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Metformin/glucophage

Letrozole

Ovarian drilling

Gonadotropins


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Thoughts on polycystic ovaries

Polycystic ovaries or PCO is a common problem for infertility patients. Patients present with an array of symptoms and at times the diagnosis is far from obvious. The patients more difficult to diagnosis usually require a good antral follicle count which requires a transvaginal ultrasound done by an individual skilled in assessing this problem.

DIRECT LINK TO OVARIAN DRILLING

Polycystic ovaries, PCO, or PCOS is a common gynecological condition that affects fertility. Some patients have a classic form of PCOS defined by having infrequent menstrual periods and physical findings of androgen excess (dark terminal hairs on the face, chest or abdomen). However, there are more subtle forms of PCOS that can also have fertility consequences. Such patients may ovulate most of the time, have mild androgen changes that don't require cosmetic intervention, and have polycystic ovaries (greater than 10 antral follicles in each ovary) on ultrasound. Patients with non-classical forms of PCO are sometimes overlooked in non-specialty practices. Recent research suggests that a very elevated anti-Mullerian Hormone level can also be used to make the diagnosis.

Many patients with PCO are overweight. Many will have been placed on oral contraceptives in their post-adolescent years to help regulate their periods. PCOS becomes more apparent the longer they are off the oral contraceptives. For some patients with PCOS, the fundamental underlying problem is insulin resistance. Insulin is used by the body to regulate the blood sugar. Women with PCOS may produce more insulin than normal to keep their blood sugar in the standard range or they may have abnormal insulin responses to glucose. This abnormal insulin response can only be diagnosed in a research hospital setting; no simple clinical test is available. The most severe cases of this abnormal insulin response may lead to physical exam findings (skin tags and darkened rough skin behind the neck). Elevated insulin levels have a detrimental impact inside the ovaries.

Metformin/glucophage

The drug most commonly used for insulin resistance in this infertility setting is glucophage or metformin. Glucophage helps normalize the body's response to insulin. It also decreases the androgens produced by the ovary. Many women will ovulate after being placed on this drug alone. Many will feel physically better (more energy) and some will lose weight without changing their diet. Traditionally the drug used to help women with PCOS ovulate is clomiphene citrate. Clomiphene blocks estrogen receptors and causes the body to keep producing FSH to stimulate follicle growth in the ovary well past the length of time that the body would normally produce this much FSH. Clomiphene citrate used together with glucophage is three to four times as effective in causing pregnancy than the use of either of them alone.

Letrozole

A recent alternative to clomiphene citrate is letrozole. It works on the pituitary in the same way as clomiphene to prevent the normal decrease in FSH which occurs as a follicle grows, but it does so without blocking estrogen receptors. This results in fewer infertility related side-effects. We use this drug only in patient for whom clomiphene has not worked and only after they completely understand the risks and benefits of its use. The manufacturer of letrozole has stated that the drug should not be used for infertility because of concern about possible cardiac congenital anomalies in babies born to mothers who took the drug. There are a number of publications suggesting that this not a realistic problem. However, it is impossible to prove that a drug does not cause a given problem, and this risk will always be there and needs to be understood by a patient who wishes to use this drug rather than move to more advanced therapy.

Ovarian drilling

Ovarian drilling is a surgical treatment for PCOS, which involves causing intra-ovarian scarring to enable some follicles to develop in a more normal environment than they otherwise would have. It is particularly effective in helping the younger patient achieve pregnancy. Endocrinologically, it appears to work similarly to glucophage with decreased testosterone and insulin levels. For about 20% of patients, the effect is long term, but for most the situation returns back to PCOS after pregnancy. In fact, I have had several patients who achieved pregnancy easily after ovarian drilling, but had to have the procedure repeated for each additional child.

Gonadotropins

Failure to achieve pregnancy with variations on the above regimens can be managed several ways. Such patients usually have a very high threshold for gonadotropins (FSH containing drugs) and when that threshold is reached, they are likely to over-respond with many simultaneous ovulations. This may make ovulation inductions with IUI or intercourse unsafe due to risk of high order multiple gestations. Such patients should undergo IVF where the number of possible embryos can be limited. Patients with PCO who undergo IVF have a higher success rate than other subgroups of IVF patients.

Patients with PCOS also typically do better at older ages getting pregnant than patients without PCOS, because it is easier for them to produce more eggs. However, when they approach menopause, they too will exhaust all of the eggs in their ovaries and the ovarian manifestations of PCOS will improve. The insulin resistance and its consequences will likely remain however. Such patients are at risk for developing diabetes at some point in their lives.

DIRECT LINK FOR GENERAL INFORMATION ON PCOS