disorders of early fetal development Flashcards
what are the causes of pregnancy loss
Errors in embryo-fetal development
Failure of the embryo to implant in the uterine lining
Inability to sustain development of an implanted embryo/fetus
what defines a miscarriage
what defines an early pregnancy loss
what defines a late pregnancy loss
Miscarriage: loss of a pregnancy prior to ~23 weeks gestation
Early clinical pregnancy loss (<12 weeks gestation)
Late clinical pregnancy loss (<24 weeks gestation)
what defines a Recurrent Miscarriage (RM) / Recurrent Pregnancy Loss (RPL) in the UK and US
UK: three or more pregnancy losses (consecutive or non-consecutive)
USA/Europe: two or more pregnancy losses (consecutive or non-consecutive)
0.8-1.4% pregnancies
what percentage of pregnancies are lost in the two ways that are preclinical losses
what percentage of pregnancies are lost that are clinical losses
30% conceptions lost prior to implantation
30% following implantation but before the missed menstrual period (3-4wks gestation)
Clinical pregnancy losses
~15% of conceptions
10% in 20-24 year olds
51% in 40-44 year olds
what is the main reason for early pregnancy loss
why is there an exponential increase in risk with pregnancy loss with increasing maternal age
Major driver likely to be aneuploidy (chromosome number errors) in embryo
~53% embryos created using donor eggs in IVF are aneuploid
~50% of lost early pregnancies display chromosomal errors
Exponential increase in risk of trisomic pregnancy with increasing maternal age
why does increasing maternal age increase aneuploidy
meoisis arrests just before ovulation
some eggs remain in the arrested state for years (if not ovulated)
Throughout meiotic arrest, the chromatids of homologous chromosomes are held together by cohesin proteins which are lost over time
These cohesin proteins are not replaced, leading to loss of cohesion between chromatids with increasing age of the oocyte
If cohesion has been lost, chromatids can separate and drift during meiotic division, rather than being segregated accurately by the spindle.
what happens when a embryo is formed from genes only expressed from the paternally-inherited copy.
what happens when an embryo is formed from genes only expressed from the maternally-inherited copy.
Promote embryo fitness at the expense of the mother (suck out resources) - results in a large placenta and a tiny embryo
Restrict embryo fitness to conserve resources for future pregnancies- results in a normal sized embryo with a very small placenta
what are gestational trophoblastic disorders
what is a benign example of this
what two forms can they arise in
GTDs are a collection of disorders characterized by overgrowth of trophoblastic tissue
hydatidiform moles
Incidence of 1/500-1/1500 pregnancies, depending on geography.
Complete hydatidiform mole- Fetal tissue absent
Partial hydatidiform mole- Fetal tissue present
what are malignant examples of GTD
Malignant: -
Gestational Trophoblastic Neoplasias
Arise following ~20% of cases of hydatidiform mole
Rare:
Invasive mole
Choriocarcinoma
Very rare:
Placental Site Trophoblastic Tumour (PSTT)
Epithelioid Trophoblastic Tumour
how do complete hydatidform moles arise
how do recurrent hydatidiform moles arise
Complete hydatidiform mole Empty egg fertilised by: 1x sperm then sperm genome duplicated or 2x sperm (no duplication) resulting in an egg with two copies of paternal chromosome
NLRP7 mutations may underly recurrent hydatidiform moles
as it results in failure to recognize and clear failed pregnancy
how do Partial hydatidiform moles arise
Normal egg fertilized by:
1x sperm then sperm genome duplicated
or 2x sperm (no duplication)
resulting in 2 paternal copies of chromosome and one maternal
what is a ectopic pregnancy
where do most ectopic pregnancies occur and what other places do they occur
Implantation of the embryo at a site other than the uterine endometrium.
98% of these implantation events occur in the fallopian tube.
Other sites include ovary, cervix, other intra-abdominal sites.
how often do ectopic pregnancies occur in the population
what treatment options are there
why is treatment risky
Incidence of 1-1.5% of pregnancies
Treatment ranges from expectant management, through chemotherapy (methotrexate) to surgery to remove the trophoblast and/or tube.
Rupture can lead to severe internal bleeding.
how does smoking increase the risk of an ectopic pregnancy
Continine, a component of cigarette smoke, regulates the expression of PROKR1, a cell surface receptor involved in regulating fallopian tube smooth muscle contractility. (PROK proteins bind to receptors to stimulate contraction of fallopian tube to move egg along)
Cotinine also induces pro-apoptosis (cell death) protein expression in fallopian tube explants- causing a change in the fallopian tube environment which leads to ectopic pregnancy
Tobacco smoke inhibits cilia function»_space; reduce tubal transit of the embryo
how many times is smoking expected to increase the risk of an ectopic pregnancy
what are other risk factors of an ectopic pregnancy (to do with reproductive system)
2-4 times
Risk factors for ectopic pregnancy include:
Prior ectopic pregnancy Prior fallopian tube surgery Certainsexually transmitted infections (STIs) Pelvic inflammatory disease Endometriosis
