Thailand IVF Hospital Ovarian Stimulation Process: Protocol Selection & Cycle Management

Scene opening: Hospital process (real consultation scenario)

1. Core Steps of the Ovarian Stimulation Process

The ovarian stimulation process at Thai fertility centers follows a standardized pathway, but each step is individualized based on the patient's age, ovarian reserve (AMH, antral follicle count), baseline hormone levels, and previous stimulation history. The complete process starts on day 2-3 of the menstrual cycle and ends with the egg retrieval procedure, typically lasting 10-14 days.

1. Pre-initiation Confirmation (Day 2-3 of Menstruation)

• Transvaginal Ultrasound: Confirm no ovarian cysts, endometrial thickness < 5 mm, and count bilateral antral follicles (AFC).
• Hormone Panel: FSH, LH, E2, P4, T, PRL. Focus on FSH (< 10 IU/L is ideal), E2 (< 50 pg/ml indicates a quiescent ovary), and LH (< 8 IU/L).
• AMH: Not affected by the menstrual cycle, but the value needs to be confirmed before initiation to estimate ovarian response.

2. Gonadotropin Injections

The doctor selects the starting dose based on AFC, AMH, FSH, age, and BMI. Commonly used medications in Thailand include:

• Gonal-F (Recombinant FSH): 75-450 IU/day, subcutaneous injection.
• Puregon (Recombinant FSH): 50-350 IU/day, subcutaneous injection.
• Menopur (Human Menopausal Gonadotropin): 75-300 IU/day, contains FSH + LH activity.
• Luveris (Recombinant LH): 75 IU/day, used for patients with low LH levels or those requiring combined LH activity.

Medication is administered via daily subcutaneous injections at a fixed time, typically for 10-12 consecutive days. Some protocols combine a GnRH antagonist (e.g., Cetrotide, Orgalutran) to prevent a premature LH surge.

3. Follicle Development Monitoring

Starting from day 4-5 after initiation, transvaginal ultrasound and hormone tests are performed every 2-3 days:

• Ultrasound Indicators: Record the diameter of each follicle (≥ 10 mm indicates a developing follicle), endometrial thickness, and pattern.
• Hormone Indicators: E2 (approximately 200-300 pg/ml per mature follicle), LH (< 8 IU/L is ideal), P4 (< 1.0 ng/ml).

4. Trigger

When the leading follicles reach 18-20 mm in diameter (usually 2-3 follicles ≥ 18 mm) and the E2 level matches the number of mature follicles, a trigger medication is administered:

• HCG (Human Chorionic Gonadotropin): Standard trigger, mimics the LH surge, suitable for patients with low OHSS risk.
• GnRH-a (e.g., Diphereline, Buserelin): Used for high-risk OHSS patients (PCOS, high AMH, E2 > 4000 pg/ml), can reduce OHSS risk.
• Dual Trigger (HCG + GnRH-a): Suitable for patients with asynchronous follicle development or difficulty in egg retrieval.

5. Egg Retrieval Procedure

Transvaginal ultrasound-guided egg retrieval is performed 34-36 hours after the trigger, under intravenous anesthesia, lasting 15-25 minutes. The number of eggs retrieved depends on the number and quality of follicles, with an egg retrieval rate typically 80%-90% of the mature follicle count.

2. Comparison of Mainstream Stimulation Protocols

Thai IVF hospitals select different protocols based on patient characteristics. Below is a comparison of four common protocols:

Protocol selection is not absolute; different doctors in the same hospital may prefer different protocols based on experience. For example, for a 35-year-old patient with normal AMH (1.0-3.5 ng/ml) and no significant medical history, both the antagonist and long protocols are viable options, mainly depending on the patient's schedule and budget.

