Subfertility Flashcards
Definition of subfertility
Inability for a couple to achieve clinical pregnancy after 12 months of regular unprotected sexual intercourse
Primary and secondary subfertility
Primary - no previous pregnancy
Secondary - at least one previous pregnancy
Incidence of subfertility within the general population
1 in 7 couples in the UK have trouble conceiving
- 84% of couples will get pregnant after having unprotected sexual intercourse for 1 year
Causes of male subfertility
Azospermia - no sperm seen in sample
- obstructive
- non-obstructive OR failure to stimulate spermatogenesis
Describe obstructive azospermia
Normal spermatogenesis, however there is an inability for sperm to leave in the ejaculate
Causes
- blockage in vas deferns or epididymis
- congenital absence of vas deferens (test for CF)
Describe non-obstructive azospermia
There is testicular failure (increased FSH)
- biopsy in case there are islands for spermatogenesis
Causes
- XXY karyotype (Kleinfelter’s)
- Y microdeletions
Rarely can be caused by failure of stimulation of spermatogenesis (decreased FSH)
- hypogonadotrophic hypogonadism
What are the female causes of subfertility
Ovulatory causes - hypothalamic-pituitary failure - HPO-axis dysfunction - ovarian failure Tubal causes Endometriosis related causes Unexplained subfertility
Important factors in the assessment of ovulatory subefertility
Primary or secondary
- primary is he failure of onset of ovulation by the age of 16 in women
- secondary is no menstruation for 6 months or more in a woman who previous had periods
Check ovulation
- day 21 progesterone (if cycle is regular) as progesterone increases once the egg is released
- retrospective diagnosis
Describe hypothalamic-pituitary failure as a cause of subfertility
GnRH release from the hypothalamus, or FSH/LH release from the pituitary is inhibited
Presents with amenorrhoea and shows a decreased LH and FSH on investigation
Causes of hypothalamic-pituitary failure
Unknown
Hypothalamus - weight, stress, exercise and craniopharyngioma
Pituitary - tumour, Sheehan’s syndrome and cerebral radiotherapy
Management of hypothalamic-pituitary failure
Increase BMI and decrease exercise
GnRH agonist
- pulsatile release
- mono-ovulation and increased live-birth success
Gonadotropin injections
- causes ovarian hyperstimulation, leading to multiple pregnancy
- FSH/LH
Causes of HPO-axis dysfunction as a cause of subfertility
Most common cause of anovulatory subfertility
Causes
- PCOS
- hyperprolactinaemia
hypothyroidism, hyperthyroidism and adrenal insufficiency
How is PCOS diagnosed
Rotterdam criteria (2 out of 3) - hyperandrogenism (increased testosterone or hirsutism) - anovulation - ultrasound shows features of PCO Bloods results expected - decreased FSH - increased LH - increased oestrogen - hyperprolactinaemia - increased free androgen index
How is PCOS managed
Weight reduction (10% weight loss causes an 80% increase in ovulation)
Letrozole
- aromatase inhibitor
- blocks oestrogen biosynthesis, so negative feedback loop is blocked, increasing FSH production and ovarian stimulation
- stimulates one follicle at a time, so has lower rates of multiple pregnancy
Clomiphene
- SERM (selective oestrogen receptor modulator)
- blocks E2 at pituitary (stops negative feedback)
- increases FSH and ovulation
- has a risk of ovarian hyperstimulation and ovarian cancer if used for >12 months
IVF (after GnRH analogue)
Ovarian drilling
What is ovarian failure as a cause of subfertility
It is a failure of the ovaries despite normal action by the pituitary and hypothalamus
- causes amenorrhoea
- increased FSH
- decreased E2
Causes of ovarian failure
Idiopathic Chemo/radiotherapy Oophorectomy Autoimmune Chromosomal (45XO - Turner's syndrome) Pure gonadal dysgenesis Androgen insensitivity (genetically male - 46XY)
Describe premature ovarian insufficiency
In women <40 years
75% of women with 46XX spontaneous POI have potentially functional graafian follicles remaining in the ovary
- some women conceive without treatment, but pregnancy rates are low
How is ovarian failure managed?
IVF with/without oocyte donation
Embryo donation
Adoption
How are the male causes of subfertility managed?
ICSI - works better in obstructive causes rather than non-obstructive
Donor insemination
What is tubal subfertility
Dysfunction either of egg reception or transportation
How is tubal patency assessed
Hysterosalpingogram
- X-Ray with radio-opaque dye in the uterus
Laparoscopy of dye insufflation
- allows assessment of pelvis and external uterus
Hysterosalpingo-contrast-ultrasonography (Hy-Co-Sy)
- assess tubal and uterine pathology
Swabs
TV USS
What other factors can be complicating conception?
Timing of intercourse
- sperm needs to be deposited BEFORE ovulation as progesterone affects cervical mucus
- 2/3 times a week
Briefly describe endometriosis related subfertility and its management
Abnormal ovum pick-up and release Management - treat symptoms - surgery for diathermy or ovarian cystectomy - IVF
Describe unexplained subfertility and it’s management
Common
Where a cause of the subfertility can’t be found
- normal examination and investigations
Spontaneous conception is common in younger people, resolves within 3 years of trying regularly
IVF offered if >3 years of trying
What factors assess fertility in both men and women
Age - mainly a female issue, some evidence of male age influence
Previous pregnancy
Duration of subfertility
Timing of intercourse
Weight (female)
- best BMI between 20 and 30
- increased weight has association pregnancy problems and a risk of miscarriage
How are are men assessed for causes of subfertility
Semen analysis - volume - concentration (>15mmol/ml) - motility (>40% motile) - normal forms (>4% normal) Sample provided after 2-5 days of abstinence Abnormal results are due to - azoospermia (absent sperm) - oligospermia (few sperm) - asthenospermia (immobile) Karyotype CF status Y microdeletions FSH
How are tubal causes of subfertility managed?
Laparoscopic salpingostomy
- success most obvious in distal blockages
What is IVF
Fertilisation outside the body, where sperm fertilises the egg of its own accord
How is IVF performed
GnRH analogues are used to prevent action of endogenous hormones
- then FSH injected to stimulate the ovary
Patient is scanned, and eggs (between 16 and 18mm are removed)
- via TV USS and needle
Sperm washing removes inactive cells and seminal fluid
Co-incubation for 1-4 hours in a test tube
Fertilised eggs are put in growth medium for 2 days until it is 4-6 cells big
- embryo transfer
What is ICSI
Intracytoplasmic sperm injection
- done in cases of low sperm count or motility
What is intrauterine insemination and when is it used?
Follicular development is induced and ovulation carried out as in IVF
36 hours after ovulation, prepared sperm is placed into the uterine cavity using intrauterine catheter
Performed in cases of donor insemination for couples where the sperm is poor quality and ICSI is unsuccessful
What is ovarian hyperstimulation and its main complications
Gonadotropin therapy can lead to ovarian hyperstimulation syndrome
- a serious condition in which the ovaries are enlarged with cysts, related to multiple follicular development
Mild
- patients experience little abdominal discomfort
Severe
- nausea and vomiting
- profound and painful abdominal distension
- fluid shifts resulting in ascites and pleural effusion
- hepatorenal failure and adult respiratory distress are possible
What are the consequences of PCOS
Reduced fertility Insulin resistance and diabetes Hypertension Endometrial cancer - due to unopposed oestrogen Depression and mood swings Snoring and daytime drowsiness
