Treatment of ovulatory dysfunction

Referral to Infertility Specialist.

The World Health Organization (WHO) classifies ovulation disorders into 3 groups.

• Group I: hypothalamic pituitary failure (hypothalamic amenorrhoea or hypogonadotrophic hypogonadism)
  
  
• Group II: hypothalamic-pituitary-ovarian dysfunction (predominately polycystic ovary syndrome)
  
  
• Group III: ovarian failure

WHO Group I ovulation disorders

• advise women with WHO Group I anovulatory infertility that they can improve their chance of regular ovulation, conception and an uncomplicated pregnancy by:
  • increasing their body weight if they have a BMI of less than 19 and/or
  • moderating their exercise levels if they undertake high levels of exercise
    
    
• offer women with WHO Group I ovulation disorders pulsatile administration of gonadotrophin-releasing hormone or gonadotrophins with luteinising hormone activity to induce ovulation

WHO Group II ovulation disorders

In women with WHO Group II ovulation disorders receiving first-line treatment for ovarian stimulation:

• advise women with WHO Group II anovulatory infertility who have a BMI of 30 or over to lose weight. Inform them that this alone may restore ovulation, improve their response to ovulation induction agents, and have a positive impact on pregnancy outcomes
• offer women with WHO Group II anovulatory infertility one of the following treatments, taking into account potential adverse effects, ease and mode of use, the woman's BMI, and monitoring needed:
  • clomifene citrate or
  • metformin
  • or a combination of the above
• for women who are taking clomifene citrate, offer ultrasound monitoring during at least the first cycle of treatment to ensure that they are taking a dose that minimises the risk of multiple pregnancy
• for women who are taking clomifene citrate, do not continue treatment for longer than 6months
• women prescribed metformin should be informed of the side effects associated with its use (such as nausea, vomiting and other gastrointestinal disturbances).

In women with WHO Group II ovulation disorders who are known to be resistant to clomifene citrate:

• for women with WHO Group II ovulation disorders who are known to be resistant to clomifene citrate, consider one of the following second-line treatments, depending on clinical circumstances and the woman's preference:
  • laparoscopic ovarian drilling or
  • combined treatment with clomifene citrate and metformin if not already offered as first-line treatment or
  • gonadotrophins
• women with polycystic ovary syndrome who are being treated with gonadotrophins should not be offered treatment with gonadotrophin-releasing hormone agonist concomitantly because it does not improve pregnancy rates, and it is associated with an increased risk of ovarian hyperstimulation

Hyperprolactinaemic amenorrhoea -dopamine agonists

• women with ovulatory disorders due to hyperprolactinaemia should be offered treatment with dopamine agonists such as bromocriptine. Consideration should be given to safety for use in pregnancy and minimising cost when prescribing

Notes:

• vaginal progesterone suppositories from the second or third day of the basal body temperature rise may be used to correct a luteal phase deficiency.
• clomifene - which promotes gonadotrophin release by blocking the hypothalamic receptor sites for oestradiol - is frequently used to correct anovulation. Treatment begins early in the follicular phase.
• follicular growth without ovulation fails implies absence of the LH surge; ovulation may be completed by the use of human chorionic gonadotrophin - hCG - when the follicle reaches 18 cm in diameter as assessed by ultrasound.
• clomifene induces ovulation in 70% of anovulatory women. The main complication is an increased risk of a multiple pregnancy. Cervical mucus may also become less receptive to sperm on account of the anti-oestrogen effect
• there is evidence that clomifene plus dexamethasone treatment resulted in a significant improvement in the pregnancy rate when compared to clomiphene alone as did clomiphene plus pretreatment with combined oral contraceptives (2)
• the review shows evidence supporting the effectiveness of the current first line treatment, clomifene (2)

Reference:

1. NICE (September 2017).Fertility problems: assessment and treatment
2. Beck JI et al. Oral anti-oestrogens and medical adjuncts for subfertility associated with anovulation. Cochrane Database Syst Rev 2005;(1):CD002249