Case 2: Infertility

 Case 2: Infertility

CASE 2: INFERTILITY
History
A 31-year-old woman has been trying to conceive for nearly 3 years without success. Her last
period started 7 months ago and she has been having periods sporadically for about 5 years.
She bleeds for 2–7 days and the periods occur with intervals of 2–9 months. There is no dysmenorrhoea but occasionally the bleeding is heavy.
She has been pregnant once in the past at the age of 19 years but that pregnancy was terminated for personal reasons. She had a laparoscopy several years ago for pelvic pain, which
showed a normal pelvis.
Cervical smears have always been normal and there is no history of sexually transmitted infection.
The woman was diagnosed with irritable bowel syndrome when she was 25, after thorough
investigation for other bowel conditions. She currently uses metoclopramide to increase gut
motility, and antispasmodics.
Her partner is fit and well, and has two children by a previous relationship. Neither partner
drinks alcohol or smokes.

INVESTIGATIONS

Normal range Follicle-stimulating hormone 3.1 IU/L Day 2–5 1–11 IU/L Luteinizing hormone 2.9 IU/L Day 2–5 0.5–14.5 IU/L Prolactin 1274 mu/L 90–520 mu/L Testosterone 1.4 nmol/L 0.8–3.1 nmol/L Thyroid-stimulating hormone 4.1 mu/L 0.5–7 mu/L Free thyroxine 17 pmol/L 11–23 pmol/L Day 21 progesterone was requested but no period occurred for 3 months and therefore the test was not performed

Questions
• What is the diagnosis and its aetiology?
• How would you further investigate and manage this couple?
100 Cases in Obstetrics and Gynaecology
6
ANSWER 2
The infertility is likely to be secondary to anovulation. Normal testosterone and gonadotrophins and high prolactin suggest the likely case of anovulation is hyperprolactinaemia.
Hyperprolactinaemia may be physiological in breast-feeding, pregnancy and stress. The
commonest causes of pathological hyperprolactinaemia are tumours and idiopathic hypersecretion, but it may also be due to drugs, hypothyroidism, ectopic prolactin secretion or
chronic renal failure. In this case the metoclopramide is the cause, as it is a dopamine antagonist (dopamine usually acts via the hypothalamus to cause inhibition of prolactin secretion,
and if this is interrupted, prolactin is secreted to excess). Galactorrhoea is not a common
symptom of hyperprolactinaemia, occurring in less than half of affected women.

!	Drugs associated with hyperprolactinaemia (due to dopamine antagonist effects)
• Metoclopramide • Phenothiazines (e.g. chlorpromazine, prochlorperazine, thioridazine) • Reserpine • Methyldopa • Omeprazole, ranitidine, bendrofluazide (rare associations)

Questions
• What is the diagnosis and its aetiology?
• How would you further investigate and manage this couple?

ANSWER 2
The infertility is likely to be secondary to anovulation. Normal testosterone and gonadotrophins and high prolactin suggest the likely case of anovulation is hyperprolactinaemia.
Hyperprolactinaemia may be physiological in breast-feeding, pregnancy and stress. The
commonest causes of pathological hyperprolactinaemia are tumours and idiopathic hypersecretion, but it may also be due to drugs, hypothyroidism, ectopic prolactin secretion or
chronic renal failure. In this case the metoclopramide is the cause, as it is a dopamine antagonist (dopamine usually acts via the hypothalamus to cause inhibition of prolactin secretion,
and if this is interrupted, prolactin is secreted to excess). Galactorrhoea is not a common
symptom of hyperprolactinaemia, occurring in less than half of affected women.

The metoclopramide should be stopped and the woman reviewed after 4–6 weeks to ensure
that the periods have restarted and that the prolactin level has returned to normal. If this does
not occur, then further investigation is needed to exclude other causes of hyperprolactinaemia, such as a pituitary micro- or macroadenoma. It would be advisable to carry out a day
21 progesterone level to confirm ovulatory cycles.
As with all women attempting to conceive, she should have her rubella immunity checked
and should be advised to take periconceptual folic acid until 12 weeks of pregnancy to reduce
the risk of neural tube defects.
If the woman fails to conceive after correction of hyperprolactinaemia, then a full fertility
investigation should be planned with semen analysis and tubal patency testing (laparoscopy
and dye test, hysterosalpingogram or hysterosalpingoconstrastsonography (hyCoSy)).

KEY POINTS

• A full drug history should be elicited in women with amenorrhoea or infertility. • Galactorrhoea occurs in less than half of women with hyperprolactinaemia. • Day 21 progesterone over 30 nmol/L is suggestive of ovulation.