Subfertility

Question 1

What is the definition to subfertility?

Answer 1

The abilty to conceive after 12 months of regular unportected sexual intercourse.

Regular intercourse is defined as 2-3 times per week. Maximum “efficiancy” is achieved if intercourse is had at least every other day

When taking a Hx, always ensure the couple is having proper vaginal sex (some people have no idea how it should work….)

Question 2

What is the incidence of subfertility?

Answer 2

In the UK, around 1 in 7 couples are affected.

Question 3

What are the likelyhoods of a healthy couple to conceive:

• Per cycle
• Within 6 months
• Within 12 months
• Within 24 months?

Answer 3

• Per cycle: 18-20%
• Within 6 months: 70%
• Within 12 months: 84%
• Within 24 months: 92%

Question 4

Name some general and lifestyle factors that affect fertility.

Answer 4

• Age: Significant decline in women >35 (decline in oocyte quality and quantity)
• Smoking: reduces both female and male fertility
• Coital frequency: minimum 2-3 timesper week recommended.
• Stress: can impact the HPO axis, interfering with normal ovulation, and decreasing libido (i.e. frequency of intercourse)
• Alcohol: affects sperm quality, and is harmful to foetus. Moderate amounts are OK.
• Body weight: both low and high extremes associated with reduced chance of conception
• Drugs: NSAIDs inhibit ovulation (as prostaglandins are involved). Other durgs also implicated in infertility
• Occupational exposure: Chemicals and radiation adversly affect male and female fertility.

Question 5

What are the categories of female causes of subfertility?

Answer 5

• Ovulatory disorders
  
  • Group I: Hypothalamic-pituitary failure
  • Group II: Hypothalamic-pituitary-ovarian dysfunction (PCOS)
  • Group III: Ovarian failure
• Tubal problems
• Uterine problems
• Lifestyle/functional factors (cigarette smoking, high and low BMI, libido)

Question 6

What are the commonest causes of female subfertility?

Answer 6

Common causes of subfertility include:

• Ovulatory disorders such as PCOS and natural decline in fertility with age
• Tubal damage secondary to infection (most common cause worldwide) or endometriosis
• Cigarette smoking
• High and Low BMIs.

Question 7

What are male factors of subfertility?

Answer 7

Sperm:

• Compromised quantitiy or quality, due to:
  
  • Post-orchitis/epididimytis (e.g. after Hx of Mumps)
  • Iatrogenic: Pelvic radiotherapy, surgery for undescended testes
  • Diabetes
  • Heat
  • Chemicals
• Erectile dysfunction/Ejacuatory dysorder
• Genetic factors (Klinefelter XXY and others)

Question 8

What invetigations would you like to perform for a couple presenting with infertility?

Answer 8

Male investigations (1/3 of infertility is caused by penis-humans):

• Seminal fluid analyses (total volume, sperm concentration, morphology, motility)
  
  • Repeat after 3 months if abnormal, as certain factors such as viral infections can lead to false negatives
• Consider karyotyping and screen for CF

Female:

• Day 2-4 FSH (the more FSH is required to stimulate follicles, the lower the ovarian reserve is)
• Day 8 LH (at day 8, LH should be inhibited by inhibin. If it is raised, this suggests PCOS)
• Oestradiol
• Mid-lueteal progesterone (should be raised if ovulating. i.e. day 21 in 28 day cycle)
• Endocrine check: TFT, prolactin, testosterone
• Test for STI: chlamydia. HIV (and Hep B/C)
• TVUSS: assess pelvic anatomy, looks for fibroids, antral follicle count
• Tubal potency assessment: Hyterosalpingogram or Hysterocontrast synography. In women with known co-morbidities (e.g. endometriosis) do laparoscopy and dye test.

(Anti-Mullerian Hormone can also be used to predict for ovarian reserve, but we were tuaght this is less commonly used)

Question 9

Describe the management approach/available options for subfertility

Answer 9

Management should be individualised and involve optimisation of the patient’s current medical problems e.g. thyroid disease. The different approaches that can be taken include:

• Lifestyle changes
• Ovulation induction
• Surgery
• Intrauterine insemination
• In-vitro fertilisation

Question 10

How successful is IVF?

Answer 10

In patients under 35, the success rates are 40-45% per cycle.

In women >40, the rates fall below 15%.

Question 11

What is ovarian hyperstimulation syndrome?

Answer 11

OHSS is a condition that can arise as part of the hormonal treatment of IVF.

It is usually the hCG injection that leads to large release of several hormones, causing ascites, enlarged multifollicular ovaries, pulmonary oedema and coagulopathy.

It affects 1-3% of women undergoing IVF.

Question 12

How can subfertility be categorised?

