Lecture 12 - Embryo and implantation disorders Flashcards

1
Q

What is an embryo?

A

Discrete entity arising from first mitotic division after fertilisation

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2
Q

What does the embryo develop from?

A

A zygote

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3
Q

What is the new grading system?

A

3 numbers

  1. Number of cells
  2. Degree of idealised blastomeres (4 is good and 1 is bad)
  3. Degree of fragmentation (4 is good and 1 is bad)
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4
Q

What is a blastocyst?

A

5-8 day old embryo with some differentiation (ICM and TE)

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5
Q

When does hatching occur?

A

Day 6-7

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6
Q

What happens at implantation?

A

Blastocyst hatching, adhesion, endometrial invasion, embryo differentiation and growth

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7
Q

What is the implantation rate?

A

Number of embryos implanted/number transferred over a period

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8
Q

What happens during failed implantation?

A

No intrauterine gestational sac

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9
Q

What is no pregnancy after 4 embryo transfers and 3 cycles classified as?

A

Repeated failed implantation

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10
Q

What are the possible outcomes of IVF?

A
  • ongoing clinical pregnancy
  • cycle cancellation
  • failed fertilisation/implantation
  • biochemical pregnancy
  • clinical miscarriage
  • ectopic pregnancy
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11
Q

How does the endometrium and embryo communicate?

A

Day 5 - free floating blastocyst in utero
Day 6 - hatching (START OF WINDOW)
Day 7 - apposition to endo
Day 8 - adhesion; LIF expressed by endo and LIFR expressed by blasto
Day 9 - invasion
Day 10 - implantation complete; END OF WINDOW

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12
Q

How does implantation occur?

A

Trophoblast cells differentiate into inner cytotrophoblast and outer syncytiotrophoblast layers. Invasion into luminal epithelium. Blastocyst secretes cytokines e.g. IL-1 which stimulate LIF expression in endometrium

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13
Q

What are some contributing factors to implantation failure?

A

Embryo, endometrium, uterine, tubal, endocrine, immune dysfunction

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14
Q

Why might an embryo be poor quality?

A

Poor sperm - unexplained, iatrogenic, chromosomal/genetic, congenital/varicocele
Reduced ovarian reserve - age, iatrogenic, chr/genetic, congenital

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15
Q

What are some possible endometrial factors?

A

Unexplained, poor endo development, infections, polyps, submucous fibroids, uterine septa, uterine synechia

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16
Q

What are some possible uterine/tubal factors?

A

Uterine: fibroids, adenomyosis, mullerian dysgeneration
Tubal: hydroalspinges

17
Q

What are some possible endocrine factors?

A

Thyroid disease, diabetes, PCOS, premature ovarian failure, immune disorders (thyroid, gonadal, abnorm endo cytokines, antiphospholipid syndrome (APS))

18
Q

How do they test for repeated implantation failure?

A

Ovarian reserve: FSH, AMH, antral follicle count
PCOS: testosterone, SHBG, free androgen index
Thyroid/autoimmune disorder: Thyroid peroxidase ab, TSH
Lupus and APS: Lupus anticoag, antiPL ab
Diabetes: glycosylated Hb
Pelvic ultrasound for uterine/tubal factors

19
Q

What are some second line tests?

A

Hysteroscopy and/or laproscopy

Parental karyotyping

20
Q

What are some tests other tests done to look for RIF? what are the issues with these tests?

A

Sperm DNA fragment test, endometrial sampling for uNK cells, blood sampling for pNK cells. These tests are of doubtful value

21
Q

How can we improve embryo quality generally?

A
  • Try early
  • Havbe a good diet
  • Reduce smoking and alcohol
  • Control weight
22
Q

What are some specific measures to improve embryo quality?

A
Sperm DNA fragmentation tests 
Ovarian stimulation protocol
Gamete donation 
ICSI and IMSI
Embryo selection 
Blastocsy trasnfer 
Assisted hatching
Improved embryo transfer techniques
23
Q

What is APS?

A

Antiphospholipid syndrome. Systemic autoimmune disease. Persistant presence of aPL abs leads to morbidity in pregnancy

24
Q

What three tests are used to evaluate APS?

A

Ab against B-2 glycopt, abs against cardiolipin and lupus anticoag

25
Q

What does aPL do?

A

Causes defective placentation. At decidual level - proinflam, neutrophil infilt, secretion of cytokines and complement activation. At trophoblast level - aPL downregs hCG, integrins and cadherins result in decreased trophoblast prolif and growth

26
Q

What is APS strongly linked to and what is it not associated with?

A

Strongly linked to recurrent miscarriages. Not associated with implantation failure

27
Q

What autoimmune disease is associated with RIF?

A

Thyroid issues

28
Q

What are the causes of persistent endometrial fluid?

A

Ovarian stimulation, high dose oestrogen, low dose oestrogen, hydroalspinges (tubal), endometrial (polyps, fibroids, stenosis, infection)

29
Q

What does persistent endometrial fluid lead to?

A

Poorly developed endometrium