| Step 1: Preparation Phase (Click to view) | Step 2: Ovulation Promotion Treatment (Click to view) | Step 3 Fertilized Egg Culture (Click to view) | Step 4 Embryo Transfer (Click to view) |
| Counseling | Determining an Ovulation Regimen | Culturing immature eggs for IVM | Pre-transfer preparations |
| Physical examination | Medication for about 14 days as prescribed by the doctor | Fertilization and follicle raising | Transplantation |
| Appointment with doctor | About 5 return visits during medication (ultrasound and blood draws) | Frozen eggs and embryos | Blastocyst grade and transfer success rate |
| Remote initial consultation | Egg and sperm retrieval and return | Pre-implantation genetic testing PGT | Blood test for pregnancy and progesterone supplementation |
| 1.Evaluate the success rate online | 2.Get more high quality eggs | 3.Cultivate and screen healthy blastocysts | 4.Embryo transfer to woman’s uterus |
1. preparatory phase
(Sales) inquiry (formal)
1. Embryo first: the specific process is 1) select the target country and doctor 2) complete the physical examination as required 3) start ovulation promotion treatment after the physical examination is normal or the doctor’s review is Ok (after about 14 days of medication) Remove the eggs (sperm retrieval on the day of egg retrieval or freezing the sperm ahead of time) 4) Fertilization in the laboratory, embryo on the third day, blastocysts on day 5-6, and sampling the blastocysts to send for PGT-A screening (optional).
2. Embryo transfer: If surrogacy in the U.S., you need to make up for the U.S. FDA test before or after egg collection (you can also sample in Hong Kong / Japan / Singapore, etc. transported to the U.S.), the test is passed before the blastocysts can be transplanted to the surrogate mother’s uterus; their own pregnant, you can wait for the next menstrual cycle after the egg collection and transplantation.
Customized consulting (not mandatory)
Medical check-up
AMH test more accurately predicts egg reserve
AMH (Anti-Müllerian Hormone) is an important indicator of ovarian age, basal follicle number and ovarian function, and is the most important basis for the development of an IVF treatment program. It has been found that the follicular granulosa cells in a woman’s ovaries are capable of secreting AMH, and the higher the number of follicles in the ovaries the higher the concentration of AMH in the blood, while the lower the number of follicles the lower the concentration.
The Sexual Stimulation Six helps to understand ovarian function.
The Sex Hormone Panel consists of follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), progesterone (P), testosterone (T), and prolactin (PRL). The sex hormone panel is a commonly used test for patients with endocrine disorders and is an important basis for developing IVF treatment regimens and monitoring treatment outcomes. It has been found that FSH and LH blood values are maintained at low levels in the early follicular phase (2-3 days of menstruation), gradually increase before ovulation, and rapidly return to follicular phase levels after ovulation.
Precision testing instruments
Blood analyzers and ultrasound are the most frequently used screening instruments in IVF treatment, and their results are an important basis for doctors to formulate ovulation and transplantation plans. Precise instruments and the doctor’s skill can accurately monitor the number and development of follicles, determine the best time for implantation, and understand the condition of follicular chocolate cysts, endometrium, polyps, and so on.
Special Treatment Needs
Special treatment needs, including and not limited to those with a family history of genetic disorders, fertility in HIV patients (through sperm washing), ovulation disorders, surrogacy, transfer of embryos or gametes (sperm or eggs) to other countries for surrogacy, egg purchase needs, sperm purchase needs, cancer treatment patients, LGBQ families, etc.
Remote initial consultation
1. File: Make an appointment for the initial consultation based on the information (documents, contact information, medical reports, medical records, etc.).
2. Ovulation cycle
Most of the whole treatment cycle is about 14 days (with an interval of 2 to 3 days to return to the clinic to see the doctor). Generally, the woman notifies the clinic on the first day of her menstrual period and takes medication and injections according to the doctor’s protocol for ovulation, and returns to the clinic for about 5 visits (ultrasound and blood sampling) for the egg retrieval procedure, and on the day of the egg retrieval, the man returns to his home country after retrieving the sperm together.
