Femara (Letrozole) or Clomid (clomiphene) for ovulation inducion: which one is better? Study shows they are equally effective.


Clomifene (INN) or clomiphene (USAN and former BAN) or Clomid or Clomifert is a selective estrogen receptor modulator (SERM) that increases production of gonadotropins by inhibiting negative feedback on the hypothalamus. It is used mainly for ovarian stimulation in female infertility due to anovulation

Letrozole (INN, trade name Femara) is an oral non-steroidal aromatase inhibitor.Estrogens are produced by the conversion of androgens through the activity of the aromatase enzyme. Estrogens then bind to an estrogen receptor, which causes cells to divide.

 Letrozole prevents the aromatase from producing estrogens by competitive, reversible binding to the heme of its cytochrome P450 unit. 

Letrozole has been used for ovarian stimulation by fertility doctors since 2001—having less side-effects than clomifene (Clomid) and less chance of multiple gestation. A Canadian study presented at the American Society of Reproductive Medicine 2005 Conference suggests that Letrozole may increase the risk of birth defect. A more detailed ovulation induction follow-up study found that letrozole, compared with a control group of clomiphene, had significantly lower congenital malformations and chromosomal abnormalities at an overall rate of 2.4% (1.2% major malformations) compared with clomiphene 4.8% (3.0% major malformations).

A recent meta analysis comparing the two treatments for ovulation induction, Clomid vs Femara  , published on RBM  online, suggests that the two treatments are equivalent outcome-wise. Side effects seem to be less for the Femara group.
In my experience the response seem to be very individualized : some patients respond better to Clomid , others to Femara.

Abstract Below

Abstract 

The aim of this study was to systematically compare the clinical efficacy and safety of letrozole with clomiphene citrate for ovulation induction in women with polycystic ovary syndrome (PCOS). The Cochrane Central Register of Controlled Trials, PubMed, EMbase, CBMdisc and CNKI were searched for eligible randomized controlled trials (RCT) comparing letrozole with clomiphene citrate in PCOS patients. Two reviewers independently extracted information and evaluated methodological quality according to the Cochrane Handbook 5.0. Meta-analysis was performed with the fixed-effects model or random-effects model according to the heterogeneity. Six eligible RCT involving 841 patients were included. Letrozole was associated with a number of lower mature follicles per cycle (standardized mean difference, SMD, –1.41; 95% CI –1.54 to –1.28; P < 0.00001) compared with clomiphene citrate. There were no significant differences in pregnancy rate (relative risk, RR, 0.97; 95% CI 0.79 to 1.18), abortion rate (RR 1.38; 95% CI 0.48 to –3.96) and multiple pregnancy rate (RR 0.34; 95% CI 0.07 to –1.72) between the two groups. The evidence from ovulation rates was not enough to support either letrozole or clomiphene citrate. In conclusion, letrozole is as effective as clomiphene citrate for ovulation induction in patients with PCOS

http://www.rbmojournal.com/article/S1472-6483%2811%2900180-5/abstract

Drugs Used For Anovulation
This list also comprises most of the drugs used for ovulation induction and IVF treatments

The medication which is most commonly used to treat anovulation is clomifene citrate (or clomid), which has been used since the 1960s. It was first used to treat cases of oligomenorrhea, and it was then applied to the treatment of anovulation. It is relatively easy and convenient to use: factors which contributed to its success. Clomifene citrate has an anti-estrogenic role, and it appears to stimulate the pituitary and therefore affect the ovarian function.It also has an effect on cervical mucus quality and uterine mucosa, which might affect sperm penetration and survival, hence its early administration during the menstrual cycle. Clomifene citrate is a very efficient ovulation inductor, and has a success rate of 67%. Nevertheless, it only has a 37% success rate in inducing pregnancy. This difference may be due to the anti-estrogenic effect which clomifene citrate has on the endometrium, cervical mucus, uterine blood flow, as well as the resulting decrease in the motility of the fallopian tubes and the maturation of the oocytes.

Another anti-estrogenic molecule called tamoxifen is often used in the prevention and treatment of breast cancer. It can therefore also be used to treat patients that have a reaction to clomifene citrate. A third anti-estrogenic compound

Femara (Letrozole) is used also as a substitute for Clomid . Estrogens are produced by the conversion of androgens through the activity of the aromatase enzyme. Letrozole blocks production of estrogens in this way by competitive, reversible binding to the heme of its cytochrome P450 unit. The action is specific, and letrozole does not reduce production of mineralo- or corticosteroids. In contrast, the antiestrogenic action of tamoxifen, the major medical therapy prior to the arrival of aromatase inhibitors, is due to its interfering with the estrogen receptor, rather than inhibiting estrogen production.

Human chorionic gonadotropin (hCG) is a molecule which is structurally similar to luteinizing hormone (LH). LH is secreted by the pituitary just before ovulation occurs, whereas hCG is released during pregnancy. On its own, hCG is not very effective in inducing ovulation, but when combined with clomifene citrate, it is much more effective. HCG should only be administered at certain points in the cycle, around the time of ovulation. A Recombinant version of hCG is available commercially and it is called Ovidrel. Ovidrel works just like hcg but it si more convenient because it does not require mixing.

Human menopausal gonadotropin (hMG) is a very powerful treatment for infertility. It consists of a combination of LH and FSH. From menopause onwards, the body starts secreting LH and FSH in large quantities due to the slowing down of the ovarian function. This excess of hormones is not used by the body and is expelled in the urine. HMG is therefore collected from the urine of menopausal women. The urine then undergoes purification and a chemical treatment. The resulting hMG induces the stimulation of several ovarian follicles. This increases the risk of producing several oocytes during the same cycle, and thus the risk of multiple pregnancies. Commercial names of hMGs are Menopur, Repronex.

Follicle-stimulating hormone (FSH or recombinant FSH) is now used as a replacement for hMG. Although hMG is a combination of FSH and LH, FSH is the main active component that has an effect on ovulation.

Metformin is an oral biguanid used to treat type 2 diabetes that has shown very promising results in the treatment of patients with PCOS. However, some experts question the efficacy of metformin. Though the results from early treatment with metformin were promising, its role and the roles of other similar molecules in reducing insulin levels among patients suffering from PCOS is not very clear.

Several studies indicate that in some cases, a simple change in lifestyle could help patients suffering from anovulation. Consulting a nutritionist, for example, could help a young women suffering from anorexia to put on some weight, which might re-start her menstrual cycle. Conversely, a young overweight woman who manages to lose weight could also relieve the problem of anovulation (losing just 5% of body mass could be enough to re-start ovulation). However, it is widely acknowledged by doctors that it is usually very difficult for PCOS patients to lose weight.