Trisomic Conceptus

Background:

– Spontaneous abortion and congenital malformation rates increase with maternal age (typically around 35 years)

-After 35, some thought to be caused by hormonal or anatomical defects

-Most are caused by chromosomal abnormalities, which increase with maternal age (see below)

-Oocytes are suspended mid prophase of meiosis I from birth until ovulation (could be many years)

-Also, over time oxidative stress accumulates, number of normal oocytes available for maturation decreases, and oocyte telomeres shorten, contributing to problem

-The chiasmata (visible connection between homologous chromosomes during the first meiotic division in gametogenesis) break down and chromosomes fall out of alignment

-This leads to nondisjunction

-When gamete divides the chromosomes:

-fail to pair up

-pair up properly but separate prematurely

-fail to separate

What is trisomic conceptus?

-A chromosomal defect, acquired at conception, in which the fetus has 3 homologs of any one chromosome

How could it be produced?

-Usually results from meiotic nondisjunction in meiosis I

-With ovulation, nondisjunction causes one gamete to have 2 copies of affected chromosome and the other to have 0

-Fertilization results in trisomy or monosomy

Risk of autosomal trisomy increases with maternal age (see figure)

-Nondisjunction affects male and female gametes at different frequencies

-3-4% of sperm

-10-20% of oocytes

-Can affect any chromosome pair – only trisomies 21, 18, and 13 can result in term pregnancy

-Other trisomies have severe abnormalities, resulting in very high rates of pregnancy loss

-Trisomy 1 has never been reported

-Trisomy 16 accounts for 16 percent of all first-trimester losses.  It is the most common autosomal trisomy and is always lethal

-Autosomal monosomy is universally incompatible with life

-Trisomy 21

-Down syndrome

-1 in 800-1000 newborns

-95% of cases from maternal nondisjunction

-Fetal death rate is 30% between 12 and 40 weeks and 20% between 16 and 40 weeks

-Trisomy 18

-Edwards syndrome

-1 in 8000 newborns

-85% of fetuses die between 10 and 40 weeks

-Median survival of 14 days, 10% live up to 1 year

-Trisomy 13

-Patau syndrome

-1 in 20,000 newborns

– Median survival rate of 7 days, 10% live up to 1 year