IVF Embryo Development by Stages

Starting with a fertilized egg, embryo development is a complex biological phenomenon that has fascinated scientists for centuries. With advances in assisted reproductive technology (ART), particularly in vitro fertilization (IVF), our understanding of embryo development has expanded dramatically — contributing to the birth of 91,771 ART-conceived babies in 2022! 

This article walks through the step-by-step processes involved in unassisted and assisted embryo development, highlighting underlying biological events, how IVF works, and the factors influencing fertilization success. Let’s jump in.

It starts with the egg 

Ovulation is the starting point of embryo development. It is the part of the menstrual cycle when one ovary releases a mature egg. Once it is released, the egg moves down into one of the fallopian tubes, where it can survive for about 24 hours. This can result in pregnancy if the egg gets fertilized by sperm during that time – if it doesn’t get fertilized, the egg will break down and eventually will shed along with the lining of the uterus when you have your period.  This typically occurs around the 14th day in a 28-day cycle, though not for everyone. The day of ovulation varies based on cycle length, anything ranging 21 - 35 days is considered normal. Hormones such as luteinizing hormone (LH) and follicle-stimulating hormone (FSH) play critical roles in inducing ovulation. These hormones are always in your body, but your FSH levels fluctuate throughout the menstrual cycle, typically peaking just before LH levels peak to trigger ovulation.

During an egg freezing / IVF cycle, understanding the timing of your menstrual cycle is important as it influences the scheduling of your treatment. Ovulation is carefully controlled through the administration of hormonal drugs that stimulate the ovaries to produce multiple eggs and bring them to peak maturity. The development of these eggs is monitored through regular ultrasounds and blood tests, which are crucial to ensure the specific medication protocol you are given is personalized to you. Once the eggs are mature, they are retrieved surgically under anesthesia.

Then, the eggs are fertilized 

Fertilization marks a pivotal stage of embryo development. During unassisted embryo fertilization, it occurs in the fallopian tubes and begins when a sperm cell breaks through the outer layer of the egg, the zona pellucida. This penetration triggers reactions that prevent other sperm from entering the egg. Then, the nuclei of the sperm merge with the nuclei of the egg, combining their genetic material to form a zygote, the earliest stage of the embryo.

During IVF, fertilization takes place in a lab setting, using the retrieved eggs and sperm. An embryologist combines each egg with sperm, under a controlled, microscopic watch to monitor daily development. Ideally, the same response occurs as during an unassisted fertilization process. To enhance success rates, especially in cases of male factor infertility and low sperm counts, a single sperm is injected directly into the egg using a technique called intracytoplasmic sperm injection (ICSI). 

The early embryo develops through cleavage 

Once the fertilized egg has created a zygote, it then begins a series of rapid divisions in a process known as cleavage. This stage of embryo development involves the embryo splitting without growing in size, essentially forming a compact ball of cells. Cleavage is vital as it transforms the single-cell zygote into a multicellular entity, setting the foundation for further differentiation and growth. Both in unassisted conception and IVF, studies have shown the quality and speed of these divisions can be an early indicator of the embryo's health and viability.

The blastocyst forms 

About five days after fertilization, the developing embryo hopefully(!) reaches the blastocyst stage. This is when the embryo is made up of two parts: a cluster of cells inside that will develop into the baby (called the inner cell mass) and a shell on the outside that will help form the placenta (called the trophoblast). 

During unassisted conception, the blastocyst travels from the fallopian tube to the uterus throughout this five day period. During IVF, however, the blastocyst first develops within the lab and then is frozen. At this point, many families opt for genetic testing of the embryo. 

Preimplantation genetic testing for aneuploidy (PGT-A) allows families to know whether embryos possess the right number of chromosomes. A “euploid” embryo is genetically healthy enough to transfer. Embryos with chromosomal additions or deletions are considered aneuploid. Mosaics are somewhere in between and we’re still learning more about their potential. 

PGT-M (preimplantation genetic testing for monogenic disorders), on the other hand, takes place if there is a specific genetic diagnosis for which both reproductive partners are carriers. This technology allows embryologists to identify embryos possessing those specific genetic abnormalities. That way, parents can choose to avoid transferring one of these embryos if it would put the future child at risk. 

A healthy embryo is transferred and grows in the uterus

Your PGT results (should you choose to pursue that testing), combined with the grades given to each of your blastocyst embryos, will both factor into your and your doctor’s decision on which embryo would be best suited for transfer. 

