Lecture 12 - Embryo and implantation disorders Flashcards
What is an embryo?
Discrete entity arising from first mitotic division after fertilisation
What does the embryo develop from?
A zygote
What is the new grading system?
3 numbers
- Number of cells
- Degree of idealised blastomeres (4 is good and 1 is bad)
- Degree of fragmentation (4 is good and 1 is bad)
What is a blastocyst?
5-8 day old embryo with some differentiation (ICM and TE)
When does hatching occur?
Day 6-7
What happens at implantation?
Blastocyst hatching, adhesion, endometrial invasion, embryo differentiation and growth
What is the implantation rate?
Number of embryos implanted/number transferred over a period
What happens during failed implantation?
No intrauterine gestational sac
What is no pregnancy after 4 embryo transfers and 3 cycles classified as?
Repeated failed implantation
What are the possible outcomes of IVF?
- ongoing clinical pregnancy
- cycle cancellation
- failed fertilisation/implantation
- biochemical pregnancy
- clinical miscarriage
- ectopic pregnancy
How does the endometrium and embryo communicate?
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
How does implantation occur?
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
What are some contributing factors to implantation failure?
Embryo, endometrium, uterine, tubal, endocrine, immune dysfunction
Why might an embryo be poor quality?
Poor sperm - unexplained, iatrogenic, chromosomal/genetic, congenital/varicocele
Reduced ovarian reserve - age, iatrogenic, chr/genetic, congenital
What are some possible endometrial factors?
Unexplained, poor endo development, infections, polyps, submucous fibroids, uterine septa, uterine synechia
What are some possible uterine/tubal factors?
Uterine: fibroids, adenomyosis, mullerian dysgeneration
Tubal: hydroalspinges
What are some possible endocrine factors?
Thyroid disease, diabetes, PCOS, premature ovarian failure, immune disorders (thyroid, gonadal, abnorm endo cytokines, antiphospholipid syndrome (APS))
How do they test for repeated implantation failure?
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
What are some second line tests?
Hysteroscopy and/or laproscopy
Parental karyotyping
What are some tests other tests done to look for RIF? what are the issues with these tests?
Sperm DNA fragment test, endometrial sampling for uNK cells, blood sampling for pNK cells. These tests are of doubtful value
How can we improve embryo quality generally?
- Try early
- Havbe a good diet
- Reduce smoking and alcohol
- Control weight
What are some specific measures to improve embryo quality?
Sperm DNA fragmentation tests Ovarian stimulation protocol Gamete donation ICSI and IMSI Embryo selection Blastocsy trasnfer Assisted hatching Improved embryo transfer techniques
What is APS?
Antiphospholipid syndrome. Systemic autoimmune disease. Persistant presence of aPL abs leads to morbidity in pregnancy
What three tests are used to evaluate APS?
Ab against B-2 glycopt, abs against cardiolipin and lupus anticoag
