Introduction of IVF In Vitro Fertilization In Vitro Fertilization Process Generations of IVF Technologies: Introduction, Success Rates and Price
In vitro fertilization is an assisted reproductive technique carried out in an embryo laboratory after the extraction of the husband and wife’s sperm and ovum, respectively. The well-developed embryo will be implanted into the uterus for gestation after a few days of fertilization and conception.
Generally, the whole process of in vitro fertilization, IVF takes place on the 21st day of the preceding menstrual cycle when the wife starts to undergo gonadotropin releasing hormone analog, GnRHa for the purpose of blocking hypothalamus stimulationto the pituitary gland in order to disable the secretion of gonad stimulating hormone. The therapeutic process takes about 14 to 18 days when ovulation stimulants will be applied to produce more ovarian follicles in the wife’s ovary once the arrival of the regular menstrual cycle is confirmed. Meanwhile, the growth of ovarian follicles will be monitored periodically by means of an ultrasonic detector, together with the execution of blood testing to track down the numerical value variation of estrogen in blood so that the prime time for octet pick up can be seized.
The diameter of the smallest ovarian follicle in a woman’s ovary is only about 0.1 to 0.2 millimeters, also known as the primal oocyte, and the growth of the follicle is affected by the motivation of follicle stimulation hormone. Despite the diameter of the ovarian follicle being only about 5 millimeters during the initial stage of menses FSH, it will continue to develop to 8 millimeters where the secretion of estrogen begins to increase. When the size of the follicle reaches 15 millimeters, the secretion of estrogen will become more hyperactive: a great deal of estrogen will activate the pituitary gland to release luteinizing hormone, LH for advancing the attenuation of partial tissue on the follicle’s surface. Then, 36 hours prior to egg harvesting, the patient must be remind to receive the human chorionic gonadotropin, HCG injection in order to complete the preparations for the entire process.
On the day of egg harvesting, the operation of egg retrieval will be guided by vaginal sonography, and the ovarian follicular fluid will be sent directly to the laboratory where the ovum will be filtered and placed inside a new petri dish. After that, the semen contributed by the husband, upon being washed and percolated, will be put together with the ovum for 2 to 5 days until the zygote eventually becomes a mature embryo ready for being implanted into the wife’s oviduct or uterus. Usually the luteinizing hormone, LH will stay in the granulocytes and endometrial cells on the follicular wall after ovulation. It will gradually develop into lutein cells that excretes a large amount of progesterone, P4, thus enabling the implantation.
Semen contributed by the husband → segregate the active spermatozoa/withdraw the egg from the wife’s ovary → the completion of in vitro fertilization → fertilization of ovum in petri plate for a few days → select the best embryo and implant into the uterus
The standard ways of embryo implantation in the in vitro fertilization process include：
（1）In-Vitro Fertilization/Embryo Transfer , IVF／ET
After the husband’s semen undergoesthe sperm wash and sperm sorting procedures, the eggs and sperm are cultured outside the body in an embryo culture laboratory. After fertilization, the fertilized eggis cultured for more than 48 hoursand enters the stageswith more than 2 cells developed (including the 4-cell stage, 8-cell stage, morula stage or blastula stage, which are transferred to the patient’s uterus on Day 2, 3, 4 and 5, respectively, depending on the patient’s clinical condition and needs) (Figure 1-20, Figure 1-21, Figure 1-22, Figure 1-23, Figure 1-24.) The embryo is then passed through the vagina and the cervix, and implanted within the uterine cavity.This in vitro fertilization/embryo implantationmethod applies to women having blocked or sticky fallopian tubes on both sides, or infertile women who have undergone in vitro fertilization failure several times.
▲Figure 1-21 Four-cell phase
▲Figure 1-22 Eight-cell phase
▲Figure 1-23 Morula phase
▲Figure 1-24 Embryo development into blastocyst stage
▲Figure 1-25 Two-Pronuclear phase , 2PN
（2）Gamete Intrafallopian Transfer , GIFT
On the day of egg retrieval, the husband’s sperm is directly mixed with the wife’s eggs, and the mixture is transferred immediately into the fallopian tube to undergo fertilization. Embryonic development also takes place in the fallopian tube. This method applies to women with healthy and unobstructed fallopian tubes.
