In vitro fertilization (IVF) is a technique in which eggs are retrieved from a woman’s ovaries and fertilized with sperm outside the body. Stimulation of the ovaries occurs with injectable medication, and the eggs that develop are aspirated from their follicles and placed in a dish (“in vitro” is Latin for “in glass”). Insemination then occurs, either by placing sperm in the dish with the egg, or by injecting one sperm directly into each egg (intracytoplasmic sperm injection, or ICSI). The resulting embryo or embryos are then transferred back into the uterus where hopefully, implantation occurs.
IVF is the most effective means of achieving pregnancy for many patients, and in some cases may be the only reasonable means for achieving pregnancy (e.g., if the fallopian tubes are blocked). IVF success rates are higher than rates for IUI or any other treatment because the technique overcomes most factors that contribute to infertility. The technique allows us to directly observe the growth of early embryos to gain valuable information about possible causes of infertility. IVF also allows for genetic testing of the embryos prior to transferring them back to the uterus (see section on preimplantation genetic testing).
The basic steps in an IVF cycle are:
In vitro fertilization (IVF) is a technique in which eggs are retrieved from a woman’s ovaries and fertilized with sperm outside the body.
Thanks to advances in technology and laboratory techniques, we now have the ability to perform genetic testing on embryos prior to transferring them back into the uterus. Testing can be performed to determine if an embryo has the correct number of chromosomes (preimplantation genetic screening, PGS) or if an embryo carries a specific genetic mutation like sickle cell anemia (preimplantation genetic diagnosis, PGD). In the case of PGS, identification of a chromosomally normal (euploid) embryo increases the pregnancy rate at all ages, while decreasing the miscarriage rate. It can nearly eliminate the risk of twins since it facilitates performing an elective single embryo transfer. PGD allows a patient/couple to avoid passing on a genetic disease that may have plagued his/her family for generations.
After fertilization, an embryo should have 46 chromosomes: 23 from the egg and 23 from the sperm. With a few exceptions, any chromosome number other than 46 (aneuploidy) is not compatible with life, and that embryo either does not implant (i.e., a negative pregnancy test) or implants but miscarries at some point, usually in the first trimester. The quality of a woman’s eggs declines with age, increasing the risk of an aneuploid embryo. This is the most significant reason the success rate of IVF decreases as a woman gets older: the chances of having a normal egg are lower. For women under 40, approximately half of the embryos created through IVF will be aneuploid. This number jumps to approximately 60%–70% for women in their early to mid-40s.
Preimplantation genetic screening (PGS) involves testing some cells from each embryo that is produced to determine whether that embryo has the correct number of chromosomes. A report is generated detailing which embryos are euploid and which are aneuploid, so we know with approximately 98% accuracy exactly what is being transferred back into the uterus. Only euploid embryos are transferred. If a patient produces a euploid embryo, the chance of IVF success increases, while the chance of miscarriage significantly decreases. This is true for patients at all ages. Since the implantation rate of a single euploid embryo is so high, we often recommend transferring only one embryo, thereby nearly eliminating the risk of twins associated with IVF. PGS can benefit all patients but can be particularly helpful in patients with recurrent pregnancy loss or those who want an elective single embryo transfer (SET) only. It is important to note that PGS determines only chromosome number; it does not screen for single gene disorders, birth defects, autism, etc.
Patients who carry a specific genetic disorder, such as sickle cell anemia or cystic fibrosis, are at risk of passing this trait, or the disease itself, onto their offspring. The chance of transmission varies with the specific condition but can be as high as 50% for certain genetic diseases. In the past, the only option for these patients was to become pregnant then undergo prenatal testing (chorionic villus sampling or amniocentesis) to determine if the child is affected. In the event that the child does have the disorder, the couple then would face the difficult decision of whether to continue the pregnancy or to undergo a pregnancy termination procedure (abortion).
Preimplantation genetic diagnosis (PGD) involves testing some cells from each embryo produced through IVF to determine which embryos are affected by a specific disease, which are carriers of the mutation and which are completely unaffected. In this case, we are looking for a specific disease that we know the couple is at risk of transmitting. PGD does not screen for all genetic diseases. In this way, we can avoid transferring an affected embryo, allowing a couple to conceive safely without risking transmission of potentially debilitating or lethal diseases. This powerful technique offers the potential to rid future generations of a disease that may have plagued a family for countless years.
In the case of recessive diseases, by transferring only completely unaffected embryos (noncarriers), the couple may not only prevent the birth of a child affected by a serious medical condition, but they may also prevent the birth of children who are healthy carriers like themselves. This then prevents the possibility of disease in their grandchildren. In effect, the mutant gene can be completely removed from their lineage (or, if you will, it can be totally pruned from the family tree).