How is Thailand In Vitro Maturation (IVM) Technology? Suitable Candidates and Process

Scene opening (real consultation scenario)

1. Direct Answer on IVM Technology

In Vitro Maturation (IVM) is an assisted reproductive technology where immature oocytes (at GV or MI stage) are retrieved from follicles that have not yet matured (follicle diameter 5‑12 mm), cultured in a specific laboratory medium for 24‑48 hours to develop to the MII stage (mature oocyte), and then fertilized via ICSI (Intracytoplasmic Sperm Injection).

For the patient described above, IVM is a viable option but requires specific conditions: normal or high ovarian reserve, confirmed PCOS diagnosis, and no other uncontrolled endocrine disorders. IVM can significantly reduce the risk of OHSS, but oocyte maturation, fertilization, and blastocyst formation rates are generally lower than conventional IVF, requiring a comprehensive assessment based on personal expectations and medical advice.

2. Suitable Candidates

IVM technology is primarily suitable for the following groups:

• Patients with Polycystic Ovary Syndrome (PCOS): High follicle count leads to a high risk of OHSS after ovulation induction; IVM can significantly reduce this risk.
• Patients with a history of OHSS: High risk of OHSS recurrence during subsequent ovulation induction; IVM is an important alternative.
• High responders to ovulation induction medications: History of excessively high E2 levels (>4000 pg/ml) or excessive follicle development (>20 follicles) during previous cycles; IVM reduces medication stimulation.
• Intolerance to ovulation induction medications: Experience of severe bloating, nausea, mood swings, or allergic reactions.
• Estrogen-dependent diseases: Such as breast cancer, endometriosis, etc.; IVM avoids a high-estrogen environment.
• Emergency fertility preservation: Cancer patients needing oocyte preservation quickly; IVM allows oocyte retrieval before follicle maturation without waiting for an ovulation induction cycle.

3. Unsuitable Candidates

IVM is not recommended in the following situations:

• Diminished ovarian reserve: AMH < 1.0 ng/ml, antral follicle count < 6; the number and maturation rate of retrieved immature oocytes are suboptimal.
• Age over 40: Declining oocyte quality limits in vitro maturation capacity, with live birth rates significantly lower than conventional IVF.
• Requirement for PGT (Preimplantation Genetic Testing): IVM embryos have slightly lower developmental potential, potentially yielding fewer blastocysts available for biopsy, affecting screening efficiency.
• Uncontrolled endocrine disorders: Such as hyperthyroidism, hypothyroidism, hyperprolactinemia, or adrenal dysfunction; these require medical stabilization before evaluation.
• Severe male factor infertility (oligoasthenozoospermia): Although IVM typically uses ICSI, the male factor itself does not affect the choice of IVM, but sufficient viable sperm must be ensured.

4. Technical Principle: Why IVM Reduces OHSS Risk

The core of IVM lies in mimicking the natural in vivo maturation process of oocytes. In natural or minimally stimulated cycles, when follicles develop to 5‑12 mm in diameter, the oocytes are still at the GV or MI stage. Conventional IVF requires an HCG trigger for final oocyte maturation, whereas IVM retrieves these immature oocytes and completes the final maturation steps in the laboratory.

Laboratory culture conditions are critical for IVM success:

• Culture Medium: Basal medium (e.g., TCM‑199 or α‑MEM) supplemented with FSH, LH, EGF, insulin, transferrin, selenium, etc.
• Culture Time: 24‑48 hours, adjusted based on oocyte maturation speed.
• Culture Conditions: 37 °C, 5‑6 % CO₂, 95 % humidity.

Since oocyte retrieval occurs before follicle maturation, minimal exogenous ovulation induction medications are needed, making the risk of OHSS near zero, which is its most prominent advantage. However, the in vitro maturation process cannot fully replicate the in vivo microenvironment, resulting in slightly lower maturation rates (60‑80 %) and embryo developmental potential compared to conventional IVF.

5. Physician's Perspective Analysis

From a reproductive medicine standpoint, IVM is a valuable but non-primary option. For PCOS patients, IVM significantly reduces OHSS risk, which is its greatest value. However, it must be clear: the live birth rate per IVM cycle is generally lower than conventional IVF (approximately 15‑25 percentage points lower) and requires higher laboratory standards.

In Thailand, some fertility centers have the technical capability to perform IVM, including specific culture media and systems. However, laboratory standards vary significantly between centers. When choosing, attention should be paid to:

• The center's cumulative number of IVM cycles and experience
• Whether the laboratory has an independent IVM culture system and quality control standards
• Historical data on maturation, fertilization, and blastocyst formation rates from IVM cycles (industry reference: maturation rate 60‑80 %, fertilization rate 70‑85 %, blastocyst formation rate 30‑50 %)

IVM is not suitable for those seeking the highest live birth rate per cycle but is appropriate for patients who prioritize safety and medication tolerance.

6. Actual IVM Cycle Process

The IVM cycle differs significantly from conventional IVF in its流程. The specific steps are:

7. Timeline

From cycle initiation to transfer, an IVM cycle typically takes 3‑5 weeks, slightly shorter than a conventional IVF cycle (about 4‑6 weeks), primarily due to reduced ovulation induction time:

• Cycle initiation to oocyte retrieval: 7‑14 days (natural or minimally stimulated cycle)
• Laboratory culture: 24‑48 hours (additional time for IVM)
• Embryo culture: 3‑6 days
• Endometrial preparation (if frozen embryo transfer): 12‑18 days

If PGT or frozen embryo transfer is required, the total time will be extended accordingly.

