In-vitro fertilization (IVF) is a fertility treatment consisting of a series of medical and surgical procedures to help conceive a child. IVF is one of the assisted reproductive technologies (ART) available as treatment for infertility and it is the most effective one, but it is also the most expensive and invasive technique. The term “in-vitro” comes from Latin and means “in glass”, due to the fact that the egg fertilization process happens in a laboratory dish instead of inside the human body.
In-vitro fertilization was first performed in 1978 and its inventor, Dr. Robert Edwards, has been awarded the Nobel prize for Medicine in 2010 thanks to his work and research. Millions of children have been born since then thanks to this technology which is in continuous evolution with improvement of the techniques and increased success rate, while at the same time decreasing risks and complication rates. At present, 1-3% of all children born in the USA and other developed countries are conceived via IVF.
IVF is indicated when other less invasive treatment options have failed and is rarely suggested as first line treatment for infertility. Lifestyle interventions, supplements, fertility drugs and intrauterine insemination are usually tried first.
IVF may be indicated in the following cases:
- Women over 40
- Fallopian tube issues, such as blockage, ligation and damage.
- Uterine fibroids
- Ovulation disorders.
- Unexplained infertility
- Male factor infertility, due to sperm quality and quantity.
- Polycystic ovarian syndrome (PCOS)
- Potential genetic issues, requiring genetic embryo screening.
- Fertility preservation prior to cancer treatment.
IVF Procedure Steps
In-vitro fertilization involves several steps that constitute what is known as an IVF cycle.
- Ovarian stimulation.
- Egg retrieval
- Sperm retrieval
- Fertilization, with standard insemination or with intracytoplasmic sperm injection (ICSI)
- Embryo development
- Pre-Implantation genetic diagnosis (PGD)
- Embryo transfer
Step 1: Ovarian Stimulation
Ovarian stimulation, or more precisely ovarian hyperstimulation, is a medical treatment using fertility drugs to stimulate the ovaries to produce and mature multiple eggs, while delaying their release. Multiple eggs are needed to increase the chances of success of IVF as not all of them will fertilize, grow healthy embryos and finally be candidate for implantation.
Gonadotropins are used to stimulate the ovaries to develop multiple follicles and mature multiple eggs.
GnRH agonist or antagonists are used to prevent the LH surge which causes the release of the mature eggs in the fallopian tubes.
hCG is used to cause the LH surge just at the right time for egg retrieval.
During the ovarian hyperstimulation process, regular blood tests are performed to check hormone levels as well as regular transvaginal ultrasounds to examine the ovaries and monitor the development of the follicles and the maturation of the eggs.
The ovarian hyperstimulation typically lasts between 1 and 2 weeks and starts on day 1 of the menstrual cycle (period).
Step 2: Egg Retrieval
The egg retrieval process is a minimally invasive surgical procedure performed at the fertility clinic taking about 15-30 minutes to complete.
At the end of the ovarian hyperstimulation step, when the doctor deems appropriate based on the transvaginal ultrasound and blood work, a final injection containing human chorionic gonadotropin (hCG) is administered to trigger the release of the mature eggs from the follicles. The egg retrieval is scheduled 24-36h after the hCG injection.
Light sedation is administered to not feel any pain. The procedure is guided by transvaginal ultrasound to locate the mature ovarian follicles. A thin needle pierces the wall of the vagina to reach the ovarian follicles containing the eggs which are then aspirated and collected. On average, 8-20 eggs are collected. The eggs are then examined and placed on a culture plate filled with nutrients and then placed into an incubator.
The procedure is safe and with rare complications. Some cramping or other minor side effects from the anesthesia may be possible. Antibiotics are usually administered to prevent infections.
Step 3: Sperm Retrieval
The sperm retrieval is performed on the same day of the egg retrieval. The sperm sample may be provided by the partner through masturbation or it may be surgically collected by performing minimally invasive procedures when the male partner is not able to produce a sperm sample. We talked about the PESA, TESA, TESE, MESA and microTESE procedures in the article on intrauterine insemination (IUI). Frozen or donor sperm may also be utilized in this step.
Sperm are separated from the seminal fluid by washing and the best sperm for fertilization purposes are selected in the lab after analyzing the sample.
Step 4: Fertilization
There are two different methods to perform the fertilization step of IVF:
- Standard insemination, when the sperm and the eggs are placed in the same culture dish and placed in the incubator. With standard insemination, the sperm will have to find the egg and fertilize it as it would naturally occur inside the human body.
- Intracytoplasmic Sperm Injection (ICSI), when a single sperm is injected directly into the oocyte (egg). This procedure is usually performed when fertilization rate through standard insemination is low or when sperm quality and quantity is low.
The fertilized eggs are placed in a growth culture into the incubator and left and monitored there for 3 to 5 days.
Step 5: Embryo development
When a fertilized egg starts the cell division process it becomes an embryo. Not all eggs from the previous steps will be fertilized and not all fertilized eggs will become an embryo. Not all embryos keep dividing and growing. This is one of the reasons why multiple eggs are collected in the previous stages.
By day 3 the embryo should have divided to 6-8 cells reaching what is known as cleavage stage of the embryo.
By day 5 the embryo cells should have divided multiple times to 100-200 total cells reaching what is known as the blastocyst stage.
