Disorders of Early Pregnancy

Question 1

What is the range of estimates for loss before implantation/pregnancy detection?

Answer 1

1. Probably ~40% but uncertain

2. Estimates range 30% - 75% loss before implantation

Question 2

What is the total loss between fertilisation and birth estimated?

Answer 2

between 46% - 90%

Question 3

What are the monthly probability of conception?

Answer 3

• 15-25%

- So very high estimates (>80%) of loss are unlikely

Question 4

What are the number of loss after clinically determined pregnancy?

Answer 4

1. 10% of all clinically-recognized pregnancies lost

2. 80% of those losses occur in the first trimester

Question 5

What is the cause of maternal age increasing risk of of miscarriage?

Answer 5

1. loss of cohesion between homologous chromosomes in oocyte with increasing age
2. loss of proteins (cohesins) holding homologues together

Question 6

What is a recurrent miscarriage?

Answer 6

loss of three or more consecutive pregnancies, affects 1% of couples trying to conceive

Question 7

What is recurrent implantation failure?

Answer 7

cases in which women have had three failed in vitro fertilization (IVF) attempts with good quality embryos

Question 8

What is the key difference between recurrent implantation failure and recurrent miscarriage?

Answer 8

Failure to implant or sustain pregnancy by natural conception (recurrent miscarriage) vs failure of transferred embryo to implant/sustain pregnancy (RIF)

Question 9

What are the initial diagnostic approaches for recurrent implantation failure and recurrent miscarriage?

Answer 9

-same (possible common/overlapping causes):
1,. check for uterine anatomical defects or presence of fibroids/polyps that might disrupt implantation
2. Determine presence of auto-immune antibodies (anti-nuclear, anti-phospholipid antibodies)
3. Test for paternal DNA sperm integrity/fragmentation?

Question 10

What is LIF?

Answer 10

leukemia inhibitory factor (cytokine)

Question 11

What signalling pathways may underpin RM/RIF?

Answer 11

1. Normal embryo development but failed implantation in Lif-deficient mouse models
2. LIF promotes decidulaisation of human endometrial stromal cells in culture
3. Reduced LIF in the uterine secretions of subfertile women

Question 12

What is endometrial scratching?

Answer 12

use of pipette or hysteroscope to damage endometrial mucosa before embryo transfer in IVF

Question 13

What is the mechanism of endometrial scratching?

Answer 13

mechanism unknown but thought to stimulate immune cell infiltration and wound healing cytokine production

Question 14

When is endometrial scratching beneficial?

Answer 14

1. Evidence in support variable – possible benefit in selected groups (eg RIF)
2. Large NZ study suggests no benefit in any group

Question 15

What are the smooth muscle adaptations in fallopian tubes?

Answer 15

contractions drive embryo along the fallopian tube

Question 16

What are the epithelial fallopian tube adaptations?

Answer 16

Epthilium coated in cilia (microvilli) to promote fluid movement

Question 17

What is continine?

Answer 17

1. component of cigarette smoke

2. shown to regulate the expression of PROKR1 a regulator of fallopian tube smooth muscle contractility

Question 18

How else does continine affect fallopian tubes?

Answer 18

increases expression of pro-apopotic proteins in fallopian tube explants

Question 19

How does tobacco smoke affect fallopian tubes?

Answer 19

• likely to inhibit ciliary function
• reducing transit of the embryo through the tube.
• Epidemiological studies: OR: 1.7-4 for tubal pregnancy in smokers

Question 20

What receptors are expressed in fallopian tube?

Answer 20

expresses CB1 and CB2 cannabinoid receptors

Question 21

How does CB1 affect pregnancies?

Answer 21

• CB1 reduced in ectopic pregnancy patients

- CB1 KO in mice causes embryo retention in the fallopian tubes.

Question 22

Levels of what are elevated in ectopic pregnancy fallopian tubes?

Answer 22

endocannabinoids

Question 23

How does components such as THC in cannibas affect fallopian tubes?

Answer 23

may act directly on the fallopian tube to peturb transit, or alter the balance of endocannabinoids (the ‘endocannabinoid tone’) in the tube leading to a disrupted embryo environment