IVF – In Vitro Fertilization
IVF is a procedure involving the stimulation of multiple eggs using medications similar to natural hormones that cause eggs to grow – gonadotropins. The growing follicles each contain 1 egg and are monitored using ultrasound exams. When the follicles reach the appropriate size, they are retrieved, or harvested, at the appropriate time. After the eggs are collected, they are combined with the sperm in a dish (conventional insemination), or the sperm is directly injected into the sperm (ICSI, or intracytoplasmic sperm injection). After fertilization in the lab, the subsequent embryos are grown (cultured) for 5 to 6 days. The embryos may be transferred at this point or frozen for use at a later time. It has been demonstrated that the stimulation of multiple eggs during the IVF process can cause the uterine lining to become less favorable for transfer. By freezing all of the embryos and transferring them later using a process called a frozen embryo transfer, or FET, the pregnancy rates can be significantly higher.
Candidates for IVF
In vitro fertilization may be the preferred choice of fertility treatment for a variety of different situations. As the success of IVF continues to improve, IVF is becoming much more popular as a primary form of infertility treatment. Reasons for undergoing IVF include:
While some people may know they wish to proceed with IVF before having a fertility consultation, all patients will start with a consultation with one of our physicians. After reviewing the patient’s medical history, a diagnostic plan is outlined for each individualized patient. After all diagnostic testing is completed, the physician provides guidanance regarding the appropriate options for fertility treatment. Patients are then given the option to select the type of treatment that best fits their needs and desires. Our facility does not select out patients, or decline patients, that may not be likely to conceive. There are no attempts to turn away couples in hopes of maintaining good statistics. Often, patients with the lowest chances of conceiving are the ones that can benefit the most from aggressive fertility treatment. With this said, however, realistic expectations need to be established. During the consultation and subsequent visits, the physician will need discuss your individual treatment options and the potential for success.
The IVF process can seem overwhelming on first glance. Part of the preparation for IVF is completing a series of classes that are designed to cover the details of the IVF process. Coordinators are available to assist patients with each step of the IVF procedure and to answer questions that may arise. California IVF has seen steady improvements in success rates while maintaining a patient-centric approach to treatment. We also encourage questions at every step of the process so patients can remain fully informed on their journey to parenthood.
Prior to any type of treatment, one of our physicians will meet with you and review your history and desires. Any recommended fertility blood tests or imaging studies will be completed prior to starting treatment. When your evaluation is complete, the IVF coordinator will provide you with information about the IVF process. An IVF information session is conducted to discusses the IVF process, medications, and risks. You will also learn how to self-administer the fertility medications you will be taking as part of the IVF process. In addition to learning about the injections, the medication class with also review the purpose of the medications, possible side effects, and any other questions patients may have. Individualized treatment calendars are provided with all of the details needed to complete the IVF cycle. Another class is scheduled to review the embryology process. During the meeting with the embryologist, details regarding the IVF laboratory process from egg collection to embryo transfer is reviewed. Patients should review and save all documents provided during the various visits and reference this information as the progress through treatment.
There are various different treatment plans, or protocols with fertility medications that can be used to prepare the eggs during the IVF cycle. Each patient receives detailed instructions specific to their own plan, and these details are outlined on the medication calendar. Before medications are started, patients undergo a baseline ultrasound. This initial ultrasound is comparable to a “before” image of the ovaries prior to starting medications. The baseline ultrasound may reveal ovarian cysts or other abnormalities which could delay or cancel the IVF cycle. Ultrasounds during the IVF process are completed using a trans-vaginal ultrasound probe. A vaginal ultrasound probe is smaller and usually more comfortable than a speculum (used for gynecologic exams). An empty bladder is preferred for trans-vaginal ultrasounds.
Medication protocols usually involve two types of medications. There are medications designed to prevent ovulation and medications used to stimulate the ovaries. It is important for patients to follow their medication schedules for proper development of the follicles and eggs. Gonadotropins are medications that stimulate egg development. The most common brand names that are used include Gonal-F and Follistim. The results of the egg stimulation is monitored with additional ultrasound exams. The monitoring ultrasound will evaluate the size and number of follicles, or fluid sacs containing eggs, and evaluate the lining of the uterus. The monitoring phase of the IVF cycle usually requires 2-3 visits before the egg collection procedure. The monitoring ultrasound will also look at the endometrial lining. The endometrium will preferably be greater than 8 mm, and the target size for the follicles is 18-20 mm for the lead, or largest follicle, and > 14-15 for the other follicles.
Once the follicles are thought to be mature, patients are instructed to stop the medications they have taken up to this point and use a medication to time the egg collection process. Medications most commonly used to prepare the eggs for collection include, HCG, Ovidrel, or Lupron. Patients will be given written instructions on what to do for the retrieval. Medications that tune the egg collection are administered approximately 36 hours before the scheduled egg retrieval, or harvest. This injection is timed in conjunction with the retrieval so the oocytes will be “released” from the wall of the follicle but not “released” from the ovary into the abdomen. Detailed instructions are reviewed in the pre-operative process including when to stop eating and drinking. Generally patients will need to refrain from eating and drinking for 8 to 10 hours before the procedure.