（3）Zygote Intrafallopian Transfer , ZIFT
After 24 hours of culturing, the fertilized egg develops and enters the 2 pronuclear stage (2PN Stage,) which means the embryo develops and enters the pronuclear stage. At this stage, direct laparoscopic transfer of the embryo into the fallopian tube is necessary. This method applies to women with healthy and unobstructed fallopian tubes.
（4）Tubal Embryo Transfer , TET
The fertilized egg develops and enters the 2- to the 4-cell stage after 48 hours of culturing. At this stage, direct laparoscopic transfer of the embryo into the fallopian tube is necessary. This implantationmethod can be used to further observe how the fertilized egg division goesto choose the best embryo for implantation, which also increases the rate of implantation. This method applies to women with healthy and unobstructed fallopian tubes.
（5）Trans Myometral Embryo Transfer , TMET
The embryo is directly implanted in the myometriumwith the use of transvaginal ultrasound. This method can be taken into consideration for women with seriously anteverted or retroverted uteruses, or when implantation failure occurs using the methods mentioned above.
In vitro fertilization, short for IVF (fertilization outside the body,) can be divided into two courses of treatment that last two months. The in vitro fertilization process in the first month basically involves the use of medicines, whereas the process in the second month involves ovulation induction by injection, blood test, egg retrieval, and embryo implantation. The detailed in vitro fertilization process is described below：
（1）The in vitro fertilization flow chart in the first month (the use of medicines)
One pill of YAZ and Actos each is taken daily after mealsstarting from Day 5 of the menstrual cycle. One newpillis taken orally after each of the three meals from Day 16 to Day 25 of the menstrual cyclefor endometrium thickening. One Aspirin is taken daily from Day 21 of the menstrual cycle until the pregnancy test is performed. At the same time, Lupron is administered once dailyuntil egg retrieval is performed.
- Day 3 ~ Day 31 of the menstrual cycle：take one YAZ pill and Actos pill each daily after meals.
- Day 16 ~ Day 25 of the menstrual cycle：take one pill orally after each of the three mealsfor endometrium thickening.
- Day 21 ~ Day 31 of the menstrual cycle：take one Aspirin + administer Luprondaily.
（2）The in vitro fertilization flow chart in the second month (the treatment cycle)
The patient needs to make a return visit to the hospital on Day 2 or Day 3 of her menstrual cycle in the second month to do the E2, P4, and LH blood tests and have an ultrasound examination. At the same time, the patient needs to start injecting drugs for ovulation induction, while continuing to inject Lupron that she has already started injecting earlier until egg retrieval.
The patient needs to arrange a return visit to the hospital approximately on Day 8 ofher menstrual cycle to track the size of follicles, do blood tests, and continue injecting drugs for ovulation induction (patient needs to remind the husband to go to the hospital for fresh semen collection.) Depending on the state of the folliclesbetweenDay 12 and Day 16 of the menstrual cycle, the patient needs to inject human chorionic gonadotropin (HCG) in preparation for egg retrieval. The husband also needs to go to the hospital to collect fresh semen for the follow-up embryo culture. The doctor will perform embryo implantation two to five days after egg retrieval depending on the number and quality of eggs and the blood test index. A pregnancy test will be carried out 18 days after egg retrieval.
- Day 3 ~ Day 7 of the menstrual cycle：E2, P4, and LH blood tests + ultrasound examination + drug injection for ovulation induction.
- Around Day 8 of the menstrual cycle：track the size of follicles, blood tests, drug injection for ovulation induction (start on semen storage.)
- Day 12 ~ Day16 of the menstrual cycle：HCG injection in preparation for egg retrieval depending on the state of the patient’s follicles, and fresh semen collection.
- Day 18 ~ Day 21 of the menstrual cycle：perform embryo implantation after 2 ~ 5 days of embryo culture (the doctor will decide based on the number and quality of eggs, and the blood test index.)
- Day 33 ~ Day 36 of the menstrual cycle：pregnancy test.
The in vitro fertilization process looks complicated and inconvenient, yet every step is done to improve the in vitro fertilization success rates. Drugs are used to induce follicle growth, increasing the number of mature follicles. Blood tests and ultrasound exams are used to help doctorsdeterminefollicular numbers, sizes, and maturity, which are essential factors that help increase the in vitro fertilization success rates. The process is inconvenient but necessary for the retrieval of a higher number of mature eggs.
