In Vitro Fertilization
Advanced Techniques for Treating Infertility
At The Center for Reproductive Medicine and Fertility, we are dedicated to providing precise, comprehensive treatment for each of our patients. We understand the difficulty and frustration that patients who suffer from infertility go through, and offer the latest procedures to combat these issues. Dr. Louis R. Manara is a skilled fertility specialist, offering in vitro fertilization to patients throughout New Jersey who have been unsuccessful at previous attempts to conceive. This detailed procedure is among the most advanced fertility treatments available today.
To find out if you are a candidate for in vitro fertilization, contact Dr. Manara’s Voorhees, New Jersey practice today.
What Is In Vitro Fertilization?
In-vitro fertilization literally means fertilization of eggs outside of the body. While originally intended for patients whose fallopian tubes are absent or severely damaged, it has found application in couples where the woman has endometriosis, or where infertility is unexplained. In addition, it is our most powerful treatment to overcome severe male factor infertility and is commonly utilized for couples who have tried all other treatment options unsuccessfully.
Most commonly, patients undergoing in-vitro fertilization at our New Jersey practice go through a month of preparation of the ovaries termed down-regulation. This approach allows the ovary to be stimulated with medications to mature multiple eggs. Typically stimulations result in 5-15 eggs maturing so they may be removed. At the appropriate time, the patient is given a light anesthetic so that the eggs may be removed through a procedure which allows the physician to see the ovaries with vaginal ultrasound, and "aspirate" the eggs by passing a needle directly into the ovary and applying suction to remove the eggs. Once the eggs are removed, they are incubated with the partner's sperm and maintained in an incubator for 3-5 days. At the end of this incubation, the designated number of embryos is returned to the patient's uterus through the cervix. This part of the process is painless and requires no anesthesia. After the embryos are returned to the uterus, a pregnancy test is done about 10-12 days later to determine if implantation has occurred. Any embryos not returned to the woman's uterus may be frozen for possible future transfer.
An Overview of In Vitro Fertilization
While in vitro fertilization is a relatively common fertility treatment these days, it is an intricate process that takes place over several stages. Below is a synopsis of the main steps of in vitro fertilization that occur at Dr. Manara’s Voorhees, New Jersey practice.
- Ovarian Stimulation and Monitoring: This is the process of maturing multiple ovarian follicles (eggs) through the use of pituitary hormone injections (FSH /LH). Usually this process of ovarian stimulation requires pre-treatment to suppress the pituitary gland so that the eggs are not released early. The medications most commonly used to accomplish this are leuprolide acetate (Lupron) and ganirelix acetate (Ganirelix).
- Egg Retrieval: The removal of eggs by transvaginal, ultrasound-guided follicle aspiration. This part of the in vitro fertilization process is performed at our New Jersey center, utilizing “conscious sedation.” It typically takes 15 minutes to complete.
- Fertilization and Embryo Development: Once the eggs have been removed they are placed in incubators which are precisely controlled environments with carefully monitored oxygen, carbon dioxide, nitrogen concentrations, temperature, humidity and pH levels. Within a few hours each egg will either be mixed with a pre-determined number of sperm or in the case low or abnormal sperm counts, the eggs will each be injected with an individual sperm cell.
- Embryo Transfer: After several days of incubation, the embryos are transferred into the uterus. In most cases this is performed on either the 3rd or 5th day after the eggs were removed.
- Luteal Support: Progesterone is administered by vaginal tablets or gel beginning shortly after the eggs are removed and continuing through the first few weeks of pregnancy.
- Freezing of Embryos: In some situations, extra embryos above and beyond the number that can safely be transferred to the uterus, are available and may be frozen for future use. In our program, freezing is usually done on the 5th or 6th day following removal of the eggs. at the blastocyst stage of development.
Success rates for in-vitro fertilization vary according to the reason for the procedure, as well as the patient's age. The average patient can expect a 35% "take home baby rate" each time she undergoes a cycle of in-vitro fertilization treatment.