Ovulation Promotion Program
| 1.Natural cycle egg collection | 2.Microstimulation method | 3.Lutealization method | 4.Traditional Ovulation Promotion Method | |
| Ovulation Program | Essentially no use of fertility drugs (low cost of a single treatment) with few or no side effects. |
There are two types of microstimulation, and enhanced microstimulation, depending on the amount of medication used to promote ovulation. Clomid is often used in conjunction with other conventional ovulation-promoting drugs to stimulate the pituitary gland to secrete more natural FSH and LH; some clinics also use letrozole instead of Clomid. |
After ovulation is detected (hormone hormones such as FSH and LH drop), then ovulation promotion is started. Depending on the clinic, there are two types of ovulation promotions in one menstrual cycle, referring to the 2nd as luteal ovulation, and the 1st promotion only after ovulation is monitored. |
Routine urges are commonly referred to as big urges and are subdivided into three regimens: long regimens, short regimens, and antagonist regimens. One of the antagonist regimens is relatively mild, and GnRH-antagonist drugs (e.g., Ganirelix/Cetrotide) are also used during ovulation promotion to block the body’s own release of LH and FSH. |
| Fits the crowd | Older (age or ovarian age), about 1 AFC (basal follicle), AMH <0.2, early amenorrhea or anovulation; normal or abnormal endocrinology (high FSH) | 1. Microstimulation: older (age or ovarian age), AFC and and AMH at low baseline, normal or abnormal endocrine. 2. Enhanced stimulation: any age, normal or low AFC and AMH, normal or abnormal endocrinology, or ovary-related diseases affecting egg quality. |
The age range of adaptation is relatively wide, with normal or low AFC and AMH. However, caution is recommended in cases of endocrine abnormalities, or ovarian-related diseases that affect egg quality. | 1. Long or short regimen: especially for patients younger or older than 35 years of age with normal or high AFC and AMH values and normal endocrine profile. 2. Antagonists: for patients >35 years of age with normal or abnormal AFC and AMH values and normal or abnormal endocrine secretions |
| egg collection | 0 to 1 | 1. microstimulation ≈ AFC (basal follicle count) 2. enhanced microstimulation >AFC |
>AFC, or much larger than AFC. |
Drugs used for treatment
A woman usually produces multiple eggs each month, but only one will mature naturally and be released for fertilization. In order to increase the chances of a successful pregnancy, women undergoing IVF treatment need to take certain medications to allow multiple eggs to mature at the same time during the month, be removed for in vitro fertilization, and undergo fertilized egg culture (also known as embryo culture).
Initial IVF treatment initiation: Medications or combinations that may be involved are, monitoring hormones or ovulation, taking birth control pills, estrogen pills or patches, GnRH agonist (Lupron) injections, and/or testosterone topical gels or patches.
Ovum extraction
During the egg retrieval procedure, the doctor, guided by an ultrasound probe, inserts an egg retrieval needle through the vaginal wall to the ovary to suck out the egg. The procedure usually takes 5 to 10 minutes to complete, and under normal circumstances, you can leave after 20-30 minutes, or be accompanied by a chaperone upon request.
Egg collection needles are usually 21G (0.8mm) to 19G (1.1mm), the thinner the needle, the longer it takes to retrieve the eggs, usually the doctor will decide the thickness of the needle according to the number of follicles; when the needle is punctured through the vaginal wall to the ovaries, the woman will feel pain (similar to a shot), which can be eliminated through the pre-insertion of painkiller pills, local anesthesia, or general anesthesia.
Sperm retrieval or sperm retrieval procedures
Sperm retrieval is divided into self-service sperm retrieval, and surgical sperm retrieval. Under normal circumstances, on the day of the woman’s egg retrieval, the man will be notified of self-service sperm retrieval or early sperm freezing. The hospital has an independent sperm extraction room, which is convenient for men to operate independently and protect their privacy. If the visa application is unsuccessful or you can’t leave the country, you can contact us to take off-site sperm extraction. Surgical sperm retrieval: there are various ways as follows
1. Testicular Sperm Aspiration (TESA): TESA is a procedure that uses a fine needle and syringe to extract sperm from the testicles. The procedure requires local anesthesia and takes about 20-30 minutes.TESA is a treatment option for men who have had a vasectomy or who are unable to produce sperm in the ejaculate but produce sperm in the testes.
2. Testicular Sperm Extraction (TESE): TESE is a surgical procedure performed under a microscope, where a tiny incision is made inside the scrotum of the testicle to remove a small portion of testicular tissue and extract viable sperm.
3. Microscopic Epididymal Sperm Aspiration (MESA): MESA is a minimally invasive procedure that involves making a small incision to access the epididymis and using a microscope to help remove sperm from the epididymal ducts.MESA is performed by a skilled microsurgeon under general anesthesia.
