PBL 35 Flashcards
Stages of IVF
- Suppress natural menstrual cycle
- Suppress follicular growth in ovarian follicles
- GRH agonist
- Causes suppression of FSH and LH - Superovulation
- Suppression of FSH and LH has allowed lots of follicles to reach pre-antral phase
- Give FSH to increase number of eggs produced - Collect eggs
- Needle passed through vagina into ovary to collect eggs - Fertilise egg
- Co-incubate gametes with eggs for around 24 hours in a dish
- Let them grow in a lab for up to 6 days before being transferred into the womb
- ICSI = each egg is individually injected with single sperm
- Give hormone to help prepare lining of womb to receive embryo
- Embryo transfer
- Embryo transferred into womb using a catheter passed into the vagina
- Similar to having a cervical screen test
What is intrauterine insemination?
A type of artificial insemination where the sperm have been washed and concentrated before being placed directly into the uterus around the time your ovary releases one or more eggs to be fertilised
- Co-ordinated with normal menstrual cycle
When is IUI supported?
When there is presence of physical barriers such as:
- Cervical scarring
- Poor cervical mucus
- Chronic cervical inflammation (cervicitis)
- ED
- Mild sperm abnormalities
When is IUI not supported?
Blocked fallopian tubes
Severe endometriosis
History of pelvic infections
Pharmacology of superovulation
GnRH receptor agonist causes the GnRH to stimulate release of pituitary hormones, FSH and LH
- After initial ‘flare’ response, the continued stimulation with the agonist desensitises the pituitary gland by causing down-regulation of GnRH receptor
- Pituitary gland desensitisation reduces secretion of LH and FSH, inducing a state of hypogonadotrophic hypogonadal anovulation AKA ‘pseudomenopause’
What is the criteria for NHS funding of IVF?
Women under 40:
- Offered 3 cycles of treatment if they:
1. Have tried unprotected sex for 2 years
2. Not been able to get pregnant after 12 cycles of artificial insemination with at least 6 cycles using IUI
Women 40-42:
- Will be offered 1 cycle of IVF if:
1. They have tried to get pregnant through regular unprotected sex for 2 years
2. Not been able to get pregnant after 12 cycles of artificial insemination with at least 6 using IUI
3. Never had IVF before
4. No evidence of low ovarian reserve - Further criteria: discretion of CCG
1. Not having children already
2. Being a healthy weight
3. Not smoking
4. Falling into the age range
Causes of infertility in women
- Polycystic ovary syndrome (PCOS)
- Thyroid problems
- Premature ovarian failure
- Scarring from surgery
- Cervical mucus problems
- Fibroids (prevent fertilised egg from attaching itself in womb or blocks fallopian tube)
- Endometriosis
- Pelvic inflammatory disease
- Sterilisation
- Medicines and drugs - NSAIDS, chemo, neuroleptic medicines, spironolactone (but spironolactone’s infertile side effects stop 2 months after stopping)
What is pelvic inflammatory disease?
Infection of upper genital tract: uterus, fallopian tubes and ovaries
- Can be caused by STI and cause scarring of the fallopian tubes making it impossible for an egg to travel down the womb
Causes of male infertility
- Lack of sperm
- Sperm not moving properly
- Abnormal sperm: abnormal shape makes it harder to move and fertilise
- Testicular damage - infection, cancer, surgery, 1 not descending, injury, congenital defect
- Sterilisation - vasectomy
- Ejaculation disorders
- Hypogonadism - low testosterone so you don’t make enough sperm
- Medicines and drugs - Sulfasalazine (anti-inflammatory for Crohn’s disease and rheumatoid arthritis), anabolic steroids, chemotherapy
How can hypogonadism be caused?
- Tumour
- Taking illegal drugs
- Klinefelter syndrome (involves extra female chromosome)
What are the 3 parts of the oviducts?
- Ampulla (wide)
- Isthmus (narrow)
- Ampullary-isthmic junction
What is the site of fertilisation?
Ampullary-isthmic junction
How long can sperm survive in the reproductive tract?
5 days
How long can eggs last in the reproductive tract?
24 hours
What is capacitation?
The process of the sperm being able to fertilise eggs:
- Hyper-activation - start swimming
- Removal of the acrosome cap
What causes the removal of the sperm acrosome cap?
Spending time in the female reproductive tract.
- pH
- Temperature
- ^ change the composition of the membrane to allow calcium to penetrate
Which enzymes are found within the acrosome cap?
- Acrosin
- Hyaluronidase
Overview of sperm–>egg fertilisation
- Penetration
- Hyaluronidase allows penetration of the cumulus cells (corona radiata) surrounding the egg
- Acrosome reaction (digest through zona pellucida) due to acrosin. Sperm binds ZP2/3 glycoproteins on the surface of the zona pellucida
- Fusion
- After binding ZP2/3, the sperm is enveloped into the egg
- The sperm then binds to the plasma membrane and the head and tail of the sperm are engulfed
- Sperm contributes DNA and PLC-gamma to the egg.
- PLC-gamma starts a signalling cascade which causes >Ca2+ levels.
- > Ca2+ allows egg to undergo second meiotic division by destruction of the cyclin B which is part of the MPF
- Syngamy
- Fusion of 2 cells, or of their nuclei, in reproduction
- Coming together of female and male pronucleus
- Don’t form a single nucleus
Overview of the menstural cycle
- Follicular phase
- LH and FSH act to produce a surge in oestrogen
- Oestrogen acts on the ovary and switches from a neg feedback loop to a positive feedback loop, causing the hypothalamus to increase LH production and trigger ovulation - Luteal phase
- After ovulation
- Egg is picked up by fimbriae in the fallopian tube, we now see a decrease in FSH and LH
- Oestrogen and progesterone levels start to RISE, as the remnants of the graafian follicle form the corpus luteum
- The corpus luteum produces progesterone necessary to sustain and nourish pregnancy
Which hormone is responsible for endometrial proliferation in preparation for ovulation?
Oestrogen
- During the follicular phase
- When the corpus luteum is present, following ovulation, the endometrium enters the secretory phase. During the secretory phase, successful implantation can begin