Types of Multiple Pregnancy

Abstract

Multiple pregnancy is condition where more than one offsprings are formed. This result from either fertilization of more than one ovum individually by separate sperms or division of fertilized ovum. The implantation sites may be in different part of the genital organs and even the peritoneal cavity. The physiology of monozygotic multiple pregnancy is not fully understood as the trigger has not yet been identified. The incidence of multiple pregnancy is increasing, and this is as a result of assisted reproductive technologies.

1. Introduction

Multiple pregnancy refers to a pregnancy with more than one embryo. The embryos may grow in the same uterine pregnancy as a result of either two or three separate ova were fertilized or one ovum fertilized, and the embryo divided two or more embryos developed. Where two or more ova are fertilized individually the resultant pregnancy is called dizygous if two ova were fertilized and multizygous multiple pregnancy if three or more ova were fertilized. The implantation site also determines the naming of the type of multiple pregnancy. The dizygous or multizygous multiple pregnancies result in each embryo having its own placenta and amniotic sac and are independent of each other. Where one ovum is fertilized, and the embryo divides it is called monozygous multiple pregnancy. Zygosity is the degree of identity in the genome.

The incidence of multiple pregnancy is increasing as a result of increasing use of assisted reproductive technology [1, 2]. Twin pregnancy account for 2–4% of the total number of births. Spontaneous twin pregnancy rates vary worldwide [3]. The incidence of higher order multiple pregnancy is not fully reported but there are lot of case reports noted. The incidence of triplet pregnancies has been estimated to be one in thousand pregnancies [4]. Different types of multiple pregnancy will be discussed.

2. Dizygous multiple pregnancy

Dizygotic multiple pregnancy is derived from fertilization of two ova by two sperms and they may be of same sex or different sex. Their genetic composition is different because it comes from different ova and different sperms. These are just two siblings in the same patient. Dizygotic multiple pregnancy contributes two thirds of all multiple pregnancies. The implantation may be at the same site or different sites. Each of the embryo has its own chorion (placenta) and amniotic membrane as in Figure 1. They are also called fraternal multiple pregnancy [5]. Fertilization may occur during the same sexual activity or different sexual activities during the same menstrual cycle. Fertilization of the second ovum during different sexual exposure is called superfecundation. This means that fertilization of the ovum when there is an existing early embryo. If fertilization of the second ovum and implantation occurs in subsequent menstrual cycle, this is superfetation. Upregulation of hypothalamic-pituitary-ovarian axis by luteal progesterone and then placental progesterone in the first trimester of pregnancy suppresses ovulation and makes the possibilities of superfetation unlikely [5, 6]. The physiology of superfetation is not well understood.

Figure 1.

Site of implantation of dizygotic multiple pregnancy.

3. Intra uterine dizygotic multiple pregnancy

Implantation of all the embryos inside the endometrial cavity. This is the most common type of all multiple pregnancies. There may be two or more fetuses. The naming of the subtype depends on the number of fetuses (see Table 1).

One fetus	singleton
Two fetuses	Twins
Three fetuses	Triplets
Four fetuses	Quadruplets
Five fetuses	Quintuplets
Six fetuses	Sextuplets
Seven fetuses	Septuplets
Eight fetuses	Octuplets
Nine fetuses	Nonuplets
Ten fetuses	decuplets

Table 1.

Subtypes of multiple pregnancy.

4. Dicavitary multiple pregnancy

This is a type of multiple pregnancy occurring in a woman with embryological developmental malformation of the Mullerian or Wolffian ducts, characterized by complete failure of Mullerian ducts to fuse, resulting in two separate uterine cavities and cervices (Figures 2 and 3). There may associated vaginal anomalies like septum which may be longitudinal or transverse [7]. The anomalies may of different degrees with either fully developed or under developed and each with separate fallopian tube and endometrial cavity [8, 9]. Both uterine horns achieve a pregnancy at the same time when double ovulation has taken place (Figure 4). This only follows dizygotic multiple pregnancy and not possible with monozygotic pregnancy.

Figure 2.

Uterine didelphus.

Figure 3.

Uterine anomaly.

Figure 4.

Pregnancy on each uterus.

5. Heterotopic pregnancy

This refers to the occurrence of two pregnancies in different implantation sites simultaneously, mostly manifested as intrauterine and ectopic pregnancies 9ampullary in 80%). Heterotopic pregnancy is rare and estimated to occur in about 1 per 30,000 (0.006%–0.001%) spontaneous pregnancies while a higher prevalence may occur in assisted reproductive techniques that may reach up to 1 case per 100 cases (1–3%) (Figure 5) [10, 11].

Figure 5.

Heterotopic oregnancy.