3. Stimulation Medications and Dose Adjustment Logic

Starting Dose Reference

• AMH > 3.5 ng/ml, AFC > 20: Starting dose 75-150 IU/day (antagonist or PPOS protocol).
• AMH 1.0-3.5 ng/ml, AFC 8-20: Starting dose 150-225 IU/day.
• AMH 0.5-1.0 ng/ml, AFC 4-8: Starting dose 225-300 IU/day.
• AMH < 0.5 ng/ml, AFC < 4: Starting dose 300-450 IU/day, or consider a mild stimulation protocol.

Dose Adjustment Principles

After the first assessment on day 4-5 of stimulation, the dose is adjusted based on follicle growth rate and E2 levels:

• Slow follicle growth (average daily diameter increase < 1.2 mm): Increase FSH dose by 25-75 IU/day.
• Rapid follicle growth (average daily diameter increase > 2.5 mm): Be alert for a premature LH surge, consider adding an antagonist or adjusting the trigger timing.
• Low E2 level (disproportionate to follicle count): May indicate poor follicle development or LH deficiency; consider adding LH-active medication.

4. Key Monitoring Indicators and Clinical Decisions

The above indicators must be evaluated comprehensively; no single value should determine the plan. For example, if E2 is 3500 pg/ml but there are only 8 follicles, the E2 per follicle is high, warranting caution for ovarian hyperstimulation; if E2 is 3500 pg/ml and there are 18 follicles, the OHSS risk is significantly increased.

5. Differences in Stimulation Strategies by Age Group

Under 35 Years

Ovarian reserve is generally good, with a median AMH of 2.5-4.0 ng/ml. Standard doses (150-225 IU/day) typically yield 8-15 follicles. The main risk is OHSS, especially in those with a PCOS constitution. An antagonist or PPOS protocol is recommended, with GnRH-a preferred for triggering.

35-40 Years

Ovarian reserve begins to decline, with a median AMH of 1.0-2.5 ng/ml. The starting dose needs to be increased to 225-300 IU/day, and some patients may require the addition of LH-active medication (e.g., Menopur or Luveris). The stimulation cycle may extend to 12-14 days. Follicle synchrony should be monitored, and a dual trigger may be considered if necessary.

40-43 Years

Median AMH is 0.5-1.0 ng/ml, and FSH may be > 10 IU/L. Starting dose is 300-450 IU/day, often using a PPOS protocol or short protocol. The number of eggs retrieved is typically 2-6, and uneven follicle development is common. Growth hormone (GH) pretreatment for 2-4 weeks may be considered to improve follicle quality.

44 Years and Above

AMH is often < 0.5 ng/ml, and FSH > 12 IU/L. Conventional stimulation has a low egg retrieval rate. Some patients are suitable for a mild stimulation protocol (Clomiphene + low-dose FSH) or a natural cycle. Expectations need to be managed; 1-3 eggs per cycle may be retrieved, and multiple cycles may be needed to accumulate embryos.

6. Five Most Easily Overlooked Details During Stimulation

1. Premature Progesterone Elevation

Elevated progesterone (P4) > 1.5 ng/ml in the late stimulation phase alters endometrial gene expression, reducing the pregnancy rate in fresh embryo transfers. Many patients and doctors focus only on follicle size and E2, neglecting progesterone monitoring. It is recommended to check P4 with every ultrasound from day 6 of stimulation onwards.

2. Premature LH Surge

A premature LH surge (LH > 10 IU/L and E2 > 200 pg/ml) can cause premature luteinization of follicles, reducing egg quality. In antagonist protocols, the antagonist should be added when LH starts to rise (LH 6-8 IU/L), rather than waiting until LH exceeds 10 IU/L.

3. Endometrial Pattern and Thickness

Excessive endometrial growth (> 16 mm) or a poor pattern (type C or unclear triple-line sign) during stimulation may affect transfer. Estrogen levels need to be managed concurrently, and the plan may need to be adjusted to a freeze-all approach.

4. Cold Chain Storage of Medications

Biological preparations like Gonal-F and Puregon require refrigeration at 2-8°C and must not be frozen or shaken vigorously. Some patients store them improperly during travel or in hotels, leading to drug inefficacy and arrested follicle growth. It is recommended to use a portable cooler and check the hotel refrigerator temperature.