4. Percutaneous Epididymal Sperm Aspiration (PESA): PESA involves inserting a needle attached to a syringe into the epididymis to gently remove fluid.PESA is performed under local or general anesthesia and is a treatment option for men with obstructive azoospermia.
5. Microsurgical Testicular Sperm Extraction (Micro-TESE): Micro-TESE is a surgical procedure that involves making small incisions in the testicular shell to open it up and examine the interior for areas that are more likely to produce sperm, and is performed by urologists who are highly skilled in microsurgery.
Condensed sperm (liquid soap)
Sperm washing is the process of separating sperm from semen. Washed sperm are then used for intrauterine insemination (IUI) and in vitro fertilization (IVF), and can even be used to reduce the risk of transmission of HIV in HIV-positive men. Sperm washing involves the removal of seminal plasma, dead sperm, inflammatory cells, anti-sperm antibodies, and bacteria from the semen, and is a standard procedure in infertility treatment. There are three commonly used methods of sperm washing:
1. Basic washing method: a method in which a semen specimen is diluted with culture fluid and placed in a centrifuge to spin at high speed and collect the precipitated sperm cell mass.
2. Direct upstream method: A method in which a culture solution is added above or below the semen sample and motile spermatozoa automatically swim to the surface of the culture solution and are collected. This technique is not suitable for oligospermic men (men with low sperm count), men with poor sperm motility, and men with male infertility.
3. Density gradient centrifugation: The semen is placed on top of a culture solution with different density gradients, and during centrifugation it is separated due to the difference in sedimentation coefficients of live sperm, dead sperm, leukocytes, and bacteria, in order to obtain a sample of sperm with at least 90% motility. This is the most commonly used method of “sperm washing” in the United States.
Cycle management
The two most important phases of IVF are the preparation of the female patient before going to the U.S. to the completion of the egg retrieval procedure, and the pre-transplantation examination before going to the U.S. to the completion of the transplantation procedure.
1. Time in the United States. During the period of ovulation promotion: the patient needs to visit the clinic about 5 times, each time about 2 to 3 days apart, and the time in the United States is about 14 days (some clinics are 2 to 3 months, and it is required to visit the clinic for examination before treatment).
2. Time in the U.S. Embryo transfer: transfer in the U.S. cycle is about 20 days, if you need to do hysteroscopy, laparoscopy and other tests before the transfer, you need to plan a separate time.
3. Getting medication and taking injections: Because of the separation of medicine and pharmaceuticals in the United States, only a small number of clinics provide medication; most clinics will write prescriptions for medication to the clinic or to a pharmacy designated by the patient, and the patient will go there to buy it on his or her own after receiving a medical prescription, which will require that the patient be able to obtain the prescription in time to get the medication before the pharmacy goes off duty even after he or she has left the clinic.
4. Other considerations: customization of the physical examination program, creation of a medical file, initial consultation, communication of treatment options and medical time planning, accuracy and timeliness of medical advice (contingency plan for questions about medical advice after leaving the clinic), answers to ultrasound and surgical questions, answers to and communication of embryo culture reports, sperm freezing and abandonment, billing, and so on.
3. fertilized ovum culture
After the eggs are removed from the body, they will be placed in a pre-prepared embryo culture solution in the laboratory and cultured for several hours before fertilization, which is generally referred to as day 0 of embryo culture. Fertilized egg culture in the U.S. refers primarily to blastocyst culture, which has a higher potential for live births and usually takes 5 to 7 days. Blastocyst culture is a very delicate task that requires a high level of laboratory hardware and software facilities and embryologists.
IVM immature egg culture
Fertilization
Fertilization is divided into various fertilization methods such as single sperm microinjection ICSI, natural fertilization, PICSI, IMSI, ISOLATION, and so on. The most commonly used method is: ICSI fertilization.
Principle of fertilization: Natural fertilization, also known as conventional in vitro fertilization, is a method in which a number of sperm are placed in a petri dish containing an embryo culture medium, and the sperm release an enzyme called hyaluronidase from their heads, which dissolves the granulosa cell that surrounds the egg and fertilizes the egg. This method of fertilization requires multiple sperm, and when the hyaluronidase released by the sperm reaches a concentration suitable for fertilization, it further dissolves the egg’s zona pellucida and enters the interior; when the first sperm reaches the egg cell, the zona pellucida and membrane of the egg cell are altered so that the other sperm are unable to enter, and the sperm and egg that do enter the egg cell form a prokaryotic nucleus that eventually fuses.