On the day of the retrieval, a semen specimen is collected for fertilization of the eggs. The sperm sample will be prepared for the fertilization process which may or may not involve directly injecting the sperm into the eggs – ICSI. Due to the serious nature of identity, we will request photo identification and a signature before the specimen can be accepted. A collection room is available for privacy. Materials are available in the collection room to provide the appropriate visual stimulus that males often need.
When patients arrive at the clinic, they will be identified and complete the final consent process. An identification band will be used once identities have been verified. An anesthesia provider will place in an intravenous catheter (IV) and administer sedatives for the egg collection procedure. Sedatives and pain medication will be given as needed during the procedure. Women are sleeping and will rarely remember anything from the procedure. A breathing tube is not needed during the egg collection procedure. While the procedure can provoke a great deal of anxiety, most women are pleasantly surprised how “easy” the procedure can be.
The egg retrieval procedure takes approximately 10-15 minutes once patients are situated and prepared in the procedure room. The procedure involves a transvaginal ultrasound with a needle guide. The guide helps direct the needle into the follicles so the eggs can be collected while monitoring the process on the ultrasound machine. The needle is used to aspirate the fluid from the follicles in both ovaries. The fluid is collected in test tubes that are then passed to the embryology lab. The eggs, or oocytes, are identified in the follicular fluid by an embryologist under a microscope. Once all of the follicles have been aspirated, the patient is taken back to the recovery room. The embryologist will report the total number of eggs collected during the oocyte retrieval procedure.
The recovery usually takes 30 minutes and patients are able to walk out of the procedure room. You will be given discharge instructions by the nurse. Because the medications used for the retrieval often cause memory impairment and drowsiness you should plan to have the remainder of the day free of any activities. Most importantly, you will not be allowed to drive yourself home, and must have an adult present at the time of discharge. Patients may experience mild cramping and bloating symptoms after the egg collection. Most patients are able to resume normal activities the following day.
Patients planning to freeze eggs for fertility preservation will have the eggs frozen on the same day as the egg retrieval. Fertilization will be delayed until the eggs are used in the future. For patients proceeding with embryos, the eggs are fertilized with the partner’s sperm or donor sperm. The day of fertilization is considered day 0 for the embryos. The day after the egg retrieval, patients are called with fertilization results. Not all of the eggs will fertilize and not all of the fertilized eggs will progress to form embryos. There is no good way to predict how many eggs will actually fertilize as fertilization can be influenced by egg quality and sperm quality. The embryos will then be cultured, or grown for 5 days. Traditionally, embryos were transferred in the same cycle in which the eggs were collected. Drastically improved freezing techniques have shown that egg stimulation has harmful effects on the lining of the uterus. Most patients are now advised to freeze all of the embryos after extended culture to day 5 or day 6 blastocyst stages. After menses occurs, patients can begin the frozen embryo transfer process. In general patients are able to see 15 to 20% improvements in pregnancy rates. Not all embryology laboratories have perfected the more advanced freezing techniques and may not have the same advantage from freezing the embryos. Patients should consult with their doctor regarding the recommended treatment plan.
There are times when cycles will need to be canceled. A few examples are presented here for information purposes. If your cycle is canceled, the doctor will discuss the reasons as well as the management plan. The most common cause for cancellation of a cycle is lack of adequate ovarian response. If you do not have a good number of follicles you may be better served by attempting pregnancy by timed intercourse or intrauterine insemination. For some patients this saves financial resources for future attempts at IVF where the follicular response may be improved. There are a good number of pregnancies that have resulted from “canceled” cycles. Other reasons a cycle may be canceled include ovarian hyperstimulation, and premature ovulation (very uncommon in patients taking Lupron).
Monitoring ultrasounds will give an estimate of the numbers of follicles that are growing in response to the stimulation medications. It is important to remember the number of follicles on ultrasound is not always the same as the number of eggs collected at the egg collection procedure. Follicles may be empty and not contain eggs or poor quality eggs can deteriorate following HCG administration. Sometimes there are very few oocytes retrieved when the number of follicles looks encouraging. There is always a possibility that no oocytes are collected, no eggs fertilize, or no embryos survive to the blastocyst stage for of transfer. Frozen embryos may not survive the thawing process in the future.
During the egg collection process the sedation medication could cause over-sedation and patients need to have a breathing tube placed. The risk of needing a breathing tube is estimated to be less than 1 in 10,000. The needle used to collect the eggs can cause bleeding in the abdomen or vagina. The need for a blood transfusion is likely less that 1 in 5,000. A severe infection in the abdomen or ovary could require hospitalization or drainage of the infection from the ovary. An infection from the egg retrieval is estimated to be less than 3 in 1,000. Severe pain requiring heavy pain medications is less than 2%. Overall the egg retrieval process has a very low risk of serious complications and most patients tolerate the procedure very well.