5. Male Partner Synchronization

The male partner needs to provide a semen sample on the day of egg retrieval. Some couples fail to confirm the collection time in advance, or the male partner has difficulty producing a sample. It is recommended to complete a semen analysis and confirm the collection method (masturbation/surgical retrieval/use of frozen sperm) at the start of stimulation.

7. Management Strategies for Special Situations

Can I still do IVF in Thailand with low AMH (< 0.5 ng/ml)?

Yes, but the protocol and expectations need to be adjusted. Low AMH does not mean no follicles at all, but rather limited ovarian reserve. Management strategies include:

• Using a mild stimulation protocol (Clomiphene + low-dose FSH) to reduce excessive ovarian consumption.
• Using growth hormone (GH) or DHEA pretreatment for 4-8 weeks to improve follicle quality.
• Considering a multi-cycle accumulation strategy: collecting eggs or embryos over 2-3 consecutive cycles.
• Lowering expectations for a single cycle, aiming for 1-3 eggs.

High-dose FSH (> 450 IU/day) is not recommended for patients with low AMH, as it does not increase the number of eggs retrieved but adds to medication costs and physical burden.

Polycystic Ovary Syndrome (PCOS)

PCOS patients have a high risk of OHSS. The core stimulation strategy is “mild stimulation”:

• Starting dose 75-150 IU/day, using an antagonist or PPOS protocol.
• Trigger preferentially with GnRH-a or a dual trigger, avoiding HCG alone.
• If E2 > 4000 pg/ml or total follicle count > 25, recommend freeze-all embryos.

History of OHSS

The peak E2 level, follicle count, and trigger method from the previous OHSS episode should be evaluated. The current protocol should be a PPOS protocol or a low-dose antagonist protocol, with close monitoring of E2 and follicle count throughout. Consider cycle cancellation or early trigger if necessary.

Chromosomal Abnormalities or Genetic Disorders

Genetic counseling and chromosomal testing must be completed before stimulation. The stimulation protocol itself is the same as for a standard cycle, but PGT (Preimplantation Genetic Testing) needs to be arranged after the trigger. The number of eggs retrieved should account for the expected embryo attrition during PGT; it is recommended to obtain at least 6-8 mature eggs.

8. How Doctors Develop Individualized Stimulation Protocols

In Thai fertility centers, doctors follow these priorities when developing a stimulation protocol:

1. Safety First: Assess OHSS risk (AMH, AFC, history, BMI) and choose the lowest effective dose.
2. Egg Retrieval Goal: Set a realistic target based on age and AMH. For example, a 38-year-old with AMH 1.2 ng/ml typically aims for 4-6 mature eggs.
3. Protocol Matching: Select a protocol based on the patient's schedule (ability to attend frequent monitoring), budget, and cycle expectations (fresh or frozen transfer).
4. Concurrent Preparation: Confirm the male partner's semen status, uterine cavity environment (perform a uterine cavity assessment if necessary), and infectious disease screening results.
5. Contingency Planning: Pre-plan the trigger method and transfer strategy (fresh transfer/freeze-all/PGT cycle).

For example, for a 39-year-old patient with AMH 0.9 ng/ml, AFC 5, and no history of OHSS, the doctor's decision logic would be:

• Low safety risk → PPOS protocol not required; an antagonist or short protocol can be chosen.
• Egg retrieval goal 3-5 → Starting dose 300 IU/day (Gonal-F or Menopur + Gonal-F).
• Patient desires fresh transfer → Close monitoring of P4 and endometrium; if P4 > 1.5 ng/ml on trigger day, switch to frozen transfer.
• Male partner's semen analysis normal → Proceed with standard semen collection.

Risk Reminders

This article is compiled based on clinical pathways and industry consensus from multiple fertility centers in Thailand, intended as a reference for assisted reproductive knowledge. Please follow the individualized recommendations of your attending reproductive specialist for specific treatment plans.