In Vitro Fertilization (IVF)

What is in vitro fertilization?

In vitro fertilization (IVF) represents one of the most significant medical technologies of the 20th century, which led to a true revolution in the treatment of infertility and has helped millions of people worldwide become parents.

The term in vitro fertilization refers to the union of the egg with sperm (fertilization) occurring not inside the woman’s body, but in the laboratory (in vitro). In vitro fertilization was developed by Robert Edwards, Patrick Steptoe, and Jean Purdy in the 1970s to help patients suffering from tubal factor infertility (who had no fallopian tubes or whose tubes were blocked), where there was no way for sperm to meet and ultimately fertilize the egg.

Louise Brown was the world’s first baby born after IVF. Her parents had been trying to conceive for more than nine years but were unable to due to tubal factor infertility. The IVF procedure performed in November 1977 at the clinic of Robert Edwards, Patrick Steptoe, and Jean Purdy was successful, and Louise Brown was born 9 months later, in July 1978.

It is estimated that more than 10 million children have been born through IVF worldwide to date. The contribution of IVF technology to treating infertility is of paramount importance, a fact that led to the awarding of the Nobel Prize in Medicine in 2010 to Robert Edwards.

Who needs to undergo in vitro fertilization?

n vitro fertilization is primarily directed at individuals or couples facing infertility issues—that is, individuals or couples unable to conceive despite having regular sexual intercourse without contraception for a sufficient period of time (at least 12 months for women under 35 years or at least 6 months for women 35 years and older).

The causes of infertility may involve the woman (female infertility), the man (male infertility), or both. In 15-20% of cases, despite thorough investigation, the possible cause of infertility cannot be found (unexplained infertility).

IVF should also be used by individuals undergoing fertility preservation through egg freezing or ovarian tissue cryopreservation for medical or social reasons, or by individuals desiring embryo cryopreservation for the same reasons.

Finally, IVF is particularly useful for patients who will undergo preimplantation genetic testing (PGT) to avoid transmission of a genetically inherited disease or to reduce the risk of miscarriage.

Depending on the method of uniting the egg with the sperm, IVF is divided into classical or conventional IVF and intracytoplasmic sperm injection (ICSI).

In classical IVF, each egg is incubated in the laboratory with approximately 20,000-50,000 sperm for 18-24 hours. In this way, one sperm will typically be able to fertilize the egg. In ICSI, the sperm is selected by the embryologist under a microscope and then injected into the egg using a special needle.

What is the IVF procedure?

In vitro fertilization includes the following stages:

Initial assessment by a Fertility/Reproductive Medicine specialist, including history taking, clinical and laboratory testing related to fertility, and discussion of the treatment plan.
Ovarian stimulation with medications to develop and collect more than one egg. Collection of multiple eggs (when feasible) ensures maximum IVF effectiveness, and modern stimulation strategy involves attempting to collect as many eggs as possible using patient-friendly stimulation protocols. Typical ovarian stimulation usually lasts 10-12 days (8-14 days).
Monitoring: During stimulation, typically 2-3 visits to the Fertility/Reproductive Medicine specialist will be required for hormonal (blood draw) and ultrasound examination (transvaginal ultrasound). These tests allow the physician to monitor the smooth progress of ovarian stimulation and estimate the number of eggs to be retrieved.
Completion of stimulation and egg retrieval: When the physician observes on ultrasound a group (usually >2) of follicles of adequate size (usually ≥17mm in mean diameter), final oocyte maturation proceeds with administration of a final injection. Egg retrieval is usually performed 36 hours (34-38 hours) after this injection. Egg retrieval is performed under sedation (a form of general anesthesia), without pain, and usually lasts 20-40 minutes. It involves retrieving eggs under ultrasound guidance through a relatively thin needle that passes through the thin vaginal wall and aspirates fluid from each follicle. After egg retrieval, patients may feel some discomfort similar to menstrual cramps and may have a small amount of vaginal bleeding. These symptoms usually resolve completely within 24-48 hours.
Fertilization: After egg retrieval, within 2-3 hours, the collected eggs will be fertilized either by classical fertilization or by ICSI. After 16-24 hours, the embryologist will check to determine how many eggs have been successfully fertilized.
Embryo culture, embryo transfer, and cryopreservation of suitable embryos: Fertilized eggs are now considered embryos and are cultured in the laboratory, usually for 5-6 days. The purpose of culture is to reveal which embryos have the potential to result in a pregnancy, as many of the early embryos will stop developing in the first hours/days of culture.

On the 5th day of culture, the number of embryos that have survived and their quality are assessed. The best quality embryo(s) will be transferred to the uterus through a simple, painless procedure lasting 15 minutes. The woman will know if she is pregnant approximately 10-14 days after embryo transfer. If on the 5th-6th day of embryo culture there are additional good quality embryos, these will be cryopreserved for future use (either if the first embryo transfer is unsuccessful or if the woman wishes to attempt another pregnancy in the future).

What determines IVF success?

The success of IVF depends on two main factors:

The number and quality of eggs: It is now known that the more eggs retrieved during egg collection, the greater the probability of achieving a child from this procedure. While there can never be absolute certainty that a pregnancy will result from egg cryopreservation, studies have shown that, generally, retrieving a larger number of eggs results in a higher probability of success. For this reason, many women will choose to undergo the procedure more than once to increase the probability of success. Perhaps an even greater impact on the probability of success than the number of eggs is their quality. This quality is mainly determined by the woman’s age and is considered excellent between 25-32 years, with a gradual decline after 32 years. This means that a woman who has frozen 10 eggs at age 30 has approximately the same chances of success as a woman who has frozen 30 eggs at age 37. Other factors that determine egg quality are genetic factors, smoking, obesity, etc.
Laboratory methods used for fertilization, culture, cryopreservation (freezing), and thawing of eggs: The presence of a modern embryology laboratory with well-trained staff is very important. The application of modern embryo culture and cryopreservation methods such as vitrification ensures the best possible results.

Are there risks from the IVF procedure?

In vitro fertilization is a procedure that, when performed by specialist fertility/reproductive medicine physicians, has high safety standards.

The most well-known complication of ovarian stimulation, ovarian hyperstimulation syndrome (OHSS), can now be completely prevented with modern stimulation protocols. The egg retrieval procedure carries risks of bleeding, bowel injury, and pelvic inflammation, which are again extremely small when the procedure is performed by experienced fertility/reproductive medicine physicians.

A common question from patients undergoing ovarian stimulation is whether taking medications will increase the likelihood of developing some form of cancer in the future. This question has strongly concerned the medical community, and most studies conducted are reassuring, as they do not support the existence of such an association.

Finally, another concern for patients undergoing IVF is whether the health of children conceived through this method is similar to children born after natural conception. Although a small increase has been observed in rates of preterm birth, the likelihood of birth of newborns with low birth weight or with some congenital anomaly, the overall health of these children is considered comparable to children after natural conception. It is important to note that any differences in the health of children after IVF appear to be mainly due to their parents’ infertility rather than the IVF method itself.