What is the washout period in Oral Contraceptive Pills (OCP) pre-treatment for In Vitro Fertilization (IVF)?

OCP Washout Period in IVF Pre-treatment

The recommended washout period after OCP pre-treatment in IVF is 5 days before starting ovarian stimulation with GnRH antagonist protocols. 1, 2

Standard Washout Protocol

• Start gonadotropin stimulation 5 days after stopping OCPs in GnRH antagonist IVF cycles 1, 2
• This 5-day interval allows for adequate clearance of exogenous hormones while maintaining follicular synchronization 1
• The washout period is critical because FSH suppression from OCPs can persist for 5-7 days after discontinuation 2

Evidence Supporting the 5-Day Washout

• A large retrospective study of 4,116 patients demonstrated that using a 5-day washout period after 12-30 days of OCP treatment resulted in comparable live birth rates (32.4%) and cumulative live birth rates to non-OCP cycles 1
• Multiple randomized controlled trials have consistently used and validated the 5-day washout interval, showing no detrimental effects on oocyte yield, embryo quality, or pregnancy outcomes 2, 3

Alternative Washout Considerations

Some protocols have explored a 6-day washout period when comparing OCPs to estradiol valerate pre-treatment, though this appears to offer no additional benefit over the standard 5-day interval 2

Duration of OCP Pre-treatment

• OCPs are typically administered for 12-30 days before the washout period begins 1
• Shorter durations (12-16 days) are commonly used and appear equally effective as longer courses 3
• The OCP formulations studied include ethinyl estradiol 30 μg with either desogestrel 150 μg or levonorgestrel 150 μg 1, 2, 3

Clinical Outcomes with Standard Washout

• No negative impact on live birth rates when using the 5-day washout protocol 1
• No differences in oocyte maturity, embryo quality, or implantation rates compared to cycles without OCP pre-treatment 1, 4
• The number of oocytes retrieved may be slightly higher with OCP pre-treatment (adjusted β 0.22,95% CI 0.12-0.31), though this does not translate to improved pregnancy outcomes 1

Special Population: PCOS Patients

• In women with PCOS undergoing IVF, a 7-day washout period after OCP pre-treatment has been studied, with ovarian stimulation starting on Day 7 of the washout 4
• This approach resulted in non-inferior embryo quality and comparable live birth rates (78.3% cumulative) to immediate stimulation without OCP pre-treatment 4
• The rationale for OCP pre-treatment in PCOS (lowering LH levels) may not provide additional benefit, as embryo quality and pregnancy outcomes are similar with or without OCPs 4

Common Pitfalls to Avoid

• Do not start stimulation immediately after stopping OCPs without the appropriate washout period, as residual FSH suppression may impair follicular recruitment 2
• Avoid excessively long washout periods (>7 days), as this provides no additional benefit and only delays treatment 1, 2
• Do not assume longer OCP pre-treatment duration improves outcomes—12-16 days is sufficient and comparable to longer courses 3

Practical Implementation

• Stop OCPs after 12-30 days of administration 1
• Wait exactly 5 days (standard) or up to 7 days (in PCOS) 1, 4
• Begin recombinant FSH on the designated day regardless of bleeding pattern 4
• Use GnRH antagonist protocol as planned with no modifications needed for the washout period 1, 2, 3