Week 1- assisted conception Flashcards
What is assisted conception treatment?
Any treatment which involves gametes outside of the body.
Why is demand for assisted conception treatment increasing?
Increasing parental age Increasing chlamydia Male factor infertility ACT more successful Bigger range of ACT
Other than parents struggling to have babies, when else may you use ACT?
Cancer patients- for preservation of eggs
Treatment to avoid transmission of blood borne viruses between patients
Treatment for single parents or same sex couples.
What advice is given to couples before they undergo ACT?
Females are limited to 4 units a week of alcohol.
BMI must be between 19-29
Stop smoking
Give 0.4mg folic acid from preconception-12 weeks gestation
Check if female is immune to rubella- if not immunise
Check cervical smears are up to date
Occupational factors- exposure to hazards
Drugs- prescribed, over the counter and recreational.
Screen for blood borne viruses
Assess ovarian reserve
Counselling
What ACT treatments are available?
Donor insemination Intra-uterine insemination In-vitro fertilisation Intra-cytoplasmic sperm injection Fertility preservation Surrogacy
What indications are there for intrauterine insemination?
Sexual problems, unexplained infertility, mild or moderate endometriosis, mild male factor infertility
Describe the process of intrauterine insemination?
The sperm is inserted into the uterine cavity around the time of ovulation.
What indications are there for in-vitro fertilisation?
Unexplained infertility (> 2 years) Pelvic disease (endometriosis, tubal disease, fibroids) Anovulatory infertility (after failed ovulatory induction) Male factor infertility (if greater than 1 x10^6 motile sperm present)
Describe the down regulation stage in IVF?
Give a synthetic GnRH analogue or agonist. This reduces cancellation from ovulation and improves success rates. Allows precise timing of oocyte recover by using a HCG trigger.
A scan is also performed.
What side effects can be experienced in the down regulation stage of IVF?
Hot flushes and mood swings
Nasal irritation
Headaches
Describe the ovarian stimulation stage of IVF?
This occurs once you are happy the patient is down-regulated.
Then injections of gonadotrophins (FSH or LH) are given. Can be self-administered as a subcut injection.
This causes follicular development.
What is the mans semen assessed for in IVF treatment?
Volume
Density- numbers of sperm
Motility- what proportion of the sperm are moving
Progression- how well they move
What risks are there with oocyte collection in theatre?
Bleeding
Pelvic infection
Failure to collect oocytes
How do you select an egg in IVF?
In the embryological lab- they go through follicular fluid and identify eggs and the surrounding mass of cells. They collect them and incubate them.
How many eggs fertilise normally in IVF?
Approximately 60%.
Describe the hormones, egg release and development of the normal human embryo?
Normal LH surge
Egg is released 36 hours later
Fertilisation occurs in the ampulla normally.
By day 4 the morula is formed. By day 5 they differentiate into a blastocyst.
At what day does transfer and cryopreservation (cooling to low temps) occur?
Day 5.
When does implantation of the embryo into the uteral cavity occur in IVF?
Day 7.
How many embryos are usually transferred in IVF?
Usually 1- but a maximum of 3 in exceptional circumstances.
What support do you need to give patients once the fertilised eggs have been transferred?
Progesterone depositories for 2 weeks.
Pregnancy test 16days after oocyte extraction.
What are the indications for intra-cytoplasmic sperm injection?
Severe male factor infertility
Previous failed fertilisation with IVF
Preimplantation genetic diagnosis.
What do you do if the man has azoospermia in ICSI?
Surgical sperm aspiration- can be withdrawn from epidydimus if obstructive or testicular tissue if non-obstructive.
Describe the process of intra-cytoplasmic sperm injection
The egg is stripped
The sperm is demobilised
The sperm is injected into the egg.
Incubated
What complications are associated with ART?
Ovarian hyperstimulation syndrome
What is ovarian hyper stimulation syndrome?
Enlarged ovaries- due to excess follicles
What symptoms are associated with ovarian hyper stimulation syndrome?
