The Stages of In-Vitro Fertilization (IVF): What to Expect

The Stages of IVF: What to Expect

In Vitro Fertilization (IVF) encompasses a series of carefully timed steps before and after sperm and egg are combined in a laboratory to produce an embryo. It is the most effective fertility treatment available, offering the highest success rates per cycle of any Assisted Reproductive Technology (ART). Though the technology has been around since 1978, there have been updates to techniques that have improved its success allowing it to be used for medically required and elective reasons alike.

In simple terms, IVF removes eggs from the intended mother or donor, fertilizes them with partner or donor sperm, and places the fertilized egg (now an embryo) back into the carrier’s uterus where it continues to develop throughout gestation.

This process can easily be understood through 4 main steps:

· Ovarian Stimulation

· Egg Retrieval

· The Laboratory: fertilization and early stage embryo development

· The Embryo Transfer

Now that we have a very basic understanding of the IVF process, let’s dive on in for more!

Step One: Ovarian Stimulation

Most women release just one mature egg each month. The goal of ovarian stimulation is to produce more than one mature egg with the help of hormone-based medications (namely Follicle Stimulating Hormone – FSH.

The idea here is simple: more FSH means more follicular development; more follicles mean more eggs; more eggs mean more embryos; more embryos means higher odds of having a baby from that IVF cycle.

The injectable medications usually begin on days 2-4 of a woman’s natural cycle (if the woman has regular cycles) following a “baseline” appointment in which the woman’s uterine lining, follicular size, and hormones are measured to establish their starting or “baseline” levels. The daily injections are usually taken for approximately 7-10 days. Around the 6th day of FSH injections, the woman most often begins another medication which prevents early ovulation.

During this entire process, the woman is closely followed with monitoring appointments every few days to track uterine lining and follicular development as well as hormone levels.

Once the egg-containing follicles reach the appropriate size as seen on ultrasound (usually around day 8), the first two medications are stopped, and a third medication (the trigger) is introduced for either one or two days to promote the final maturation of the eggs.

Step Two: Egg Retrieval & Sperm Collection

The egg retrieval is performed 35 hours after the first “trigger” shot. It’s a minor outpatient procedure performed under light anesthesia that collects the developed eggs from the woman’s ovaries so they can be fertilized in a laboratory. A physician uses a tiny hollow needle with suction capabilities to pierce through the vaginal wall and drain the fluid from the follicles. The fluid contains the developed eggs. The retrieval itself lasts only 5-10 minutes.

The follicular fluid that contains the eggs is immediately transported to an IVF laboratory where an embryologist will locate, isolate, and nurture the eggs in media similar in environment to the fallopian tubes as they await fertilization. The number of eggs retrieved will depend largely on the female’s age, medical history, fertility diagnosis, medication protocol, and the response to medications.

If a male partner is providing the sperm, it is usually collected into a sterile cup the morning of the egg retrieval. It can also be collected beforehand, frozen, and then thawed the morning of the retrieval. The sperm is washed, concentrated, and suspended in a solution, then transferred to the embryology lab. Sperm may also be provided by a donor or surgically retrieved from the man if there is no sperm present in the ejaculate.

Step Three: The Laboratory

Fertilization

After retrieval, it generally takes about 4-6 hours for eggs to reach final maturity. At this point, the eggs are ready for fertilization. In IVF, there are generally two fertilization methods used:

Conventional: In conventional fertilization, a large number of sperm are combined in a Petri dish with the eggs. They are left together in an incubator for about 18 hours, giving them the time to fertilize through a rather natural process.

ICSI: During Intracytoplasmic Sperm Injection or ICSI, a single sperm is injected directly into the egg using an extremely small needle under a microscope. ICSI was originally developed to help couples with male factor infertility, but many labs use ICSI as their primary method of fertilization regardless of male factors.

Once fertilized, the eggs, now embryos, continue to grow in the IVF laboratory.

Embryo Development

Embryos are grown in nourishing media for 3-7 days or until the embryo reaches a cleavage or blastocyst, at which point the embryo must be transferred into the carrier’s uterus or frozen for future transfer. An embryologist regularly examines each developing embryo looking for progressive development.

Cleavage Stage: The cleavage stage of embryo development usually reached on day 3. They are called cleavage embryos because the cells in the embryo are dividing (or cleaving), but the embryo itself is not growing in size. Typically, a healthy day 3 embryo will contain between 6 and 10 cells.

