PCOS – The Leading Cause of Female Infertility!

Polycystic ovary syndrome, or PCOS in short, is a common condition in women which prevents 12-21% of them from getting pregnant. However, thanks to recent advances in reproductive medicine, getting pregnant with PCOS has become possible.

Insulin resistance is the hallmark of PCOS. Excessive blood insulin adversely affects ovulation – that main reason why getting pregnant with PCOS is very difficult in these women. Insulin resistance also predisposes women to becoming overweight, which also affects ovulation.

Bearing this in mind, the first line of treatment for PCOS involves intensive lifestyle intervention. It has been shown that a change in diet, by consuming more calories in the morning than in the afternoon and evening can help relive PCOS symptoms, paving the way to successful pregnancy.

When lifestyle interventions fail, drugs can be administered to stimulate ovulation to help women with PCOS get pregnant. The most commonly used drugs to combat PCOS-induced infertility are metformin and Clomid (clomiphene citrate). Currently, there is a good deal of debate as to which is the ideal agent, balancing efficacy versus adverse side effects and BMI (Body Mass Index) considerations.

Understanding the pros and cons of Metformin and Clomid.

As the most prominent feature of PCOS is resistance to insulin, restoring sensitivity to insulin can restore ovulation and increase the chances of getting pregnant with PCOS. Metformin, which had been used as an anti-diabetic drug to reduce excessive blood sugar level for over six decades, has no serious side effects, does not increase the risk of multiple pregnancies and is relatively well tolerated.

Clomid operates a little differently – it does not target insulin resistance in PCOS patients. Instead, it stimulates ovulation by modulating the levels of key sex hormones. Clomiphene has been used as first-line ovulation induction agent since 1967. Today, it is widely used to help women with PCOS get pregnant. However, Clomid is implicated in higher twin and triplet pregnancies and furthermore, prolonged treatment with this drug might increase the risk of ovarian tumors.

***Bottom line: Which is best for you, Metformin or Clomid?

Metformin is low cost, directly combats the underlying cause of PCOS, carries only minor side effects and does not require a specialist to prescribe. However, recent clinical reviews points to Clomid as a better treatment option for PCOS-induced infertility as it is more effective in helping women get pregnant with PCOS along with a higher live birth rate. Therefore, it has been suggested in scientific literature that Clomid should be the first line of pharmacological intervention, and metformin should be used as a second line therapy option.

So I go for Clomid then? Wait, there’s more to the story.

Up to 30% of women treated with Clomid do not respond to treatment and fail to ovulate. This is due to genetic variations in the gene that produces a liver enzyme, CYP2D6, which converts Clomid to its active components.

***Your CYP2D6 activity dictates the efficacy of Clomid!

Genetic variations of CYP2D6 determine how effectively the enzyme will function, ranging from ultrarapid (UM) to poor (PM) metabolizer. As a result, a woman with poorly functioning CYP2D6 enzyme will not be able to activate Clomid, and the treatment will not result in ovulation.

How will you know if your CYP2D6 enzyme functions normally? Or, do you carry genetic variations that results in a poorly functioning CYP2D6 enzyme (if so, Metformin might be the better drug for you)?

A simple genetic test can determine which drug is right for you…

Determining which medication is right for you and the starting dosage is not a trivial task, even for your doctor. We can help make this process a little simpler…

A simple and painless genetic test can identify variations in your CYP2D6 enzyme and determine how well you will respond to Clomid. This information can assist your doctor in devising a personalized treatment schedule with a starting dosage that is tailored to your genetic makeup. And if you find that Clomid might not be the right drug for you, you can start with metformin right away, bringing you closer to successfully getting pregnant with PCOS.

There is more…

It is known that PCOS patients are at higher risk of multiple miscarriage, a recent study showed that MA/ANXA5 genetic variation in some PCOS patients puts them at a higher risk of multiple miscarriage. Further more, genetic variation in CYP19 gene can affect success of assisted reproduction in PCOS patients. Therefore, a simple genetic test here at GeneYouIn can help you and your doctor take precautionary steps against these complications.

To learn more about which of these two drug is good for you AFTER pregnancy, stay tuned for my next blog on PCOS management during pregnancy. If you have additional questions or concerns, please feel free to drop us an email or call us.

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