disorders of early development

Question 1

what are some causes of pregnancy loss (common in humans)

Answer 1

errors in embryo fetal development
failure of the embryo to implant in the uterine lining
inability to sustain development of an implanted embryo/fetus

Question 2

what is a miscarriage

Answer 2

loss of a pregnancy prior to ~23 weeks gestation

Question 3

when is early clinical pregnancy loss

Answer 3

<12 weeks gestation

Question 4

when is late clinical pregnancy loss

Answer 4

> 24 weekends

Question 5

what is recurrent miscarriage (RM)/Recurrent Pregnancy Loss (RPL)

Answer 5

3 or more losses (consecutive or nonconsecutive)

Question 6

what are the major causes of early pregnancy loss

Answer 6

major driver likely to be aneuploidy (chromosome number error) 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

Question 7

what can oocytes experience

Answer 7

oocytes are cells in the ovary which may undergo meiotic division to form an ovum
prolonged meiotic arrest

Question 8

when does recombination occur in testes and ovaries

Answer 8

two chromatids > exchange of genetic material (in testes, after recombination occurs - 1st and 2nd meiotic division occurs straight after) whereas (in ovaries, after recombination - goes into rest until ovulation)

Question 9

what do cohesin proteins do

Answer 9

throughout meiotic arrest, the chromatids of homologous chromosomes are held together by cohesin proteins

Question 10

how does cohesion get lost with increasing age

Answer 10

these cohesin proteins are not replaced, leading to loss of cohesion between chromatids with increasing age of the oocyte

Question 11

what happens when cohesion is lost

Answer 11

if cohesion has been lost, chromatids can separate and drift during meiotic division rather than being segregated accurately by the spindle

Question 12

what happens when some genes are only expressed from the paternally-inherited copy

Answer 12

promote embryo fitness at the expense of the mother (overgrowth of placenta)

Question 13

what happens when some genes only expressed from the maternally-inherited copy

Answer 13

restrict embryo fitness to conserve resources for future pregnancies (undergrowth of placenta)

Question 14

what are GTDs - Gestational Trophoblastic Diseases

Answer 14

GTDs are a collection of disorders characterised by overgrowth of trophoblastic tissue

Question 15

what are benign GTDs

Answer 15

hydatidiform moles

Question 16

what are complete hydatidiform moles

Answer 16

fetal tissue absent

Question 17

what are partial hydatidiform moles

Answer 17

fetal tissue present

Question 18

what are malignant GTDs

Answer 18

gestational trophoblastic neoplasias

Question 19

what are rare gestational trophoblastic neoplasias

Answer 19

invasive mole

choriocarcinoma

Question 20

what are very rare gestational trophoblastic neoplasias

Answer 20

placental site trophoblastic tumour (PSTT)

epithelioid trophoblastic tumour

Question 21

how do complete hydatidiform moles arise

Answer 21

empty egg fertilised by (no maternal DNA)
1x sperm then sperm genome duplicated
or 2x sperm and there is no duplication

Question 22

how do partial hydatidiform moles arise

Answer 22

normal egg fertilised by (maternal DNA)
1x sperm then sperm genome duplicated
or 2x sperm and no duplication

Question 23

failure to recognise and clear failed pregnancy?

Answer 23

HM they are benign and should be surgically removed, if left to develop further - can become cancerous

Question 24

what is ectopic pregnancy - extra-uterine implantation

Answer 24

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

Question 25

what is the treatment for ectopic pregnancy

Answer 25

treatment ranges from expectant management, through chemotherapy (methotrexate) to surgery to remove the trophoblast and/or tube
rupture can lead to severe internal bleeding

Question 26

what is the impact of smoking on the fallopian tube

Answer 26

fallopian tube is lined with cilia
cotinine, a component of cigarette smoke, regulates the expression of PROKR1, a cell surface receptor involved in regulating fallopian tube smooth muscle contractability
cotinine also induces pro-apoptosis (cell death) protein expression in fallopian tube explants
tobacco smoke inhibits cilia function&raquo_space; reduce tubal transit of the embryo

Question 27

what are the risk factors for ectopic pregnancy

Answer 27

prior ectopic pregnancy
prior fallopian tube surgery 
certain sexually transmitted infections (STIs)
pelvic inflammatory disease
endometriosis

cigarette smoking
cannabis use?
age older than 35 years
history of infertility
use of assisted reproductive technology, such as in vitro fertilisation (IVF)