In vitro fertilization or “test tube baby” is one of the biggest advances in the field of infertility, bringing its inventor the Nobel Prize. The simple concept behind IVF is to “unite” the sperm and egg in a test tube dish, unimpeded by various factors causing infertility. These factors can include tubal blockage, pelvic scarring, exceptionally low sperm counts/motility or abnormally shaped sperm, advanced age/low ovarian reserve, endometriosis, unexplained infertility, ovulation problems not solved by ovulation induction or IUI, need for genetic testing on the embryo, fertility preservation and others.
IVF is the ultimate fertility treatment. In-Vitro means "in-the glass", thereby In- Vitro Fertilization is fertilization occurring in the glass petri dishes in the embryology laboratory. In-Vivo ("inside-the-body") Fertilization, on the other hand, is the natural process of fertilization occurring inside the body after sexual intercourse during natural conception. Anything we do in the fertility clinic that requires fertilizing the egg in the laboratory is called IVF.
IVF has many variations and components. Variations in IVF ovarian stimulation can range from IVF without using any medications (Natural Cycle IVF) [https://www.fertilitypreservation.org/contents/infertility-services/minimal-stimulation-and-natural-cycle-protocols] to using very few medications (Low Dose- or Mini-IVF) [https://www.fertilitypreservation.org/contents/infertility-services/minimal-stimulation-and-natural-cycle-protocols] to using varying doses of medications (Conventional or Full IVF). Variations of IVF components include traditional insemination, assisted fertilization using Intra-Cytoplasmic Sperm Injection (ICSI), genetic testing of embryos (PGTa, PGTm, PGTsr) varying types of petri dishes, culture media, incubators, micromanipulation tools, and embryo culture techniques.
While IVF can be performed without ovarian stimulation (called natural cycle IVF) , to increase the success rates and number of eggs and embryos available, typically an ovarian stimulation protocol is needed. The ovarian stimulation can be performed with various ways, but the two main types are “agonist” and “antagonist” cycles. To prevent your ovaries from ovulating during the stimulation, we need to administer certain drugs which are called GnRH agonists (e.g., lupron) or antagonists (e.g., ganirelix, antagon, orgalutron etc.). Because agonists have an initial stimulatory effect on the follicles and to minimize the risk of cyst formation due to this stimulatory effect, it is usually started before the menstrual period preceding the IVF cycle, typically 7-10 days prior. The antagonists on the other hand do not have this “flare” effect hence they are started after your ovarian stimulation is under way and when your largest follicle reaches certain size where the risk of early ovulation is high. We generally prefer the antagonist cycle because of its ease on our patients and lower need of medications. However, either protocol seems to be equally successful and antagonist protocol allows more timing flexibility. With the antagonist protocol, we must start the stimulation by the third day of your menstrual cycle. In contrast, once you are suppressed on lupron, we can hold the start of your cycle for weeks, if needed, for scheduling or timing purposes. Unique in our program, Dr. Oktay has developed the Random Start Protocol where antagonist cycles can be started at any time during the cycle.
Ovarian stimulation is generally performed with Follicle Stimulating Hormone (FSH) injections for IVF patients. This is a hormone your body naturally produces to support the growth and ovulation of one egg. To enable your ovary to grow multiple eggs, we supplement FSH hormone in the form of subcutaneous injections (e.g., Follistim, Gonal-F, Menopur, Repronex etc.). It generally takes 10-12 days for follicles (sacs containing eggs) to reach the desired size before a final injection of hCG is given to initiate the ovulation process. Egg retrieval is scheduled 34-35 hours later, 1-2 hour before ovulation would normally occur. To determine the correct timing of the hCG shot and to ensure that you are receiving the right dose of FSH, we monitor you with ultrasound exams every 1-3 days depending on the situation.
Random Start IVF is a flexible approach to IVF which was developed by Dr. Oktay and his team. Because in most women’s ovaries there are multiple small follicles present throughout the cycle, this approach allows ovarian stimulation to be started without having to wait for the menses. This approach is especially useful when there is time pressure, such as a pending cancer treatment or any schedule conflict that precludes you from waiting for your periods. This protocol may also have advantages for patients with low ovarian reserve as the small follicle reserve may fluctuate throughout the cycle and you may have better reserve before your periods starts. Dr. Oktay’s research showed that this approach gives good results. Please ask us about this protocol. This protocol is otherwise similar to the antagonist protocol. However, with the random start protocol, embryos will have to be cryopreserved, if you are undergoing IVF, as the endometrium will not be in sync with the embryo development. You will then need a frozen embryo transfer cycle to attempt pregnancy.
The traditional IVF cycle involves the following:
1. Ovarian Stimulation. This is done in "Conventional IVF" and in "Low-Dose or Mini- IVF" so that the patient can produce more than one egg that can be retrieved. "Natural Cycle IVF" and "In-Vitro Maturation IVF" do not involve ovarian stimulation.
2. Egg Retrieval involves a procedure in the operating room where the contents of the ovarian follicles are aspirated into test tubes, and a process in the embryology laboratory whereby the contents of the test tubes are poured into a petri dish where the hunt for the eggs begin to identify and subsequently isolate the eggs into the egg culture dish. Oocytes are collected in the office under light anesthesia via transvaginal ultrasound guided needle aspiration. Typical recovery is around 30 minutes and you will be able to leave the premises accompanied by an adult after that time. In natural and mini-cycle IVF, egg retrieval can also be performed under local anesthesia. In that case you will recover immediately and discharged home.
3. Fertilization of recovered eggs by allowing the eggs and sperm to interact by themselves (Conventional IVF Insemination) or by assisted fertilization using micromanipulation called ICSI.
4. Fertilized eggs are cultured in embryo culture media for the following 2 to 5 days.
5. During the 2 to 5 days of embryo culture, the embryos could undergo embryo freezing, assisted hatching, or embryo biopsy.
6. The final step is Embryo Transfer where the patient’s best quality embryo is placed in her uterus. We in general prefer single blastocyst stage embryo transfer as it gives us a longer opportunity to observe the embryos and make a better selection. Implantation rate of blastocyst embryos is higher than the earlier stage embryos, enabling us to maximize success with a single embryo transfer in most cases. This approach also reduces the risk of high-order pregnancies (twins, triplets etc.), which are associated with higher pregnancy complications. Of course, each case is unique, and we make our recommendations based on many other factors as well as following the American Society of Reproductive Medicine guidelines. We perform embryo transfer under ultrasound guidance to ensure better precision. Embryo transfer is a painless procedure similar to IUI where embryo or embryos are passed into the uterus with a thin catheter without a need for anesthesia.
7. A pregnancy test is usually performed in 10 to 14 days after embryo transfer.
8. If the pregnancy test is positive and the level of pregnancy hormone is properly rising, we perform the first ultrasound to check on the fetal sac in about 10-14 days after the positive pregnancy test.
After the egg retrieval, we typically prescribe progesterone hormone supplementation, tailored to your case. Progesterone treatment is typically continued at least until the fetal heartbeat is detected.