Using Clomiphene and Metformin

by Prof. Robert Jansen, Founder of Sydney IVF

What is clomiphene?

It's a synthetic hormone tablet that stops estrogen from working ... so it's called an "anti-estrogen".

How does it work?

It tricks the body into thinking there's not enough estrogen, so it pushes the ovary into working harder to make more estrogen. It does this by pushing up the production of follicle stimulating hormone (FSH) - and this makes it more likely that you will ovulate (release an egg from the ovary).

Who should take it?

Mostly women who aren't ovulating regularly and who want to get pregnant. Usually they have long menstrual cycles or irregular periods ... or even no periods. Sometimes it's used to give things a boost even if you are already ovulating, like if you've got "unexplained" infertility.

Does it have other names?

Clomid and Serophene ... and one is as good as the other, so get prices and buy the cheaper one.

When do I take it and how much do I take?

Only take it if your doctor has prescribed it. The usual is to take it for 5 days, starting at the beginning of your period, provided you're sure you're not pregnant. Different people need different doses. Most often you take one tablet (50 milligrams) a day for each of the 5 days, but often it needs to be more ... sometimes up to 5 tablets a day! Some people are very sensitive and need less. Your doctor will work it out with you, starting at a low dose and working up if necessary. When the bleeding starts, begin the tablets only if you can be sure it's a normal period, not an unusually light one that could be "implantation bleeding" or a threatened miscarriage. If in doubt, have a pregnancy test done - preferably a blood pregnancy test.

Will clomiphene work if I've hardly got any eggs left?

Usually not. Nothing can make eggs develop and ovulate if there aren't sensitive eggs left in the ovaries ready to start growing. Likewise if your blood level of FSH is increased then clomiphene will not help. The reason is that what clomiphene does for ovulation is to give your FSH a boost - and if you're already making a lot of FSH then there's nothing more that taking clomiphene can do.

What is metformin?

It's a tablet that helps insulin to work and lowers blood sugar levels ... so it's usually taken by patients who have diabetes.

Why might a women who wants to get pregnant need it?

Women who have polycystic ovaries, and who are not ovulating properly, and who want to get pregnant, often ovulate better if they take metformin.

What are polycystic ovaries?

In polycystic ovary "disease" or "syndrome" (PCOD or PCOS - same thing), the "follicles" that contain the eggs don't grow properly. A bunch of medium-sized follicles accumulate in the ovaries, making the ovaries bigger and "polycystic" in appearance ... and sometimes tender and sore. Because the follicles don't grow well they don't ovulate well, so the menstrual cycle is likely to be long. Sometimes the periods can be completely absent. Sometimes there can be excessive and irregular bleeding instead.

What's the connection between insulin and polycystic ovaries?

In at least half of women with PCO, part of the underlying problem is that insulin-like substances are not working well in the ovaries. Metformin then helps the follicles function better - and to ovulate better.

Can I take metformin with clomiphene?

Yes. Metformin might help ovulation by itself if you have PCO, but more often you still need clomiphene to push the follicles into growing. Clomiphene can then work better, or at a lower dose, than if metformin is not used.

Does metformin work in other causes of poor ovulation?

No, there's no evidence that it does.

What are the side effects?

There can be nausea, vomiting or diarrhea. The main serious side-effect is called "lactic acidosis", a profound disturbance of metabolism (usually in older more frail people, perhaps who are having a surgical operation done). There is a loss of appetite, muscle weakness and eventually loss of consciousness. It can be fatal. Lactic acidosis is very rare in young otherwise healthy people taking metformin, but be careful if you have kidney or liver disease or are undergoing a major operation.

How do I take metformin?

Metformin is taken as a 500 milligram tablet, up to 3 a day, depending on side effects. Unlike clomiphene, you should keep taking the tablets through your whole menstrual cycle, and from one cycle to the next.

Do I stop if I'm pregnant?

No. Several studies have shown that if metformin helps you get pregnant then taking it for the first 3 months also helps to reduce the risk of having a miscarriage. Metformin should be stopped before the second half of pregnancy because it can lower glucose levels in the baby, and this is not a good thing leading up to birth.

Does it mean I might develop diabetes?

Diabetes is more common in women with PCO, particularly if they are overweight. Your doctor should check your blood glucose and insulin levels before starting treatment with metformin.

What other names does it have?

Lots. Metformin has been available for many years and there are many companies that manufacture it. Buy according to price and availability.

How do I take metformin?

Metformin is taken as a 500 milligram tablet, up to 3 a day, depending on side effects. Unlike clomiphene, you should keep taking the tablets through your whole menstrual cycle, and from one cycle to the next.