People must first know that the in vitro fertilization technologies are divided into three generations before talking about their success rates, which are different for each generation of in vitro fertilization technology. Apart from introducing and comparing different generations of in vitro fertilization technologies and their success rates, we will also debunk common myths here today. The main difference between First and Third generation in vitro fertilization is that they apply todifferent people; hencepeople cannot judge these technologies by the thought “the newer the product, the better it is.”They must first understand each generation of technology and the differences between them to choose the right in vitro fertilization technology for themselves, hence improving the success rates.
- First Generation In Vitro Fertilization
In vitro fertilization is, in fact, external fertilization, commonly named the embryo transfer technology. First-generation in vitro fertilization was available since 1978. The eggs and sperm are placed in the same culture medium, allowing them to fuse freely,just like what happens during the “routine fertilization.” This technology is the so-called first generation in vitro fertilization-embryo transfer (IVF-ET.)
This technology is mainly directed against infertile females. It applies to patients with infertility caused by blocked fallopian tubes, endometriosis, and endocrine dysregulation. If males, however, have low sperm count, in vitro fertilization may possibly fail.
- Second Generation In Vitro Fertilization
Second-generation in vitro fertilization is also known as intracytoplasmic sperm injection (ICSI.) Unlike the free sperm-egg fusion in the first generation, the second generation in vitro fertilization needs to be performed under a microscope. After stabilizing an egg with a specific stabilizer, a sperm is drawn with a needle and injected through the zona pellucida and the cell membrane of the egg into the cytoplasm. The sperm is then released into the cytoplasm.
This technology is mainly directed against infertile males. It applies to those with, e.g., low sperm count, immotile sperm, no ejaculation (but a small amount of sperm is still present in the vas deferens,) or those having motile sperm but cannot fuse with an egg.
- Third Generation In Vitro Fertilization
Preimplantation genetic diagnosis (PGD,) also known as the thirdgenerationin vitro fertilization, is based on the technology of the second-generation in vitro fertilization but emphasizing on the preimplantation genetic diagnosis. One or two cells (blastomere) will be retrieved after the embryo has developed into a 4- to 8-cell embryo. Before the embryo transfer, genetic testing will be performed on the embryo through molecular diagnostics to make sure it carries no hereditary diseases.
This technology applies to infertile females and males. It is also suitable for women of advanced maternal age over the age of 34, the husband or the wife, or both having genetic diseases, patients having a record of repeated spontaneous abortion, and patients with chromosomal abnormalities. This technology prevents genetic diseases from being passed on from one generation to the next through preimplantation genetic screening/next-generation sequencing(PGS/NGS) and preimplantation genetic diagnosis (PGD.)
- 3.5 Generation In Vitro Fertilization
If the AI artificial intelligence system of the so-called 3.5 generation test tube "embryoscope time-lapse system” is further adopted, this machine can conduct observation up to 120 hours without removing the embryo. A special identification chip is installed in the culture dish of the embryo, which can automatically read and store the patient's embryo data and completely cut off the pollution, a what one would call a six-star culture environment! At the same time, the microscope camera in the time-lapse system takes pictures of the embryos every 10 minutes. Every embryo will have 10,000 images to fully record down the embryo’s development process.
For those who had multiple failed test tube tries, and those with multiple miscarriages.
- Fourth Generation In Vitro Fertilization
- Donor Egg In Vitro Fertilization
- Success Rate of IVF
The 3.5th and 4th generation IVF utilize the AI system of “embryoscope time-lapse system” and the “latest algorithm” method, an accumulation of 33 years of clinical experiences, to greatly increases the pregnancy rate to 80~85% . If the donor egg IVF is equipped with an AI system, the pregnancy rate can be improved to reach more than 80%. Even those advanced material aged women over the age of 45 can have a chance to make their dream come true.
Dr. Maw-Sheng Lee also pointed out that the prevalence rate of infertility in Taiwan has jumped from 10% to 15%. The cause of infertility has also evolved from fallopian tubes obstruction, abnormal ovulation, and oligospermia in men to aging of eggs due to women marrying late. Therefore, it is recommended to females who want to have a baby but have not yet got a partner, to consider freezing the eggs before the age of 34, so that the success rate of having a test tube baby will be relatively higher in the future.
- Cost of IVF