Fertility and Subfertility Flashcards
What is the definition of subfertile?
If conception has not occurred after a year of regular unprotected intercourse.
What is primary subfertility?
The female partner have never conceived
What is secondary subfertility?
Indicating that the female partner has previously conceived, even if the pregnancy ended in miscarriage or termination
What are the four conditions for pregnancy/ where it could go wrong?
- An egg must be produced
- Adequate sperm must be released
- The sperm must reach the egg
- The fertilised egg must implant
What are the main causes of subfertility?
Ovulatory problems - 30% Male problems - 25% Tubal problems - 25% Coital problems - 5% Cervical problems <5% Unexplained - 30% (more than one issue may be present, which is why it doesn't add to 100%)
What are the main ways of detecting ovulation?
Mid-luteal phase serum progesterone (standard test)
US follicular tracking (time-consuming)
LH-based urine predictor kits
PCOS causes anovulation, what is PCO?
It describes transvaginal US appearance of multiple (>12) small (2-8mm) follicles in an enlarged (>10mL) ovary.
What is needed to diagnose PCOS?
At least two of the following three:
[1] PCO on US
[2] Irregular periods (>35 days apart)
[3] Hirsutism: clinical (acne or excess body hair) and/or biochemical (raised serum testosterone)
How does the pathology of PCOS lead to increased androgens?
Disordered LH production and peripheral insulin resistance with compensatory raised insulin levels. This combination leads to increase ovarian androgen production. Raised insulin levels increase adrenal androgen production and reduce hepatic production of steroid hormone binding globulin which leads to increased free androgen levels
What is the effect of increased androgens in PCOS?
Increased intraovarian androgens disrupt folliculogenesis leading to excess small ovarian follicles and irregular or absent ovulation. Raised peripheral androgens cause hirsutism.
What are the modifiable risk factors of PCOS?
Increased body weight leads to increased insulin and consequently androgen levels. Many women have a family history of type 2 diabetes.
What are the clinical features of PCO?
Polycystic ovaries without the syndrome generally cause no symptoms
What are the clinical features of PCOS?
Obesity, acne, hirsutism and oligomenorrhoea or amenorrhoea. Miscarriage is more common in PCOS
What are the investigations needed for PCOS?
Alternative causes for the symptoms need to be excluded.
TVS US
FSH, LH (often raised), testosterone, prolactin, TSH blood tests
Fasting lipids and glucose to screen for complications
Why is FSH measured when investigating PCOS?
It is raised in ovarian failure, low in hypothalamic disease, normal in PCOS.
Why is testosterone measured when investigating PCOS?
To investigate hirsutism: possibility of androgen-secreting tumour or congenital adrenal hyperplasia if very raised
What are the complications of PCOS?
Type 2 DM, GDM
Endometrial cancer is more common in women with many years of amenorrhoea due to unopposed oestrogen action.
How do you treat the symptoms other than infertility?
Advice on weight.
Combined oral contraceptive pill
Metformin will reduce insulin levels and therefore androgens and hirsutism.
What are the hypothalamic causes of anovulation?
Hypothalamic hypogonadism and Kallmann’s syndrome
What is hypothalamic hypogonadism and how does it cause anovulation?
A reduction in hypothalamic GnRH release causes amenorrhea, because reduced stimulation of the pituitary reduces FSH and LH levels, which in turn reduces oestrodiol levels.
In which women is hypothalamic hypogonadism common?
Anorexia nervosa sufferers, women on diets, athletes and those under stress.
What is Kallmann’s syndrome and how can you treat it?
GnRH secreting neurones fail to develop. Exogenous gonadotropins or a GnRH pump will induce ovulation
What is the pituitary cause of anovulation?
Hyperprolactinaemia
What is hyperprolactionaemia and what is it usually caused by?
Excess prolactin secretion, which reduces GnRH release. It is usually caused by a benign tumour or hyperplasia of pituitary cells
How do you treat hyperprolactinaemia?
Dopamine agonist (bromocriptine or cabergoline) usually restores ovulation, because dopamine inhibits prolactin release.
What are the causes of PCOS that are not directly related to that particular hormone axis?
Hypo- or hyperthyroidism
Androgen secreting tumours
How do you treat anovulation?
Lifestyle factors, treat cause, 1st-line treatment: clomifene in PCOS, metformin to restore ovulation and laprascopic ovarian diathermy. If these fail, inject FSH and LH.
How does clomifine work?
It is an antioestrogen, blocking oestrogen receptors in the hypothalamus and pituitary, which increases FSH and LH, effectively fooling the pituitary into believing there is no oestrogen
When is clomifine given?
