed from as early as the seventh week to as late as the twelfth week of gestations. It is evident in any case that resorption of gestational sacs during pregnancy happens without affecting the co-twin. Regardless of the resorption of the vanishing twin, there are excellent chances of the survival of the other twin, as resorption mostly occurs in the first trimester.[9]

• Blighted Ovum: By definition, a blighted ovum is the gestational sacs inside which no embryo can be visualized via ultrasonography. According to some studies, most of the pregnancies that ended up with the vanishing of a fetus were subsequently found to be anembryonic pregnancy co-existing with normal pregnancy. The result could be in the form of vaginal bleeding in the first trimester, indicating the expulsion of the anembryonic sac. It is advisable, therefore, to undergo a thorough ultrasonographic examination before opting for dilation and curettage, as the process of dilation and curettage may end up in the accidental abortion of the other surviving twin.[9]

• Fetus papyraceous: Fetus papyraceous is a mummified, compressed or flattened fetus associated with the other viable fetus. This is very rare and most commonly occurs in multiple gestations. The deceased fetus gets flattened in between the membranes of the other viable fetus and the uterine wall. The demise of the fetus usually occurs right off in the early second trimester. The early demise of the twin may result in complete resorption, but as the pregnancy continues to term, the twin may become macerated and may affect the other viable twin as well, as the pregnancy continues. This course of events can be well observed via regular ultrasonographic examinations.[6][10] Additionally, a vanishing twin has also been linked with several of the fetal malformations in the surviving twin via an unknown mechanism.[6]

Histopathology

It is essential to examine the placenta after delivering the viable co-twin, to know about the morphologic characteristics of the lost twin. Although a vanished twin pregnancy can be noted via an ultrasound, no such histologic confirmatory evidence has been presented previously.[11] The results of studies after examination of the placenta ranged from histologically regular anembryonic gestational sacs to identifiable residues of fetal tissue.[12] In some cases, a mummified, compressed fetus in association with a viable fetus was observed, a condition called fetus papyraceous.[10] 

In a study, the histopathologic examination of the placenta revealed a gestational sac that was containing amorphous material, surrounded by degenerated chorionic villi up against a normal amniochorionic membrane.[11] One study based on the pathological findings in placentas from pregnancies complicated by the vanishing twin syndrome confirmed via ultrasonographic evidence revealed well-delineated plaques of fibrin deposits and embryonic tissue remnants, hinting towards the disappearance of a conceptus.[13]

History and Physical

The most likely clinical presentation of a vanishing twin pregnancy is vaginal bleeding or spotting, uterine cramps, or pelvic pain, which indicates the loss of the conceptus. This can occur during the first trimester of pregnancy and may go unnoticed by the mother as missed abortion or vanishing through later gestational ages. Studies have told that most of the patients are usually more than 30 years old.[4]

Patients who conceived via assisted reproductive technique (ART) are especially worried about the outcomes of vanishing twin pregnancy on the viable co-twin and are brought into medical attention earlier, as multiple embryos are transferred into the uterus and chances of twin gestation and vanishing twin phenomenon to occur are higher.[4] The history will usually indicate a previously documented fetal heart activity or more than one gestational sac to spontaneous reduction into singleton pregnancy as per subsequent ultrasonographic findings through later gestational ages or at the time of delivery.[14][4]

Evaluation

Examination via ultrasound during pregnancy confirms the presence of the vanishing twin phenomenon. Additionally, the examination of the placenta after giving birth provides morphological details about the vanishing twin that was established following an ultrasonographic examination.[15]

Moreover, a study performed to compare the rise of human chorionic gonadotrophin (hCG) between normally progressing twin pregnancies and pregnancies with vanishing twins demonstrated a slower rise of human chorionic gonadotrophin (hCG) in vanishing twin pregnancies as compared to the normal twin pregnancies. The reason for the slower rate of human chorionic gonadotrophin rise could be the result of poor trophoblastic activity due to embryonic causes. These findings indicate that the abnormality in the human chorionic gonadotrophin in vanishing twin syndrome is present from the earliest days of implantation and not due to some acute insult.[16]

