Fertility Services

Since early in the history of IVF, it has been clear that greater success is achieved when multiple eggs are available rather than the one egg that would be the result of a natural cycle. This is especially true with increasing age of the woman because a higher percentage of them are genetically abnormal with each additional year. In a natural cycle, there are a specific number of eggs available that is unique to each cycle. Some months there are more than others and this number varies among women. The pituitary hormones FSH (follicle stimulating hormone) and LH (luteinizing hormone) are responsible for the development of the egg that is ovulated. Similarly, in an IVF cycle FSH and LH are used to allow for the development of multiple eggs. By increasing the amount of FSH and LH, it is possible to allow all of the eggs available in a particular cycle to develop. There are several commercially available preparations of FSH and LH which are either purified from human urinary sources or synthesized in a laboratory utilizing recombinant DNA technology. In addition to FSH and LH, another medication is used to prevent the premature ovulation of the eggs that could occur if it was not given. This medication is either started prior to the FSH and LH, in the case of Lupron, or after several days of stimulation in the case of Cetrotide or Ganirelix. In general, women with a larger number of eggs are more likely to be given Lupron and women with an average or below average number of eggs are given Cetrotide or Ganirelix. The amount of FSH and LH to be given is determined by Dr. Anderson when designing the protocol and then may be adjusted depending on the response determined by the monitoring visits. All of these medications are given by subcutaneous injection.

In each cycle, an egg develops inside a structure called a follicle which is a fluid filled sac that is visible on ultrasound. During an IVF cycle, it is the follicles that are monitored by measuring their diameter with ultrasound. Once the controlled ovarian hyperstimulation process begins, ultrasound examinations are performed starting after 3 days. They are then repeated every other day and eventually daily so that adjustments in the medication can be made as needed. Along with the ultrasound measurements, blood is drawn at each visit and levels of Estrogen and Progesterone are determined to further allow Dr. Anderson to make the appropriate adjustments. When the follicle sizes and Estrogen and Progesterone levels indicate that the eggs are mature, an injection of hCG (human chorionic gonadotropin) is given to cause the eggs to release so that they may be removed from the follicles. hCG is used because it is structurally similar to the hormone LH which triggers ovulation in a natural cycle. It is important to give the hCG at the proper time to insure that the eggs release from the ovaries and are fertilizable once retrieved. Careful monitoring is therefore critical to the success of the IVF cycle and should never be replaced with pre-determined protocols designed to maximize convenience.

After cycle monitoring and egg stimulation with injectable medications, the egg retrieval is usually performed about 35 hours after the HCG injection, at a time when the eggs have completed maturation, but before ovulation. Ultrasound-guided egg aspiration is the most common method used to retrieve eggs during IVF procedures. The transvaginal aspiration (TVA) is done at the Newport Beach Surgery Center.

During the TVA, the female patient will lie on an examination table similar to that used for performing a Pap smear. An intravenous (IV) line will be placed in the patient’s arm by an anesthesiologist. This site will be used to administer the medications during the procedure. Prior to the TVA, a speculum is placed in the vagina so that it may be cleaned using sterile solutions that do not harm eggs.

The egg retrieval procedure utilizes a vaginal ultrasound probe, which has a metal guide attached to it. The guide allows a hollow needle to be placed beside the probe. The tip of the needle is etched so that it is visible on the ultrasound monitor. The needle is attached to tubing that goes to a plastic tube and a gentle suction machine. The physician uses the vaginal ultrasound probe to visualize the ovaries and the follicles within them on the ultrasound monitor. Once the patient is anesthetized, the needle is pushed through the vaginal wall into one of the follicles within an ovary. As the tip of the needle penetrates the wall of the follicle, the suction machine is started. The fluid within the follicle is aspirated and flows to the plastic tube. The egg is usually loosely attached to the inner wall of the follicle and as the fluid within the follicle is withdrawn, the egg is aspirated into the tube. This tube is then given to the embryologist who examines each drop of the fluid through a microscope to look for an egg. It is common to have some follicles that do not contain eggs. Therefore, the number of follicles may not equal the number of eggs found. The procedure is finished when all the follicles from both ovaries have been aspirated. A fresh semen specimen needs to be provided by the male partner on the day of egg retrieval.

