IVF & 1st to 4th Generation IVF Technologies: ICSI / PGS / Time-lapse / AI Embryo Selection 試管嬰兒流程與1-4代技術的詳細介紹

Infertility is not a terminal condition.
Below are six major groups of individuals who may need to undergo in vitro fertilization (IVF) and the reasons why:

1. Age-related Factors:
   Women experiencing a decline in reproductive function due to age.

2. Tubal Factors:
   Women with bilateral fallopian tube blockage or adhesions, or those with moderate to severe endometriosis.

3. Ovulatory Factors:
   Women with anovulation (no ovulation), polycystic ovary syndrome (PCOS), or poor ovarian response.

4. Male Factors:
   Men with abnormal sperm parameters, severe antisperm antibodies, or azoospermia (no sperm in semen).

5. Unexplained Infertility:
   Couples whose anatomical and reproductive evaluations show no abnormalities but are still unable to conceive naturally.

6. Other Factors:
   Couples with recurrent miscarriage, repeated failed intrauterine insemination (IUI), or known chromosomal abnormalities in one or both partners.

IVF (In Vitro Fertilization) Process

Pre-treatment evaluations for both partners → Monitoring of follicles and ovulation induction with medication → Egg retrieval and sperm collection → Fertilization and embryo culture → Embryo transfer → Pregnancy test

Below is a detailed explanation of each step in the IVF process:

Step 1:

Before starting IVF, both partners must undergo fertility evaluations.

Step 2:

Once the menstrual cycle begins, the IVF treatment officially starts.

Step 3:

Day 1–Day 3: On the first days of the menstrual cycle, the patient visits the clinic for blood tests and an ultrasound. Ovulation-stimulating injections or oral medications are then prescribed.
Day 3: Return to the clinic for follow-up ultrasound and blood tests.

Step 4:

Day 12–Day 14: An ovulation trigger shot is administered to prepare for egg retrieval.

Step 5:

The woman undergoes egg retrieval; the man provides a fresh semen sample. The woman begins taking progesterone support until the pregnancy test.

Step 6:

Fertilization occurs, and embryos are cultured for 3 to 5 days.

Step 7:

Embryo transfer is performed 3 to 5 days after egg retrieval, depending on the individual's condition.

Step 8:

A pregnancy test is done two weeks after the embryo transfer.

The IVF process may seem complex and demanding, but every step is designed to increase the chances of a successful pregnancy. Medications are used to stimulate the development of multiple follicles and improve egg maturity. Blood tests and ultrasounds help doctors assess follicle quantity, size, and maturity—all critical factors in increasing IVF success rates and ensuring the retrieval of multiple mature eggs.

1st to 4th Generation IVF Technologies: ICSI / PGS / Time-lapse / AI Embryo Selection

The main differences between each generation of IVF lie in their suitability for different patients. It's important not to assume that newer generations are inherently "better." Instead, understanding each generation's techniques and purposes will help you choose the most appropriate IVF treatment for your specific condition and improve your chances of success. It is strongly recommended to consult with your fertility specialist to determine the best course for you.

1st Generation IVF:

In vitro fertilization (IVF) + embryo transfer
This method involves placing sperm and egg together in the same culture medium to allow natural fertilization. It is suitable for patients with infertility caused by fallopian tube obstruction, endometriosis, or endocrine disorders.

• However, if the male partner has a low sperm count, natural fertilization may fail, resulting in a relatively lower success rate of around 20%–30%.

2nd Generation IVF:

Intracytoplasmic Sperm Injection (ICSI)
In this method, an embryologist uses a microscope to immobilize the egg with a holding pipette and injects a single sperm directly into the cytoplasm using a fine needle that penetrates the zona pellucida and cell membrane.

Piezo-ICSI (Piezoelectric Intracytoplasmic Sperm Injection) is an advanced version of traditional ICSI that uses piezoelectric pulses for more precise sperm injection, helping improve fertilization rates and reduce egg damage.

• The second-generation IVF is especially suitable for male factor infertility (low sperm count or motility) and women with low egg retrieval numbers. The success rate is approximately 50%–60%.

3rd Generation IVF:

Preimplantation Genetic Testing for Aneuploidy (PGT-A)
When the embryo reaches the blastocyst stage (Day 5–6), a biopsy is performed to remove 5–10 cells from the outer trophectoderm. Molecular diagnosis is then used to examine the chromosome count and detect abnormalities. Only embryos with normal chromosomal sets are selected for implantation to increase pregnancy success rates.