Other risks associated with IVF and fertility treatments include:
- Ovarian Hyperstimulation Syndrome (OHSS) — this is a combination of symptoms that result from the elevated levels of hormones and other factors that result from excessive stimulation of the ovaries. There is a fine line that exists in many women between just the right amount of stimulation and OHSS. Click here to read more. Fortunately newer methods of assessing ovarian reserve and strategies for stimulating eggs prior to the egg collection procedure have made OHSS very rare.
- Multiple gestations — the use of medications to stimulate increased numbers of follicles will also increased the rate of multiple pregnancies. IVF is associated with a 3% risk of identical twinning. When 2 embryos are transferred there is often a 50% rate of twins and a 3% rate of triplets. Single embryo transfers will reduce the complications associated with multiple gestations.
- Ectopic pregnancies (tubal) — during the embryo transfer procedure, embryos are placed into the uterus under ultrasound guidance. The risk of ectopic pregnancy is estimated to be 1-2%.
- Ovarian torsion — with ovarian stimulation from gonadotropins., the size of ovaries is increased. This increase in size can lead to a twisting of the ovaries which interrupts the blood supply. Surgery is often required to alleviate the problem. Torsion occurs in less than 1% of patients.
- Ovarian cancer — there is much debate about ovulation induction agents increasing a woman’s risk for ovarian cancer. Studies show that if there is any increased risk in cancers from ovarian stimulation, it is likely less than 1 in 10,000 risk of developing cancer. Pregnancy and breast feeding has been shown to decrease the risk of breast cancer as do birth control pills.
- Perforation — Injury to intra-abdominal organs and vessels is always a concern during the retrieval process. Organs at risk include the bowel, bladder, and vessels. Because the needle is relatively small this complication is not as common as one would expect. Keep in mind needles are used to puncture vessels in order to draw blood. Punctures of intra-abdominal organs likely seal themselves in a similar fashion.
- Infection – Bacteria from the vaginal canal can enter the abdomen and ovary through the needle used to collect the eggs. This is actually very rare and is estimated to occur less than 3 in 1000 cases. Severe infections and abscesses could require hospitalization for intravenous antibiotics though this is even less common than abdominal infections.
- Bleeding – The needle used to collect the eggs can cause injury to blood vessels. Significant bleeding that would require a blood transfusion is extremely rare. In most cases the total amount of blood loss is less than the amount of blood drawn in a single tube of blood used for laboratory testing.
ICSI and Other Techniques
Male-factor infertility occurs in approximately 40% of couples who are unable to achieve a pregnancy. Typically more than half of patients undergoing IVF will require intra-cytoplasmic, sperm injection, or ICSI. ICSI is indicated when there are not enough normal sperm in terms of the number of moving sperm and the number of normally shaped sperm. ICSI is also used frequently when there are poor fertilization results in previous IVF cycles. ICSI is a micromanipulation technique originally developed in Belgium. By using a powerful microscope we are able to isolate a single sperm, aspirate it into an extremely thin glass pipette, and inject it into a single egg. The process is repeated until all eggs have been treated. This technique does not require large numbers of motile sperm and bypasses the need for the sperm to penetrate the egg by itself. With the help of ICSI, fertilization is achieved and embryos that continue to divide are ready for transfer into the uterus in several days. No increase in congenital anomalies (birth defects) have been observed with ICSI other than the small risk that male factor infertility may be passed on to male offspring. [More Information about ICSI]
Assisted Hatching is a technique involving the removal of a small portion of the zona pellucida (outer layer of the oocyte or early embryo). This process is done prior to transfer when it appears that the embryos may benefit from additional assistance. Age and poor egg quality are the most common determining factors for using assisted hatching. Assisted hatching is considered on an individual basis. More advanced embryo hatching techniques have been used with improved results for a larger portion of patients. Assisted hatching can be discussed with the physician and embryologist responsible for a patient’s treatment cycle.
Embryos are stored in liquid nitrogen for future use. Traditionally a fresh embryo transfer resulted in the left-over embryos being stored. In more modern approaches, all of the developing embryos may be stored for use in the future. Cryopreservation offers a means to save the fertility potential of embryos and may allow the uterine lining to be developed under more favorable conditions. The frozen embryo transfer (FET) process does not involve taking injectable gonadotropins and the ovaries are not stimulated. This allows for a uterine lining to develop without excessive stimulation. Coordinating the frozen embryo transfer can be done with or without medications. Cryopreservation allows for attempts at achieving pregnancy without the high-cost of a repeat IVF cycle. Cryopreservation of embryos is also a method of fertility preservation. Some patients will use multiple IVF cycles to collect and store embryos before proceeding with embryo transfer procedures. Treatment plans will vary among patients and should be discussed with the physician. Information provided on this website should not be used as a substitute for medical advice.