During IVF, an embryo transfer procedure is done with great care under ultrasound guidance to optimize the placement of the embryo(s) within the uterine cavity, enhancing the chances of successful implantation. The timing of this transfer is crucial and is carefully synchronized with the recipient's menstrual cycle to ensure the uterine lining is optimally receptive. 

Implantation and fetal development

Ideally, the hope is that the transferred blastocyst will attach itself to the uterine wall— a process known as implantation. During implantation, the outer layer of the blastocyst, known as the trophoblast, connects itself to the uterine lining. As we mentioned, timing is everything — implantation success is influenced by the hormonal balance of the body and the receptivity of the uterine lining, which needs to be thick enough to “accept” the embryo. This will eventually grow into placenta, and will be an essential connection for the transfer of nutrients and oxygen to the embryo as it develops into a fetus and, ultimately, a baby. 

The heart is the first organ to develop within an embryo — by the sixth week of pregnancy, the embryo may have developed an actual heartbeat, which can be measured on ultrasound.

Factors influencing embryo development success

Several factors affect the success of both unassisted and assisted embryo development:

1. Age and quality of eggs: Older women tend to have fewer eggs, and the quality of eggs decreases with age, affecting fertilization rates and embryo development. Utilizing donor eggs can significantly improve outcomes in IVF treatments.
2. Sperm quality: Parameters such as sperm count, motility, and morphology are crucial in both unassisted and assisted fertilization processes.
3. Clinic and lab quality: Not all fertility clinics are created equal, and the same goes for labs. If you have not yet begun the IVF process, ask your clinic about their blastocyst development success rates (it’s key to use this language, as opposed to fertilization rate, for example) and feel free to call other local clinics and do the same. 
4. Embryonic development: The ability of an embryo to reach the blastocyst stage is a key indicator of its viability and potential for successful pregnancy.
   

A recent study examined a few reasons why embryo growth may stall — in summary, this is largely due to chromosomal fragility and abnormalities. If possible, we recommend undergoing genetic carrier screening before pursuing IVF so as to make the experience as successful as possible and ideally provide a healthy pregnancy. 

Summing it up

In conclusion, the path from egg to blastocyst formation is pretty incredible and requires the completion of several successful steps even before a transfer attempt. As technological capabilities expand within the field of embryology, so too does the potential to assist those facing challenges in unassisted conception. 

FAQs about embryo development

What percentage of fertilized embryos make it to day 5?

About one-half of fertilized embryos continue developing to become a day 5 blastocyst. When an embryo is created using donor eggs, this stat jumps to 60%. 

How long does it take for an embryo to develop after IVF?

In IVF, embryos are typically cultured in the laboratory for 5-6 days to reach the blastocyst stage, which is considered optimal for transfer. However, occasionally embryos may be transferred earlier, at the cleavage stage (day 3). 

Where does the embryo develop?

In unassisted conception, the embryo develops in the uterus. After fertilization, the embryo travels down the fallopian tube and reaches the uterus, where it undergoes several stages of development starting from a zygote to a blastocyst. Successful implantation into the uterine wall is essential for the continued growth and development of the embryo.

While the implantation process remains the same for an embryo’s development during IVF, the actual fertilization process for assisted conception takes place within a lab, where an embryologist combines an egg with sperm under close watch. Only once the embryo has spent 5 days developing into a blastocyst is it transferred into the recipient’s uterus, or may be frozen for a future embryo transfer cycle. 

What is the first organ to develop in the embryo?

The first organ to develop in the embryo is the heart. The heart begins as a simple tube-like structure and starts beating and pumping blood by around the 22nd day after conception, which is essential for the circulation of nutrients and oxygen to the developing embryo.

When does an embryo develop a heartbeat?

An embryo typically develops a heartbeat by the end of the fifth week of pregnancy, which is about three weeks after fertilization. This milestone can often be seen during an early ultrasound scan, and is a crucial indicator of the embryo's viability.

‍What is preimplantation genetic testing (PGT)?

PGT is a process that screens embryos created through IVF for specific genetic conditions or chromosomal abnormalities. This can help increase the chances of a healthy pregnancy and reduce the risk of miscarriage. Read more about PGT testing here.

Does using frozen eggs affect embryo development?

Research suggests that eggs frozen through vitrification have similar success rates to fresh eggs in IVF. However, the success rates of utilizing frozen eggs still depends on the age of the egg when it was frozen. The younger the egg(s), the greater its potential for successful fertilization and development into a healthy embryo.