A 31 Year Old Woman Presents With Difficulty Conceiving....

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 an interval of 2–9 months. There is no dysmenorrhoea but occasionally the bleeding is heavy.
She was pregnant once before at the age of 19 years and had a termination of pregnancy.
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: 
Follicle-stimulating hormone = 3.1 IU/L ( Normal = Day 2–5 1–11 IU/L)
Luteinizing hormone = 2.9 IU/L ( Normal = Day 2–5 0.5–14.5 IU/L)
Day 21 progesterone = 12 nmol/L (>30nmol/L indicates ovulation)
Prolactin = 1274 mu/L ( Normal = 90–520 mu/L)
Thyroid-stimulating hormone = 4.1 mu/L ( Normal = 0.5–7 mu/L)

1. What is the diagnosis and its etiology?
2. How would you further investigate and manage this couple?

Answers And Discussion:


Diagnosis
The infertility is secondary to anovulation as shown by the day 21 progesterone (>30 nmol/L suggests ovulation has occurred). Normal 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 excreted 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)

Management In This Case:
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 macro-adenoma. It would be advisable to repeat the day 21 progesterone level to confirm ovulatory cycles. The woman should have her rubella immunity checked and should be advised to take preconceptual folic acid until 12 weeks of pregnancy.

If the woman fails to conceive then a full fertility investigation should be planned with semen analysis and tubal patency testing (hysterosalpingogram or laparoscopy and dye test).

Points to Remember
• 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.