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
Which hormone is responsible for entry into the secretory phase?
Progesterone
Hormones involved in early pregnancy
- Human chorionic gonadotropin
- Progesterone
- Oestrogen
- Oxytocin
- Prolactin
- Relaxin
Role of HCG
Produced by the corpus luteum (placenta)
- HCG binds to LH receptors in the corpus luteum and stimulates continued secretion of 17-b oestradiol and more importantly progesterone. It may also block signals in the corpus luteum that cause luteal regression
Which cells produce progesterone?
Syncitiotrophoblast cells
Roles of progesterone?
- Convert the endometrium to its secretory stage to prepare uterus for implantation
- Decrease maternal immune response to allow pregnancy
- Decreases contractility of uterine smooth muscle
- Inhibits lactation during pregnancy (fall of progesterone triggers milk production)
The foetus and placenta work together to produce what? How?
Oestrogens
- Foetal adrenal synthesis C19 androgens
- The placenta aromatises these to oestrogens
Which hormones does the corpus luteum secrete?
Oestrogen
Progesterone
Roles of oestrogen?
- Stimulate hormone production in the foetus’ adrenal gland, stimulating growth of the adrenal, and enhancing the mother’s uterus, enabling it to respond to oxytocin
- Development in the foetus, triggering the development of several organs and bodily systems
Role of oxytocin
- Cervical dilation before birth, causes contractions during the second and third stages
- Involved in lactation
Role of relaxin
Loosens the ligaments that hold the pelvic bones together and for relaxing the uterine muscle, both in preparation for delivering the baby through the birth canal
What do pregnancy tests look for?
Beta subunit of HCG
- This eliminates possibility of cross-reaction with pituitary LH
- This enables high sensitivity
What is a blastomere?
The cells produced by the division of a zygote/embryo
2-4-8-16-32 (cell stages)
At which division stage does the embryo begin to make its own genes?
4-cell stage
What is a morula?
At the 32-cell stage, the blastomeres flatten, compact and start to form junctions between themselves. When we cannot see individual blastomeres, this is called a MORULA!
What is a blastocyst? Significance of this
Term for when the morula starts pumping in sodium through the Na/K ATPase, creating a cavity inside.
- This is important as now the embryo can hatch from the zona pellucida coat, necessary to enable full growth and support implantation
- It signifies the point at which the embryo leaves the fallopian tube and move into the uterus
How does cell differentiation occur in the morula? Which 2 cell types arise?
- Morula starts pumping sodium ions into the internal space forming the blastocoel cavity.
- The first stage of cell differentiation gives two cell types:
1. Trophoblasts - the outside cells, they are differentiated, epithlium cells
2. Inner cell mass (pluriblast) - less differentiated. Embryonic stem cells are isolated from the ICM, which are pluripotent stem cells which can make every cell type in the body.
When the ICM/pluriblast undergoes differentiation, which cell types arise?
- Epiblast (ectoderm)
- Hypoblast (endoderm)
- BILAMINAR DISK
Impact of alcohol on the baby? Effects of foetal alcohol syndrome
Foetal alcohol syndrome
- Alcohol can pass from the mother’s blood to the baby’s blood
- This can damage and affect the growth of the baby’s cells, including brain and spinal cord
FAS:
- Distinctive facial features - small head, flat face, narrow eye openings
- Growth problems - smaller
- Birth defects
- Problems bonding or feeding as a new-born
- Heavy alcohol use during pregnancy can also lead to miscarriage, stillbirth, or being premature
Which cell type arises from the differentiation of the epiblast cells?
Mesoderm cells
- Form a gap between the epiblast and hypoblast
- Now we have the trilaminar disc, where these three layers meet
Impact of smoking on the baby
- Low birth weight
- > infant mortality rate
- Not an effect on the baby but > risk of ectopic pregnancy
Socioeconomic disadvantages of pregnancy
- Still birth
- Pre-term delivery
- Higher neonatal and infant mortality
- Worse health
- Growth retardation
- Neurological problems
- Hypertension
- Stroke
- CHD
When may abortion be seen as allowed even by those who object?
