Sporadic miscarriage is the most common complication of early pregnancy. It is considered to primarily represent failure of abnormal embryos to progress to viability. Fewer than a third of all fertilization events result in successful pregnancy, even for young, fertile couples (Zinaman 1996, Wilcox 1998, Wang 2003).
An estimated 30% of human conceptions are lost prior to implantation and a further 30% following implantation but before the missed menstrual period, that is in the third or fourth week of gestation. These are often termed preclinical losses. This means that many pregnancies begin and end before the mother even notices. Finally, the incidence of early clinical pregnancy loss is estimated to be 15% of conceptions with a significant variation according to age. Thus, the incidence ranges from 10% in women aged 20 to 24 years to 51% in women aged 40 to 44 years (Nybo 2008). Late losses between 12 and 22 weeks occur less frequently and constitute around 4% of pregnancy outcomes.
(see also Pregnancy losss iceberg diagram, adapted from Chard 1991)
Reasons for the ‘physiological’ early pregnancy loss
The generally accepted explanation for sporadic pregnancy losses occurring before an embryo has developed represent a ‘physiological’ phenomenon. It prevents conceptions affected by serious structural malformations or chromosomal aberrations incompatible with life from progressing to viability. This concept is supported by clinical studies in which embryoscopy was used to assess fetal morphology prior to removal by uterine evacuation. Fetal malformations were observed in 85% of cases presenting with early clinical miscarriage (Philipp 2003). The same study also demonstrated that 75% of the fetuses had an abnormal karyotype (chromosome).
During fertilization, the sperm and egg fuse so that the resulting embryo will have 23 chromosomes inherited from the father and 23 chromosomes inherited from the mother. In normal circumstances, the subsequent cell divisions in the embryo (called mitotic divisions) simply replicate this 46-chromosome set as new cells are formed. Chromosomes contain genes, the blueprints for human development. When processes go awry in meiosis or mitosis, chromosomes can go into the wrong cell or get lost completely, drastically altering this blueprint. The resulting cell will not possess the standard 46-chromosome set – an imbalance or abnormal chromosome is formed (aneuploidy). This means that many genes will either be missing or present in extra copies, placing cells under stress.
Embryos with many aneuploid cells rarely survive. Trisomy 21, the genetic cause of Down syndrome, is one of the rare forms of aneuploidy in which the baby can survive to live birth. The vast majority of embryos affected with other aneuploidies perish in early development.
Aneuploidy is associated with maternal age. Female meiotic errors (these are errors in the eggs themselves) increase from a frequency of less than 20% in mothers younger than 30 years old to greater than 60% in mothers older than 45. Errors in sperm, called paternal meiotic errors, are comparatively rare, affecting fewer than 5% of sperm cells.
Reproductive failure is a common complication in early pregnancy, with up to two-thirds of all fertilized oocytes not producing live births. Thus, a large number of conceptions either fail to implant or are categorized as biochemical pregnancies and clinical miscarriages. Although, the incidence of karyotypic abnormalities in the parents is low, this high rate of early losses is most certainly connected to a high frequency of sporadic karyotypic abnormalities in the products of conception.
Larsen et al., BMC 2003
Nybo A et al., BMJ 2008
Philipp T et al., Hum Reprod 2003
Wang X et al., Fert Steril 2003
Wilcox AJ et al., NEJM 1998
Zinaman MJ et al., Fert Steril 1996