Polycystic ovary syndrome and subfertility

Infertility is not absolute in individuals with polycystic ovary syndrome (PCOS). Some ovulate spontaneously, and may conceive without needing ovulation induction; however, time to conception is usually prolonged. In those who are obese or have impaired glucose tolerance, the risk of early miscarriage is increased and pregnancy complications are more frequent (including gestational diabetes, pre-eclampsia and delivery problems).

First-line therapy for infertility in individuals with PCOS is lifestyle modification, including diet and exercise. A 5% reduction in body weight in overweight or obese anovulatory individuals may improve fertility and reduce the risk of gestational diabetes. For detailed information, see the lifestyle algorithm in the PCOS Practice Tools for Health Practitioners, available from Monash University 

Note: Diet and exercise are first-line fertility therapies for overweight or obese individuals with PCOS.

If lifestyle changes do not improve fertility, refer to a specialist experienced in reproductive medicine for consideration of ovulation induction with letrozole, clomifene or gonadotrophins.

Metformin can induce ovulation in individuals with PCOS (it also has other indications in PCOS). It is not as effective as clomifene or letrozole. It is most likely to benefit individuals with a body mass index over 30 kg/m2. Measurement of insulin resistance does not predict who will respond to metformin for ovulation induction. Metformin can be considered:

  • while awaiting specialist referral
  • if other drugs (clomifene, letrozole, gonadotrophins) are contraindicated
  • if monitoring for other drugs is not available
  • if the individual is not in a hurry to conceive (more effective drugs are preferred).

Metformin can be trialled alone for up to 1 year; consider clinical review after 3 months. See Metformin for individuals with PCOS for dose recommendations.

Individuals with PCOS have an unpredictable response to letrozole, clomifene and gonadotrophins, and are more likely to develop multiple follicles than females with other anovulatory conditions; response may vary from one cycle to the next. Risks of a multiple pregnancy or OHSS are increased.

Note: Ovulation induction with letrozole, clomifene or gonadotrophins for females with PCOS requires specialist referral; risks are greater than for females with other anovulatory conditions.

Combination therapy with clomifene and metformin may improve pregnancy rates in individuals with PCOS who do not respond to clomifene alone. The effect of combining metformin and letrozole is not known.

If letrozole or clomifene treatment does not achieve ovulation, gonadotrophins can be used.

If other therapies have not been effective, options include:

  • laparoscopic ovarian drilling—this involves diathermy or laser to create punctures in the ovary, which are thought to disrupt follicles and possibly improve ovulation by reducing androgens and inhibins
  • in-vitro fertilisation —particularly if the partner is also infertile. Strategies are required to reduce the risk of OHSS and a single embryo is transferred to avoid multiple pregnancies.