Can I get pregnant with PCOS?
Written and medically reviewed by Zahraa Sater, M.D., M.P.H.
Reviewed August 12, 2026 · Next review due August 12, 2028
Short answer
Most women with PCOS can conceive. The barrier is usually absent or unreliable ovulation, which is treatable. The 2023 international guideline names letrozole as the first-line drug for ovulation induction in PCOS, ahead of clomiphene. In the largest head to head trial, letrozole produced live births in 27.5 per cent of women against 19.1 per cent with clomiphene.
PCOS is the most common cause of anovulatory infertility, and anovulation is one of the more treatable causes of infertility there is. The 2023 International Evidence-based Guideline states that "letrozole should be the first-line pharmacological treatment for ovulation induction in infertile anovulatory women with PCOS, with no other infertility factors". That sentence displaced decades of clomiphene-first practice.
Why letrozole is first line
Letrozole is an aromatase inhibitor. By reducing oestrogen production it removes negative feedback on the pituitary, which raises FSH and recruits a follicle. In the double-blind trial by Legro and colleagues, published in the New England Journal of Medicine in 2014, 750 women with PCOS were randomised. Live birth occurred in 103 of 374 women on letrozole, 27.5 per cent, against 72 of 376 on clomiphene, 19.1 per cent (P=0.007). Cumulative ovulation was 61.7 per cent of letrozole cycles against 48.3 per cent of clomiphene cycles.
Letrozole is off-label for this use
Letrozole is FDA approved for hormone receptor positive breast cancer in postmenopausal women, not for ovulation induction, so its use in fertility is off-label and evidence-based. The label is worth understanding: letrozole is contraindicated in pregnancy, states that it "can cause fetal harm when administered to a pregnant woman", and requires a pregnancy test in females of reproductive potential before starting. In ovulation induction it is given for five days early in the cycle and cleared before implantation, which is why this is standard practice worldwide.
What comes after letrozole
The guideline sequences second and third line clearly. Clomiphene alone, or in combination with metformin, gonadotrophins, or laparoscopic ovarian surgery, has a second-line role. In vitro fertilisation, potentially with in vitro maturation, is third line where other ovulation induction has failed and there is no absolute indication for IVF. Metformin alone can improve ovulation rates but is not the first-line fertility drug.
| Line | Option | Note |
|---|---|---|
| First | Letrozole | Higher live birth than clomiphene in PCOS |
| Second | Clomiphene, with or without metformin | Also gonadotrophins or ovarian surgery |
| Third | IVF | Where ovulation induction has failed |
Before ovulation induction starts, a semen analysis and an assessment of tubal patency should be done, because treating anovulation is only useful if it is the actual obstacle. Ask for thyroid function and prolactin to be checked too, since both affect ovulation and both are simple to correct.
The clinical detail
Legro et al, NEJM 2014, PMID 25006718: 750 women, up to five treatment cycles. Live birth 27.5 per cent letrozole versus 19.1 per cent clomiphene, rate ratio 1.44 (95% CI 1.10 to 1.87), P=0.007. Cumulative ovulation 834 of 1352 letrozole cycles versus 688 of 1425 clomiphene cycles, P less than 0.001. Twin pregnancies 3.4 per cent letrozole versus 7.4 per cent clomiphene, not significantly different. Four major congenital anomalies in the letrozole group versus one with clomiphene, P=0.65, a difference not statistically significant but reported transparently.
Practical points: baseline thyroid function, prolactin, a semen analysis and tubal assessment before ovulation induction. Monitoring for multiple follicular development reduces multiple pregnancy risk. Weight optimisation before conception is recommended where relevant, and anti-obesity medications should be stopped before conception is attempted.
Written and medically reviewed by Zahraa Sater, M.D., M.P.H.
Reviewed August 12, 2026 · Next review due August 12, 2028
Sources
- International Evidence-based Guideline for the Assessment and Management of PCOS, 2023 summary. Monash University Centre for Health Research and Implementation
- Letrozole versus clomiphene for infertility in the polycystic ovary syndrome. New England Journal of Medicine. PMID 25006718
- FEMARA (letrozole) prescribing information, 2024. US Food and Drug Administration
- Recommendations From the 2023 International Evidence-based Guideline for the Assessment and Management of Polycystic Ovary Syndrome. Journal of Clinical Endocrinology and Metabolism. PMID 37580314
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