Fertilization of an egg requires that the genetic material (DNA) contained in a single sperm enters the cytoplasm of the egg. In the laboratory there are two ways to accomplish this. Sperm may be added to the eggs and allowed to fertilize the eggs by first attaching to the outer shell of the eggs and then penetrating them enough for the DNA to be transferred inside. This is the way that eggs are fertilized in a natural cycle. Sometimes however, the sperm are not able to attach to and penetrate the eggs. Unfortunately, there is no way to absolutely predict this in advance. Occasionally there are instances where the sperm and eggs appear normal but fertilization does not occur. The other way to obtain fertilization is to inject the sperm directly into the egg. This procedure is called ICSI (Intracytoplasmic Sperm Injection). ICSI is performed with a microscopic needle and most of the sperm is actually injected. This procedure has been available since 1993 and has been found to be effective and safe. ICSI is used whenever the number of sperm available is insufficient for natural fertilization. However more and more ICSI is being used with every IVF cycle to maximize the number of embryos that can be created. This strategy allows for a greater chance of finding a normal embryo to transfer, thus improving the likelihood of a successful result.

Assisted Hatching is a procedure, which involves creating a small opening in the outer coating of the embryo, the zona pellucida, when the embryo has reached at least the six to eight cell stages. This opening allows the cell mass to more easily hatch out following embryo transfer, a factor that in theory facilitates embryo implantation by insuring contact with the lining of the uterus. Initially, Assisted Hatching was used in selected situations such as women over the age of forty, those with unusually thick zona pellucidae and where previous IVF attempts had resulted in failure. Assisted hatching is now performed in our IVF laboratory routinely in all cases of embryo transfer.  While it was debated that not all fertility clinics performing Assisted Hatching have had similar results, it should be understood that there are currently several ways of creating the opening ranging from use of an acidic solution to application of a special type of laser. It is also important that the size of the opening, the way in which the embryos are transferred following hatching and quality of the embryos at the time of hatching are critical in achieving success. It must be emphasized however that Assisted Hatching does not change the genetic composition of an individual embryo. Even though the overall implantation rate can be helped by Assisted Hatching, the loss of a particular pregnancy is an age dependent event that is determined primarily by the chromosomal makeup of the pregnancy.

The final step of an IVF cycle is the transfer of embryos into the uterus. Historically, embryos have been transferred anywhere from one to five days after egg retrieval. As knowledge about the physiological needs of the embryo accumulated, the day of transfer was gradually extended. Some genetically abnormal embryos will stop developing during the five days following egg retrieval, so by waiting longer it is possible to better select the embryos that will most likely lead to a successful pregnancy. However not all IVF laboratories are geared toward growing embryos to the blastocyst (day 5) stage. The type of incubator used and the expertise of the laboratory staff are major determinants of this.  Our preferred day of embryo transfer is day 5. When selecting the embryos to transfer, either their appearance under the microscope or the results of genetic testing (PGS) is used. The number of embryos to transfer is determined by the age of the woman and the day of transfer. In general, the older the woman and the earlier the day of transfer, the larger the number of embryos that are used. Once the embryos are selected, the actual technique for transfer into the uterus is determined by the expertise of the physician.

During the evolution of In Vitro Fertilization, the transfer of embryos to the uterus has not been given the same amount of attention afforded other aspects of the procedure. Over time, however, it has become apparent that indeed this is probably one of the most important areas to be considered and may explain a lot of the variability in success between different transfer techniques. It is clear that it is advantageous to place the embryos into the uterus in as atraumatic a manner as possible. It is intuitively obvious that the embryos should be placed in an area within the uterus most likely to allow implantation. However, the vast majority of embryo transfers have been performed by a blind procedure similar to intrauterine insemination. Some have suggested that ultrasound guidance of the embryo transfer procedure may be of benefit because the tip of the embryo transfer catheter can be visualized to insure that the embryos are placed in the proper location. Evidence suggests that blind embryo transfer may result in placement of the embryos out of the uterine cavity in as much as 25-30% of cases.

A high IVF success rate has been reported with a technique utilizing transabdominal ultrasound guidance accompanied by a full bladder. We have found that a transvaginal approach is much easier, does not require a full bladder and facilitates very precise localization of the placement of embryos within the uterus. Dr. Anderson first performed this technique in 2000 and instantly demonstrated a significant improvement in pregnancy rates using both fresh and frozen embryos. Additionally, we found that the embryo implantation rate increased significantly. These higher rates were observed immediately at the time that transvaginal ultrasound guided transfer was instituted. There were no other variables at that time that explained this change. This technique has subsequently been adopted by physicians all over the world since originally described by Dr. Anderson.

Our results with this procedure were presented at the Annual Meeting of the Pacific Coast Reproductive Society in 2001 for which Dr. Anderson won the Practicing Physician Award. The paper describing this technique was published in the journal Fertility and Sterility in April 2002. Dr. Anderson wrote a chapter in the book “Embryo Transfer” entitled “Transvaginal Guided Embryo Transfer” which further documented this technique.