Metformin for Infertility: A Complete Guide

Key Takeaways

Some evidence suggests metformin treatment improves egg quality in polycystic ovary syndrome (PCOS) patients undergoing in vitro fertilization (IVF) and reduces the risk of IVF complications.
Some women with PCOS may be able to ovulate regularly and become pregnant after treatment with metformin.
Nearly 70% of IVF cycles have reported that metformin reduced the incidences of miscarriage.

The antidiabetic drug metformin helps to control blood glucose levels in people with type 2 diabetes mellitus. It can also improve fertility in women with polycystic ovary syndrome (PCOS) and obese men with decreased fertility. Please continue reading to learn more about infertility treatment with metformin.

Does metformin help with ovulation induction?

Women with polycystic ovary syndrome (PCOS) have anovulation (lack of ovulation) or oligo-ovulation (infrequent or irregular ovulation). Ovulation is the release of the egg from the ovary and is necessary for pregnancy to be achieved.

Some women with PCOS may be able to ovulate regularly and become pregnant after treatment with the insulin response sensitizer metformin. This drug works best along with lifestyle changes, such as diet and exercise, for weight reduction.

Metformin is especially used in those women with PCOS who also present symptoms of insulin resistance or have previously been diagnosed with diabetes.

Can metformin improve egg quality?

There is some evidence that metformin treatment improves egg quality in PCOS patients undergoing in vitro fertilization (IVF). Metformin also reduces the risk of ovarian hyperstimulation syndrome, a complication caused by gonadotropin ovarian stimulation in assisted reproduction techniques like IVF.

However, research indicates that adding metformin to the ovarian stimulation protocol in PCOS patients undergoing IVF has no impact on pregnancy and live birth rates. Yet some studies have shown that in women who do not have polycystic ovary syndrome and who are undergoing repeat IVF after two or more previous IVF failures, low-dose metformin (500 mg per day) can result in significantly improved follicular development and embryo quality and a higher pregnancy rate compared to previous IVF cycles.

Learn more about fertility options like IVF and intrauterine insemination (IUI).

How much metformin should I take for fertility?

Doctors usually start metformin at 500 mg once daily and increase the dose to 500 mg twice daily after one week, then to 500 mg three times daily after one more week. If the thrice daily dose is not tolerated due to gastrointestinal side effects, it can be reduced back to 500 mg twice daily. The most effective dose of metformin for PCOS and infertility is usually 500 mg three times a day.

Which is better: clomiphene citrate versus metformin treatment?

Clomiphene citrate is an FDA-approved fertility drug that can induce ovulation and result in successful pregnancy in PCOS patients. It is also used to treat male infertility because it increases serum testosterone levels.

In terms of metformin versus clomiphene citrate, metformin is not generally used as a first-line therapy for anovulation in PCOS patients. Ovulation induction agents such as clomiphene citrate or letrozole are much more effective in increasing ovulation, pregnancy, and live birth rates.

In addition, clomiphene citrate works faster than metformin in inducing ovulation. Also, the combination of metformin and clomiphene citrate has a higher success rate than metformin or clomiphene citrate alone.

Is metformin for polycystic ovary syndrome?

PCOS patients often have insulin resistance. This means their bodies can make insulin but cannot use the hormone effectively. Metformin is an insulin-sensitizing agent. It improves tissue insulin sensitivity and can, therefore, have beneficial effects in women with PCOS.

In some countries, metformin is prescribed for ovulation induction in PCOS patients and pregnant women with PCOS and gestational diabetes. However, in the US, metformin is not an FDA-approved fertility drug.

How does metformin work?

Metformin suppresses gluconeogenesis in the liver (hepatic glucose production). It also reduces intestinal glucose absorption. In addition, metformin improves insulin sensitivity and peripheral glucose uptake (cellular glucose uptake in peripheral tissues). These effects of metformin result in lowered blood glucose levels in people with type 2 diabetes mellitus. Learn more about how metformin works.

Takeaways

The antidiabetic drug metformin inhibits hepatic gluconeogenesis (glucose production in the liver) and absorption of glucose from food in the intestines, lowering blood glucose levels in people with type 2 diabetes mellitus.
Metformin may be beneficial for infertile patients (women with PCOS or men with decreased fertility).
Metformin therapy improves menstrual cycle regularity in women with PCOS. However, while metformin has been shown to improve fertility outcomes, fertility treatments like clomiphene citrate are more effective. It also takes a longer time for metformin to cause ovulation induction compared to clomiphene citrate. In head-to-head trials of clomiphene citrate versus metformin, the former comes out on top.
Metformin and clomiphene citrate treatment together may benefit women with polycystic ovary syndrome and result in better pregnancy outcomes. If this combination causes ovulation induction and results in pregnancy, it can avoid more invasive and expensive treatments such as injectable medications or in vitro fertilization (IVF) in reproductive-age women with PCOS.
The benefit of metformin in IVF patients has only been confirmed with regard to a reduction in the incidence of miscarriage and ovarian hyperstimulation syndrome, a complication of IVF.
The usefulness of metformin during pregnancy remains unclear. However, there is encouraging evidence that metformin can prevent gestational diabetes mellitus. It does not have any impact on premature births or cesarean sections. More research is needed on the effects of in-utero metformin exposure (the effects of metformin on the developing baby).
Long-term treatment with metformin, coupled with lifestyle changes, may be beneficial for women with polycystic ovary syndrome (PCOS). However, fertility treatments like clomiphene citrate have better pregnancy outcomes compared to metformin.

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