Author Archive for Megan

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

Anti-inflammatories and Ovulation

As someone who suffers from an autoimmune disease, anti-inflammatories (or more specifically NSAIDs Non-Steroidal Anti-Inflammatory Drugs) are often my best friend. I’ve been on and off them for probably close on 15 years and have often relied on them to help me make it through the day. So when my husband and I were trying to conceive I kept on popping them without a thought, while weaning myself off of all the hectic autoimmune disease drugs such as methotrexate that I was advised to get off of before conception (you need to be off of methotrexate for at least 4 months before you conceive). Then because things were taking a little longer than I would of hoped, I started to investigate the effect of the NSAID I was still taking on fertility. I was stunned by what I found, even more so because not one of my doctors had mentioned it.

NSAIDs can interrupt, delay or stop ovulation due to the action of the NSAID on the cox-2 enzyme and its role in the development of prostaglandins (a fatty molecule involved in the regulation of inflammation) [1]. If you think about ovulation, it is essentially an inflammatory process with the follicle on the ovary swelling and eventually bursting to release the egg. If you don’t allow for this inflammation then ovulation cannot occur.

In fact some NSAIDs are so good at stopping ovulation that they have been investigated for their use as contraceptives or as morning-after pills [2, 3]! Unfortunately it is not just prescription anti-inflammatories (such as Arcoxia and Celebrex, Mypaid and Myprodol) that can cause this, anti-inflammatories available over the counter are responsible as well (such as Voltaren, Cataflam, Nurofen , Advil) [4].

So if you are trying to conceive, think carefully about popping a pill for a headache or backache.


[1] M. Gaytán, C. Morales, C. Bellido, J.E. Sánchez-Criado and F. Gaytán, “Non-steroidal anti-inflammatory drugs (NSAIDs) and ovulation: lessons from morphology”, Histol Histopathol Vol. 21, pp. 541-556, 2006

[2] Edelman AB, Jensen JT, Doom C, Hennebold JD, “Impact of the prostaglandin-synthase 2 inhibitor celecoxib on ovulation and luteal events in women. “, Contraception, 87(3), pp. 352-357, 2013

[3] McCann NC, Lynch TJ, Kim SO and Duffy DM, “The COX-2 inhibitor meloxicam prevents pregnancy when administered as an emergency contraceptive to nonhuman primates”. Contraception. 88, 2013

[4] Salman S, Sherif B & Al-Zohyri A, “Effects of some non-steroidal anti-inflammatory drugs on ovulation in women with mild musculoskeletal pain.” Annual European Congress of Rheumatology, 2015


Welcome to Evidence Based Moms

As the old trope goes, Babies don’t come with a manual! And neither does getting pregnant with those babies or dealing with them as they grow out of babyhood. Many people claim to have the answers, online forums, parenting articles, your parents and in-laws (and especially random people you meet in the supermarket). But if everyone’s advice is different, how do you know which is correct?

This is when we turn to science. Modern medicine is based on the practice of being evidence based, which means that you can’t claim something works unless you can prove that it works. Proving something works is not that easy, as you have to show repeatable, predictable results in enough people that you can extrapolate to the general population and then publish this work so that others can read it and critique it and act upon it. The Internet is filled with journals, white papers and conference proceedings outlining all this work.

So if all this information is available why don’t people access it? The primary reason is because you generally have to have multiple years of graduate level education to cut through the jargon and understand what the information is about. This is what we hope to do on this blog. We want to take the questions that we come up against in our everyday parenting lives and answer them to the best of our ability with the latest science and medicine has to offer. We also want to make sure that everyone who stumbles onto our blog can understand and take out actionable points of information.

Please note that we are providing the latest information to the best of our abilities, however we are NOT your medical doctor! Any information you find on this blog that you find interesting, wish to implement etc should be thoroughly discussed with your health care provider before you do anything. We are not here to diagnose or advise, we are just providing information which may or may not be relevant to you.