3.5th Generation IVF:

Time-lapse Embryo Monitoring
Incorporates a high-precision, 24-hour monitoring system that captures images of embryo development continuously. This allows for more accurate and faster assessments of embryo quality.

• 3rd + 3.5th generation IVF focuses on preimplantation genetic screening and embryo quality monitoring, particularly helping patients with recurrent miscarriage or repeated implantation failure. The success rate can reach 60%–70%.

4th Generation IVF:

PGT-A + Time-lapse + AI-Based Embryo Selection
This approach integrates chromosome screening, real-time embryo monitoring, and AI embryo scoring. Using a large-scale database of embryo development patterns based on data from over 40,000 IVF babies globally, artificial intelligence is applied to select embryos with the highest potential for successful implantation.

• With AI-assisted embryo selection, the 4th-generation IVF offers an improved pregnancy success rate of approximately 70%–80%.

What Is the Success Rate of IVF in a Single Cycle?

In Taiwan, the average success rate of becoming pregnant after a single embryo transfer via IVF is around 30%, which is higher than the natural conception rate.

Key Factors to Improve IVF Success Rates:

• Choose a fertility center with a strong laboratory and experienced IVF specialists.

• Egg quality directly affects embryo quality. Doctors can help develop an egg quality improvement plan to enhance outcomes.

• A healthy uterine environment is crucial for embryo implantation. Conducting an Endometrial Receptivity Analysis (ERA) can help identify the best implantation window—also known as the "Window of Implantation"—to increase implantation and pregnancy chances.

• Embryo chromosomal abnormalities are a common reason for IVF failure. Selecting chromosomally healthy embryos for transfer can significantly improve implantation and pregnancy rates. Techniques include:

  • PGT-M (Preimplantation Genetic Testing for Monogenic disorders, formerly PGD)

  • PGT-A (Preimplantation Genetic Testing for Aneuploidy, formerly PGS)

  • PGT-SR (Preimplantation Genetic Testing for Structural Rearrangements)

Does the Number of Embryos Transferred Affect IVF Success?

Transferring more embryos may increase the chance of pregnancy, but also raises the risk of multiple pregnancies (twins or more), which in turn increases the risk of complications for both the mother and the babies (e.g., preterm birth, low birth weight).

Doctors will determine the appropriate number of embryos to transfer based on the patient's age and overall health, following the guidelines set by the Taiwan Society for Reproductive Medicine.

Recommended Number of Embryos to Transfer:

• Under 35: 1–2 embryos
• 35–37: Up to 2 embryos
• 38–40: Up to 3 embryos
• 41 and above: Up to 4 embryos
• Embryo confirmed normal via PGT-A: 1 embryo
• For patients who: have previously had a successful embryo transfer, or undergoing their first IVF cycle, or high-quality embryos, additional embryos available for freezing, aged 36 or younger → Transferring a single embryo is often recommended to minimize the risk of multiple pregnancies.

Relationship Between Embryo Grades (A, B, C) and Success Rates

Clinical observations show that implantation failure is often linked to embryo quality. During an IVF cycle, embryologists monitor embryo development on Day 1, Day 3, and Day 5, and decide on the best time for embryo transfer (D3 or D5) based on embryo grading.

Higher-quality blastocysts (Day 5 embryos) are typically associated with higher implantation success rates, indicating better developmental potential.

Embryo Grading Overview:

• High-quality embryos: AA

• Good-quality embryos: AB, BA, BB

• Average-quality embryos: AC, BC, CA, CB

• Poor-quality embryos: CC

Is Day 3 or Day 5 Embryo Transfer Better?

• Day 3 transfer is a quantity-over-quality strategy—transferring more embryos to increase chances.

• Day 5 transfer is a high-precision approach—fewer embryos, but better-targeted implantation.

However, the best choice depends on the number and quality of eggs retrieved, so it's essential to consult your doctor for a personalized recommendation.

Day 3 Embryo Transfer (Cleavage-stage embryos)

• On Day 3, embryos are at the cleavage stage, typically consisting of 6–8 cells.

• Grading system:
  Number of cells + First letter: cell symmetry + Second letter: cell fragmentation level

Who is it for?

• Recommended for patients with poor ovarian function or fewer eggs retrieved. Transferring more than one Day 3 embryo may improve pregnancy chances.

Things to note:

• Higher risk of multiple pregnancies

• PGT-A (chromosomal screening) and PGT-M (genetic diagnosis) cannot be performed at this stage.

Day 5 Embryo Transfer (Blastocyst-stage embryos)

• On Day 5, embryos reach the blastocyst stage, forming an outer trophectoderm (future placenta) and an inner cell mass (future fetus).