Abdominal pain/bloating
Nausea/diarrhoea
Breathless
What treatment can be offered if ovarian hyper stimulation syndrome occurs before embryo transfer?
Electric freeze- freeze the embryos and wait 2-3 months to transfer them then.
Single embryo transfer
What treatment can be offered if ovarian hyper stimulation syndrome occurs after embryo transfer?
Monitoring with scans and bloods
Reduce risk of thrombosis- fluids, TED stockings, fragmin
Analgesia
Hospital admission if IV fluids are required.
What other issues are there with ART?
No eggs retrieved (however very uncommon)
Surgical risks of oocyte retrieval
Surgical risks of surgical sperm aspiration
Failed fertilisation
Problems in early pregnancy e.g. ectopic pregnancy
Increased risk in on-going pregnancy
Psychological problems
What determines our gender?
The presence/absence of a Y chromosome.
Even if you have one X, you are still a girl.
Describe the development of the internal reproductive tract?
The Y chromosome has the sex-determining region, causing the development of testis from the biopotential gonad.
Fetal testes secrete testosterone and mullerian inhibiting factors.
What are the two primitive genital tracts called?
Mullerian- produce female genital system
Wolffian- produce male genital system
If you are going to be female, what primitive tracts will be suppressed and which will be left?
Wolffian will be supressed
Mullerian will be allowed.
If you are going to be male, what primitive tracts will be suppressed and which will be left?
Mullerian will be surpressed
Wolffian will be allowed.
At what stage can you determine whether a baby will be a boy or a girl?
16 weeks gestation.
What is testicular feminisation?
Someone is born looking like a female but when they hit puberty they don’t develop breasts. They actually have a male chromosome but female genitalia.
What causes testicular feminisation?
Congenital insensitivity to androgens.
X linked recessive disorder
Androgen induction of Wolffian duct does not occur however Mullarian suppression does. Causes them to be born phenotypically female with external genitalia female, absent uterus and ovaries and a short vagina.
When does testicular feminisation commonly present?
At puberty with lack of pubic hair and amenorrhoea.
Why is it important that the testes descend?
Lower temp outside the body to facilitate spermatogenesis.
What muscle controls where the testis sit in the scrotal sac?
Dartos muscle.
What is the medical term for undescended testis?
Cryptorchidism- the individual has reached adulthood but the testis are not yet descended.
What is the implications on fertility in cryptorchidism?
If unilateral they are usually still fertile however it reduces the sperm count.
Do you treat cryptorchidism?
Orchidoplexy should be performed if they are below 14 years to minimise the risk of testicular germ cell cancer..
If an adult- consider orchidectomy
What are the erectile tissues in the penis?
Corpus cavernosum
Corpus spongiosum
What is the function of the testes?
Spermatogenesis (occurs in the seminiferous tubules)
Production of testosterone.
What cells in the testes produce testosterone?
Leydig cells.
What is the role of Sertoli cells?
Form a blood-testis barrier- this protects the sperm from antibody attack. Provides a suitable fluid composition which allows later development of sperm
Provide nutrients
Phagocytosis- destroy defective cells and removes surplus cytoplasm
Secrete seminiferous tubule fluid
Secrete androgen binding globulin
Secrete inhibin and activin hormones
What is the function of androgen binding globulin?
Keeps the concentration of testosterone high (by binding to it) in the lumen
What is the role of inhibin and activin hormones?
Regulates FSH secretion and controls spermatogenesis.
What is the role of seminiferous tubule fluid?
Carries the sperm to the epididymis.
What hormone stimulates the production of testosterone?
LH.
What does gonadotrophin releasing hormone do?
Which hormone controls this by negative feedback?
Stimulates the anterior pituitary to release FSH and LH.
Testosterone causes less GnRH to be released by negative feedback.
What does lutinising hormone do on the male reproductive tract?
Stimulates the leydig cells to produce testosterone.
What does follicle stimulating hormone do to the male reproductive tract?
Which hormone regulates FSH?
Acts on Sertoli cells to enhance spermatogenesis.
Regulates by negative feedback from inhibin
Where is testosterone secreted into?