Note: When the spermatozoa show more than 15% DNA debris, or when the spermatozoa have low normal morphology or low motility, it is necessary to consult a doctor for surgical sperm retrieval, or other methods of fertilization.
Intracytoplasmic single sperm microinjection ICSI
It is a method of injecting sperm by inserting a needle into the egg under a microscope. This method is used for severe male infertility (inability to obtain the number of motile sperm required for routine IVF) and fertilization failure (inability to fertilize with IVF).
Laser-assisted incubation
Fertilized eggs are encased in a protein shell called the zona pellucida. When the zona pellucida thickens and stiffens in some embryos, it is difficult for the fertilized egg to divide and hatch. In this case, a small opening in the outer layer around the egg is needed to help peel off the zona pellucida, making it easier for the fertilized egg to hatch and aiding in the process of growing the embryo for implantation.
Fertilized egg culture (sac raising)
Blastocysts are usually formed on the 5th to 7th day after fertilization of the egg. Studies have shown that implantation of chromosomally normal blastocysts into the mother results in higher pregnancy rates and lower miscarriage rates.
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Timeline of embryonic development |
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Day 0 |
Day 1 |
Day 2 |
Day 3 |
Day 4 |
Day 5-7 |
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Egg collection and fertilization operations |
Fertilization results |
2 to 4 cells |
6 to 8 cells |
Embryonic fusion stage or mulberry embryo (16-32 cells) or cavitation |
Early cavitation (CAV) or transformation into blastocysts |
Pre-implantation genetic testing PGT (PGS and PGD)
The technique of third generation IVF, also known as preimplantation genetic testing (PGT), refers to the method of taking the genetic material of blastocysts (note: they must be blastocysts) for analysis to diagnose any abnormalities and screen for healthy blastocysts for transfer to prevent the transmission of genetic diseases prior to blastocyst transfer for IVF-ET.
Technology: NGS III is the latest and most mature technology of PGS at present (PGS has a total of three generations of FISH→ACGH→NGS).
Freezing of embryos and eggs
1. Frozen Embryos: During IVF treatment, embryos grown after egg retrieval are frozen for subsequent transfer, which is called cryopreservation.
2. Egg freezing: i.e. fertility preservation, for women who may not be ready to have children. For example, not having found a suitable partner, or for medical reasons (e.g. undergoing cancer treatment). As women age, the number and quality of eggs decline (mainly due to too many or too few chromosomes in the eggs).
At age 25, 75% of women have chromosomally normal eggs.
At age 35, approximately 50% of women with chromosomally normal eggs.
At age 40, about 10-15% of eggs are chromosomally normal.
By preserving young and healthy eggs, women can plan their future fertility on their own terms. This medical service is currently available in several countries around the world, including Beijing, China.
3. Freezing technology: At present, the most advanced technology for freezing eggs and embryos is the vitrification freezing technology, i.e., the use of nitrogen to freeze eggs and embryos quickly, and this rapid freezing method prevents the formation of ice crystals in the fluid of eggs and embryos, which would destroy the eggs and embryos; the other method of freezing is known as slow freezing or controlled freezing, as the speed of freezing has to be slow to easily form ice crystals, and the survival rate is lower.
IVF laboratories and embryologists
The environment, technology, equipment, and especially the expertise of the embryologist in the IVF laboratory are important factors in producing high quality embryos. Take one of the TOP 10 live birth rate laboratories in the US as an example:
1. Air: Custom air purification systems are used in X Clinic laboratories, for example, to ensure the highest air quality and strict environmental controls to optimize embryo development. These systems not only filter out particulate matter, but also control levels of harmful volatile organic compounds (VOCs) and yield levels well below the recommended parts per billion.
2. Temperature, humidity and gases: Embryos need to grow in an environment that mimics a woman’s stable reproductive environment, and it is important to minimize changes in the environment to avoid stressing the embryo and interfering with its development. For example, the X Clinic routinely handles embryos in a mobile incubator (modified preterm incubator) to maintain a constant temperature (37°C), humidity, and gaseous environment for the medium (the liquid in which the embryos are grown).
