A 32-year-old woman with unexplained infertility and normal ovulatory cycles (confirmed by mid-luteal progesterone) is undergoing assisted reproductive technology. Which agent is the drug of choice for controlled ovarian hyperstimulation (COH) in an IVF cycle?

Explanation

## Controlled Ovarian Hyperstimulation in IVF **Key Point:** Recombinant FSH combined with a GnRH agonist (or antagonist) is the gold-standard regimen for COH in IVF cycles. The GnRH agonist suppresses endogenous LH, preventing premature ovulation. ### Rationale for GnRH Agonist Co-Administration 1. **Pituitary downregulation:** GnRH agonist causes initial FSH/LH surge, then sustained suppression (downregulation) 2. **Prevention of premature LH surge:** Blocks spontaneous ovulation before egg retrieval 3. **Improved cycle control:** Allows precise timing of oocyte maturation and retrieval 4. **Higher oocyte yield:** Enables superovulation with multiple follicles ### Standard IVF Protocol | Protocol | Timing | Advantage | |----------|--------|----------| | **Long GnRH agonist** | Start in luteal phase of prior cycle | Best pituitary suppression, lowest cycle cancellation | | **Short GnRH agonist** | Start on day 1 of stimulation | Shorter overall duration | | **GnRH antagonist** | Start when leading follicle ≥14 mm | Avoids flare effect, shorter protocol | **High-Yield:** Recombinant FSH (rFSH) is preferred over hMG in IVF because: - Pure FSH without LH contamination - More predictable dose-response - Lower batch-to-batch variability - Better oocyte quality in some studies **Clinical Pearl:** GnRH antagonist protocols are increasingly popular because they: - Shorten stimulation duration (8–10 days vs. 10–14 days) - Reduce OHSS risk - Allow flexible start timing - Avoid flare effect of GnRH agonist **Warning:** ~~Clomiphene citrate alone~~ is inadequate for IVF COH — it produces only 1–2 mature follicles, insufficient for embryo selection and multiple embryo transfer.