Does Sildenafil (Viagra) increase pregnancy rates?

Does Sildenafil Increase Pregnancy Rates?

Sildenafil may improve pregnancy rates in specific infertility contexts—particularly when added to clomiphene citrate in women with unexplained infertility or thin endometrium—but it is not recommended for treating fetal growth restriction during pregnancy and lacks sufficient evidence for routine use in assisted reproductive technology.

Evidence for Sildenafil in Infertility Treatment

Unexplained Infertility with Clomiphene Citrate

The most compelling evidence supports sildenafil use in women with unexplained infertility undergoing ovulation induction:

• Adding sildenafil (25 mg twice daily, days 8-12) to clomiphene citrate significantly increased pregnancy rates to 65% versus 40% with clomiphene alone (P=0.043) in a randomized controlled trial 1
• A second trial confirmed these findings, showing pregnancy rates of 28.92% with sildenafil plus clomiphene versus 20.83% with estradiol valerate plus clomiphene (P=0.04), along with superior Applebaum scores (17.05 vs 15.14, P=0.000) 2
• The mechanism involves improved endometrial thickness (10.4 ± 1.4 mm vs 9.2 ± 1.9 mm, P=0.007) through enhanced uterine blood flow 1

Common pitfall: Headache is the most frequent adverse effect, reported in 20% of patients receiving sildenafil, with overall adverse effects occurring in 42.5% versus 22.5% with clomiphene alone 1

Assisted Reproductive Technology (IVF/ICSI)

Evidence for sildenafil in IVF is more limited and mixed:

• In women with repeated IVF failures and thin endometrium (<7 mm), vaginal sildenafil (100 mg suppository daily) showed a two-fold increase in chemical pregnancy rates compared to placebo, though this was not statistically significant due to small sample size 3
• A retrospective cohort of 105 women with poor endometrial development showed that 70% achieved endometrial thickness ≥9 mm with vaginal sildenafil (25 mg four times daily), with implantation rates of 29% and ongoing pregnancy rates of 45% in responders 4
• However, 30% of patients did not respond to sildenafil, particularly those with a history of endometritis (59% in non-responders vs 44% in responders) 4

Male Factor Infertility

For male patients attempting conception:

• Sildenafil has not demonstrated a clinically relevant negative impact on offspring outcomes and can be continued in men trying to conceive, according to EULAR 2025 guidelines 5
• This applies even though sildenafil is primarily used for erectile dysfunction rather than directly improving fertility parameters 5

Contraindications During Pregnancy

Fetal Growth Restriction

Sildenafil is explicitly NOT recommended for treating fetal growth restriction:

• The Society for Maternal-Fetal Medicine (2020) provides a Grade 1B recommendation against sildenafil for in utero treatment of FGR, stating "there is no evidence that therapeutic interventions, including sildenafil to augment uteroplacental perfusion through vasodilation, improve placental perfusion and outcome in pregnancies with FGR" 5
• A meta-analysis found that sildenafil may increase fetal weight at birth by 222.58 grams [27.75 to 417.41] in placental insufficiency, but this evidence has significant limitations and heterogeneity 6

Safety Profile in Pregnancy

• The FDA classifies sildenafil as Pregnancy Category B, with no evidence of teratogenicity in animal studies at doses 32-68 times the recommended human dose 7
• However, safety and efficacy during labor and delivery have not been established 7
• It is unknown whether sildenafil is excreted in human breast milk, requiring caution during lactation 7

Clinical Algorithm for Sildenafil Use in Fertility

Step 1: Identify the clinical scenario

• Unexplained infertility with clomiphene induction → Consider sildenafil addition 2, 1
• Repeated IVF failure with thin endometrium (<7-9 mm) → Consider vaginal sildenafil 3, 4
• Fetal growth restriction during pregnancy → Do NOT use sildenafil 5
• Male partner with erectile dysfunction → Continue sildenafil 5

Step 2: Dosing regimens with evidence

• For ovulation induction: 25 mg oral sildenafil twice daily from cycle days 8-12 1
• For IVF with thin endometrium: 25 mg vaginal suppository four times daily for 3-10 days OR 100 mg vaginal suppository once daily 3, 4

Step 3: Monitor response

• Assess endometrial thickness on hCG trigger day (target ≥9 mm) 1, 4
• Discontinue if patient develops intolerable headaches or other adverse effects 1
• Consider alternative approaches if history of endometritis (lower response rate) 4

Step 4: Contraindications to verify

• Concurrent nitrate use (absolute contraindication) 8
• Potent CYP3A4 inhibitors requiring dose adjustment 8
• Active cardiovascular disease requiring risk assessment 8

Key Limitations and Caveats

The evidence base has important weaknesses:

• Most positive studies are small single-center trials with sample sizes of 40-105 patients 2, 1, 3, 4
• The IVF studies show high heterogeneity and lack statistical power for pregnancy outcomes 3, 6
• Female sexual dysfunction guidelines explicitly state that sildenafil is NOT recommended due to contradictory results in clinical trials 5
• No major fertility society (ASRM, ESHRE) has incorporated sildenafil into standard treatment algorithms 5