What Is In Vitro Fertilization (IVF)?
In vitro fertilization (IVF) is a method of assisted reproductive technology (ART) whereby eggs and sperm are combined outside the womb in a specialized laboratory, called an IVF or embryology lab. If the egg fertilizes and begins cell division, the resulting embryo may be transferred into the woman’s uterus where it will hopefully implant in the uterine lining and further develop to a healthy infant.
IVF is currently the most effective form of assisted reproductive technology. The procedure can be done using a woman’s own eggs and a partner’s sperm, or sperm or eggs from a known or anonymous donor. Additionally, a gestational carrier/surrogate may be used to carry the pregnancy.
There are various technologic procedures that may occur within the context of IVF, such as intra-cytoplasmic sperm injection (ICSI), assisted hatching (AH), and embryo biopsy for genetic evaluation.
When Is It Used?
IVF is offered as a treatment for infertility in various situations, and often as a primary treatment for women older than 40 years of age. IVF may be an option when dealing with:
- Prior failed treatments (e.g., clomid, IUI, etc.)
- Poor ovarian reserve
- Male factor – Impaired sperm production or function.
- Recurrent pregnancy loss (repeat miscarriage)
- Family planning/embryo banking
- Elective Fertility preservation (i.e., egg or embryo freezing)
- Fertility preservation for cancer (Oncofertility) or other health conditions.
- Embryo testing for chromosome screening (PGS/CCS) and/or hereditary genetic diseases (i.e., PGD)
- Fallopian tube damage, tubal sterilization, or tubal removal
- Egg donor (i.e., age-related or premature ovarian failure)
- Gestational carrier/surrogacy
- LGBT/Same-sex couples
If you or your partner are at risk of passing on a genetic disorder to your child, or if advanced maternal age has led to repeated chromosome abnormalities, IVF may be combined with Preimplantation Genetic Screening (PGS)/ Comprehensive Chromosome Screening (CCS) to help ensure a healthy embryo is implanted.
What Do I Need to Know?
IVF involves several steps: Ovarian stimulation, retrieval of eggs, sperm retrieval, fertilization to create embryos and embryo transfer.
Typically synchronized with the beginning of the menstrual cycle, a patient begins treatment that involves injecting daily hormone medications designed to stimulate the ovaries to mature multiple eggs instead of the single egg that normally ovulates each month. This therapy does not take away from the future pool of eggs but recruits eggs that would otherwise have dissolved without reaching maturity.
Luckily for us, eggs are contained within the ovary in a fluid-filled cyst or sac called a follicle. This follicle is visible by pelvic ultrasound and provides a method to monitor ovulation progression, and consequently treatment response. Follicles that are immature and incapable of being fertilized typically measure less than 10mm; whereas mature follicles that would normally be ovulated and potentially fertilized grow to approximately 20mm in size.
During treatment, patients frequently return for follow-up visits where the patient’s fluid-filled ovarian follicles are monitored by ultrasound to determine their number, size, and rate of growth. Blood tests are also used to measure a woman’s hormonal response to the medications. This process of monitoring eggs until maturity usually takes 10-14 days.
When the follicles are ready for egg retrieval based on the information gathered at monitoring appointments, an injection of human chorionic gonadotropin, Lupron®, and/or Ovidrel® is administered to finalize the egg maturity process within a specified time. This is a very time-sensitive injection and determines the timing of the procedure to remove the eggs.
Retrieval of Eggs
The egg retrieval is necessarily done at a specific time when most of the eggs have predictably reached maturity, but haven’t yet been released into the pelvis (where they can’t be easily accessed). During the retrieval process, a pelvic ultrasound probe is inserted into the vagina to identify follicle cysts (each often measures more than 20mm). Using the ultrasound as a guide, a thin needle is then traced through the back of the vagina and into each ovary and follicle to puncture and drain each follicle cyst and retrieve the egg contained within it. At the time of surgery and under a microscope the embryologist identifies the eggs from within the follicular fluid.
Not every follicle will necessarily contain an egg or a healthy egg. Additionally, not every egg that is retrieved is viable. Those eggs that are mature can be frozen, or combined with sperm to create embryos.
If using a partner’s sperm, then he can provide a semen sample by ejaculation on the morning of the egg retrieval, or an earlier frozen sample may be used if needed. In cases where there may not be enough or any sperm in the ejaculate, then a testicular sperm aspiration procedure (such as TESE or PESA) may be required by a Urologist. Donor sperm may also be frozen in advance and then prepared for use. In either case, sperm are separated from the semen fluid and washed in the lab prior to use. This helps ensure the best chances for fertilization.
Fertilization can occur through two main techniques. Either healthy sperm and mature eggs are combined in a culture dish (traditional IVF); alternatively, one sperm is inserted into one egg using a technique called ICSI. After one day, the eggs are checked to see how many have successfully fertilized (combined their DNA).
A portion of the fertilized eggs that result in embryos will develop in culture and may be transferred after they develop for three (cleavage stage) to five or six days (blastocyst). They may also be biopsied for genetic testing and/or frozen for future use. There is the possibility of having excess embryos remaining after treatment and those can be stored (banked in the frozen state) for future pregnancies.
In certain situations, your doctor may recommend preimplantation genetic screening (PGS)/ Comprehensive chromosome screening (CCS) and/or preimplantation genetic diagnosis (PGD). Both require biopsy of embryo cells to analyze the DNA contained within the cells. In the former, cells are evaluated for the correct chromosome number (euploidy) – 23 pairs for humans; and the latter identifies specific hereditary genetic mutations on chromosomes that may result in disease in the offspring, such as cystic fibrosis.
Embryo transfer, either fresh or frozen, usually takes place at the blastocyst stage (an embryo that has grown for five to six days after egg retrieval and fertilization).
With ultrasound guidance, a long, thin, flexible tube (called a catheter) is passed through the cervix. A syringe that contains the embryo(s) is attached to the end of the catheter. Using the syringe, the doctor will place the embryo(s) between the upper and lower uterine lining.
At OC Fertility and CCRM Orange County, we use transvaginal ultrasound guidance to provide the clearest view of the embryo(s) placement within the uterine lining, which is essential to optimize the likelihood of a pregnancy.
If successful, the embryo will begin to implant in the lining of the uterus about six to 10 days after egg retrieval or a few days after the embryo transfer procedure. The embryo takes weeks to fully implant itself in the uterus.
After the embryo transfer, we advise women to limit their activity for a few days and leading up to their pregnancy test. We will provide detailed instructions on the “dos and donts” during this time. If doing a fresh embryo transfer, the ovaries may still be enlarged, and more restrictions may be recommended.
One cycle of IVF takes at least two to three weeks from the time of starting injection medications to the time of an egg retrieval procedure. It is possible that more than one cycle may be required to obtain enough eggs to optimize your outcome.
Increasingly, research supports the decision in many instances to cryopreserve (i.e., freeze) embryos and perform a frozen versus fresh embryo transfer. Results suggest healthier placental implantation, fetal development, and infant outcomes. Additionally, freezing embryos rather than performing a fresh embryo transfer allows adequate timing to complete embryo biopsy for accurate genetic testing on all potentially viable blastocysts, rather than limiting the option to only those that are developed to the blastocyst stage by day-5 of embryo culture.
Information Source: Mayo Clinic