Another rare combination of heterotopic pregnancy is a combination of intrauterine and ovarian [12]. The occurrence of an ovarian heterotopic pregnancy is a singular event as it comprises only 2.35 of all heterotopic pregnancies. However, in the last decade there has been a significant increase of ectopic pregnancy and subsequent increase in heterotopic pregnancy. This increase has been attributed to higher incidence of pelvic inflammatory disease and the extended use of assisted reproductive technologies [12]. The implantation outside the endometrial cavity can be anywhere including any part of the fallopian tube, ovary and any part of peritoneal cavity as indicated on Figure 6.

Figure 6.

Different sites for heterotopic pregnancy.

6. Twin ectopic pregnancy

In ectopic pregnancy, the implantation occurs outside the uterine cavity post fertilization, either in singleton or multi-gestational ectopic pregnancy. The incidence of twin ectopic pregnancies is quite rare and is estimated to be 1 in 125,000 pregnancies and that of twin tubal pregnancies to be 1 in 200 ectopic pregnancies (Figure 7) [13, 14, 15].

Figure 7.

Twin ectopic pregnancy.

7. Monozygotic multiple pregnancy

Monozygotic (MZ) twins, also called identical twins, occur when a single egg cell is fertilized by a single sperm cell. The resulting zygote splits into two very early in development, leading to the formation of two separate embryos. MZ twins occur in 3–4 per 1000 births worldwide. Research suggests that most cases of MZ twinning are not caused by genetic factors. However, a few families with a larger-than-expected number of MZ twins have been reported, which indicates that genetics may play a role. It is possible that genes involved in sticking cells together (cell adhesion) may contribute to MZ twinning, although this hypothesis has not been confirmed. Most of the time, the cause of MZ twinning is unknown [16].

The theory proposes that monozygotic twin are formed when the blastocyst contains two inner cell masses, each of which lead to a separate fetus rather than by the embryo splitting while hatching from the zona pellucida. Monozygotic twins may be created artificially by embryo splitting. Monozygotic twins are genetically nearly identical and are always of the same sex unless there has been a mutation during development [16]. The timing of the division determines the chorionicity and amnionicity. Chorionicity refers to the placenta and amnionicity to amniotic sac on whether they are shared by the twins or not as indicated on Figure 8.

Figure 8.

Dichorionic diamniotic multiple pregnancy from monozygotic twins.

When the division occurs within 3 days of fertilization, a dichorionic twin pregnancy results, when the division occurs between 4 and 8 days a monochorionic diamniotic twin pregnancy develops and when division occurs from day 8 until day 12 or 13 the monochorionic mono amniotic twin pregnancy develops. After day 13 the division leads to conjoined twins. All this means is that the placenta is determined within 3 days otherwise no further division could take place after this period in regard to the placenta. Amniotic sac is determined between day 4 and day 8 after fertilization and complete fetal division within 12–13 days [17].

Monozygotic multiple pregnancies are not genetically inherited. The twinning is random, due to the splitting of the embryo, so all parents have equal chance of conceiving these types of twins [18]. The rate of monozygotic twins is 2,25 times higher in assisted conceptions than natural conceptions. Monozygotic twins have a chorionicity that relates to how early the fertilized egg divides. Of the live born twins 70–75% are monochorionic diamniotic, 25–30% are dichorionic diamniotic and 1% are monochorionic monoamniotic [19, 20].

Division of the fertilized ovum occurs within 3 days. Placental development is independent of each other, though genetic material is identical. This constitutes 25 to 30 percent of monozygotic twins [19].

8. Monochorionic diamniotic multiple pregnancy

This is the commonest type of twin pregnancy arising from monozygotic multiple pregnancy as its occurrence is 70–75%. The fetuses share a placenta but have different amniotic sacs. The division takes place between 4 and 8 days after fertilization. Overall 1 in 3 spontaneous twins or 1 in 300 pregnancies become monochorioninic diamniotic.

9. Monochorionic monoamniotic twins

This is the least common type of multiple pregnancies as it is just around 1% of all monochorionic multiple pregnancies. This type of multiple pregnancy is associated the highest rate of congenital anomalies starting with vascular malformation to conjoined twins.

10. Conclusion

Multiple pregnancy refers to conception with more than one embryo. There are different types of multiple pregnancy depending on the site of implantation and the number of embryos. Multiple pregnancy can develop from fertilization of more than one embryo (dizygotic) or from division of a single fertilized embryo (monozygotic). Dizygotic embryos have different genetic makeup while monozygotic embryos have almost the same genetic makeup unless mutation has taken place during development. Dizygotic multiple pregnancy is more common than monozygotic pregnancies because of assisted reproductive technology. The division of the embryo is guided by the time of division to achieve a particular type of monozygotic multiple pregnancy. Monochorionic multiple pregnancy is the commonest type of monozygotic multiple pregnancy compared to dichorionic and monoamniotic types.