Archive for Metformin

Getting pregnant with PCOS using Metformin (Glucophage) and Clomiphene Citrate (Clomid)

It is unknown whether insulin resistance is a cause of PCOS or a symptom, but regardless one of the large contributing factors to my infertility due to PCOS is/was insulin resistance. When you have insulin resistance, the cells in the body are resistant to insulin, thus they don’t take up glucose from the blood easily; and the body increases the amount of insulin produced, to force the sugar into the cells [1]. High insulin levels affect the ovaries and cause them to produce too much LH (Luteinising Hormone) which then disrupts the cycle and prevents ovulation [2]. Thus in order to ovulate, your insulin levels have to be lowered and more regulated. There are a few ways in which to do this, you can change your diet (follow a low-carb/ketogenic diet) and/or you can take an insulin-sensitizer such a metformin. Sometimes your menstrual cycles will right themselves after some weight loss (about 5% of your body mass) or after being on the metformin for at least 6 months.

Clomiphene Citrate (Clomid) is often the first suggested therapy for anovulation (not ovulating like in PCOS). However many women are Clomiphene resistant (don’t ovulate no matter what the dose). In this case it is recommended that both Metformin and Clomiphene are taken, as the metformin can possibly reduce the clomiphene resistance [3].

In my case I had only been on a low dose of Metformin before I was put on 50mg of Clomid, and I didn’t ovulate. I then decided to give myself 6 months on a higher dose of Metformin (recommended level is over 1500mg/day, I use 2 x 850mg tablets per day) before trying another cycle of Clomid, and the next Clomid cycle I ovulated at 50mg! In total to conceive my son, I did 5 rounds of Clomid (all at 50mg) and got pregnant twice (one miscarriage and one live birth). I truly think I would be resistant to the Clomid if I didn’t take a high dose of Metformin.

Women with PCOS have an incredibly high early miscarriage rate (1st trimester) of between 30-50% (per pregnancy) versus 10-15% for non-PCOS women [4]. Luckily you can take Metformin throughout your pregnancy and drop your chance of early miscarriage to the regular 10-15% as well as decreasing your chances of premature-birth [5, 6].

So after all the wonderful stuff Metformin can do for you why isn’t everyone taking it? Metformin can cause some unfortunate gastro-intestinal side effects (mostly diarrhoea). However by starting at a low dose and slowly increasing it or by using the extended-release version most people eventually tolerate it [7]. In fact, according to [8], although about 25% of people will experience some GI issues until they get used to the drug, only 5% of people are completely unable to tolerate metformin.


[1] Roberts CK, Hevener AL, Barnard RJ, “Metabolic Syndrome and Insulin Resistance: Underlying Causes and Modification by Exercise Training. “, Comprehensive Physiology. Vol. 3(1), pp.1-58, 2013

[2] Franks S, Gilling-Smith C, Watson H and Willis D, “Insulin action in the normal and polycystic ovary.”, Endocrinol Metab Clin North Am. Vol 28(2), pp. 361-78, 1999

[3] Dasari P, Pranahita G. “The efficacy of metformin and clomiphene citrate combination compared with clomiphene citrate alone for ovulation induction in infertile patients with PCOS.”, Journal of Human Reproductive Sciences.Vol 2(1), pp.18-22, 2009

[4] Kamalanathan S, Sahoo JP, Sathyapalan T. “Pregnancy in polycystic ovary syndrome.”, Indian Journal of Endocrinology and Metabolism;Vol.17(1), pp.37-43. 2013

[5] Jakubowicz DJ, Iuorno MJ, Jakubowicz S, Roberts KA and Nestler JE., “Effects of metformin on early pregnancy loss in the polycystic ovary syndrome.”, J Clin Endocrinol Metab. Vol. 87(2), pp.524-9, 2002

[6] Feng L, Lin XF, Wan ZH, Hu D, Du YK, “Efficacy of metformin on pregnancy complications in women with polycystic ovary syndrome: a meta-analysis.” Gynecol Endocrinol. Vol. 31(11), pp. 833-9, 2015

[7] Hostalek U, Gwilt M and Hildemann S. “Therapeutic Use of Metformin in Prediabetes and Diabetes Prevention.” Drugs. Vol. 75(10), pp.1071-1094, 2015

[8] McCreight LJ, Bailey CJ and Pearson ER. “Metformin and the gastrointestinal tract.”, Diabetologia.;Vol. 59:pp 426-435, 2016