Step 6: Pre-Implantation Genetic Diagnosis (PGD)
Usually around day 4-6 it is time to perform the genetic testing of the embryo. This is done by gently taking one or two cells from the embryo and analyzing their DNA.
This can be done to prevent genetic disorders when one of the parents is a known carrier or to screen for genetic conditions. There are also other indications for PGD, but laws allowing such indications vary depending on the country. In Thailand for example PGD is legally used to choose the gender of the baby.
Step 7: Embryo transfer
From day 3, the embryo may be ready to be transferred into the woman’s uterus. The procedure is quick and painless and is done at the clinic or doctor’s office; a catheter is inserted into the vagina and through the cervix while the embryo is loaded into a syringe suspended in a small amount of fluid and delivered into the uterus through this thin tube.
More than one embryo may be transferred into the uterus depending upon many variables, such as the maternal age. With more than one embryo transferred there is a higher chance of success, but also a chance of multiple pregnancy which increases the risks for both the babies and the mother.
9 to 14 days after the embryo transfer, a blood test to measure the hormones (hCG) is performed to confirm the pregnancy.
The unused embryos may be frozen for later use or donated.
Before and after the implantation, progesterone may be administered to increase the chances of a successful implantation of the embryo and to decrease the chances of miscarriage.
IVF Risks and Complications
Serious complications from IVF are rare, but like any other medical or surgical procedure there are some risks.
The medications used during IVF have mostly mild side effects, such as hot flushes, headaches, bloating and mood swings. The most serious complication from taking fertility drugs is ovarian hyperstimulation syndrome (OHSS) which is rare and causes abdominal pain with fluid buildup in the abdomen; severe cases of OHSS require hospitalization and medical treatment.
The egg retrieval process has risks related to the administration of anesthesia and from the puncturing with the needle to retrieve the eggs: this can cause bleeding, infections and damage to the surrounding structures like bowel and bladder, but these complications are rare.
When more than one embryo is transferred, there is a risk of multiple pregnancy. Multiple pregnancies have an increased risk of premature birth, low birth weight and miscarriage. A multiple pregnancy increases the risks for the mother too: there are more chances of suffering from anemia, gestational diabetes and hypertension.
Contrary to past beliefs, most recent studies have not found an increased risk of cancer for women after IVF.
In-vitro fertilization is a safe treatment and the most successful for infertile couples. With the increasing knowledge and improved techniques in IVF, the need for multiple embryo transfer has decreased compared to the past, thus lowering one of the most common complications which is multiple pregnancy.
IVF Success Rate
Success rate for in-vitro fertilization varies depending upon multiple factors such as maternal age, lifestyle factors, reason for infertility, previous successful pregnancies, quality of the embryo, number of embryos transferred…
Success rate vary also across different clinics; ask your physician for more details.
On average, success rate goes from almost 50% to just about 1%. Multiple IVF cycles increase the chances of success.
The cost of in-vitro fertilization (IVF) varies depending on the chosen clinic and on the medications used.
The average cost for each IVF cycle is:
- 10,000-20,000 USD in the USA
- 80,000-150,000 HKD (10,000-20,000 USD) in Hong Kong
- 12,000-20,000 SGD (8,500-14,000 USD) in Singapore
- 12,000-15,000 AUD (7,500-10,000 USD) in Australia
- 5,000-15,000 EUR (5,500-16,000 USD) in Ireland
- 3,500-5,000 GBP (4,200-6,000 USD) in the United Kingdom
- 20,000-50,000 CNY (2,800-7,000 USD) in China
- 10,000-15,000 CAD (7,000-10,500 USD) in Canada
- 150,000-320,000 THB (5,000-10,000 USD) in Thailand
These costs are per cycle of IVF. Often multiple cycles (3 to 6) are needed to which the clinics add other costs such as the costs of storing, freezing and unfreezing eggs and embryos which is in the 5,000-20,000 USD range in the USA. Some treatments may be covered by health insurance.
Different legislation that allows for different treatments and techniques such as gender selection, the absence of long waiting lists, quality of care and the overall cost of multiple IVF treatment cycles are factors that favor medical tourism in the field of fertility treatment.
Check out our other articles on infertility and fertility treatments:
- Causes of male infertility
- Causes of female infertility
- Supplements for female infertility
- Supplements for male infertility
- Fertility drugs for women
- Intrauterine Insemination (IUI)
- The BOSTON IVF Handbook of Infertility – Fourth Edition
SR Bayer, MM Alper, AS Penzias – CRC Press, 2018
- Are we overusing IVF? (Analysis)
EI Kamphuis, S Bhattacharya, F Van der Veen – The British Medical Journal, Feb 2014
- Use of fertility medications and cancer risk: A review and update.
L Kroener, D Dumesic – Current Opinion in Obstetrics and Gynecology, Aug 2017
- Maternal Factors and the Risk of Birth Defects After IVF and ICSI: A Whole of Population Cohort Study.
MJ Davies, AR Rumbold, JL Marino – British Journal of Obstetrics and Gynaecology, Oct 2017
- American Society for Reproductive Medicine (ASRM)
- Society for Assisted Reproductive Technology (SART)
- Human Fertilisation & Embriology Authority (HFEA)