Ovarian stimulation: procedure, protocols, medications & risks

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Zappelphilipp Marx•
Ultrasound monitoring of the ovaries during ovarian stimulation in a fertility clinic

Controlled ovarian stimulation (COS) is a core step in many fertility treatments worldwide. The aim is to allow multiple oocytes to mature in a single cycle, improving the chances with IVF/ICSI or IUI. Contemporary guidelines emphasise safety, individualised dosing and close monitoring rather than pursuing “maximum numbers”. Reliable patient information and evidence-based recommendations are provided by organisations such as NICE, the HFEA and ESHRE.

What is ovarian stimulation?

This refers to hormonal stimulation of the ovaries using tablets or injections to promote growth of multiple follicles. In IVF/ICSI the oocytes are then collected; in IUI the aim is usually 1–3 mature follicles to limit multiple pregnancy risk. Final maturation 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 good 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 approach is emphasised in international recommendations (NICE, ESHRE).

Protocols

Antagonist protocol (short)

Often the standard: daily FSH/hMG injections from cycle day 2–3; once follicles start to grow, a GnRH antagonist prevents a premature LH surge. Final trigger with hCG or a GnRH agonist. Advantages: flexibility, good safety profile and lower OHSS risk.

Agonist protocol (long)

Downregulation with a GnRH agonist before starting stimulation, then FSH/hMG. Useful in selected cases but involves longer duration and potentially more side effects.

Mild / natural‑modified stimulation

Lower gonadotropin doses or oral agents (letrozole/clomifene), focusing on fewer but adequate oocytes. May reduce side effects and costs; not suitable for all profiles. Patient-friendly overviews are available from the HFEA.

Medications

ClassPurposeExamplesNotes
Gonadotropins (FSH/hMG)Follicle growthFSH pens, hMGDose based on AMH, AFC, age, BMI, previous response
GnRH antagonistPrevents premature LH surgeCetrorelix, GanirelixCommon in the short protocol
GnRH agonistDownregulation / trigger optionLeuprorelin, TriptorelinUsing as a trigger reduces OHSS risk
TabletsStimulation mainly for IUI/mild approachesLetrozole, ClomifeneInexpensive, lower oocyte yield
ProgesteroneLuteal phase supportVaginal capsules/gelStandard after IVF/ICSI

Patient‑facing drug summaries: HFEA: Fertility drugs.

Monitoring & start criteria

Before starting, a medical history, ultrasound (AFC), hormone status (including AMH) and, depending on the region, infection screening assess baseline risk. During stimulation, 2–4 ultrasound scans and, if indicated, estradiol checks guide dose adjustments and trigger timing.

  • Start criteria: AMH/AFC, age, BMI, cycle pattern, previous treatments, comorbidities.
  • Target sizes: IUI usually 1–3 dominant follicles; IVF/ICSI aims for a moderate “good” oocyte number.
  • Trigger: when leading follicles are around 17–20 mm (clinic-specific).

General recommendations on management are available from NICE and the ESHRE guideline.

Step-by-step process

  1. Start: cycle day 2–3 with tablets or injections.
  2. Monitoring: ultrasound and, if needed, E2 to adjust dose; antagonist added when follicles are sufficiently developed.
  3. Trigger: hCG or a GnRH agonist for final maturation.
  4. Next steps: IVF/ICSI egg collection ~34–36 hours after trigger; IUI performed shortly after ovulation is induced.
  5. Luteal phase: progesterone according to clinic protocol.

Further detail: overview of methods for IVF/ICSI, IUI and differentiation from ICI/home insemination.

Success & oocyte yield

Success rates depend strongly on age, cause of infertility, laboratory processes and embryo stage. Many centres aim for a moderate oocyte number in IVF/ICSI; for IUI a single dominant follicle is often sufficient. Guidelines recommend choosing protocol and dose based on individual risk rather than maximum numbers (ESHRE).

Safety & OHSS prevention

OHSS (ovarian hyperstimulation syndrome) is uncommon but important. Risk factors include high AMH/AFC, PCOS, young age, high estradiol levels and aggressive dosing. Prevention measures include antagonist protocols, conservative dosing, a GnRH agonist trigger, possible “freeze‑all” strategies 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

ApproachTypical forAdvantagesConsiderations
Antagonist protocolIVF/ICSIFlexible, lower OHSS riskDaily injections, frequent monitoring
Agonist protocolSelected indicationsPredictability, laboratory advantagesLonger duration, potentially more side effects
Mild / natural‑modifiedIUI, mild IVFFewer side effects, sometimes lower costLower oocyte yield; not suitable for all profiles

Options with lower medication burden are explained in patient‑friendly language by the HFEA.

When to see a doctor?

Seek urgent assessment for severe abdominal pain, shortness of breath, persistent vomiting, dizziness, rapid weight gain or a marked increase in abdominal size during or after stimulation. Also review the strategy if there is absent follicle growth, repeatedly too many follicles for IUI, or significant side effects. Ovarian stimulation should always be managed by clinicians with structured monitoring.

Conclusion

International guidance is clear: plan individually, monitor closely and manage risks proactively. With the right protocol choice, conservative dosing, safe trigger selection and clear warning signs, ovarian stimulation can be carried out effectively and responsibly for both IUI and IVF/ICSI.

Disclaimer: Content on RattleStork is provided for general informational and educational purposes only. It does not constitute medical, legal, or other professional advice; no specific outcome is guaranteed. Use of this information is at your own risk. See our full Disclaimer.

Frequently Asked Questions (FAQ)

Usually 8–12 days from cycle day 2–3, depending on AMH/AFC, age, dose and response; monitoring determines the exact timing.

Common effects include abdominal tugging, bloating, mood changes, breast tenderness and minor irritation at injection sites; serious symptoms should be assessed promptly by a clinician.

No. The goal is an appropriate and safe oocyte number; excessively high doses increase side effects and OHSS risk without guaranteed benefit.

Both induce final maturation; a GnRH‑agonist trigger lowers OHSS risk in high‑risk patients, but its use varies by protocol.

No. Often a single dominant follicle is sufficient; more follicles increase the multiple pregnancy risk and are deliberately limited in IUI cycles.

Yes. Oral agents are used for IUI or certain cycle disorders; suitability depends on diagnosis and treatment goals.

Age, AMH, AFC, BMI and previous treatment response are typical starting points; the dose is adjusted during stimulation based on ultrasound and hormone levels.

Warning signs include increasing abdominal size, severe pain, shortness of breath, rapid weight gain, nausea or vomiting; seek medical assessment immediately.

Progesterone is standard after IVF/ICSI; after IUI it is used depending on protocol and individual circumstances.

Light to moderate activity is usually acceptable; contact or very strenuous activities should be avoided during stimulation and until shortly after the trigger.

Yes. Mild or natural‑modified protocols use lower doses or oral agents; however, they are not equally suitable for all diagnoses and goals.

The risk increases with the number of mature follicles; in IUI it is managed by strict follicle limits and possible cycle cancellation, and in IVF by embryo transfer strategies.