A special thank you to Dr. Gad Lavy, MD, F.A.C.O.G, medical director and founder of New England Fertility (NEF) for helping us write this blog on IVF and how it works.
IVF – or, in vitro fertilization – was introduced in the late 1970s, and has since revolutionized treatment for infertile couples.
In the early days, the IVF process was completed all in one cycle. Doctors would harvest the eggs for the woman, fertilize them, grow them and transfer them back into her uterus all in one cycle. Over the years, new technologies have allowed us to improve the success of IVF dramatically.
Fertility drugs have been around for over 50 years. Initially, fertility drugs were developed in the late 1950s/early 1960s. Over the years there has been a great deal of experience using these drugs. Any issues with the drugs have been evaluated extensively over the years, and the drugs have been refined to not only make them safer and more effective, but to also have fewer side effects. Having used the drugs for so long now, we can say with certainty that fertility drugs do not increase the risk of ovarian cancer or breast cancer.
The way IVF is performed today is divided into two distinct parts: creating embryos and transferring embryos.
How Embryos Are Created
Embryo creation happens when a woman takes fertility drugs for 2 weeks to increase her production of eggs. During a woman’s normal cycle, only 1 egg is produced. When a woman takes fertility drugs, she can produce about 10 eggs. Two weeks after she starts her medications, the eggs are ready to be harvested. The egg retrieval procedure is simple; it is done in the office with mild sedation. Eggs are retrieved with a needle that is guided by an ultrasound. The egg retrieval procedure takes about 10 minutes. A woman’s recovery from an egg retrieval is very quick.
Once the eggs are harvested, they are assessed under a microscope and sperm is introduced. With the advancements in IVF, doctors are now able to inject the sperm directly into the egg. By doing this, we are able to maximize the number of eggs that are fertilized. Only the best sperm is used (no low quality sperm will be used). Once eggs are fertilized, they will grow in the laboratory for 5 or 6 days. This step is another advancement made possible by creating the best conditions that allow the embryos to grow. The embryos require strict conditions, such as a specific temperature, humidity and nutrients. Today, we have almost perfected this environment in the lab so that the embryo will grow just as it would inside of the woman’s body.
Embryos are given only 5-6 days to grow in the lab because beyond that point the embryo needs to attach to the uterus to continue growing. Having the embryos grow 5-6 days in the lab enables us to identify the viable embryos. At the end of the embryo “culture” the embryos are all frozen. In most cases, before freezing we can perform genetic testing on each embryo to determine the embryo is genetically balanced – that it has the correct number of chromosomes.
Genetic Testing of Embryos
Genetic testing is done at this stage of embryo growth by removing a few cells from the embryo – each embryo has about 200 cells and those cells are differentiated so that we can see which cells will be the baby and which cells will be the placenta. We remove a few cells for testing and the test assures that the chromosome number is balanced; and, at this point, we can also identify the gender.
Genetic testing allows doctors to identify “normal” embryos (embryos with the correct number of chromosomes) and achieve the highest number of successes on the first embryo transfer. Doctors are able to select the one embryo that will have a 70-80% chance of success. Keep in mind that removing cells from the embryo does not harm it or reduce its viability. Embryos are then frozen until we are ready for embryo transfer. It’s important to note that freezing and thawing embryos does not reduce the chances of success.
The Embryo Transfer
Once the eggs are retrieved, tested and frozen, the second part of the IVF process is the embryo transfer. In order to do the embryo transfer, we focus our attention on the woman’s uterus – more specifically, the uterine lining. We want to create the perfect conditions for the embryo to attach. This involves using some hormones – specifically estradiol and progesterone in combination – to make sure the uterus is developing properly and is in the perfect condition to accept an embryo.
You can ensure a uterus is ready for the embryo one of two ways: 1. Using a woman’s natural cycle (this utilizes minimized hormones) or 2. Using an “artificial” cycle that requires medications. Either way, we get the uterus to be perfectly receptive. At just the right time we remove the embryo from the freezer and do the transfer. The transfer is not a medical procedure, it’s actually very simple. The embryo is loaded into a small plastic catheter; the catheter is inserted into the uterus through the cervix, as the doctor uses an ultrasound on the abdomen to guide the embryo to the right spot. This allows us to achieve the perfect placement with minimal discomfort.
In the past, it was more common to transfer several embryos at a time because the success rate was low, so in order to increase our success we’d attempt with multiple embryos. One side effect of this process was a multiples pregnancy. Today, the standard procedure is to transfer a single embryo. One embryo is removed from the freezer and we make sure it survives the defrost; 95% of embryos survive the defrosting. That embryo is inserted into the uterus and we keep the other embryos frozen.
Your frozen embryos can stay frozen forever, theoretically. Hopefully, the first transfer is successful and embryos remain frozen until you decide to have another baby (if you do). If the first transfer isn’t successful, we will repeat the transfer with one of the remaining frozen embryos. Keeping the embryos frozen means you can attempt pregnancy again without having to go through the egg retrieval process again.