3. Quality control: For example, X has implemented an additional level of quality control testing on all manufacturer-developed media and contacts. This additional testing requires the use of an ultra-sensitive bioassay to ensure that the media and contact supplies are not toxic to the developing embryo.
4. Incubation Technology: When observing or working with embryos under a microscope, they are removed from the incubator in many laboratories and simply placed on a heated surface in a room atmosphere. x clinic’s mobile incubator allows embryologists to perform most of these tasks in a regulated and stable environment.
5. Day 7 Biopsy: Many labs will not culture embryos after day 5 because the process is both labor intensive and requires additional supplies and expense. x The clinic performs biopsies on day 7 to ensure that the patient has as many embryos as possible available for biopsy.
6. Second day ICSI technique: Usually, eggs are retrieved and mature eggs are subjected to single sperm microinjection ICSI on the same day. however, sometimes eggs take more time to mature and many laboratories do not perform second day ICSI because it requires more work, and involves additional supplies and costs, and they are not confident that it will produce high quality embryos.
Embryologists: are usually categorized as Junior Embryologists, Senior Embryologists, and IVF Laboratory Directors. They work to ensure that the laboratory is the ideal environment for the growth and storage of embryos.
4. fertilized ovum culture
Embryos that have been cultured in vitro are transferred to the woman’s uterus at the right time. Research has demonstrated that: 1. Frozen embryos have a higher rate of live births when they are transferred, i.e., they are thawed and transferred after the woman’s pro-ovulatory hormones return to normal. 2. Pre-implantation Genetic Testing (PGT) requires frozen blastocysts, and chromosomally normal blastocysts can be transferred when the patient’s body is ready for them. Chromosomally normal blastocysts are less likely to cause miscarriage and are more likely to result in a successful pregnancy.
Pre-transplantation preparation
1. Screening for uterine related diseases: To ensure that the embryos have a healthy environment in which to thrive and continue to develop in the fertile “soil” of the uterus. Prior to the transfer, you may undergo a hysterosalpingogram (HSG), hysterosalpingogram, or other tests or treatments (to assess the shape of the uterus and the presence of fibroids, polyps, scar tissue, and other material that may prevent the egg from attaching to the uterus), and you will need to speak with your doctor in advance to arrange your schedule.
(Organ) transplant operation
On the day of the transfer, you will either hold your urine (allowing a full bladder to help your doctor see your uterus better on the ultrasound) or urinate (requirements vary from doctor to doctor), depending on your doctor’s requirements, to ensure that your embryos are placed in the best possible position in your uterus.
Grade of blastocysts
Blastocysts are subdivided according to the total number of cells, the cohesion of the inner cell mass (ICM) and trophoblast ectoderm cells, and the degree of expansion of the blastocyst lumen, subdividing them into good quality embryos AA, good embryos (AB/BA), fair embryos (BB/AC/CA), and poor embryos BC/CB/CC. the better the quality chromosomal blastocysts the higher the grade, and the greater the rate of chromosomal normalization.
For example.4AA, the first number indicates that the embryo has entered the expander. The 2nd and 3rd letters represent the inner cell mass and the trophoblast cell grade. Of course, the number of days to blastocyst formation is also an important indicator of its developmental potential.
blastocyst cavity (in embryology) | Grade 1. Early blastocyst (EBL): blastocyst cavity <1/2 of the embryo volume. Grade 2. Blastocyst (BL): blastocyst cavity ≥ or equal to 1/2 of embryo volume Grade 3. Blastocyst (BL): the blastocyst cavity is completely filled with embryos. Grade 4. Expanded blastocyst (EXBL): blastocyst cavity >Primary volume of embryo, thinning of zona pellucida. Grade 5. HBL: Nourished ectoderm begins to escape from the zona pellucida. Grade 6. Hatched blastocyst CHBL: The blastocyst has completely detached from the zona pellucida in preparation for the developmental stage of implantation into the endometrium. |
Inner cell mass ICM (developing into an infant) | A Cells are numerous and tightly packed B Cells with less data and loosely arranged C Sparse cell number |
Trophoblast TE (develops into placenta) |
Blood test for pregnancy
Blood test for pregnancy: The 1st blood test is conducted around the 7th or 12th day after embryo transfer (requirements vary from clinic to clinic) to monitor whether the embryo is implanted or not.
Heartbeat detection: about 30 days after transplantation.
Full-term labor: 8 months and 20 days post-transplantation.