From days 2-6, it can initiate the process of follicular maturation which is thereafter self-perpetuating for that cycle.
What are the side-effects of clomifine?
As it is an anti-oestrogen it has negative effects on the endometrium and, on higher doses, may cause a thin endometrium of <7mm.
What are the side effects of ovulation induction?
Multiple pregnancy and ovarian hyperstimulation syndrome
What are the risk factors of ovarian hyperstimulation syndrome (OHSS)?
Gonadotrophin stimulation, over 35 years old, previous OHSS, and ovaries of a polycystic morphology on US scan.
How is sperm produced?
LH acts via testosterone in the Leydig cells of the testis. FSH and testosterone control Sertoli cells, which are involved in the synthesis and transport of sperm.
What are the rules regarding the sperm for semen analysis?
Last ejaculation must be 2-7 days previous.
Sample must be analysed within 1-2 hours.
An abnormal analysis result must be repeated after 12 weeks
What is a normal semen analysis?
Volume - >1.5mL
Sperm count - >15 million/mL
Progressive motility - >32%
What is azoospermia?
No sperm present
What is oligospermia?
<15 million/mL
What is severe oligospermia?
<5 million/mL
What is asthenospermia?
Absent or low motility
What are the common causes of abnormal semen analysis?
Unknown Smoking/alcohol/drugs/chemicals/inadequate local cooling Varicocoele Genetic factors Antisperm antibodies
How do you treat oligospermia?
Mild: intrauterine insemination
Moderate to severe: IVF +- intracytopalsmic sperm injection (ICSI)
How do you treat azoospermia?
Examine for presence of vas deferens
Check karyotype, CF, hormone profile
Surgical sperm retrieval and then IVF + ICSI or donor insemination
Why might the sperm not meet the egg?
Tubal damage: infection, endometriosis, surgery/adhesions
Cervical problems
Sexual problems
What does the fallopian tube do at ovulation?
It moves so the fimbrial end collects the oocyte from the ovary. The tube needs adequate motility for this. Peristaltic contractions and cilia in the tube help sweep the oocyte along towards the sperm. The cervical mucus helps the sperm get through the cervix
What infections cause tubal damage and how, also how would you treat this?
PID causes adhesion formation within and around the fallopian tubes. Laparoscopic adhesiolysis can be performed.
What are the causes of tubal damage?
Infection, endometriosis and previous surgery
How can you treat endometriosis to improve tubular function?
Surgery to remove endometriotic deposits. IVF if this does not work
What investigations can be done to detect tubal damage?
Laparoscopy and dye test (allows visualisation and assessment of the fallopian tubes)
What are the indications for assisted conception?
When any/all other methods have failed Unexplained subfertility Male factory subfertility (ICSI) Tubal blockage (IVF) Endometriosis Genetic disorders
What is intrauterine insemination (IUI)
Washed sperm are injected directly into the cavity of the uterus. It can be performed during a normal or gonadotropin ovulation induced cycle.
Who is IUI most suited for?
Couples with unexplained subfertility, cervical and sexual and some male factors
How is IUI compared with IVF?
Cheaper but much less successful
What does IUI rely on?
The tubes still being patent, as the oocyte still needs to travel from the ovary to the sperm
What are the stages of IVF?
Multiple follicular development; ovulation and egg collection; fertilisation and culture; embryo transfer
How is IVF multiple follicular development achieved?
‘Long-protocol’ Daily GnRH needed from day 21 of cycle to supress pituitary FSH and LH. Once supressed (confirmed by low serum oestrodiol/thin endometrium) 2 weeks of SC gonadotrophin injections (FSH +- LH).
What happens during IVF ovulation and egg collection?
Once scan confirms adequate mature ovarian follicles, the GnRH analogue and gonadotrophins are stopped. Single hCG/LH injection is given. 35-38hrs later, eggs are collected
What happens during IVF fertilisation and culture?
The eggs are incubated with washed sperm and transferred to a growth medium. Embryos are cultured til cleavage (2-3days) or blastocyst (5-6days)
What is intracytoplasmic sperm injection (ICSI)?
An injection of one sperm right into the oocyt cytoplasm.
Who is ICSI useful for?
Male factor infertility when there are not enough motile sperm available to incubate a sufficiently high concentration with each oocyte for standard IVF.
What happens during oocyte donation?
Donor goes through IVF, original partners sperm is fertilised with egg and gets inserted to original woman. Often done during IVF with ‘egg sharing’.
What are the complications of assisted conception?
Superovulation; egg collection; pregnancy complications
