implantation disorders Flashcards
what 3 numbers are used to grade embryos?
1st - number of cells
2nd - degree of idealised blastomeres
3rd - degree of fragmentation
higher numerical score = good quality embryo
lower numerical score = poor quality embryo
what numbers are given for what percentage of fragmentation in embryos to grade them?
4 = < 10% 3 = 10-20% 2 = 20-50 % 1 = >50%
what are the stages of embryo development?
- pronuclear stage (1 day after retrieval)
- 2 cell stage (1.5 days after retrieval)
- 4 cell stage (2 days after retrieval)
- 8 cell stage (3 days after retrieval)
- Morula (4 days after retrieval)
- Early blastocyst (5 days after retrieval)
- Expanded blastocyst (5.5 - 6 days after retrieval)
what are the three parts of a blastocyst?
bloastocoel
trophoectroderm
inner cell mass
when does the blastocyst hatch from the bona pellucid?
days 6-7
how is a blastocyst graded?
graded 1 - 4 according to degree of expansion (and 5-6 degree of hatching)
Blastocysts of grades 3 or higher are further graded A-D for Inner Cell Mass (ICM) and Trophectoderm
A - Tightly packed, many cells. ICM easily seen and consisting of many cells. Many small cells form a continuous trophectoderm.
B - Loosely packed, several. trophectoderm has few cells with gaps- not a continuous layer
C - Very few cells - icm barley visible and hard to distinguish from trophectoderm. fewer small cells with more large cells. Cells do not form a continuous layer.
D – Degenerating cells - no visible icm, or presence of bectrotic cells. Trophectoderm - very few cells or degenerate cells.
what is implantation?
implantation in the series of stages including blastocyst hatching, adhesion, endometrial invasion and growth to produce a stage of clinical pregnancy.
what is implantation rate ?
number of embryos implanted out of number transferred over a period,
what is repeated implantation failure?
failure to achieve clinical pregnancy - following the transfer of at least 4 embryo, at least 3 transfer cycles in which embryos were good quality, in woman
what are the possible outcomes of IVF
- ongoing clinical pregnancy
- cycle cancellation
- miscarriage
- failed implantation
- failed fertilisation
- ectopic pregnancy
- biochemical pregnancy
what happens during day 5-10 after fertilisation?
day 5 - free floating blastocyst in utero
day 6 - blastocyst hatching - start of implantation window
day 7 - blastocyst apposition to endometrium at the beginning of implantation window
day 8 - blastocyst adhesion occurring when LIF is maximal expressed and blastocyst expresses LIF receptor
Day 9 - blastocyst invasion
day 10 - implantation complete (end of the implantation window)
what is implantation?
differentiation of trophoblast cells into inner city-trophoblast and outer syncto-trophoblast layers and invasion into the luminal epithelium, where the blastocyst the commences to secrete cytokine such as IL1 which stimulates LIF expression in the endometrium.
what are the causes of implantation failure?
embryo actors - sperm/egg factors endometrium uterine tubal endocrine immune IVF lab factors
what IVF lab factors can affect implantation?
handling of eggs insemination incubation conditions aldehydes cheap culture media culture dishes embryo transfer catheters exposure of embryos to light
what are the contributors to poor embryo quality?
poor sperm (unexplained, iatrogenic (surgery, radiation) chromosomal/genetic, congenital/varicocele) reduced ovarian reserve (age, iatrogenic, chromosomal/genetic, congenital)
what are possible endometrial factors that may cause implantation failure?
unexplained poor endometrial development infections polyps submucosal fibroids congenital (uterine septa) uterine syenchia
endocrine factors which may affect implantation?
poorly condtrolled diabetes mellitus
poorly controlled thyroid disease
PCOS
premature ovarian failure
uterine/tubal factors that affect implantation?
uterine fibroids, adenomyosis, mullein dysgenesis.
hydrosalpinges
immune disorders which may affect implantation?
autoimmune thyroid disease
autoimmune gonadal disease
abnormal endometrium cytokines (elevated NK cells in endometrium)
antiphospholipid syndrome
what test can be used to investigate implantation failure?
- FSH, AMH, astral follicle count (ovarian reserve tests)
- testosterone index, SHBG and free androgen index (PCOS)
- thyroid peroxidase antibodies and TSH (thyroid disorder, autoimmune disorders)
- glycosylated haemoglobin (Hba1C) (DM)
- pelvic USS, hysterosalpingography - (uterine, endometrial, tubal or ovarian factors)
- lupus anticoagulant, antiphospholipid antibodies (lupus, antiphospholipid syndrome)
test for embryo implantation that have doubtful value?
- sperm DNA fragmentation
- endometrial NK cells
- Blood for pNK cells
what are general measures which improve embryo quality?
encourage couples to try early good diet stop smoking reduce alcohol weight control
what are specific measure to improve embryo quality?
- sperm DNA fragmentation tests (done in private clinics)
- insemination by ICSI/IMSI
- ovarian stimulation protocol
- assisted hatching
- gamete donation
- careful embryo selection
- blastocyst transfer (embryoscope)
- improve embryo transfer techniques
What is antiphospholid syndrome?
a systemic autoimmune disease characterised by vascular thrombosis and pregnancy morbidity in the persistent presence of antiphospholipid antibodies
APS is strongly linked to recurrent miscarriages.
what 3 tests are used evaluate antiphospholipid antibodies?
- antibodies against beta-2 glycoprotein
- antibodies against cardiolipin (aCL)
- lupus anticoagulant (LA)
how do antiphospholipid antibodies affect pregnancy?
- they cause defective placentation by interacting with both sides of the placenta
- at the decidual level aPL is pro inflammatory with neutrophil infiltration, secretion of cytokines and complement activation.
- at the trophoblast level aPL down regulates hGG, intergrins, cadherins, resulting in decreased trophoblast proliferation and growth
does treatment of APS improve recurrent miscarriage and implantation failure?
it improves RCM
does not improve implantation failure.
what are the causes of endometrial fluid?
ovarian stimulation (uterine or cervical)
high dose oestrogen
low oestrogen
hydrosalpinges
endometrial problems (polyp or fibroid, ashermans synechia, cervical stenosis, chronic infection)
