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M6112 > L9: Embryo Implantation Disorders > Flashcards

L9: Embryo Implantation Disorders Flashcards

1
Q

How is an embryo graded?

A
  • Grade 1 to 4 (good to bad)
  • Considers size distribution and level of fragmentation
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2
Q

How is a blastocyst graded?

A
  • 1 - 4 according to degree of expansion
  • If 3+ -> A-C for inner cell mass and trophectoderm
  • A: tightly packed, many cells
  • B: Loosely packed, several cells
  • C: Very few cells
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3
Q

Define embryo:

A
  • Discrete entities arising from the first completed mitotic division after fertilisation
  • Develops from a zygote
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4
Q

List all of the stages that implanation encompasses:

A
  • Free-floating blastocyst -> blastocyst hatching
  • Apposition then adhesion (Start of WOI)
  • Endometrial invasion
  • Embryo differentiation and growth (End of WOI)
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5
Q

Embryo-endometrium communication once implantation is complete:

A
  • Blastocyst, once implanted into epithelium of endometrium, secretes cytokines like IL-1
  • This, in turn, stimulates LIF expression in the endometrium
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6
Q

Define implantation rate:

A
  • Number implanted out of number transferred over a period -> KPI
  • Usually measured by number of gestation sacs on scans
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7
Q

Fully define recurrent
implantation failure: (4 parameters)

A
  • Failure to achieve clinical pregnancy after….
  • Transfer of at least 4 embryos
  • In at last 3 transfer cycles (fresh/frozen)
  • Good quality embryos
  • Woman under 40
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8
Q

Define implantation failure:

A
  • Failure to reach a stage in which there is ultrasound evidence of intrauterine pregnancy
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9
Q

List 6 outcomes causing repeated IVF failure:

A
  • Cycle cancellation (various reasons)
  • Failed fertilisation
  • Failed implantation
  • Biochemical pregnancy
  • Clinical miscarriage
  • Ectopic pregnancy
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10
Q

What 5 lifestyle factors can impact embryo quality (women):

A
  • Age
  • Diet and supplements (folate and vitamin D both pro-implantation)
  • BMI may reduce implantation (<18, >30)
  • Smoking (increases FSH dose, reduce egg yield, embryo quality and implantation)
  • Stress (cause-effect relationship difficult to establish)
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11
Q

What 4 factors contribute to poor sperm quality?

A
  • Iatrogenic (surgery, radiation etc)
  • Chromosomal / genetics
  • Congenital / varicocele
  • Lifestyle factors (including chemical exposure such as anabolic steroid use or occupational substance exposure)
  • Note that a large proportion of poor sperm goes unexplained
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12
Q

What factors reduce egg quality? (x2)

A
  • Reduced ovarian reserve (age, iatrogenic, chromosomal / genetic, congenital)
  • Issues with cumulus cells
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13
Q

What factors in the laboratory might negatively impact implantation rate? (list 7)

A
  • Stimulation protocol (serum Pr at hCG trigger)
  • Handling of eggs (number of flushes, denuding etc, ICSI vs IVF)
  • Aldehydes / noxious volatile organic compounds
  • Cheap culture media, culture dish and embryo transfer catheters
  • Exposure of embryos to light
  • Incubator conditions (controlled pH, thermal environment)
  • Embryo transfer technique (operator experience)
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14
Q

Give some examples of endometrial factors for implantation failure: (x7)

A
  • Poor endometrial development
  • Infection (e.g. after previous pregnancy or injury)
  • Polyps
  • Submucous fibroids
  • Uterine synechia (uterine walls adhere)
  • Adenomysosis (endometrial tissue grows into muscular wall)
  • Congenital (e.g. uterine septa, can be caused by mullerian dysgenesis)
  • N.B. Endometrial factors largely unexplained
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15
Q

Tubal factor for implantation failure:

A
  • Hydrosalpinges (damaged tubes leak water)
  • Blockage due to infection (gonorrhea, chlamydia)
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16
Q

List some immune factors for implantation failure: (x4)

A
  • Poorly controlled thyroid disease (Hashimoto etc)
  • Poorly controlled diabetes mellitus
  • PCOS
  • Premature ovarian failure
17
Q

List some immune disorders which can cause implantation failure:

A
  • Autoimmune thyroid disorders (hashimoto)
  • Autoimmune gonadal diseases (addison’s)
  • Abnormal endometrial cytokines (e.g. elevated NK cells in endometrium)
  • Antiphospholipid syndrome (APS)/thrombophilia
18
Q

Common chemical tests after implantation failure: (grouped by diagnosis/es)

A
  • FSH, AMH, antral follicle count -> ovarian reserve, autoimmune ovarian disorders
  • Testosterone, SHBG, Free androgen index -> PCOS
  • Thyroid peroxidase antibody, TSH -> thyroid disorder, autoimmune disorder (hereditable/acquired)
  • Lupus anticoagulant, Antiphospholipid Ab -> Lupus, APS aka thrombophilia
  • Glycosylated haemoglobin (Hb A1C) -> diabetes
19
Q

First line tests after implantation failure (anatomical): (x2)

A
  • Pelvic ultrasound (TVS/TAS)
  • Hysterosalpingography
20
Q

Second line tests after implantation failure:

A
  • Hysteroscopy and/or laproscopy (confirming uterine/endometrial/tubal or ovarian factor)
  • Parental karyotyping (if strongly indicated only)
21
Q

