Selecting optimal embryos for day 3 or 5 blastocyst transfer

Overview

In vitro fertilization (IVF) is a complicated set of techniques designed to improve fertility, avoid genetic abnormalities, and aid in pregnancy. During IVF, mature eggs are extracted from the ovaries and fertilized in a laboratory using sperm. The fertilized egg (embryo) or eggs (embryos) are then placed in the uterus. A whole IVF cycle takes roughly three weeks. When these processes are divided into sections, the procedure might take longer.

The most effective kind of assisted reproductive technology is IVF. The treatment can be performed with the couple's own eggs and sperm. Alternatively, IVF may use eggs, sperm, or embryos from a known or anonymous donor. A gestational carrier, or someone who has an embryo implanted in their uterus, may be employed in some instances.

Many variables influence your odds of having a healthy baby with IVF, including your age and the cause of infertility. Furthermore, IVF can be time-consuming, costly, and intrusive. IVF can result in a pregnancy with more than one fetus if more than one embryo is implanted to the uterus (multiple pregnancy). Your doctor can explain how IVF works, the dangers involved, and if this way of treating infertility is suitable for you.

What are the steps of IVF cycle?

Ovarian stimulation, egg retrieval, sperm retrieval, fertilization, and embryo transfer are all milestones in the IVF process. A single IVF cycle might take two to three weeks. It is possible that more than one cycle will be required.

Ovulation induction:

An IVF cycle begins with the use of synthetic hormones to encourage the ovaries to create numerous eggs rather than the single egg naturally matures each month. Because some eggs will not fertilize or develop normally following fertilization, many eggs are required. Your doctor and you will decide which drugs to take and when to take them. Typically, one to two weeks of ovarian stimulation is required before your eggs are ready for retrieval. Blood tests and a vaginal ultrasound may be performed to identify when the eggs are ready for harvest.

Egg retrieval:

Egg retrieval can be done 34 to 36 hours after the final injection and before ovulation in your doctor's office or a facility.

You will be sedated and given pain medication throughout the egg retrieval procedure.
The most common form of retrieval is transvaginal ultrasound aspiration. To locate follicles, an ultrasound probe is put into your vagina. The eggs are then extracted by inserting a small needle into an ultrasound guide and passing it through the vagina and into the follicles.
If your ovaries cannot be reached through transvaginal ultrasound, an abdominal ultrasound may be utilized to guide the needle.
The eggs are extracted from the follicles using a needle attached to a suction equipment. In around 20 minutes, many eggs can be extracted.
Cramping and sensations of fullness or pressure may occur after egg retrieval.
Mature eggs are incubated in a nutritive liquid (culture media). Healthy and mature eggs will be combined with sperm in an attempt to form embryos. However, not all eggs will be fertilized successfully.

Sperm collection:

If you're utilizing your partner's sperm, you must deliver a sperm sample at your doctor's office or clinic the morning of egg retrieval. Masturbation is commonly used to gather sperm samples. Testicular aspiration — the use of a needle or surgical technique to collect sperm straight from the testicle — is occasionally necessary. Donor sperm can also be used. In the lab, sperm is isolated from the sperm fluid.

Fertilization:

Fertilization can be undertaken using one of two commonly used procedures:

Conventional insemination. Healthy sperm and mature eggs are combined and incubated overnight during traditional insemination.
Intracytoplasmic sperm injection (ICSI). ICSI involves injecting a single healthy sperm straight into each maturing egg. ICSI is frequently utilized when sperm quality or quantity is an issue, or when fertilization efforts during previous IVF cycles have failed.

Embryo transfer:

Embryo transfer is done at your doctor's office or a clinic and usually takes place two to five days after egg retrieval.

You might be given a mild sedative. The procedure is usually painless, although you might experience mild cramping.
The doctor will insert a long, thin, flexible tube called a catheter into your vagina, through your cervix and into your uterus.
A syringe containing one or more embryos suspended in a small amount of fluid is attached to the end of the catheter.
Using the syringe, the doctor places the embryo or embryos into your uterus.

If successful, an embryo will implant in the lining of your uterus about six to 10 days after egg retrieval.

What is embryo transfer?

Embryo transfer is a straightforward operation that occurs after in vitro fertilization (IVF) and is frequently regarded as the easiest and final phase in the process. The goal of embryo transfer is to facilitate conception during in vitro fertilization.

The final stage of in vitro fertilization (IVF) is embryo transfer. Fertility drugs are used during IVF to stimulate the ovaries into producing healthy eggs. These eggs are then extracted from the ovaries of a woman and fertilized in a laboratory. The embryos are transplanted to the woman's uterus once the fertilized eggs have multiplied. The embryo must next attach itself to the wall of the womb or uterus in order for a pregnancy to begin.

