Conception & Sub-Fertility Flashcards
How much ejaculate does a male produce?
1.5-5ml
What is in male ejaculate?
- Seminal vesicles secretions: rich in fructose (nutrient), proteins, semen clotting factors, ILs and PG E
- Prostate gland secretions: PO4 and HCO3- buffers, PSA, coagulase (liquefying), zinc, citric acid, spermine, spermidine and putrescine
- Testicles and epididymis secretions: sperm, testosterone and L-carnitine (anti-oxidant affecting motility)
- Bulbourethral and urethral gland secretions: lubrication which can include anti-sperm Abs
What is the key characteristic of male ejaculate?
It is ALKALINE (pH 7.2) so must get out of the vagina quickly to survive the acidic environment
What concentration of white blood cells in the ejaculate indicates an infection?
> 5 million per ml
If a womens period is irregular, what phase is this usually in?
Follicular phase
What are the key characteristics of a mature human oocyte?
Oolemma
Ooplasm (contains nutrients)
Polar body
Zona pellucida
Arrested in metaphase II of meiosis ideally
What are the 4 main events which must happen to sperm that are essential for fertilization?
- Motility to swim against action of tubal cilia (perhaps by chemotaxis)
- Capacitation: changes to outer glycoprotein coat
- Sperm needs to get there before the egg or the egg will decrease in quality (have sex just before ovulation)
- Acrosome reaction to penetrate the oocyte’s zona pellucida
What female characteristic aids fertilisation?
Uterine contractions (not directly orgasm related although it is thought that this helps too)
What occurs in the process of fertilisation?
- Mature capacitated sperm meet the metaphase Ii oocyte in the ampulla of the oviduct
- Hyperactivation and acrosome reaction of sperm allows it to penetrate the zona pellucida and bind to oolemma
- Final maturation of oocyte and release of 2nd polar body
- Sperm entry and binding to oolemma causes Ca2+ transients that:
- Activate oocyte for further development
- Release cortical granules avoiding polyspermy
How does the movement of the sperm change as it moves through the female reproductive tract?
Starts by quickly moving forward in a straight line
Begins to thrash head aggressively when it gets to the egg to breach the zona pellucida (caffeine makes these movements occur too early so sperm do not get far enough)
What can happen if a fertilisation is dispermic?
Abnormal conceptus e.g. diploid
Possible abortion
What are the stages of embryo development?
- Pronucleate (6-20hrs)
- Cleavage (18hr-3dys)
- Compaction (3-4dys)
- Blastocyst (5-6dys)
- Hatching out of zona pellucida to interact with endometrium (5-7dys)
What occurs in embryonic genome activation?
mRNA inherited from oocyte supports embryo development through fertilisation and early cleavage and then mRNA production from the embryonic genome occurs principally at the 4-8 cell stage (but some transcription from pn stage) - oocyte has capacity for DNA damage repair
What arrests the oocyte at the 4-8 cell stage?
α -amanitin found in several species of the mushroom genus Amanita
Why is prediction of embryo viability difficult?
They are often mosaic in the early stages where individual blastomeres differ from eachother so there is differences between cells that are both genetic and biochemical
What is the inner cell mass?
Undifferentiated area that becomes the embryo with stem cell markers but making up the minority of cells (~20%)
What is the trophectoderm?
An invasive/adhesive structure that accommodates some abnormal cells (pre-natal diagnosis is via Chorion Villus Sampling) and secretes hCG
What occurs in implantation?
Immunologically complex process including apposition, adhesion and attachment occurs in the upper part of the uterus around 7 days after ovulation via specific orientation and maternal/embryonic communication mechanisms - difficult to study in humans
What is the most likely stage of failure of IVF treatment?
Implantation of embryo into uterus: 40% manage and 60% fail - if it manages failures after this stage only occur in ~15-20%
What is happening to the population of women having babies?
The amount of babies being born to women over 40 years old has more than doubled so the population of pregnant women is getting dramatically older
What is infertility?
1-2 years of attempting pregnancy occurring in ~ 1 in 6 Western couples
What is the average age of a women’s first pregnancy?
31 (35 for IVF patients)
What is the average age of menopause?
51 although fertility declines from 30 years declining rapidly at 37 years (bi-exponential fall of follicles in ovaries) and being very low from 40 years
What are the common causes of infertility?
Coital problems Endometriosis/cervical mucous Tubal damage Ovulatory failure Sperm problem Age Unexplained Combination
What medical diagnoses of females can cause infertility?
- Anovuation/oligoovulation
- Tubal disease or blockage
- Uterine anomaly
What IVF diagnoses of females can cause infertility?
- Egg anomaly e.g. genetic, cytoplasmic or maturation issue
- Fertilisation failure/abnormality
- Abnormal embryo development
- Implantation problem
What are issues with ovulation normally associated with?
1ry/2ndary ovarian failure
Polycystic ovarian disease
Endocrine issues e.g. high basal LH, high androgens or insulin insensitivity
Overweight
What test can be used to inform on ovarian reserve and intensity of stimulation required?
Serum Anti-Mullerian Hormone (AMH) produced on small growing follicles
How can you treat ovarian issues? What must you be careful of?
Endocrine treatments for anovulation include anti or partial estrogens (e.g. Clomiphene) or FSH to aim for more eggs
Be careful of understimulation as hormones have side effects and it won’t be helping but especially overstimulation if attempting pregnancy by intercourse as OHSS may occur which can be mild or severe causing death
What is IVF/ICSI treatment?
Involves ovarian stimulation but also brings gametes together more reliably and selects embryos for quality using an embryoscope placing them in the uterus instead of relying on intercourse and then cryopreserve additional spare embryos - does not fix infertility cause just gets around it
How successful is IVF?
~35% live births at 25 years old and then this declines so it is not THAT successful
What is the risk if women get pregnant later in life?
More chance of genetic anomalies in the oocytes perhaps due to disintegration of spindles or increasing environmental insults e.g. trisomy 21 Down Syndrome
What are the causes of male infertility?
- Impotence (psychosexual, drug-induced, paraplegia)
- Azoospermia
- Oligozoospermia (idiopathic/genetic/acquired)
- Astheozoospermia
- Teratozoospermia
- Necrozoospermia
- Anti-sperm Abs
- Y chromosome microdeletions so no/few sperm made (son will inherit this and need IVF in future)
- Sperm DNA damage
- Sperm do not bind to/fertilise egg
What are some important causes of azoospermia?
- 1ry/2ndary testicular failure
- Obstruction inc. vasectomy or congenital bilateral absence of the vas deferens (CBAVD)
- Retrograde ejaculation (into bladder) - sometimes associated with diabetes
How do you treat male infertility?
- Correct hormonal imbalance/blockage/psychological problem
- Obtain best possible ejaculate sample
- If poor, obtain best possible sample from surgical retrieval from testicle
- Apply sperm to female partner in order of least invasiveness, appropriate to any female factor of infertility and age (intrauterine insemination > IVF > ICSI)
- If no sperm available or ICSI declined consider sperm donor
Why is there a low amount of sperm donors in the UK?
Because the requirement is for the donation to be non-anonymous so when the child is 18 years old, he/she can find their father (not the same in other countries e.g. Spain where the information legally must be anonymous)
What in intracytoplasmic sperm injection (ICSI)?
Injection of 1 immobilised sperm into egg avoiding presumed position of oocyte spindle - fertilisation, embryo development and pregnancy rates similar to IVF with normal sperm but some increased abnormality rates likely due to parental factors
What are the risks of fertility treatment?
Failure Overstimulation Multiple pregnancy Psychological/financial Risks of embryology processes e.g. inheritance