A recent study, including a large series of pregnancies with a vanishing twin, was performed to determine the use of maternal serum pregnancy-associated plasma protein-A (PAPP-A) and serum-free B-human chorionic gonadotrophin (B-HCG) in first-trimester screening for trisomies in relation to the interval between embryonic death and blood sampling. Compared to the previous studies, this study revealed that multiples of the median (MoM) values of maternal serum free B-human chorionic gonadotrophin (B-HCG) were not altered, but that of PAPP-A (MoM) was increased in both pregnancies with an empty gestational sac or a dead embryo.[17]

If the pregnancy is conceived via an assisted reproductive technique, complicated by advanced maternal age, chances of vanishing twin phenomenon to occur get higher, most probably due to the increased chances of chromosomal abnormalities in the fetus associated with advanced maternal age.[18] The regular prenatal examination is highly advisable in such cases, which includes: ultrasonographic examinations and first and second-trimester maternal serum markers.[19][20]

Treatment / Management

There is no special medical care necessary for an uncomplicated vanishing twin pregnancy when the twin is lost during the first trimester of pregnancy. The mother may experience vaginal bleeding or spotting or pelvic pain, which needs regular medical care. The other fetus has higher chances of survival and could be delivered normally.[1](B3)

On the other hand, if the disappearance of a twin complicates the pregnancy during the second or third trimester, then the pregnancy could be treated as high-risk pregnancy, as the outcomes of such pregnancies through later gestational ages might affect the other twin adversely. Regular prenatal visits to assess any signs of complications and keep a check on both maternal and fetal health is necessary to avoid adverse outcomes and their effect on both maternal and fetal health.[4](A1)

Differential Diagnosis

Careful ultrasonographic assessment is required to diagnose a vanishing twin in early pregnancy, as any artifact may incorrectly indicate the presence of an additional gestational sac or any pathology of the placenta, such as; placental cysts may incorrectly imply multiple gestations. Histologic examination of the placenta by the experts after delivery is necessary in such cases.[2]

Prognosis

Chances of survival of the viable co-twin are excellent if the demise of the twin occurs during the first trimester of pregnancy. Also, the health of the mother is not affected, except for some mild vaginal bleeding that may be experienced by the mother as a sign of the loss of the embryo in early pregnancy. In other words, the earlier the loss of the fetus, the more likely is the chance that the mother doesn’t even notice the twin being vanished, as chances of survival of the other fetus and the health of the mother may not be affected by the loss of the fetus.[1][21]

Complications

Depending upon the trimester of pregnancy, if the fetus is lost during the first trimester of pregnancy, i.e., in the embryonic stage, the mother is most likely to experience the complication of the vanishing twin in the form of vaginal bleeding or spotting, pelvic cramps or back pain. The chances of survival of the viable co-twin are good in such cases.[22]

On the other hand, chances of complications are higher in the existing co-twin if the demise of the twin occurs later in gestation, which may include cerebral palsy of the viable twin, intrauterine growth retardation (IUGR) of the viable twin, premature labor, and other congenital anomalies accompanied by a fetus papyraceous.[6] A study was performed recently among singleton pregnancies, twin pregnancies, and women with vanishing twin pregnancies. The results of the study revealed adverse maternal and neonatal outcomes among vanishing twin pregnancies compared to the other two. Among maternal complications, gestational diabetes, premature rupture of membranes, oligohydramnios, cervical insufficiency, labor induction, and preterm labor were higher in vanishing twin pregnancies than singleton and twin pregnancies.[23] 

Among neonatal outcomes, fetal malformations were recorded more in vanishing twin pregnancies than singleton and twin pregnancies.[23] Although cerebral palsy has no specific etiology, it is known through general consensus, that the death of a twin in late gestation is associated with higher chances of surviving twin to have cerebral palsy.[21] The pregnancies diagnosed with the vanishing twine syndrome after in-vitro fertilization compared with those were originally singleton carried a higher rate of obstetric complications with regards to preterm deliveries and low birth weight.[24]

It is advisable to have regular prenatal follow up and have the pregnancy assessed with the help of ultrasonographic examinations, to have knowledge about the fetal anomalies associated with the demise of the twin. However, most of the vanishing twin pregnancies will end up uncomplicated throughout gestation and birth. However, studies show that the birth weight was found to be slightly lower in the co-twin in vanishing twin pregnancy as compared to non-vanishing twin pregnancy.[22]