Overview of In Vitro Fertilization
Assisted reproductive technology (ART) refers to methods where eggs or “oocytes” are handled outside the body. The most popular type of ART is in vitro fertilization (IVF). The term ‘in vitro’ means outside the body, so in the case of IVF, the eggs are fertilized in a lab dish instead of in the woman’s body.
The first successful live birth using IVF happened in July 1978 in England, thanks to the work of Robert Edwards, Ph.D., and Patrick Steptoe, MD. This major achievement led to Dr. Edwards receiving the Nobel Prize in Medicine in 2010.
Since then, the use of IVF has become quite common and has helped advance the field of reproductive health. It now accounts for 1.6% of all live births in the United States and 4.5% in Europe. Although IVF was first developed to help women with damaged fallopian tubes, it is now used to treat several types of infertility. This includes issues due to endometriosis, male-related factors, or unexplained infertility. Women who are unable to use their own eggs due to conditions like primary ovarian insufficiency (POI) or age-related decline in egg number can now still have a chance to get pregnant by using donor eggs with IVF.
Anatomy and Physiology of In Vitro Fertilization
Understanding the structure of a woman’s pelvis is very important for the process of In Vitro Fertilization (IVF), a technique used to help women become pregnant. Certain physical features can influence the success rate of collecting eggs and transferring an embryo during IVF. The uterus, a part of the female reproductive system, plays a crucial role in this. It is built mainly for supporting a pregnancy. The uterus has three layers: the serosa, the myometrium, and the endometrium. The endometrium, or the inner lining of the uterus, is made of gland tissue that changes throughout a woman’s menstrual cycle in response to hormone levels.
It can be difficult for some couples to become pregnant. About 10% to 15% of couples will have trouble conceiving. Infertility is when a woman cannot get pregnant after a year of unprotected sex if she’s under 35, or after six months if she’s 35 or older. If a woman has irregular or no menstruation, known conditions like endometriosis, problems with her fallopian tubes, or if the male partner has known fertility issues, further evaluation may be needed sooner. Couples facing infertility will usually undergo tests to check the woman’s ovulation and egg reserves, the shape of the uterus, if the fallopian tubes are open, and a semen analysis. If issues such as endometriosis, blockages in the fallopian tubes, or adnexal adhesions (scar tissues that can stick organs together) are detected, a diagnostic laparoscopy may be needed. This is a minor surgical procedure that allows doctors to look at the organs within the abdomen directly.
Why do People Need In Vitro Fertilization
About a quarter to a third of women having difficulty getting pregnant have issues related to their fallopian tubes or the area around it, usually caused by an infection known as pelvic inflammatory disease (PID). The main culprit here is often a bacterial infection called Chlamydia trachomatis. This condition can lead to blockages or stickiness around the tubes that make it difficult for eggs and sperm to come together, leading to fertility issues. In these scenarios, In Vitro Fertilisation (IVF) can be an effective method, as it circumvents the damaged area by transferring fertilised eggs straight into the womb.
Another common issue is endometriosis, a condition where tissues that typically line the womb begin to grow elsewhere in the body. This condition seems to be much more common in women having troubles getting pregnant. It’s not entirely clear why endometriosis affects fertility, but it could be related to unusual growths, or adhesions, chronic inflammation in the lower abdomen, interrupted egg growth, or issues with embryo attachment. Undergoing keyhole surgery can hugely elevate chances of becoming pregnant, but unfortunately, women with endometriosis are often less successful with IVF, particularly if the disease is advanced.
Male fertility plays a part too, being the sole cause in about a fifth of couples with infertility, and playing a part in another fifth. Issues like low sperm count, poor sperm movement, or abnormal sperm shapes can often be managed with medication or surgery, resulting in successful pregnancies about 50% of the time. If these methods are not successful, a treatment that directly inserts sperm into the womb can work. In cases where these treatments do not work, IVF can be used, sometimes with a procedure that involves injecting a single sperm into an egg.
Some women experience something called Primary Ovarian Insufficiency (POI) or “diminished ovarian reserve,” conditions which mean they aren’t producing viable eggs. Such women can still get pregnant, however, by using eggs donated by a younger woman. IVF is commonly used in these cases as well, particularly in women above 35, an age group where fertility naturally begins to decline.
Female cancer patients or those with other serious illnesses often use IVF to safeguard their chances of having children in the future. Treatments like chemotherapy or radiation can harm the ovaries, so women can choose to freeze their eggs or embryos before treatment to be used when they’re ready to have children.
Lastly, egg freezing is gaining popularity among women who wish to postpone starting a family. Since women’s fertility begins to decline in their 30s, with both the quantity and quality of eggs decreasing, freezing eggs during one’s younger years can be a viable option to ensure future fertility.
When a Person Should Avoid In Vitro Fertilization
While there are no absolute reasons that someone couldn’t undergo In Vitro Fertilization (IVF), this procedure should not be carried out in women who are likely to experience serious health risks or even death if they were to become pregnant and IVF was successful. Some conditions that might make pregnancy dangerous include Marfan syndrome (a genetic disorder that affects the body’s connective tissue), severe heart failure as defined by the New York Heart Association (class 3 or 4), Eisenmenger syndrome (a type of heart defect), severe narrowing of heart valves (valvular stenosis), high blood pressure in the lungs (pulmonary hypertension), and a narrowing of the large blood vessel that carries blood from the heart to the rest of the body (coarctation of the aorta).
