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Clomid vs Letrozole to induce ovulation

By Dr. Jesús Alberto Félix Atondo

Polycystic Ovary Syndrome (PCOS) is a heterogeneous endocrine disorder, which is characterized by cysts formation on the ovaries, anovulation and hormonal alteration that severely impact a woman´s life, since it is one of the main infertility causes.

Abnormal hormones levels such as LH, FSH, estrogen and testosterone are common in PCOS, and cause oligomenorrhea, amenorrhea and other irregularities in the menstrual cycle that cause anovulation, which consists of a lack of eggs released by the ovaries.

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In order to treat this condition, and others that cause anovulation, fertility specialists often recommend ovulation-inducing agents such as clomiphene citrate (CC) and letrozole, an aromatase inhibitor. Below we will tell you more about both treatments.


Clomiphene Citrate (CC)

It is the first choice drug for the anovulatory infertility treatment. It is a selective modulator that blocks estrogen receptors in the brain, so it makes it believe that there are low levels to stimulate the pituitary gland to produce more FSH and LH; meaning, it increases the FSH level and inhibits the estrogen receptor to obtain more growth cycles of multiple follicles.

Success rates to achieve ovulation and pregnancy improve when women with PCOS and who are overweight manage to reduce their body mass index (BMI) with diet and exercise, since it has been proven that BMI less than 30 increases the pregnancy rate although with a modest decrease in body weight ovulation can begin.

Some of clomiphene´s disadvantages are that in some patients it can slightly affect the implantation as well as it could take up to two weeks to eliminate from the body and cause a prolonged estrogen receptors blockage and an increased LH and FSH production after having stopped the drug, so it has a relatively high rate of multiple pregnancies (3 to 8%) and side effects such as mood swings and hot flashes.


Clomiphene resistance

In some patients ovulation is not induced with clomiphene treatment and the specialist may consider increasing the dose; however, if the increase does not work, resistance to clomiphene is considered. This situation is common in women with a BMI greater than 25, in patients with high levels of prolactin in the blood, as well as in patients with PCOS who have insulin resistance or hyperandrogenia.



Letrozole is a non-steroidal aromatase inhibitor. It´s mechanism of action is to block the estrogens synthesis from androgen precursors; and therefore, it reduces estrogen levels in the body so that the FSH and LH production is increased.

More and more specialists recommend letrozole to stimulate folliculogenesis since estrogen receptors are not depleted and, therefore, an antiestrogenic effect on the endometrium is not obtained; It also causes fewer adverse side effects since it remains less time in the body and is eliminated faster, so the risks of causing a thin endometrial lining and multiple pregnancies are very low. In addition, studies have shown that you get a higher pregnancy rate with letrozole than with clomiphene.

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What do the statistics say?

  • Ovulation disorders are the most common cause of infertility, affecting between 30 and 40% of women who have not been able to become pregnant.
  • PCOS is the most common cause of general and anovulatory infertility diagnosis.
  • Recent research indicates that the use of letrozole results similar to or better than clomiphene in inducing ovulation and producing live births.
  • The ovulation rate with letrozole is higher than that of clomiphene, and pregnancy can be obtained in less time. In addition, multiple pregnancies chances are lower with letrozole by having more monofollicular growth.
  • Letrozole helps induce ovulation in women with resistance to clomiphene, who were unsuccessful with such treatment. It has also been shown to be more effective in PCOS patients.



It is necessary to individualize based on the medical assessment of each patient in order to know the situation in which they are and to address which of the drugs is the best candidate.

Both clomiphene and letrozole are effective treatments to induce ovulaion in patients with polycystic ovary syndrome or another condition that causes lack of ovulation, and are affordable, reliable drugs that can be purchased at a lower cost than others such as gonadotropins and can be combined with other fertility treatments to increase the chances of achieving a pregnancy either naturally, or to prepare the female body for an In Vitro Fertilization (IVF) cycle.

If after several attempts you still do not manage to get pregnant, schedule your appointment at The Fertility Center, where our specialists will help you choose the treatment with which you will fulfill your dreams of being a mother. We have procedures like intrauterine insemination or embryo freezing, contact us through our form to schedule your appointment or request more information. We will gladly assist you!

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Dr. Jesús Alberto Félix Atondo

Gynecology, Obstetrics and Biology of Human Reproduction Surgeon at the Autonomous University of Guadalajara, specialist Biologist of Human Reproduction by the Mexican Institute of Infertility.

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