Ovarian stimulation (controlled ovarian stimulation, COS) is a core step in many fertility treatments worldwide. The aim is to mature multiple eggs in one cycle to improve the chances with IVF/ICSI or IUI. Modern guidance emphasises safety, individualised dosing and close monitoring rather than pursuing "maximum numbers". Patient information and evidence-based recommendations are provided by organisations such as NICE, HFEA and ESHRE.
What is ovarian stimulation?
This refers to hormonal stimulation of the ovaries with tablets or injections so that multiple follicles grow. In IVF/ICSI the eggs are then retrieved; in IUI the goal is usually 1–3 mature follicles to limit multiple pregnancy risk. The final maturation step is triggered with a "trigger" injection (hCG or a GnRH agonist).
Goals & realistic expectations
Successful stimulation does not mean "as many eggs as possible" but "enough, safely and of good quality". The optimum depends on age, AMH/AFC, history, the method used (IUI vs. IVF/ICSI) and laboratory capacity. Good centres tailor dose and timing so that chances and safety are balanced; international recommendations emphasise this balance (NICE, ESHRE).
Protocols
Antagonist protocol (short)
Common standard: daily FSH/hMG injections from cycle day 2–3; once follicles grow, a GnRH antagonist prevents a premature LH rise. Final trigger with hCG or a GnRH agonist. Advantages: flexibility, good safety profile, lower OHSS risk.
Agonist protocol (long)
Downregulation with a GnRH agonist before stimulation start, then FSH/hMG. Selectively useful, but longer duration and potentially more side effects.
Mild / natural-modified stimulation
Lower gonadotropin doses or oral agents (letrozole/clomiphene), focusing on fewer but sufficient eggs. May reduce side effects and cost; not suitable for all profiles. Patient-friendly overviews are available from HFEA.
Medications
| Class | Purpose | Examples | Notes |
|---|---|---|---|
| Gonadotropins (FSH/hMG) | Follicle growth | FSH pens, hMG | Dose according to AMH, AFC, age, BMI, prior response |
| GnRH antagonist | Prevents premature LH surge | Cetrorelix, Ganirelix | Common in the short protocol |
| GnRH agonist | Downregulation / trigger option | Leuprorelin, Triptorelin | As a trigger it reduces OHSS risk |
| Oral agents | Stimulation mainly for IUI/mild protocols | Letrozole, Clomiphene | Lower cost, fewer eggs |
| Progesterone | Luteal phase support | Vaginal capsules / gel | Standard after IVF/ICSI |
Patient-friendly drug overviews: HFEA: Fertility drugs.
Monitoring & start criteria
Before starting, history, ultrasound (AFC), hormone status (including AMH) and—depending on region—infectious screenings are reviewed to assess baseline risk. During stimulation, 2–4 ultrasound checks and, if needed, estradiol controls guide dose adjustments and trigger timing.
- Start criteria: AMH/AFC, age, BMI, cycle pattern, prior treatments, comorbidities.
- Target sizes: IUI usually aims for 1–3 dominant follicles; IVF/ICSI aims for a moderate "good" egg yield.
- Trigger: when leading follicles are approx. 17–20 mm (clinic-specific).
General recommendations for management can be found in NICE and the ESHRE guideline.
Step-by-step procedure
- Start: cycle day 2–3 with tablets or injections.
- Monitoring: ultrasound and, if needed, E2 for dose adjustment; antagonist if follicle growth is sufficient.
- Trigger: hCG or GnRH agonist for final maturation.
- Next steps: IVF/ICSI retrieval ~34–36 h after trigger; IUI timed shortly after trigger.
- Luteal phase: progesterone according to clinic protocol.
Further reading: overview of methods IVF/ICSI, IUI and distinction from ICI/home insemination.
Success & egg yield
Success rates depend strongly on age, cause, laboratory processes and embryo stage. Many centres aim for a moderate egg yield in IVF/ICSI; for IUI a single leading follicle is often sufficient. Guidelines recommend selecting protocol and dose based on individual risk rather than aiming for maximal numbers (ESHRE).
Safety & OHSS prevention
OHSS (ovarian hyperstimulation syndrome) is uncommon but important. Risk factors include high AMH/AFC, PCOS, young age, high E2 levels and aggressive dosing. Prevention measures include antagonist protocols, conservative dosing, GnRH agonist trigger, possible "freeze-all" and close monitoring. Warning signs: rapid weight gain, increasing abdominal girth or pain, shortness of breath, persistent vomiting. Patient information: NHS on OHSS.
Luteal phase support
After IVF/ICSI, progesterone support is standard; after IUI practice varies internationally. Forms include vaginal gel, capsules and less commonly injections. Duration is usually until the pregnancy test or into early pregnancy, depending on clinic protocol.
Comparison & alternatives
| Approach | Typical for | Advantages | Considerations |
|---|---|---|---|
| Antagonist protocol | IVF/ICSI | Flexible, lower OHSS risk | Daily injections, monitoring intensity |
| Agonist protocol | Selective indications | Predictability, laboratory advantages | Longer duration, potentially more side effects |
| Mild / natural-modified | IUI, mild IVF | Fewer side effects, sometimes lower cost | Lower egg yield; not suitable for all profiles |
The HFEA explains options with a lower medication burden in patient-friendly language: HFEA.
When to see a doctor?
Seek immediate assessment for severe abdominal pain, shortness of breath, persistent vomiting, dizziness, rapid weight gain or a markedly increasing abdominal girth during or after stimulation. If follicles fail to grow, if there are repeatedly too many follicles for IUI, or if side effects are severe, the strategy should be adjusted. Ovarian stimulation should always be managed by clinicians with structured monitoring.
Conclusion
The international consensus is: plan individually, monitor closely, and manage risks actively. With the appropriate protocol choice, conservative dosing, a safe trigger and clear warning signs, ovarian stimulation can be carried out effectively and responsibly—whether for IUI or IVF/ICSI.