However, for women who have these health issues yet still wish to have their own biological child, they can go through the IVF process with egg (oocyte) retrieval and fertilization using their partner’s sperm. Instead of the woman carrying the fetus, the embryos would be transferred to someone else, a gestational carrier, who carries and gives birth to the child.
Equipment used for In Vitro Fertilization
In an embryo lab, here are some of the main tools and instruments used:
Triple gas control incubators: These are special devices that maintain a constant environment (such as temperature and humidity) for growing embryos.
MultiBlok heaters: These are used to heat multiple samples evenly at the same time.
Precision water bath: This is a container of water kept at a very specific temperature. It’s used to carefully warm or cool items.
Stage warmers: These keep the area where embryos are examined at a steady temperature.
Hoods with a stereomicroscope and heated stage: A kind of microscope that provides a 3D view. The ‘hood’ is a protective cover that keeps the microscope and its stageâthe platform where samples are placedâclean and at a steady temperature.
Inverted microscopes with micromanipulation technology (ICSI): A type of microscope designed for looking at cells from the bottom up. ICSI, or intracytoplasmic sperm injection, is a tool used with this microscope to insert a single sperm directly into an egg.
Anti-vibration tables: These tables limit movement to prevent disturbances when precise work is being done, like the micromanipulation mentioned above.
Laser for embryo biopsy for preimplantation genetic diagnosis (PGT): A laser used to safely remove cells from an embryo to test them for genetic conditions.
Tabletop incubators for embryo culture: These small, desktop-sized devices provide a carefully controlled environment for growing embryos.
Air-filtration systems: These systems clean the air in the lab to help keep the embryos healthy.
Alarm system: Monitors the lab to alert personnel to any potential problems.
Wireless monitoring systems for liquid nitrogen tanks: These systems allow the lab staff to remotely check the status of the tanks where eggs, sperm, and embryos are frozen and stored.
Liquid nitrogen tanks for sperm, oocyte and embryo cryopreservation: These are where sperm, eggs (oocytes), and embryos can be preserved at very low temperatures for future use.
Who is needed to perform In Vitro Fertilization?
The American Society for Reproductive Medicine committee suggests that people seeking fertility treatment should look for a team of well-trained professionals. This team should include:
1. A doctor who has finished a three-year special course in fertility problems and hormone difficulties related to the reproductive system, approved by the American College of Graduate Medical Education. This doctor should also have a certification provided by the American Board of Obstetrics and Gynecology.
2. A nurse who has specialist training in reproductive medicine and techniques to assist with reproduction in the clinic. They know how different treatments work and help in making sure the procedures are done safely.
3. A doctor or nurse who knows how to perform ultrasounds to make images of women’s reproductive organs – this is called gynecological ultrasonography.
4. A person who directs and oversees the lab where embryos are studied. This person should either be a doctor or have a Ph.D. This person should also have special certifications that show they are qualified to manage labs that deal with complex issues or specifically labs that study embryos.
5. Lab staff who are trained in processes related to freezing (cryopreservation) and close study (micromanipulation) of eggs and embryos. They make sure everything is stored and handled correctly to improve the chances of successful implantation.
Preparing for In Vitro Fertilization
Before starting in-vitro fertilization (IVF), which is a process of fertilization where an egg is combined with sperm outside the body, doctors need to perform several tests on both partners. For women, they perform tests to gauge the quality and quantity of eggs she produces, something known as ovarian reserve. This can include measuring levels of specific hormones, such as follicle-stimulating hormone (FSH), estradiol (E2), and anti-Mullerian hormone (AMH), or counting the number of small sacs filled with fluid (follicles) in the ovaries. If a woman is found to have a lower-than-average chance of producing a healthy egg based on these measures, she can still move forward with IVF. However, she might need to think about using donor eggs.
For men, doctors analyze a semen sample, checking things like the shape (morphology), count, and movement (motility) of the sperm. This helps the doctors decide if a process called ICSI (intracytoplasmic sperm injection) is needed. ICSI is a technique where a single sperm is injected directly into an egg to achieve fertilization.
Doctors also take images of the woman’s uterus to spot any physical issues, like polyps, fibroids, adhesions, or septa that might mess with the embryo attaching itself to the uterus, which is a necessary step for pregnancy. Along with this, tests are done to check for the presence of infectious diseases like HIV, hepatitis B and C, and syphilis for both partners.
How is In Vitro Fertilization performed
The process of IVF, or In Vitro Fertilization, begins with stimulating the ovaries. What this means is the doctors are trying to get your ovaries to produce multiple eggs instead of just one, as they usually do. Different medicines are used to do this, like letrozole and other hormone preparations called gonadotropins.
In a natural menstrual cycle, your body releases a hormone which causes the ovaries to release an egg. In IVF procedures though, doctors use particular drugs to control timing of egg release, so that they can collect the egg at the right time. During this phase, they will monitor how your follicles (the structures in your ovaries that contain the eggs) are growing through ultrasounds and blood tests.