IVF and embryo transfer are required when spontaneous fertilization is not a possibility or is difficult to achieve. Embryo transfer can be done for a variety of reasons, including:

Ovulation disorders: If ovulation is infrequent, fewer eggs are available for successful fertilization.
Damage to Fallopian tubes: The Fallopian tubes are the pathways that embryos take to reach the uterus. It is difficult for fertilized eggs to enter the womb if the tubes become damaged or scarred.
Endometriosis: When uterine tissue implants and develops outside of the uterus. This can have an impact on how the female reproductive system functions.
Premature ovarian failure: If the ovaries fail, they do not generate enough estrogen or release eggs on a regular basis.
Uterine fibroids: Fibroids are tiny, benign tumors that grow on the uterine walls. They can obstruct an egg's ability to implant in the uterus, preventing conception.
Genetic disorders: Some genetic disorders are known to prevent pregnancy from occurring.
Impaired sperm production: Natural fertilization may fail in males due to inadequate sperm production, poor sperm motility, testicular injury, or sperm abnormalities.

How embryo transfer is done?

The doctor will select the best eggs to transfer to the womb about 2 or 3 days before the embryo transfer. There are other approaches available to help selection, including non-invasive technologies such as metabolomic profiling, which are now being investigated.

The technique of choosing the most helpful eggs based on a variety of criteria is known as metabolomic profiling. In the future, this might reduce the need for invasive operations. These eggs will be fertilized in a laboratory and cultured for 1-2 days. If a substantial number of high-quality embryos develop, those that will not be transferred can be frozen.

In some cases, your doctor may advise you to undergo further treatments prior to embryo transfer.

Assisted hatching. An embryo "hatches" from its surrounding membrane (zona pellucida) about five to six days after fertilization, allowing it to implant into the uterine lining. If you're an older woman or have had numerous unsuccessful IVF efforts, your doctor may consider assisted hatching, which involves making a hole in the zona pellucida immediately before transfer to help the embryo hatch and implant. Because the technique can thicken the zona pellucida, assisted hatching is especially beneficial for previously frozen eggs or embryos.
Preimplantation genetic testing. After five to six days of growth, embryos are placed in an incubator and left to develop until a tiny sample can be taken and examined for certain genetic illnesses or the proper number of chromosomes. Embryos with affected genes or chromosomes cannot be transplanted to your uterus. While preimplantation genetic testing can minimize the possibility of a parent passing on a genetic issue, it cannot completely remove the danger. Prenatal testing may still be advised.

The embryo transfer procedure is identical to that of a pap smear. To keep the vaginal walls open, the doctor will introduce a speculum into the woman's vagina. The doctor will next use ultrasonography to guide a catheter through the cervix and into the womb. The embryos are then transported through the tube and into the womb.

The procedure is normally painless and does not necessitate the use of sedatives. Some women may experience discomfort as a consequence of the speculum being placed or from having a full bladder, both of which are necessary for ultrasonography. The procedure is quick, and the bladder may be emptied right away. A second appointment Checking in two weeks to see if the embryo has implanted will reveal whether or not the transfer was successful. Women may suffer cramps, bloating, and vaginal discharge following the operation.

What are the types of embryo transfer?

Doctors normally use the same procedure every time to retrieve and fertilize the eggs during IVF. Once fertilization has happened, there are several alternatives for embryo transfer:

Fresh embryo transfer: After fertilization, the eggs are cultivated for 1-2 days. The finest embryos are chosen for direct transfer to the woman's uterus.

Frozen embryo transfer: Any viable embryos not utilized in the initial transfer can be frozen and kept for later use. These can be thawed and implanted in the uterus.

Blastocyst embryo transfer: It is typical to wait to see if many viable embryos grow after fertilization to check if the embryos develop into blastocysts. A research found that blastocyst (day 5) embryo transfer is more successful than conventional embryo transfer on day 3. However, according to another recent study, it may offer concerns later in pregnancy and may not always be advised.

Assisted hatching (AH): According to one study, assisted hatching, which involves weakening the embryo's outer shell before transferring it to the uterus, did not enhance pregnancy and implantation rates in women who had fresh embryos implanted. However, the researchers emphasized that women who had frozen embryos implanted benefit from having their embryos handled in this manner.

How many embryos are transferred?

In practice, there are still variances in how many embryos are transplanted into a woman's uterus. In many circumstances, just one fertilized embryo is transported to the uterus, despite the fact that some specialists feel that two viable embryos boost the odds of a healthy pregnancy.

The quantity of fresh embryos to be transplanted varies depending on the woman's age and perspective, according to standards established by the International Journal of Gynecology and Obstetrics. In many circumstances, just two embryos will be utilized. Doctors will explore utilizing only one embryo for women under the age of 35 who have a high possibility of pregnancy.

A recent study found that single embryo transfer in women under the age of 38 reduced the likelihood of multiple births while having no effect on live birth rates. This is significant since many doctors advise utilizing many embryos to assure conception. This study suggests that numerous embryos may not be required.

When a woman's prospects of becoming pregnant appear to be poor, physicians may employ a method known as heavy load transfer (HLT), in which three or more embryos are delivered to the uterus. According to one study, HLT should be advised in patients with a poor natural prognosis since it has the potential to increase pregnancy rates to an acceptable level.