Blastocyst Stage: The blastocyst stage of embryo development is usually reached on day 5, thought it make take up to 7 days to be achieved. A blastocyst embryo has developed into a single-layered sphere of cells (the trophectoderm which will differentiate into the placenta) encircling a fluid-filled cavity with a dense mass of cells (endoderm which will develop into the fetus/baby) grouped together. Blastocysts contains anywhere from 60 to 120 cells.

Further developed embryos have a higher probability of being genetically normal and result in live births than earlier stage cleavage embryos.

Step Four: Embryo Transfer

The Process

The embryo transfer itself is a rather quick stage of the treatment. Anesthesia is very rarely necessary, but the use of a muscle relaxer or Valium is quite common.

During the transfer itself, a catheter containing the embryo(s) is passed through the vagina and cervix and into the uterus using an ultrasound to guide the process. The embryo is then gently deposited into the uterus.

Key Questions

Two major determinations affecting embryo transfers are WHEN and HOW MANY. The goal is always to transfer the highest-quality embryo(s) in order to give you the greatest chance of reproductive success, so there are a lot of variables to consider along with your physician.

Cleavage vs. Blastocysts: All things equal, blastocyst embryos have higher odds of resulting in live births than cleavage stage embryos. That is because embryos fail to thrive at all stages of development so the farther you let them develop in a lab the more confident you can be that the embryo you are transferring is of higher quality.

While it is true that blastocyst embryos have higher odds of implanting and resulting in a live birth than cleavage stage embryos, there are certainly reasons to transfer day 3 cleavage stage embryos. As good as embryology labs have gotten, most fertility experts will agree that a best place for an embryo to thrive is in the womb.

During embryo development in an IVF lab, there is a constant drop off or funnel. For instance, 15 eggs may be retrieved, but only 10 of them are fully mature and able to be fertilized. Of those 10 that fertilization is attempted on, only 8 are actually fertilized. Of those 8, only 6 make it to cleavage stage. Of those 6, only 4 make it to Blastocyst. As you see, in this theoretical example (that is based on a very likely scenario) 2 embryos were lost from cleavage to blastocyst stage. But could those embryos have resulted in a healthy baby if they were transferred as a cleavage stage embryo? Well, maybe.

If fact, many patients are simply unable to make day 5 embryos in a lab at all. That is, they have gone through multiple cycles trying to make blastocyst embryos but the embryos always fail to thrive between day three and day five. On a subsequent cycle, embryos are transferred on day three resulting in a live birth.

To balance the risk, many clinics have set standards for when they will transfer cleavage embryos and when they will attempt to take embryos to blastocyst, where other clinics only do one or the other. It is important to remember most clinics will only perform genetic testing on blastocyst stage embryos. While genetic testing is usually not recommended for everyone, it may be beneficial to help reduce the odds of miscarriage, avoid known genetic disorders, and even choose the sex of a the child.

Fresh vs. Frozen: While fresh embryo transfers were the preferred method for many years, vitrification (freezing) methods have improved considerably making frozen embryo transfer an equally if not more attractive option in many cases. The downside of ovarian stimulation is that medications used to optimize egg development often cause a hormone imbalance that interferes with endometrial receptiveness. When doctors believe successful implantation unlikely, they may recommend freezing all embryos and switching to a frozen embryo transfer (FET).

A Frozen Embryo Transfer is a cycle in which frozen embryos from a previous IVF or donor egg cycle are thawed and then transferred into a woman’s uterus. A frozen transfer allows a woman’s body to recover from her stimulation cycle, optimize progesterone/estrogen levels, and make sure the endometrial lining is ideal for implantation.

One Embryo vs. Two: A single embryo transfer is the practice of transferring only one embryo into a woman’s uterus and has quickly become the gold standard practice. This offers a reduced chance of multiples and is less risky for the mother and fetus while simultaneously achieving the same cumulative success rates (success rates that include all FETs from the one IVF stimulation). This does not mean that multiple embryos are never transferred, it simply means that each case is treated individually. ASRM recommends a single embryo transfer in all patients under 38 years of age.

Pregnancy Support:

While the IVF process is technically over with the embryo transfer, most patients are routinely supported with medications and watched by their fertility doctor for a number of weeks before being handed off to their OBGYN for pregnancy care.

Bottom Line: IVF is no piece of cake. It involves a great physically, emotionally, and often financial investment. But when compared against the options of no or other treatment’s like an IUI (or Artificial Insemination), many find it to be the best option and would agree that the joy of parenthood far surpasses the financial, emotional, and physical toll of IVF.

Guest Post by CNY Fertility

Medical Disclaimer:

The information provided in this blog is intended for general informational purposes only and should not be considered as a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your healthcare provider or qualified medical professional with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read in this blog.