Disorders of Early Development Flashcards
Recurrent miscarriage/recurrent pregnancy loss
UK - three or more pregnancy losses (consecutive or or non-consecutive)
USA/Europe - two or more pregnancy losses (con or non-con)
0.8-1.4% pregnancies
Proportion of conceptions lost before pregnancy is detectable by ultrasound scan
60%
Major underlying cause of most pregnancy losses that occur before 12 weeks gestation
Aneuploidy - chromosome number errors
Why does aneuploidy increase with maternal age
Throughout f meiotic arrest, chromatids of homologous chromosomes are held together by cohesin proteins
These proteins are not replaced, leading to loss of cohesion between chromatids with increasing age of oocyte
If cohesion has been lost, chromatids can separate and drift during meiotic division, rather than being segregated accurately by spindle
Benign GTD
Complete hydatidiform moles - Fetal tissue absent
Partial hydatidiform moles - Fetal tissue present
Causes of pregnancy loss
Errors in embryo-fetal development
Failure of embryo to implant in uterine lining
Inability to sustain development of implanted embryo/fetus
Miscarriage
Loss of pregnancy prior to ~23 weeks gestation
Early clinical pregnancy loss - <12 weeks gestation
Late clinical pregnancy loss - >24 weeks gestation
After 23 weeks there is potential for foetus to survive outside of womb
Signalling pathway that underpin recurrent pregnancy loss in humans
LIF pathway
Normal embryo development but failed implantation in LIF-deficient mouse models
Reduced levels of LIF in uterine secretion of subfertile women
Meiosis in oocyte
Paternal and maternal homologous chromosomes pair up, and DNA is replicated generating two chromatids per chromosome
Genetic material is exchanged between homologues through recombination
Meiosis then arrests, resuming just before ovulation (up to 50 years later)
Non-selective uterus hypothesis
Uterus permits implantation of poor quality embryos
Changes in uterine mucin expression in women with RM/RPL
Genomic imprinting
Some genes only expressed from paternally-inherited copy - promote embryo fitness at the expense of mother
Some genes only expressed from maternally-inherited copy - restrict embryo fitness to conserve resources for future pregnancies
Gestational trophoblastic disease
Collection of disorders characterised by overgrowth of trophoblastic tissue
Malignant GTD
Following ~20% cases of hydatidiform moles
Rare - invasive mole and choriocarcinoma
Very rare - placental site trophoblastic tumour and epithelioid trophoblastic tumour
How do complete hydatidiform moles form
Empty egg fertilised by 1x sperm then sperm genome duplicated or 2x sperm with no duplication
How do partial hydatidiform moles form
Normal egg fertilised by 1x sperm then sperm genome duplicated or 2x sperm with no duplication
