Management options for the infertile PCOS patient

PCOS is the most common endocrine disorder affecting reproductive ages women. It is characterised by the complex interplay of hyperandrogenism, insulin resistance and increased adiposity. These factors influence fertility primarily by reducing the frequency of ovulation thereby reducing the chance of conception. PCOS also interferes with fertility by affecting oocyte development and quality, embryo quality, endometrial receptivity and embryo implantation. You can read more about the factors that affect fertility in the PCOS patient here.

Management of infertility in the PCOS patient should be individualised and tailored to the unique goals of the patient. With all PCOS patients, dietary and lifestyle advice is necessary and often all that is required in order to establish menstrual regularity and improve chances of conception.  The following article will outline some of the main management options for PCOS associated sub-fertility.

Diet and lifestyle: Diet and lifestyle interventions are considered first line treatment for PCOS. Exercise has been shown to improve ovulation rates and menstrual irregularity as well as improve insulin resistance and assist with weight loss (21). No specific exercise is thought to be superior however most guidelines recommend regular exercise of 150 minutes a week including at least 90  minutes moderate intensity aerobic activity and strength training to help improve metabolic function (21) (22). Any diet that prioritises healthy eating habits is beneficial to PCOS (2). A dietary pattern that supports low GI foods with high fibre and adequate intake of micronutrients can help improve insulin resistance and associated free testosterone levels and weight gain (23)(2). Diet and lifestyle is often used with complementary medicines such as herbal medicines, nutritional medicine and acupuncture (28) and has shown promising results with minimal side effects. Complementary medicine has gained popularity in the management of PCOS and has relatively high satisfaction rates despite minimal evidence to confirm effectiveness (28). To read more about dietary patterns beneficial for PCOS click here.

Weight loss: Traditional weight loss diets have high failure rates and often contribute to a rise in obesity over time due to the dysregulation of metabolic pathways and hunger signalling hormones (18).  However, increased adiposity worsens insulin resistance leading to a more severe PCOS presentation (18). A modest weight loss of 5% of body weight has shown improvements in menstrual cycle regularity and ovulation (22). Prescription of weight loss diets are not advised for the PCOS patient due to increase metabolic damage over time, however sustained weight loss can be achieved through nutrition and blood sugar management education and positive and sustained behavioural change.  Most weight loss pharmacotherapy should be avoided in women wishing to conceive due to teratogenic properties (24). If deemed necessary, bariatric surgery can be considered in the morbidly obese PCOS patient however the patient should be advised that fertility rates improve quickly with rapid weight loss and pregnancy should not be attempted until one year post surgery when weight in stabilised (2). This will reduce the risk of prematurity, small for gestational age and increased hospital stay for the infant (2).

Behavioural therapy: PCOS is associated with poor body image, depression and anxiety which has negative impacts on sexual function and may reduce frequency of intercourse (27). Behavioural therapy through a combination of psychotherapy and pregnancy safe pharmacotherapy (if necessary) can improve PCOS symptoms and sexual function which may in turn lead to better fertility outcomes (21).

Ovulation induction medications: Ovulation induction medications such as clomiphene citrate and letrozole can be used to help encourage ovulation and increase chances of conception (21). Clomiphene citrate is considered first line treatment for ovulation induction with minimal side effects however carries a small increased risk of ovarian hyper stimulation syndrome in women with PCOS (21). Letrozole is becoming a preferred choice for the PCOS patient as it has demonstrated superior pregnancy and live birth rates with lower chances of ovarian hyper stimulation syndrome (21)(2).

Insulin sensitising agents: Metformin is used as an oral insulin-sensitising agent and is a popular prescription in the PCOS patient which can be used alone or in conjunction with ovulation induction medication (21). Currently metformin is not routinely used in pregnancy due to potential side effects such as B12 deficiency. Safety profiles of metformin in pregnancy remain an active area of debate (2). Inositol can be used as a natural metformin alternative for all PCOS patients and in particular for those wishing to conceive (2). Inositol has a similar mechanism of action to metformin but has not shown to have the same level of clinical benefits for PCOS (2). However, Inositol may be preferable to the PCOS patient attempting pregnancy as it is pregnancy safe and can additionally reduce the risk of gestational diabetes, hypertensive pregnancy disorders and preterm birth (25).

Gonadotropins: Gonadatropins are used as second-line agents for ovulation induction following unsuccessful treatment with first-line oral ovulation induction agents or undesirable anti-oestrogenic side effects (21).

Laparasocopic ovarian drilling: Laparascopic ovarian drilling can be used as second line treatment following failed ovulation induction, as an alternative to gonadotropins or as a surgical alternative to medical treatment (26). The surgery involves applying heat or laser to the ovaries with a laparoscope passed through a small incision. This procedure is thought to improve ovarian function, increasing the chance of ovulation (26).

IVF: In vitro fertilisation is considered a third-line treatment option for anovulatory PCOS if first or second line ovulation induction treatments have failed (21). IVF can be highly effective, especially in young women, however carries a higher risk of ovarian hyper stimulation syndrome and multiple births (21). In vitro maturation has been suggested in women with PCOS to help counteract the risk of ovarian hyper stimulation syndrome (21)(2).

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