DDx Multiple Miscarriages

· “bad luck” (can easily occur by chance due to normal rate of miscarriage)

· ~78% of all conceptions fail to go to term

· 42% of implanted conceptions are lost

· 23% of pregnancies are lost following the first missed period

· Net overall fecundity for patients 20-30 y is 20-30%

· Most losses occur very early in gestation

· Parental chromosomal abnormality:

· Translocations are found in 0.5 % of couples with recurrent miscarriage (2-5% in some studies with some patient selection)

· Incidence in males is ~half of that in females likely due to increased risk of sterility (infertility)

· Lower risk for abnormal offspring for a male carrier, in general

· Compare to 0.2% incidence in newborns

· Typically the translocation is of sufficient size to be readily detectable by standard karyotype

· Cytogenetic analysis to rule out structural rearrangements and genetic counseling are indicated for couples who havef experienced two or more losses (although recurrent spontaneous abortion is often defined as three consecutive losses)

· Robertsonian translocations are the most frequent cause of unbalanced translocations in miscarriages

· Inversions

· others

· Risk of repeat miscarriage is slightly higher (23% vs. 16%) when the prior loss is chromosomally normal

· Recessive genes

· Gonadal mosaicism

· Satellite association

· Predisposition to recurrent aneuploidy (maternal)

· Maternal age

· Uterine abnormality

· Endocrine dysfunction

· Immunological disorders

· SLE

· Alloimmune disorders

· Parental sharing of HLA antigens

· Others

·

References:

· Gersen et al. The Principles of Clinical Cytogenetics, 2^nd ed. Humana, New Jersey, 2005.

· Gardner RJM & Sutherland G. Chromosom Abnormalities and Genetic Counselling, 3^rd ed. Oxford University Press (2004)

·