Two weeks following embryo transfer you can do a pregnancy test to determine if the embryo transfer was successful. Two weeks after that you can do an ultrasound to see the pregnancy in the uterus and the heartbeat.
For the first few weeks of the pregnancy we like to add some hormone supplements to ensure the pregnancy is supported. Very soon – around 7 to 8 weeks of pregnancy – the pregnancy itself starts to make its own hormones so there’s no need for additional supplements. Around 8-9 weeks we check the levels and confirm they’re where they should be. If they are, we stop the supplements and the pregnancy continues as if the woman conceived naturally.
IVF Medications (Fertility Drugs)
Fertility medications are used to boost up the woman’s ovarian function. Typically, a woman with a normal cycle will ovulate one egg each month. When we do fertility treatments, the woman will produce more eggs with her cycle.
The type of fertility treatment needed will determine the type of medications prescribed. When we perform insemination, we try to limit the eggs being produced to 2, 3 or 4 at most to reduce the risk of a multiples pregnancy. When we perform IVF, we aim to produce more eggs because we’re removing them to fertilize them and watch them grow so we can identify the best of the best. The fertility treatment needed determines what protocol of medication we use (what combination of drugs).
Types of Fertility Drugs and Side Effects
The fertility drugs come in 2 types: oral (pills) and injectable (needles).
Oral medications like Clomid or Letrozole are drugs that work in the brain and boost the production of an FSH (follicle stimulating hormone), which are the hormones that control the ovaries. Oral medications don’t work directly on the ovary, and can sometimes have minimal side effects such as hot flashes, headaches, trouble sleeping or moodiness. We try to limit the dosage when necessary and monitor the side effects as much as possible. Oral medications are considered to be milder, producing fewer eggs (as used in insemination). Injectible drugs are more potent.
Injectables come under the name of gonadotropins – hormones that are produced in the pituitary gland in the brain that control ovarian functions – primarily FSH (follicle stimulating hormone) and a hormone called LH.
The drugs that are used for IVF are one or the other (pills or injectables) or a combination of both. These drugs are essentially the natural hormones, just given in a higher dose than the body normally produces. This enables a woman who produces one egg a month the potential to produce 10, 15 or 20 eggs in a month, depending on her ovarian function.
Because the injectable drugs work directly on the ovary and are more potent, they have fewer side effects. Since the ovaries are more stimulated, side effects you’ll experience may be feeling a little more bloated and crampy. You should not experience the moodiness or hot flashes or sleeping issues you would with oral medications.
When using fertility medication, it’s important to customize the protocol and combination to each individual patient and her needs. We sometimes use the pills, sometimes the injections, and sometimes a combination. For IVF, we usually use mostly injections because we are trying to get a lot of eggs. For insemination cycles we’re hoping for fewer eggs, so we’ll likely use the oral medications alone or in some combination with injectable drugs.
When you’re taking the medications, it’s important to follow the directions given to you by your clinic because these are potent medications that need to be monitored carefully. When taking the medications you’ll likely need to have appointments every 2-3 days to be monitored and checked: an ultrasound to look at ovaries, count the number of follicles (number of eggs) and measure the size and have a blood test. From these tests we can determine how many are growing, the size and when they are ready to ovulate or be harvested for IVF.
What To Do If You Aren’t Becoming Pregnant
Fertility doctors may limit the number of fertility treatments, usually because after a few unsuccessful cycles you’ll likely need to reevaluate the situation and come up with a different approach.
If you aren’t becoming pregnant, a next step would be to talk to your fertility doctor about what your options are. For some, those options may include egg donation or even surrogacy. For others, they may choose to take a break and then try again in the future.
Gad Lavy, M.D., F.A.C.O.G, is the medical director and founder of New England Fertility (NEF), the first non-hospital-based outpatient in vitro fertilization (IVF) center in the state of Connecticut. Dr. Lavy received his training at Hadassah Medical School at Hebrew University in Israel and completed his residency at Yale University School of Medicine in New Haven, Connecticut, where he served on the medical faculty of the Department of Obstetrics and Gynecology. Prior to founding New England Fertility in 1991, Dr. Lavy was an assistant professor in the Division of Reproductive Endocrinology at Yale University School of Medicine for four years and served as the director of the Yale program for assisted reproduction. Dr. Lavy is Board Certified in Obstetrics and Gynecology and Reproductive Endocrinology. In addition to being medical director of New England Fertility, he is a medical staff member in the Department of Obstetrics and Gynecology at Stamford Hospital in Stamford, Connecticut, and a consulting physician in the Department of Obstetrics and Gynecology at Greenwich Hospital in Greenwich, Connecticut. A member of the American Society of Reproductive Medicine and the Society of Reproductive Surgeons, Dr. Lavy is an internationally recognized speaker and author on the topics of infertility, assisted reproductive technology (ART), and gestational surrogacy and egg donation.