• Grading system:
  Two-part code based on blastocyst expansion and trophectoderm quality (e.g., 4AA, 5AB)

Who is it for?

• Ideal for younger patients or those with a higher number of eggs retrieved. Day 5 embryos that reach this stage are more developmentally advanced, offering higher implantation potential.

Things to note:

• Not all embryos make it to Day 5, so there is a risk of having no embryos for transfer.

• Slightly higher risks of preterm birth or low birth weight have been observed in Day 5 embryo transfers.

Is IVF Risky? What Are the Possible Side Effects?

In fact, even in natural conception, there is a 2–3% chance that the embryo may have congenital defects. With the help of advanced reproductive technologies, IVF can actually help infertile couples select higher-quality embryos, potentially reducing this risk.

• A study published in the journal Human Reproduction by the European Society of Human Reproduction and Embryology (ESHRE) found that the intelligence and behavioral development of IVF babies are no different from those conceived naturally.

• Similarly, a 2020 report from the American Society for Reproductive Medicine showed no significant difference in academic performance between IVF and naturally conceived children. Intelligence levels are not significantly higher or lower with IVF; genetics and environment are the main factors affecting a child's IQ.

Common Side Effects After IVF Embryo Transfer

• Discomfort from ovulation stimulation medications:
  Symptoms may include bloating, gastrointestinal discomfort, fatigue, nausea, headaches, and temporary weight gain. These are generally mild and short-lived.

• Ovarian Hyperstimulation Syndrome (OHSS):
  In rare cases, the ovaries may overreact to stimulation medications, especially when too many follicles develop. Symptoms can include bloating, abdominal pain, thirst, nausea, decreased urination, and difficulty breathing. Most patients recover within 1–2 weeks, but severe cases may require hospitalization.

• Multiple pregnancies:
  Because ovulation-stimulating medications are used during IVF, the chance of multiple embryos implanting increases. This is one of the more common side effects of IVF, with about 20% of cases resulting in twins.

• Ectopic pregnancy:
  Although rare, ectopic pregnancy (when the embryo implants outside the uterus) can still occur with IVF. If it does, medication or surgery is required to terminate the pregnancy early and protect the mother's life.

How to Reduce the Risks of IVF？

In addition to the above-mentioned risks—such as medication side effects, OHSS, multiple pregnancy, and ectopic pregnancy—there are other procedural risks during IVF, including:

• Bleeding or infection from the egg retrieval procedure

• Pelvic infection or bleeding after embryo transfer

To minimize these risks, it is important to:

• Choose a reputable fertility clinic

• Work with experienced reproductive specialists

A professional team will not only help reduce complications but also increase your chances of success throughout the IVF process.

Important Guidelines for IVF Treatment

Before Embryo Transfer

• Adopt a Mediterranean diet and supplement with vitamin D3, DHEA, CoQ10, myo-inositol, and folic acid to improve egg quality.

• Maintain a healthy lifestyle and balanced diet. Avoid staying up late, smoking, and drinking alcohol.

• Engage in moderate exercise to strengthen physical fitness and enhance overall reproductive health.

During the IVF Process

• Prior to embryo transfer, doctors will prescribe medications tailored to your treatment plan. Be sure to follow all medical instructions carefully.

• Abstain from sexual activity before egg retrieval, as multiple follicles are developing and the ovaries may become enlarged. Avoid vigorous exercise to reduce the risk of ovarian torsion.

• If you experience discomfort or need to take any medication, inform your doctor that you are undergoing IVF treatment, so they can prescribe medications that do not interfere with the process.

After Embryo Transfer

After embryo transfer, the following precautions are highly recommended:

• Avoid strenuous activities, heavy lifting (over 3 kg), or excessive physical labor.

• Refrain from sexual intercourse from the time of embryo transfer until the end of the first trimester of pregnancy.

• Manage stress levels—avoid anxiety and maintain a calm, positive emotional state.

• Avoid hot baths and hot springs, as high temperatures may interfere with embryo development.

• Avoid prolonged squatting, abdominal straining, or sleeping on your stomach.

Dietary Advice After Embryo Transfer

• Maintain a balanced and nutritious diet. Prioritize fresh vegetables and fruits, protein-rich foods, and whole grains to support the body's nutritional needs.

• Avoid highly processed foods, deep-fried or grilled items.

• Do not consume barley (Job's tears), sesame oil, Chinese herbal medicine, iced foods or drinks, alcohol, and foods that are overly "heaty" (yang) or "cold" (yin) in nature, or those that promote blood circulation, as these may cause uterine contractions and negatively affect implantation.