When the lead (or largest) follicle is of the right size, doctors will give you an injection, acting as a substitute for body’s normal signals to release the egg, preparing the eggs for retrieval.
There are a few methods to stimulate the ovaries. One involves taking a medicine from the previous month which suppresses normal hormonal changes, then taking gonadotropins (hormones that stimulate egg production) starting on the second day of your cycle. The other method has you take the gonadotropins from the second day of your cycle, then taking a drug that blocks the hormone surge when the follicle reaches a certain size.
In both methods, when a number of good-size mature follicles are present, the egg retrieval is prepared. There’s also a “minimal stimulation” protocol which uses lower doses of drugs and can be less costly than the other methods.
Regardless of the method used to stimulate the ovaries, eggs are usually collected 34 to 36 hours after the final injection. This typically involves a small procedure where doctors use ultrasound guidance to collect the eggs through the vagina.
After the eggs have been collected, they have to be fertilized with sperm. The sperm is prepared through a process that makes them ready to fertilize the egg, and then they are mixed in with the eggs. If there might be issues with the sperm’s ability to fertilize the egg, a procedure can be performed to inject individual sperm directly into each egg.
The fertilized eggs, or embryos, are then cultured in the lab for 3 to 5 days after which they are put back into the uterus using a small catheter. The number of embryos transferred depends on various factors, such as age, the quality of the embryos, and patient preference.
After the embryo transfer, doctors usually start progesterone supplementation. This hormone helps to prepare the lining of the uterus to receive the embryos and to increase the chances of a successful pregnancy. If there are high-quality embryos remaining after the transfer, they can be frozen for future use.
Possible Complications of In Vitro Fertilization
Ovarian hyperstimulation syndrome is a serious risk that can happen with ovarian stimulation. In simple cases, women may experience bloating, nausea, and vomiting. However, in more complex cases, a condition called ascites can develop in which fluid fills up the belly causing severe pain. There’s also a risk of a condition called pleural effusion, which is basically fluid around your lungs. This could make it hard to breathe and decrease the oxygen levels in your body. Some women might also have signs of low body fluid levels, reduced urine output, higher creatinine (a waste product in your blood), increased liver enzymes, increased white blood cell counts, and abnormal electrolyte levels. An over-concentration of cells in your blood could increase your risk of blood clots. In the worst scenarios, one might face kidney failure and a condition causing abnormal blood clotting which could potentially be fatal. According to the World Health Organization (WHO), serious cases of this syndrome happen in about 0.2 to 1% of all ovarian stimulation cycles.
The number of twin births has been on the rise from 1980 to 2015 and it’s estimated that 19% of all twin births and 25% of all triplet births happen because of In Vitro Fertilization (IVF) treatments. However, because of new recommendations to limit the number of embryos transferred during IVF, the number of triplets has been going down. Pregnancies with multiple babies can increase the risk of high blood pressure problems during pregnancy and premature birth. Still, it’s interesting to note that the rate of high blood pressure disorders in twin pregnancies from IVF isn’t any different than in twins conceived naturally.
Similarly, there doesn’t appear to be any major difference in premature birth rates between twins from IVF and twins conceived naturally. This is likely due to the fact that twin pregnancies in general are already at a higher risk for both high blood pressure and preterm birth. However, when you compare single-baby pregnancies, things start to look different. A summary of many studies found that single-baby IVF pregnancies have a higher risk of high blood pressure disorders during pregnancy, premature delivery, gestational diabetes, hemorrhaging before birth, birth defects, cesarean sections, low birth weight, being small for their gestational age, and death around the time of birth.
What Else Should I Know About In Vitro Fertilization?
Infertility is a challenge that affects about 1 in 8 couples in the United States. The good news is that since 1978, over 5 million children around the world have been brought into existence through a process known as IVF, or In Vitro Fertilization.
According to data from 2018 by the Society for Assisted Reproductive Technology, the chance of a live birth from an attempted egg retrieval for IVF varies by age group as follows:
For women under 35 years old:
– About 48 out of 100 attempts result in live births.
– Of these live births, nearly 90% are single babies, about 10% are twins, and a very small number (0.2%) are triplets.
For women aged 35-37 years:
– About 31 out of 100 attempts result in live births.
– Of these live births, roughly 90% are single babies, about 9.5% are twins, and a similar tiny amount (0.2%) are triplets.
For women aged 38-40 years:
– About 22 out of 100 attempts result in live births.
– Of these live births, about 91% are single babies, around 9% are twins, and only 0.1% are triplets.
For women aged 41-42 years:
– About 10 out of 100 attempts result in live births.
– Of these live births, around 94% are single babies, roughly 6% are twins, and again only 0.2% are triplets.
For women aged over 42 years:
– About 3 out of 100 attempts result in live births.
– Of these live births, about 95% are single babies, roughly 5% are twins, and there are effectively no triplets.
Overall, these figures show that while the chances of successful IVF decrease with age, it still often results in a live birth, especially among younger women. Additionally, the majority of those births are single babies.