Causes and treatments of subfertility

Question 1

State 4 requirements for conception

Answer 1

1. Progressively motile normal sperm capable of reaching and fertilising the oocyte
2. Timely release of a competent oocyte
3. Free passage for the sperm to reach the oocyte and for the embryo to reach the uterus
4. A mature endometrium that allows implantation

Question 2

What is infertility?

Answer 2

Failure to successfully conceive a child after 2 years of frequent unprotected intercourse.

(fertility increases as time of unprotected intercourse increases)
- Investigate after 1 year if concerned

1/6 couples have problems concieving

Question 3

State 6 causes of infertilty

Answer 3

1. Idiopathic (30%)
2. Ovulatory (27%)
3. Male factor (19%)
4. Tubal (14%)
5. Endometriosis (5%)
6. Other (5%) - uterine, endometrial, gamete or embryo effects

**combine male and female = 39%

Question 4

What indications might lead to early referral in a woman?

Answer 4

• older than 35
• Amenorrhoea/oligomenorrhoea
• Previous abdominal/ pelvic surgery
• Previous PID/STD
• Abnormal pelvic examination

Question 5

What indications might lead to early referral in a man?

Answer 5

• Previous genital pathology (Hx of testicular maldescent, surgery, infection, trauma, abnormal semen parameters)
• Previous STD
• Significant systemic illness
• Abnormal genital exam

Question 6

Outline the normal parameters of semen analysis

Answer 6

Count > 15 million/ml
Motility > 40%
Morphology >4%
Volume: 1.5-6mls

Question 7

What reasons might cause abnormal semen analysis?

Answer 7

• No reason in 50%
• Primary testicular failure is the commonest cause for oligo/azoospermia
• Obstructive or non-obstructive azoospermia –> FSH, LH and T
• Y Chromosome microdeletion and cystic fibrosis if sperm count <5 million

Question 8

Why is female age the most important factor in fertility?

Answer 8

Fertility declines with female age due to the decline in oocyte number and quality rather than uterine receptivity

The increased rate of chromosomal abnormalities in the oocyte also result in higher aneuploidy and miscarriage rates

Question 9

What clinical assessments might you conduct when assessing female fertility?

Answer 9

• Screen for chlamydia and rubella
• Ovarian reserve (Early follicular phase hormone level- FSH, LH, E2, Anti-mullarian hormona and antral follicle count)
• Ovulation test
• Tubal test

Question 10

Outline the development of a follicle

Answer 10

Primordial follicles (whichi lie in the ovarian cortex) undergo a series of histological and hormonal changes

Primary follicles turn into secondary follicles that transition antral follicles.

Antral follicles become dependent on hormones, particularly FSH which causes a substantial increase in their growth rate. (Maturing follicles)

The pre-ovulatory follicle ruptures and discharges the oocyte (that has become a secondary oocyte), ending folliculogenesis.

Question 11

Outline the fate of follicles

Answer 11

99% will degenerate (atresia)

• at primordial level (primary transition)
• at antral stages upon FSH deprivation

Question 12

What is anti-mullarian hormone (AMH) and where is it produced?

Answer 12

A glycoprotein hormone whose key function is in growth differentiation and folliculogenesis

• Produced by granulosa cells of pre-antral and small antral stages
• Levels of AMH constant throughout monthly periods but decline with age
• High AMH levels predict a good response

Question 13

How can we track ovulation?

Answer 13

• BBT
• Ovulation detection kits
• Cervical mucous pattern
• Follicular tracking (reliable but costly and labour intensive)
• mid-luteal phase P4 (7/7 before menstruation)
  (If >30nmol/L –> evidence of ovulation)

Question 14

What is the commonest cause of anovulation and primary/secondary amenorrhoea?

Answer 14

PCOS

If oligo/amenorrhoea check FSH/LH, E2, Prolactin, TFT, androgens and SHBG

85% of PCOS cases have normal FSH/LH and E2
5% have high FSH, low E2
10% hypogonadotrophic hypogonadism (low FSH and low E2)

Question 15

Tubal patency is when a womans fallopian tubes are not blocked.

Discuss tubal disease
How would you diagnose it?

Answer 15

• Can be proximal (25%) or distal (75%)
• PID secondary to chlamydia is the commonest cause of tubal damage
• Risk of tubal damage is 12% after 1 episode of pelvic infection, 23% after two, 54% after 3
• Other causes: septic abortion, ruptured appendix, pelvic surgery, ectopic pregnancy

DIAGNOSTIC TOOLS: hysterosalpingogram (HSG), Hysterosalpingo-contrast-ultrasonography (HyCoSy), Laparascopy and dye

• If low risk of tubal disease offer HSG or HyCoSy
• Screen for chlamydia first