Give 3 further fertility tests with doubtful clinical value:

A
  • Sperm DNA fragmentation test
  • Endometrial sampling for natural killer (uNK) cells
  • Blood for pNK cells
  • Note: These tests are still informative in research setting
22
Q

List some general measures to take in order to improve embryo quality:

A
  • Encourage couple to try early
  • Good diet
  • Reduce/eliminate cigarette smoking
  • Reduce alcohol
  • Weight control (difficult in some cases e.g. PCOS, due to interaction of condition with metabolism)
23
Q

Name two procedural measures that could improve embryo quality alongside embryo selection:

A
  • Coculture with cumulus
  • Assisted hatching
  • In some cases, outsourcing the gamete is necessary -> donation (e.g. for parental aneuploidies)
  • In sperm factors, issue may be circumvented using ICSI
24
Q

When might TESA/TESE be applied:

A
  • In cases where sperm DNA fragmentation is strongly suspected
25
Q

Define APS (thrombophilia):

A
  • A systemic autoimmune disease characterised by vascular thrombosis and/or pregnancy morbidity in the persistent presence of antiphospholipid antibodies (aPL)
26
Q

How do we test for aPL? (x3)

A
  • Lupus anticoagulant (LA)
  • Abs against beta-2 glycoprotein I
  • Abs against cardiolipin (aCL)
  • Any positive results would need retesting over time before a diagnosis could be reached
27
Q

How does aPL affect placentation and pregnancy outcomes?
Treatment?

A
  • aPL is able to interact with both sides of the placenta
  • At the decidual level, it is proinflammatory with neutrophil infiltration, secretion of cytokines and complement activation
  • At trophoblast level, it downregulates hCG, integrins and cadherins resulting in reduced trophoblast proliferation and growth
  • APS is thus strongly linked to recurrent miscarriages, but not with implantation failure
  • Treat with LMWH and aspirin
28
Q

What is thyroid autoimmunity and how is it treated?

A
  • Presence of autoantibodies against thyroid peroxidase (TPO) and/or thyroglobulin (TG)
  • Associated with recurrent implantation failure
  • Treated with thyroxine supplements
29
Q

What are uNK cells?

A
  • Related to natural killer cells (subpopulation of lymphocyte in peripheral blood)
  • uNK found in in uterine lining at implantation
  • Function essentially unknown but suggested to regulate placentation and trophoblast cell invasion
  • Consequently, uNK tests have no agreed range of normality and there is no agreed treatment protocol
30
Q

What can cause excess fluid in endometrium:

A
  • Excess ovarian stimulation -> high dose oestrogen
  • Low dose oestrogen
  • Tubal factors (hydrosalpinges)
  • Endometrial factors (poylp/fibroid/synechia. cervical stenosis/infection)
  • Other/unknown
31
Q

Why might diagnostic hysteroscopy be used in a clinic?

A
  • Geographical difference in success rate of other tests (particularly reliability of USS)
  • e.g. UK, not justified
  • e.g. developing countries (Nigeria) where USS less reliable
  • In cases of recurrent implantation failure
32
Q

How are polyps managed before vs during fertility treatment?

A
  • If detected before further IVF: Remove (see below)
  • If detected during stimulation: Freeze all
  • If detected during egg collection or after: If >1cm, freeze all, if very small and poor embryo, transfer
  • Research provides mixed evidence for clinical value
  • Convincing evidence shows that hysteroscopic polypectomy is significantly more effective than diagnostic hysteroscopy + biopsy only prior to IVF
33
Q

Management of fibroids before and during IVF treatment:

A
  • If detected before IVF: Remove using hysteroscopic myomectomy -> convincing research evidence
  • If detected during stimulation: Freeze all
  • If detected during egg collection or after: If significant distortion of endometrium, freeze all, If very small, low and type-2 - consider transfer
  • N.B. Skillfull and cautious removal is key as can have iatrogenic impact on fertility
34
Q

Effect of uterine septum on pregnancy:

A
  • Doesn’t prevent pregnancy itself but does affect miscarriage rates
35
Q

Treatment for hydrosalpinges, efficacy:

A
  • Salpingectomy/tubal clipping
  • Before: 15% LBR -> after: 30% LBR
  • Rate of pregnancy and implantation also improved by treatment
36
Q

What are some diagnoses that may result in poorly developed endometrium?

A
  • Poor ovarian reserve / POF (age or otherwise e.g. FXPOI)
  • Iatrogenic (medical, radiation)
  • Endometrial (asherman’s synechia, chronic infection)
  • Uterine fibroids
  • Adenomysosis
  • Other
37
Q

Quality of evidence for hysteroscopic surgery of asherman synechia:

A
  • Relatively convincing
38
Q

What are fibroids, polyps and adenomyosis?

A
  • Polyps: Benign proliferation of endometrial tissue which is not removed in menses
  • Fibroids: Proliferation of connective tissue/muscle
  • Adenomyosis: endometrial tissue growing into myometrium
39
Q

Effect of smoking on fertility on various processes/organs:

A
  • Ovary: early menopause and poor quality oocytes
  • Steroidogenesis: Decreased oestrogen and progesterone, increased androgens
  • Oviduct: Increased ectopic pregnancy, effects on oviductal smooth muscles
  • Uterus/implantation: delayed implantation, decreased uterine receptivity
  • Menstrual cycle: increase oligomenorrhea, dysmenorrhea, heavy bleeding

M6112 (15 decks)

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