Answer 12

WHO categorises infertility into:

• Failure to conceive may be primary which means the woman has never before been able to bear a child.
• Or may be secondary meaning although the woman has previously had children, she is now unable to bear further children.

Question 13

What percentage of subfertility is caused by male or female (or both) factors?

Answer 13

30% caused by male factors

30% caused by female factors

25% is unexplained

15% caused by both male and female factors

Question 14

What are the common causes of female subfertility?

Answer 14

Common causes of subfertility include:

• Ovulatory disorders such as PCOS and natural decline in fertility with age
• Tubal damage secondary to infection (most common cause worldwide) or endometriosis
• Cigarette smoking
• High and Low BMIs.

Question 15

What:

• Ovulatory disorders
• Tubal disorders
• Uterine problems

commonly cause infertility?

Answer 15

Ovulatory disorders

The commonest cause of problems with ovulation is PCOS, furthermore hormonal management of PCOS (COCP, progesterone) interfere with fertility. Hypothalamic disorders, pituitary disease and endocrine abnormalities are less common causes of anovulation.

Tubal problems

Tubal blockage is usually associated with inflammatory processes in the pelvis such as pelvic inflammatory disease or endometriosis. Chlamydia in particular can produce significant degrees of tubal damage.

Previous pelvic or abdominal surgery can also result in scar tissue or adhesions that can compromise tubal function.

Uterine problems

Uterine problems such as fibroids can interfere with pregnancy, depending on size and location. Asherman’s syndrome (Endometrial scarring) from surgery or infection can be associated with lighter periods and a significantly reduced change of conception.

Question 16

Describe when and how ovarian induction is performed

Answer 16

For patients with hypothalamic or hypopituitary amenorrhoea, gonadotrophins such as menotrophin are the first-line option. This may be given with human chorionic gonadotrophin. The second-line for these patients is IVF.

For patients with PCOS, weight loss and other conservative measures are employed. Metformin has been shown to be effective in ovulation induction, however many doctors prefer beginning with clomiphene. Clomiphene is a oestrogen antagonist preventing normal negative feedback and thus a surge of gonadotrophins. Metformin can be combined with clomiphene, or started alone if the patient is also insulin resistant.

• Clomiphene often leads to multiple pregnancy (12%) and therefore growth of follicles should be monitored by ultrasound?
• 70% on clomiphene will ovulate (50% of these will get pregnant within 6 months)

Controlled ovarian stimulation (electrically shocking ovaries) and ovarian drilling can be used for treatment resistant anovulation.

Question 17

How is intrauterine insemination used to treat infertility?

Answer 17

Intrauterine insemination (IUI) can be used for mild endometriosis, mild male infertility, same-sex couples etc. A small sample of sperm is introduced into the uterine cavity by a fine urethral catheter. A couple of days prior, exogenous FSH is injected to stimulate the production of follicles, and around the time of insemination, ovulation is achieved with subcutaneous injection of human chorionic gonadotrophin.

Question 18

Describe the process of IVF

Answer 18

In vitro fertilisation:

• Hormone regimen to stimulate follicle maturation
• Final maturation of eggs using hCG (mimicks LH surge as very similar instructure)
• Eggs collected under USS guidance just before they are released
• In vitro semination
• Reimplantation of the embryos into the uterine cavity (embryo transfer)

Question 19

What are the ovulatory disorders that cause subfertility?

Answer 19

The commonest cause of problems with ovulation is PCOS, furthermore hormonal management of PCOS (COCP, progesterone) interfere with fertility. Hypothalamic disorders, pituitary disease and endocrine abnormalities are less common causes of anovulation.

• Group I: Hypothalamic-pituitary failure (hypothalamic amenorrhoea, hypogonadotrophic hypogonadism) - low weight/excessive exercise, Kalman’s syndrome
• Group II: Hypothalamic-pituitary-ovarian dysfunction (PCOS, hyperprolactinaemia)
• Group III: Ovarian failure (premature ovarian insufficiency, chemotherapy)

Question 20

What are the tubal and uterine problems that cause subfertility?

Answer 20

Tubal blockage is usually associated with inflammatory processes in the pelvis such as pelvic inflammatory disease or endometriosis. Chlamydia in particular can produce significant degrees of tubal damage.

Previous pelvic or abdominal surgery can also result in scar tissue or adhesions that can compromise tubal function.

Uterine problems such as fibroids can interfere with pregnancy, depending on size and location. Asherman’s syndrome (Endometrial scarring) from surgery or infection can be associated with lighter periods and a significantly reduced change of conception.

Question 21

How is surgery used to treat infertility?

Answer 21

Surgery can be used to treat endometriosis as there is good evidence that ablation of endometriotic tissue can help fertility. Surgery can also be used for other anatomical causes such as removal of hydrosalpinges and manage adhesions.