February Fertility eNews from GIVF

What is PCOS? PCOS is the most common female reproductive endocrine disorder, affecting between 5-10 percent of reproductive aged women. PCOS is a common cause of infertility, menstrual irregularity, hirsutism (excess hair growth) and acne.

What are the characteristics of PCOS? PCOS is defined as having at least 2 of the following three characteristics:

1)Chronic anovulation (lack of or irregular ovulation)

2)Chronic hyperandrogenism (excess male hormone production)

3)PCOS appearing ovaries

What are the effects of chronic anovulation? The most common symptom in PCOS and the cause of the associated infertility, is an ovulatory disturbance which causes irregular menstrual cycles. Women with PCOS typically have periods that occur more than thirty-five days apart or have fewer than eight periods a year. Some women do not even have periods as a result of the complete lack of ovulation.

Lack of ovulation provides fewer opportunities for sperm to encounter an egg and therefore fewer opportunities to achieve pregnancy. If ovulation is irregular, it may also become difficult to determine a woman's fertile window, which typically lasts only 24-48 hours.

Apart from fertility concerns, infrequent menstruation can increase the chance of endometrial hyperplasia (thickened lining of the uterus) and endometrial cancer.

What are the effects of hyperandrogenism? Hyperandrogenism is an excess of male hormones (like testosterone). Hyperandrogenism contributes to the ovulation disturbance that is seen and may also affect egg quality. In addition, hyperandrogenism contributes to hirsutism (excess hair growth), a condition in which coarse hairs are found on the face, chest, lower abdomen and back. Hyperandrogenism can also cause acne, oily skin and male pattern thinning or baldness of the scalp hair. Some women with PCOS can have laboratory evidence of excess androgens but they do not have hirsutism or acne.

What are polycystic appearing ovaries? Polycystic appearing ovaries are plump and contain multiple small follicles (fluid filled sacs that contain immature eggs). Twenty percent of women with normal menstrual cycles and fertility may have polycystic appearing ovaries. Therefore, additional criteria is needed to make the diagnosis of polycystic ovary syndrome.

What causes PCOS? The pathophysiologic defect (molecular cause) in PCOS is unknown. However, since it clusters in families, a genetic cause is likely. Additionally, environmental influences, such as weight, exercise and diet can modulate the severity of the symptoms.

How is weight and diet linked to PCOS? What is insulin resistance? Obesity is common in patients who have PCOS. However, weight is not a defining characteristic of PCOS as lean patients also have PCOS. A large percentage, but not all patients, who have PCOS have "insulin resistance". Insulin is a vital hormone that is primarily involved in glucose regulation. In insulin resistance, insulin does not function well and therefore in order to compensate, the body produces excess insulin. The excess insulin can increase the androgen levels that are produced by the ovaries, leading to hyperandrogenism and its associated effects.

Obesity independently increases insulin resistance and can exacerbate PCOS. Therefore weight loss (if overweight) and exercise can lower insulin resistance. Additionally, a diet with more complex carbohydrates (whole grains) can help insulin function.

Is PCOS associated with any other health effects? Women with PCOS, especially those with insulin resistance, are more likely to develop impaired glucose tolerance and diabetes. This can occur before the age of 40. Later in life, women are also more likely to develop high blood pressure, elevated cholesterol and triglycerides and coronary artery disease

Is there a classic appearance to PCOS? Are there tests that can diagnose PCOS? PCOS has a highly varied presentation. On one extreme, is the PCOS patient who is obese, has a few periods a year, and has highly visible and excess facial hair growth. On the other extreme is a lean patient who has no acne or hirsutism and has mild menstrual irregularity.

No specific test can definitely diagnose PCOS. The diagnosis is one of exclusion, which means your doctor must consider all of your signs and symptoms and then rule out other possible disorders that can cause a similar presentation. Common medical tests that can help make the diagnosis include a pelvic ultrasound to look at the ovaries, bloodwork to measure the level of androgens, testing of insulin and and glucose levels and checking thyroid function and the hormone prolactin.

What is the treatment for PCOS? The treatment varies based on whether or not a woman is trying to achieve a pregnancy. If she is interested in becoming pregnant, the management of PCOS begins with diet and exercise in order to achieve an ideal body weight. Medical treatment is available in order to bypass the defect in ovulation.

The initial ovulation induction agent is typically the medication, Clomiphene Citrate. This is an oral medication taken for 5 days each month. This medication supports the normal progression and development of the egg followed by ovulation, the release of the egg. Clomiphene can also help produce and release more than 1 egg and therefore the possibility of a multiple pregnancy does exist. Most patients do not have side effects from this medication. Those who do may experience mild headaches, mood swings, abdominal bloating, visual effects, hot flushes, and symptoms comparable to those felt in the premenstrual period. Clomiphene citrate restores normal ovulation in approximately 80% of patients with PCOS and its use can be combined either with natural timed coitus or with an intrauterine sperm insemination (IUI). Approximately 40% of patients who have PCOS and an ovulatory disturbance, deliver babies with the use of Clomid.

Patients who are resistant to Clomiphene (20% of patients) or unsuccessful with Clomid can benefit from the use of gonadotropins (injectable medication, most commonly the hormone follicle stimulating hormone (FSH). This treatment involves taking a daily injection (smaller than a blood draw needle) for approximately 7-10 days with close monitoring through bloodwork and vaginal ultrasounds. The gonadotropins can lead to a higher risk of multiple pregnancy since more eggs are produced. Therefore the monitoring is essential to minimize the risk of a high order multiple pregnancy (triplets or more). Most patients do not have side effects from this medication but those that do may experience mild abdominal bloating, headaches, mood swings and symptoms comparable to those felt in the premenstrual period. Ovulation induction with FSH is often performed in conjunction with an IUI.

For patients who are unsuccessful in achieving pregnancy with either method, in-vitro-fertilization (IVF) offers great success. IVF has the advantage of producing multiple eggs and embryos but at the same time minimizing and controlling the risk of a multiple pregnancy since the maximum number of pregnancies is generally related to the number of embryos replaced. In IVF, the medication protocol involves the same gonadotropin injections that are used in the FSH/IUI protocol but at a higher dosage and sometimes for longer duration. The eggs are collected in a procedure in an outpatient procedure called an egg retrieval. The eggs are fertilized in the dish and then transferred back into the uterus. IVF is the procedure of choice, if in addition to PCOS, there is a tubal/ pelvic or male factor involved as a cause of the couple's infertility since it can bypass all of these issues.

A commonly used adjunct to the ovulation induction medication used above is the medication, Metformin. Metformin is an oral medication that is used to restore insulin sensitivity. This in turn decreases insulin resistance, decreases insulin levels and decreases androgen levels. This in turn can lead to ovulation alone or promote the effectiveness and response to the ovulation induction regimen. Metformin is also used to treat impaired glucose tolerance and diabetes. Metformin use alone does not increase the risk of a multiple pregnancy. However, Metformin can cause gastrointestinal side effects that may limit its use.

Electrolysis, laser treatments, waxing and bleaching may be safely used to remove excess hair in patients who are interested in achieving pregnancy.

If a patient has PCOS and is not interested in achieving pregnancy, the use of oral contraceptives can restore normal menstrual cyclicity, prevent the development of endometrial hyperplasia and it can control ovarian androgen production thereby controlling hirsutism and acne. Other medications can also be used to control the hirsutism and acne if a patient is not at risk for getting pregnant (Spironolactone, Vaniqa).

The ideal medication protocol is individualized and personalized based on a patient's unique needs. If you are a patient with PCOS, please speak to your doctor to determine which is the best treatment for you.