Controlled ovarian stimulation (COS) is a core step in many fertility treatments worldwide. The aim is to mature multiple eggs in a single cycle to improve chances with IVF/ICSI or IUI. Modern guidelines emphasize safety, individualized dosing and close monitoring rather than “maximizing numbers.” Patient information and evidence-based recommendations are available from NICE, HFEA and ESHRE.
What is ovarian stimulation?
This refers to hormonal stimulation of the ovaries using oral tablets or injections so that multiple follicles grow. In IVF/ICSI the eggs are subsequently retrieved; in IUI the usual aim is 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 “sufficient, safe and of appropriate quality.” The optimum depends on age, AMH/AFC, medical history, method (IUI vs. IVF/ICSI) and laboratory capacity. Good centres adjust dose and timing so that chances and safety are balanced; this is emphasized in international recommendations (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 surge. Trigger at the end with hCG or a GnRH agonist. Advantages: flexibility, good safety profile, lower OHSS risk.
Agonist protocol (long)
Downregulation with a GnRH agonist before starting stimulation, then FSH/hMG. Selectively useful but has longer duration and potentially more side effects.
Mild / natural-modified stimulation
Lower gonadotropin doses or oral agents (letrozole/clomiphene), focusing on fewer but adequate eggs. Can reduce side effects and costs; not suitable for all profiles. Patient-friendly overviews are available from the HFEA.
Medications
| Class | Purpose | Examples | Notes |
|---|---|---|---|
| Gonadotropins (FSH/hMG) | Stimulate follicle growth | FSH pens, hMG | Dose based on 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, especially for IUI/mild protocols | Letrozole, Clomiphene | Lower cost, typically 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, medical history, ultrasound (AFC), hormone profile (including AMH) and, depending on the region, infection screening determine baseline risk. During stimulation, 2–4 ultrasound scans and, if needed, estradiol checks 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 leading follicles; IVF/ICSI aims for a moderate “good” egg yield.
- Trigger: when leading follicles are about 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 oral agents or injections.
- Monitoring: ultrasound and, if needed, E2 to adjust dose; antagonist added when follicles are adequately growing.
- Trigger: hCG or a GnRH agonist for final maturation.
- Further steps: IVF/ICSI egg retrieval ~34–36 h after trigger; IUI timed shortly after trigger.
- Luteal phase: progesterone according to clinic practice.
More detail: method overviews for IVF/ICSI, IUI and differentiation from ICI/home insemination.
Success & egg yield
Success rates depend strongly on age, cause of infertility, the laboratory workflow and embryo stage. Many centres aim for a mid-range egg number in IVF/ICSI; for IUI a single leading follicle is often sufficient. Guidelines recommend choosing protocol and dose based on individual risk, not on maximal numbers (ESHRE).
Safety & OHSS prevention
OHSS (ovarian hyperstimulation syndrome) is rare but important. Risk factors include high AMH/AFC, PCOS, younger age, high estradiol levels and aggressive dosing. Prevention strategies include antagonist protocols, conservative dosing, GnRH agonist trigger, possible “freeze-all” and close monitoring. Warning signs: rapid weight gain, increasing abdominal size/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, according to 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 |
Options with lower medication load are explained in patient-friendly terms by the HFEA.
When to see a doctor?
Seek immediate assessment for severe abdominal pain, shortness of breath, persistent vomiting, dizziness, rapid weight gain or marked abdominal swelling during or after stimulation. If there is absent follicle growth, repeatedly too many follicles for IUI, or severe side effects, the strategy should be adjusted. Ovarian stimulation should always be managed by a clinician with structured monitoring.
Conclusion
International consensus: plan individually, monitor closely and actively manage risks. With appropriate protocol selection, conservative dosing, a safe trigger and clear warning signs, ovarian stimulation can be carried out effectively and responsibly for IUI or IVF/ICSI.