The blood and seminiferous tubules.
What are the effects of testosterone before birth?
Masculinises the male reproductive tract and promotes descent of testis.
What are the effects of testosterone at puberty?
Promotes puberty and male characteristics
What are the effects of testosterone in an adult?
Controls spermatogenesis
Secondary male characteristics (male body shape, deepens voice, thickens skin, libido)
What cell secretes inhibin and activin? What is their function?
Sertoli cells
Inhibin inhibits FSH. Activin stimulates FSH.
What occurs to spermatozoa after ejaculation?
They become liquified (by enzymes in the prostate gland)
Capacitation- a series of biochemical and electrical events occurring before fertilisation
Chemoattraction to oocyte and bind to zona pellucida of oocyte.
Acrosome reaction
Hyperactive motility
Penetration and fusion with oocyte membrane
Zonal reaction.
Which area of the Fallopian tube does fertilisation occur?
Ampulla
What is the function of the epididymis and vas deferens?
Exit route from testes to urethra, concentrate and store sperm, site for sperm maturation.
What is the function of the seminal vesicles?
Produce semen into ejaculatory duct. Supply fructose Secrete prostaglandins (stimulates motility) Secrete fibrinogen (clot precursor)
What is the function of the prostate gland?
Produces alkaline fluid (neutralises vaginal acidity)
Produces clotting enzymes to clot semen inside female.
What is the function of the bulbourethral gland?
Secrete mucus to act as a lubricant
What is the definition of male infertility?
Failure of the sperm to normally fertilise the egg.
What can cause of male infertility?
Idiopathic
Obstructive
Non-obstructive
What is the most common cause of male infertility?
Idiopathic
Name some examples of obstructive pathologies causing male infertility?
Cystic fibrosis
Vasectomy
Infection
Name some examples of non-obstructive pathologies causing male infertility?
Congenital- crytorchidism Infection- mumps, Iatrogenic- chemotherapy/radiotherapy Pathological- testicular tumour Genetic- chromosonal e.g. Kleinfelters syndrome Specific semen abnormality- azoospermia, Systemic disorder Endocrine disorder
What are the common endocrine causes of male infertility?
Pituitary tumours- hyperprolactinaemia (decreases LH, FSH and testosterone), acromegaly, cushings
Hypothalmic cause-
Thyroid disorders
Diabetes
Steroid abuse (decrease LH, FSH and testosterone)
Androgen insensitivity (normal or raised LH and testosterone)
What examinations would you do in male infertility?
General examination- including secondary male characteristics
Genital examination- testicular volume, presence of vas deferens and epididymus, penis (urethral orifice), presence of variceal or swelling.
What is the normal testicular volume for adults?
In prepubertal boys?
12-25mls.
1-3mls
What testicular volume are you likely to be infertile if you are below?
5mls.
What do they analyse the semen for?
Volume Density- number of sperm Motility- what proportion are moving Progression- how well they move? Morphology
What does an obstructive male infertility show like on examination?
Normal testicular volume
Normal secondary sexual characteristics
Vas deferens may be absent
Endocrine- normal LH, FSH, testosterone
What does a non-obstructive male infertility show like on examination?
Low testicular volume
Reduced secondary sexual characteristics
Present vas deferens
Endocrine- High FSH and LH, low testosterone
What life style factors can be changed to help maximise fertility in the male?
Frequent sexual intercourse Less than 4 units a day of alcohol Stop smoking BMI less than 30 Avoid tight fitting underwear and long hot baths Certain occupations
When is intra-uterine insemination indicated?
Mildly reduced sperm count
When is intra-cytoplasmic sperm injection indicated?
Very low sperm count
When is surgical sperm aspiration indicated?
Azoospermia
When is donor sperm insemination indicated?
Azoospermia or very low sperm count
Genetic conditions
Infectious
What does oligoasthenospermia mean?
Low sperm count and motility
What does teratoasthenospermia mean?
Low motility and abnormal forms
Which drug is an ovulatory inducer?
Clomefene citrate.