8. Most Easily Overlooked Details

• Timing of oocyte retrieval: Retrieval when follicles are 5‑12 mm. Too early (<5 mm) means oocytes lack sufficient developmental potential; too late (>12 mm) means oocytes may have initiated maturation, reducing in vitro maturation rates.
• Endometrial preparation: In IVM cycles, endometrial preparation requires separate estrogen and progesterone, differing from the post-ovulation induction preparation in conventional IVF, requiring precise regulation.
• Mandatory ICSI: The zona pellucida of in vitro matured oocytes may change, leading to low fertilization rates with conventional IVF; thus, ICSI is typically mandatory for IVM.
• Embryo development speed: IVM embryos may develop 1‑2 days slower than conventional IVF embryos; the laboratory needs corresponding experience and patience.
• Specificity of culture medium: IVM culture medium differs from conventional IVF medium, requiring a specialized formula with a short shelf life after opening; laboratory quality control is essential.

9. Most Common Pitfalls

• Directly comparing success rates: Comparing IVM live birth rates directly with conventional IVF without considering differences in patient populations. In PCOS patients, IVM live birth rates may approach 70‑80 % of conventional IVF, but the gap is larger in non-PCOS populations.
• Assuming no medication is used: Some IVM protocols still require low-dose FSH or HCG priming; it is not a "zero medication" approach.
• Ignoring laboratory conditions: IVM has higher requirements for culture media, incubators, and technician expertise than conventional IVF; laboratory conditions directly impact maturation rates and embryo quality.
• Believing IVM solves all PCOS issues: IVM reduces OHSS risk but does not improve embryo quality. PCOS patients may inherently have oocyte quality issues, which IVM does not change.
• Ignoring age factors: For patients over 38, IVM maturation and live birth rates decline significantly; it is generally not recommended.

10. Differences Across Age Groups

Table note: The ratio refers to the proportion of IVM live birth rate compared to conventional IVF live birth rate for the same age group. Data is synthesized from industry literature and varies based on individual differences and center conditions.

11. Technical Differences Across Countries

The application of IVM technology varies significantly worldwide:

• Thailand: Some fertility centers (mainly in Bangkok) offer IVM. Experienced centers have independent IVM culture systems and quality control standards. Laboratory conditions vary; when choosing, inquire about the center's IVM cycle numbers and maturation rate data. The cost of IVM in Thailand is about 85‑95 % of conventional IVF, primarily saving on ovulation induction medications.
• Japan: IVM technology was adopted early, with some centers having over 20 years of experience and mature culture systems.
• Europe (Denmark, Spain, Belgium, etc.): In-depth IVM research, strict clinical application, mainly for PCOS and high OHSS risk patients.
• United States: IVM is less common, with conventional IVF being dominant; only a few academic centers offer it.
• China: Some reproductive centers offer IVM, primarily for PCOS patients, with accumulating clinical data and experience.

Thailand's advantage in IVM lies in relatively lower medical costs, and some centers have international laboratory standards. However, Thailand is not the most advanced country for IVM technology; when choosing, focus on the specific center's experience rather than the country's overall level.

12. Factors Influencing Cost

The cost structure of an IVM cycle in Thailand is similar to conventional IVF, with the following differences:

Overall, the total cost of an IVM cycle in Thailand is approximately 85‑95 % of conventional IVF, varying by center, medication protocol, culture time, and other factors. The cost difference is mainly in ovulation induction medications; laboratory culture costs are slightly higher, but the overall gap is not large.

13. Special Circumstances Management

Emergency IVM: For patients needing urgent fertility preservation (e.g., cancer patients), IVM allows oocyte retrieval before follicle maturation without waiting for an ovulation induction cycle, saving 2‑4 weeks. However, maturation and fertilization rates may be lower than planned IVM.

Failed in vitro maturation of immature oocytes: Some oocytes may not mature after 48 hours of culture. Options include continuing culture up to 72 hours (attempted by a few centers) or discarding them. Patients should be informed of this possibility and be mentally prepared.

IVM combined with PGT: Although IVM embryos have slightly lower developmental potential, some centers can still perform PGT. Note that the number of blastocysts available for biopsy may be fewer, and the biopsy timing may need adjustment.

14. Frequently Asked Questions

15. Practitioner's Observation

As a reproductive physician, I observe in daily clinics that patients have two extreme perceptions of IVM technology: one believes IVM is a "new technology" and therefore more advanced, while the other believes IVM has low success rates and is completely unacceptable. Both perceptions need correction.

IVM technology has been developed for nearly 30 years; it is not new, but its value in specific populations is clear—reducing OHSS risk, minimizing medication exposure, and improving treatment safety. For PCOS patients, those at high risk for OHSS, and those intolerant to ovulation induction medications, IVM is a validated alternative.

In Thailand, the maturity of IVM technology is directly related to the center's laboratory standards. Whether the laboratory has an independent IVM culture system, whether technicians have sufficient IVM experience, and whether the center has a complete IVM quality control process are key factors influencing outcomes. Patients have the right to request data on the center's IVM cycle maturation, fertilization, and blastocyst formation rates when choosing.