Cochrane for Clinicians

Putting Evidence into Practice

Aromatase Inhibitors Such as Letrozole (Femara) vs. Clomiphene (Clomid) for Subfertile Women with PCOS

 

Am Fam Physician. 2019 May 1;99(9):545-546.

Clinical Question

Compared with clomiphene (Clomid), are aromatase inhibitors such as letrozole (Femara) effective treatments for subfertile women with polycystic ovary syndrome (PCOS) who are trying to conceive?

Evidence-Based Answer

When treated with letrozole, subfertile women with PCOS who are trying to conceive have increased chances of pregnancy (number needed to treat [NNT] = 11) and live birth (NNT = 10) compared with those treated with clomiphene. The risk of adverse outcomes including miscarriage, ovarian hyperstimulation syndrome, and multiple pregnancy is not increased.1 (Strength of Recommendation: A, based on consistent, good-quality patient-oriented evidence.)

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SUMMARY TABLE:

CLOMIPHENE (CLOMID) VS. LETROZOLE (FEMARA) FOR SUBFERTILE WOMEN WITH POLYCYSTIC OVARY SYNDROME

Outcomes with up to six months of treatment and timed intercourseProbable outcome with clomipheneProbable outcome with letrozole (95% CI)NNT for outcome with letrozole (95% CI)Number of participants (number of studies)Quality of evidence

Pregnancy*

264 per 1,000

359 per 1,000 (330 to 390)

11 (8 to 15)

4,629 (25 RCTs)

Moderate

Live birth rate

214 per 1,000

314 per 1,000 (279 to 352)

10 (7 to 15)

2,954 (13 RCTs)

Moderate

Ovarian hyperstimulation syndrome

5 per 1,000

5 per 1,000 (5 to 6)

NA†

2,536 (12 RCTs)

High

Miscarriage rate

201 per 1,000

191 per 1,000 (150 to 240)

NA†

1,210 (18 RCTs)

High

Twin or other multiple pregnancy

17 per 1,000

13 per 1,000 (7 to 21)

NA†

3,579 (17 RCTs)

High


NA = not applicable; NNT = number needed to treat; RCT = randomized controlled trial.

*—Pregnancy was defined as the presence of a gestational sac on ultrasonography.

†—Results were not statistically significant.

SUMMARY TABLE:

CLOMIPHENE (CLOMID) VS. LETROZOLE (FEMARA) FOR SUBFERTILE WOMEN WITH POLYCYSTIC OVARY SYNDROME

Outcomes with up to six months of treatment and timed intercourseProbable outcome with clomipheneProbable outcome with letrozole (95% CI)NNT for outcome with letrozole (95% CI)Number of participants (number of studies)Quality of evidence

Pregnancy*

264 per 1,000

359 per 1,000 (330 to 390)

11 (8 to 15)

4,629 (25 RCTs)

Moderate

Live birth rate

214 per 1,000

314 per 1,000 (279 to 352)

10 (7 to 15)

2,954 (13 RCTs)

Moderate

Ovarian hyperstimulation syndrome

5 per 1,000

5 per 1,000 (5 to 6)

NA†

2,536 (12 RCTs)

High

Miscarriage rate

201 per 1,000

191 per 1,000 (150 to 240)

NA†

1,210 (18 RCTs)

High

Twin or other multiple pregnancy

17 per 1,000

13 per 1,000 (7 to 21)

NA†

3,579 (17 RCTs)

High


NA = not applicable; NNT = number needed to treat; RCT = randomized controlled trial.

*—Pregnancy was defined as the presence of a gestational sac on ultrasonography.

†—Results were not statistically significant.

Practice Pointers

PCOS is the most common cause of oligomenorrhea and amenorrhea worldwide,1 affecting one in 10 U.S. women of childbearing age.2 Women with PCOS often experience anovulation. Clomiphene has been the most widely used treatment for infertility in this group. Both clomiphene and letrozole are given at the beginning of a menstrual cycle to improve the chances of ovulation and are followed by timed intercourse (or intrauterine insemination). The authors sought to determine if letrozole, an aromatase inhibitor, is as safe and effective as clomiphene for PCOS-associated infertility.

This Cochrane review included 42 randomized controlled trials (RCTs) comparing letrozole with clomiphene. The trials were from eight different countries and included a total of 7,935 women 18 to 40 years of age with anovulatory PCOS.1 Only one trial was performed in the United States. The primary analysis included studies of ovulation induction followed by timed intercourse. The quality of evidence was moderate for the primary outcome (live

Author disclosure: No relevant financial affiliations.

References

show all references

1. Franik S, Eltrop SM, Kremer JA, Kiesel L, Farquhar C. Aromatase inhibitors (letrozole) for subfertile women with polycystic ovary syndrome Cochrane Database Syst Rev. 2018;(5):CD010287....

2. U.S. Department of Health and Human Services, Office on Women’s Health. Polycystic ovary syndrome. https://www.womenshealth.gov/a-z-topics/polycystic-ovary-syndrome. Accessed September 9, 2018.

3. American Society for Reproductive Medicine. Prevention and treatment of moderate and severe ovarian hyperstimulation syndrome: a guideline. Fertil Steril. 2016;106(7):1634–1647.

4. ACOG Practice Bulletin No. 194: Polycystic ovary syndrome. Obstet Gynecol. 2018;131(6):1174–1176.

5. Smithson DS, Vause TD, Cheung AP. No. 362–Ovulation induction in polycystic ovary syndrome. J Obstet Gynaecol Can. 2018;40(7):978–987.

6. GoodRx.com. https://www.goodrx.com/. Accessed September 9, 2018.

These are summaries of reviews from the Cochrane Library.

This series is coordinated by Corey D. Fogleman, MD, Assistant Medical Editor.

A collection of Cochrane for Clinicians published in AFP is available at https://www.aafp.org/afp/cochrane.

 

 

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