- If the mother’s health is at risk
- Where the pregnancy occured as a result of crime
- Where the child would have a poor QoL
- For social reasons - poverty, mother being too young
- Government policy
Supplements in pregnancy?
Folic acid Vitamin D Iron Vitamin C Calcium
Role of calcium in pregnancy
- Help develop the baby’s bones and teeth
- Reduce risk of hypertension and pre-eclampsia in mother
Role of vitamin C in pregnancy
- Necessary to make collagen, tendons, bones, skin
- Vit C deficiencies can impair mental development
- Essential for tissue repair, wound healing, bone growth and repair, healthy skin
Role of iron in pregnancy? Consequence of deficiency?
- Make haemoglobin
- Amount of blood increases during pregnancy, so extra iron is needed to make more haemoglobin.
- Extra iron is needed for the growing baby and placenta, especially in the second and third trimester.
- Iron deficiency anaemia during pregnancy is associated with preterm delivery, low birth weight, and infant mortality.
Role of vitamin D in pregnancy? Consequences of deficiency?
- Regulates the amount of calcium and phosphate in the body.
- Inadequate vitamin D can lead to abnormal bone growth, fractures, or rickets in new-borns
- Vit D deficiency can lead to gestational diabetes, pre-eclampsia, preterm birth, and low birth weight
Role of folic acid in pregnancy?
- Prevent birth defects known as neural tube defects e.g. spina bifida
Which women have a higher risk of having a pregnancy affected by a neural tube defect?
- They or their partner have a neural tube defect
- They have had a previous pregnancy with a neural tube defect
- They or their partner have a family history of neural tube defects
- They have diabetes
Which foods contain folate?
- Leafy, green vegetables
- Brown rice
- Certain breakfast cereals
Role of antenatal care?
- Maintenance of health of mother during pregnancy
- Promote physical, mental, and social well-being of mother and child
- Ensure delivery of a full-term healthy baby
- Early detection of high-risk cases and minimise risks by taking appropriate management
- Prevent development of complications through health education, adequate nutrition, exercise, vitamin intake, and appropriate medical and pharmaceutical intervention
- Screening for conditions and diseases such as anaemia, STIs, HIV infection, mental health problems, and domestic violence.
- Teach the mother about childcare, nutrition, sanitation and hygiene.
- Decrease maternal and infant mortality and morbidity.
- Remove the stress and worries of the mother regarding the delivery process.
- Provide safe delivery for mother and educate mother about the physiology of pregnancy and labour by demonstrations, charts and diagrams so that fear is removed, and physiology improved.
- Advice family planning and motive the couple about the need of family planning.
- Predict possible problems during pregnancy and provide an appropriate treatment.
- Provide information on pregnancy and birth and discuss with the couple about the place, time and mode of the delivery provisionally and care of the newborn.
- Ensure continued medical surveillance and prophylaxis.
- Advice the mother about breast feeding, post-natal care and immunisation.
- Advice and support to the women and her family for developing healthy home behaviours.
Effects of early pregnancy (12 weeks) on the mother
- Nausea
- due to rising oestrogen and progesterone which cause the stomach to empty
- due to heightened sense of smell - Breasts
- Tender, sensitive, sore
- Fuller, heavier - Increased urination
- Pressure from uterus on the bladder
- Increases UTI risk - Cravings
- Dizziness
- Pregnancy causes blood vessel dilatation and blood pressure to drop
- If occurs with abdominal pain or vaginal bleeding, may indicate ectopic pregnancy - Heart burn/constipation
- Food moves more slowly through digestive system to allow nutrients more time to absorb
- Hormones relax oesophageal sphincter which can allow stomach acid to leak into oesophagus - Emotions
