Clomiphene citrate, or Clomid, is a common fertility medication. It is often used in ovulatory disorders such as PCOS. Clomid works by making the body think there are low levels of estrogen, resulting in more FSH released by the brain to stimulate the ovaries.

Clomid is dosed in the follicular phase after a withdrawal or menstrual bleed, for 5 days, and is reported to increase conception rates by ~22% per cycle (1). The success of a Clomid cycle can be impacted by a number of factors, including insulin resistance, excess androgens, and obesity. In 15-40% of cases, Clomid may not work, this is something known as “Clomid resistance”, which is defined as failure to ovulate after 3 consecutive cycles.

What can we do to improve outcomes in someone with Clomid resistance?

There are 3 nutrients that I want to bring to your attention that have some interesting research for Clomid resistance.

N-acetyl-cysteine (NAC).

NAC is an amino acid that is used to generate glutathione in the body; a major antioxidant. The benefits of glutathione and fertility are discussed more here. NAC also has actions in the body, including insulin sensitivity, our vascular system, and our immune system.

In Clomid resistance cases, NAC was shown to (Thakker, 2015; Saha 2013, Saha 2015):

• Improve endometrial thickness

• Significantly increase ovulation rates

• Significantly increase pregnancy rates

The benefit of NAC was also demonstrated to improve outcomes in non-resistant cases.

Coenzyme Q10 (COQ10)

COQ10 is a fat-soluble protein found inside our mitochondria. It is an antioxidant that plays a crucial role in energy production. In this study, looking at patients with Clomid resistance, those taking COQ10 + Clomid were shown to have:

• Improve endometrial thickness

• Significantly improved ovulation rates (65.9% vs 15.5% with Clomid alone)

• Significantly improved pregnancy rates (37.3% vs 6.% with Clomid alone).

Carnitine

Carnitine is an amino acid that shuttles fat into the mitochondria for energy production. Thus, this amino acid has an important role in energy production, along with reducing oxidative stress and insulin resistance. This study reviews the use of carnitine in Clomid resistant cases, and demonstrated:

• Significantly improved ovulation rates (64.4% vs 17.4% with Clomid alone)

• Increase number of follicles reaches >17mm

• Significant increase in pregnancy rates (49.4% vs 1.1% with Clomid alone)

• Improved endometrial thickness

• Higher luteal phase progesterone levels

Further, carnitine was also shown to improve other lipid profiles.

Take home

All three of these nutrients are generally very well tolerated, and show very promising research in supporting not only a Clomid cycle but a Clomid-resistance cycle.

 If you’ve had a failed Clomid cycle, or are about to start your first Clomid cycle and want to discuss options to improve outcomes, there are some promising options. This starts with a proper assessment.

As with all therapeutic supplementation, dose, quality, and duration of treatment impact the outcome you’re looking for. Schedule a discovery call to see if these options are suitable for you.