Day 3 vs Day 5 Embryo Transfer:

As a single cell, an embryo develops. By day 3, it has developed into a 6-8 cell "cleavage" stage embryo. It will continue to grow during the next four days, hopefully reaching the blastocyst stage by day 5-7. At every level of development, there is tremendous attrition. For example, on the day of fertilization, a patient may have 10 embryos, 5 embryos on day 3, and just 2 embryos on day 5. In fact, some patients may be incapable of producing day 5 embryos regardless of how many IVF rounds they undergo.

One of the most contentious scientific controversies in IVF over the last few decades has been whether embryos should be transferred at the cleavage or blastocyst stage. These embryonic stages are normally achieved between days 3 and 7 of development. As a result, they are frequently referred to as day 3 and day 5 embryo transfers.

Transferring day 5 embryos is becoming increasingly prevalent as laboratory technology improves. The American Society of Reproductive Medicine's current stance is that Blastocyst embryo transfers are typically favored for individuals with a strong prognosis of success.

However, life is not as easy as transferring day 5 embryos because a considerable number of IVF cases do not have a positive prognosis. There are worries regarding the risks of growing an embryo in a lab for a longer period of time and if it genuinely improves patients' chances of having a live delivery. As a result, existing research does not indicate a strong consensus on the effectiveness of day 3 or day 5 embryo transfers.

Patients frequently have more embryos ready for transfer on day 3 than on day 5 since not all embryos continue to mature. Blastocyst-stage embryos have better implantation rates, most likely because they are more advanced and have a higher chance of being chromosomally normal.

While blastocyst embryos have a greater implantation rate, cleavage and blastocyst embryos appear to have comparable pregnancy and live birth rates per IVF retrieval. This is due to the fact that more embryos are accessible on day 3, allowing for either more embryos to be transferred during a single embryo transfer or a greater possibility of embryos being available for repeated transfers if the initial transfer fails.

Pros of day-5 blastocyst transfer:

Day 5 embryos are more advanced and hence have a better chance of being chromosomally normal and overall healthy (if they weren't, they would have died off by now). If an embryo has the genetic composition and "strength" to survive 5 days in a laboratory incubator, it has a greater probability of resulting in pregnancy if transplanted.

As a result, fewer embryos must be transferred. This increases success rates while decreasing the likelihood of twin or higher-order multiple pregnancies. Similarly, because spontaneous implantation following sexual intercourse normally happens on days 5-7, there is greater temporal synchronization between embryo and endometrium after a blastocyst embryo transfer. Day 5 embryos can also be genetically analyzed, however there is a similar intense dispute over the usefulness of such testing and when, if ever, it should be done.

Cons of day-5 blastocyst transfer:

There is a greater likelihood that embryos may not survive until transfer day, resulting in fewer total embryos available for transfer, or potentially none at all.
Higher risk of cycle cancelation
Embryos placed in the uterine environment later
Viable day 3 embryos may not make it to day 5 for transfer
Not a viable solution for patients who don’t produce many embryos
Some people are not capable of producing day 5 embryos

Pros of day-3 transfer:

No matter how well an embryology lab mimics the uterine environment, it is still an artificial setting that is not 100% optimum for embryo development. Embryos that have matured to day 3 have already shown enough genetic normality and resistance to warrant transfer.

Some embryos that may survive in an ideal uterine environment may die off between days 3 and 5 if left in a lab to mature; consequently, some potentially viable embryos will never have a chance at life if cultivated in a lab for so long. Despite the negative stigma associated with day 3 embryo transfers, evidence suggest that doing so may result in similar or greater live birth rates per IVF retrieval.

Cons of day-3 transfer:

Lower rates of implantation per transplanted embryo (but there are more embryos to work on day 3 as compared to day 5)
Because you have to transfer more embryos (which may be highly healthy embryos by chance) at a time to achieve comparable success rates, there is a larger probability of twin or multiple pregnancies.
Less information available from embryo grading and on embryo quality
No genetic testing options are available

Success rate comparison:

As previously stated, developing embryos over 5 days may assist embryologists to identify high-quality embryos for transfer and, in theory, improve embryo uterine synchrony. In one research, 201 women were randomly randomized to transfer groups on day 3 and day 5. Then, in both groups, 2-3 of the highest-graded embryos from each patient were transplanted.

The implantation rates for each individual embryo were somewhat higher in the day 5 transfer group (24%) than in the day 3 transfer group (21%), but because the day 3 group transferred slightly more embryos on average, the pregnancy rates were the same in both groups (39%).

Conclusion

Although days 3 and 5 of embryo development are only a few days apart, there is a major difference between these two stages of maturity. Embryos develop quickly. Every embryo begins as a single cell. Every 12 to 24 hours, that solitary cell divides. So, by the third day of development, an embryo should have between four and eight cells.

An embryo will consist of between 70 and 100 cells two days later, on day 5. The embryo is known as a blastocyst at this stage of development. A blastocyst is made up of two types of cells: those that will become fetal tissues and those that will become the placenta. Only around one-third of embryos successfully grow to the blastocyst stage.

It can be tough to choose between day 3 and day 5 embryo transplants. The good and bad news is that research has not conclusively determined what is best. That's bad news since the answer to your question, "Is a day 5 embryo transfer better than a day 3 embryo transfer?" is "well, maybe," but it's also good news because nature may have designed it this way. There might not be a better embryo type to transplant.