• Physiology of fertilization, implantation and placenta formation
  
• Classification of multiple pregnancy
  
• Assisted reproductive technology
  
• Incidence of multiple pregnancies
  
• Parental counselling
  
• Complications of multiple pregnancy

Introduction

Multiple pregnancies are a common problem in the neonatal nursery. Rates have increased since the introduction of assisted reproductive technology (ART). This chapter briefly discusses the physiology of fertilization and placenta formation and their relevance in multiple gestations. Specific complications of multiple gestations are discussed in detail.

Physiology of Fertilization, Implantation and Placenta Formation

Fertilization

Normal fertilization occurs in the fallopian tube. Once a sperm enters the ovum, the process of rapid mitotic cell division begins. At about 3 days a ball of 12–16 blastomeres enters the uterine cavity and is called a morula. Cell division continues and spaces begin to appear between the cells within the morula forming the blastocyst cavity. The outer surface of this cavity (called the trophoblast) has two layers, an inner cytotrophoblast and outer syncytiotrophoblast. At this point the embryo is referred to as a blastocyst.

Implantation

At about 6 days after fertilization, the syncytiotrophoblast comes into contact with the uterine epithelium. If conditions are favourable, there is rapid proliferation and erosion into the endometrium. The process of eroding into the endometrium is referred to as implantation. As cell division of the cytotrophoblast continues a small space appears between the inner cell mass and the outer layers; this is the beginning of the amniotic cavity. The inner cell mass will ultimately go on to form the embryo and amnion. The outer layers will go on to form the chorion and placenta. The cells in between the outer cytotrophoblast and inner cell mass are the extraembryonic mesoderm. Spaces (the chorionic cavity) then also develop in the extraembryonic mesoderm forming the extraembryonic somatic mesoderm which lines the trophoblast and covers the amnion, and the extraembryonic splanchnic mesoderm which surrounds the yolk sac.

Placenta

After implantation the syncytiotrophoblast erodes the endometrial blood vessels allowing maternal blood to form networks of lacunae. These networks are the beginning of the decidual (or maternal) layer of the placenta. The fetal layer of the placenta is due to proliferation of the synctiotrophoblasts and formation of the primary chorionic villi at approximately 2 weeks after fertilization. The external layers of the trophoblast and the extraembryonic somatic mesoderm constitute the chorion.

Amniotic Cavity

The chorion forms the chorionic sac and within lies the embryo, in its amniotic sac. The amniotic sac continues to enlarge much faster than the chorionic sac. This causes their walls to fuse, obliterating the chorionic cavity and forming the amniochorionic membrane which in turn comes in contact with the decidual layer of the placenta. The developing embryo is now suspended from the placenta by the umbilical cord and is contained within the amniotic cavity.

Classification of Multiple Pregnancy

Multiple pregnancies are normally classified by the number of placentas and the number of amniotic sacs. A multiple pregnancy may arise from the spontaneous splitting of a single zygote (monozygotic) or through the fertilization of more than one oocyte (dizygotic). If they are dizygotic or if division occurs before implantation they will have separate placentas and separate amniotic cavities. If the division occurs after implantation then they will share the placenta (monochorionic) and either share the amniotic cavity (monoamniotic) or have their own (diamniotic). Higher-order multiples are usually multizygotic (from multiple ovum) but can arise from zygotic splitting and then resplitting again. They are also classified by the number of placentas and amniotic sacs. For example, triplets may each have their own placenta (trichorionic) and their own amnion (triamniotic) or may be combinations of the above.

Assisted Reproductive Technology

Assisted reproductive technologies essentially involve manipulation of the egg or sperm to facilitate pregnancy. Technically, ART does not include therapies that simply stimulate the ovaries to produce more eggs (e.g. clomiphene). Techniques include in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), gamete intrafallopian transfer (GIFT) and zygote intrafallopian transfer (ZIFT).

With the advent of ART there was an increased incidence of multiple-fetus pregnancies. This now appears to be falling again in the UK and Australia since the introduction of legislation and professional guidelines to limit the number of embryos transferred. This is not the case in other countries where no such legislation exists.

Incidence of Multiple Pregnancies

The incidence of multiple births was first studied by Hellin in 1895. Following this work the Hellinic law was described, which stated that the incidence of twins was 1/89 pregnancies and of triplets 1/89² (1/7921) and quadruplets 1/89³ (1/704 969). The actual incidence of multiple births varies greatly between countries due to differing rates of dizy­gotic twins. Factors influencing the increased rate of dizygotic twinning other than ART are maternal age 35–39 years, high parity, tall stature, periconceptual folate and familial factors (increased risk ×4 if mother, or ×2 if sister is a dizygotic twin). As opposed to dizygotic twins, the incidence of monozygotic twins is relatively stable occurring in approximately 3.5 per 1000 births. Reasons for the development of monozygotic twins are poorly understood. There is fivefold increased risk of monozygotic twinning of an IVF embryo.

Of all naturally conceived twins, 40% are monozygotic, and of all monozygotic twins, 63% are monochorionic diamniotic (MCDA), 33% are dichorionic diamniotic (DCDA) with either separate or fused placentas, and 4% are monochorionic monoamniotic (MCMA).

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