A Detailed Look at In Vitro Fertilization
For patients who are interested in learning more about the in vitro fertilization process, here is a detailed look at the various stages.
Ovarian Stimulation and Monitoring
While going through in vitro fertilization treatment, patients are monitored in our New Jersey office with vaginal ultrasonography and blood hormone testing. During this phase of treatment patients may be treated with any or all of the following medications.
- Oral Contraceptive Pills – Birth control pills are often used to synchronize the group of follicles destined to be removed for IVF. Additionally, oral contraceptives can exert a “quieting” effect on the ovary reducing the development of cysts and improving the overall response of the ovary to the stimulation medications.
- GnRH-Agonists (Lupron) – The primary effect of this medication is to prevent premature release of the eggs. This medication is administered by subcutaneous injections on a daily basis for about 10 days leading up to the day that the ovarian stimulation begins. Side effects of this medication include irregular vaginal bleeding and menopausal symptoms, but these effects are usually short-lived and subside within a few days of the beginning of ovarian stimulation.
- GnRH Antagonists (Ganirelix, Cetrotide) - Once again, the primary desired effect is to prevent the premature release of the eggs as they are being stimulated to mature. Some of the side effects of this subcutaneous injection are pain at the injection site, nausea, allergic reaction or headache although most patients tolerate this medication quite well. Since this medication results in a much less profound suppression of the ovary, it is very useful for women who are “low responders” to the stimulatory medications. One other beneficial effect of using this medication compared to Lupron is that many fewer injections will be needed when the antagonists are used.
- Gonadotropins (Follistim, Gonal F, Bravelle, Menopur) – These subcutaneous injections are used to increase the number of eggs that will be available at the time of egg retrieval. Potential side effects of these medications include fluid retention, ovarian enlargement, extreme ovarian overstimulation (OHSS), abdominal distention, and in isolated cases extreme accumulation of abdominal fluid requiring removal.
Egg retrievals are done using mild sedation (conscious sedation) administered by licensed nurse anesthetists (CRNAs). An intravenous is placed and patients’ vital signs are carefully monitored while the procedure is done. The actual egg removal is done using intra-vaginal ultrasound guidance to precisely pass a needle through the vaginal wall and into the ovary, which is located about 1-2 cm behind the upper vaginal wall. Using slight changes in the angle of the needle, each of the follicles containing the eggs may be aspirated using gentle, carefully monitored suction. The entire egg removal procedure takes approximately 15 minutes. Vital signs are monitored for about one hour while the effects of the anesthetic agents wear off, and the patient is then discharged to rest at home for the remainder of the day. Most patients return to work the following day without difficulty.
Egg Fertilization and Embryo Development
It is important to realize that not every follicle seen on ultrasound will yield an egg and not every egg exposed to sperm will become fertilized. On average, 70% of eggs will become fertilized as a result of incubation with sperm. When the sperm count is good and the quality of the sperm is normal, it is only required that appropriate numbers of sperm be incubated with each egg in order for fertilization to occur.
In situations where the sperm count is abnormally low or the quality of the sperm is poor, an additional embryology laboratory microscopic procedure called “ICSI” (intra-cytoplasmic sperm injection) is required. This procedure may only be performed on mature eggs and involves the use of a high-powered, specially designed microscope equipped with hydraulic and electronic “manipulators.” These manipulators are used to inject one healthy sperm cell into a specific area within the egg. This procedure requires extensive experience and must be done with great care to avoid damage to the egg and allow fertilization to occur. ICSI is not performed on all couples, but is usually reserved for situations in which a male factor has been identified. There are some additional situations where ICSI is performed, one of which is when an embryo is to be genetically tested for chromosomal abnormalities (PGS or PGD). Occasionally, eggs which were inseminated in the usual fashion fail to show signs of fertilization when checked microscopically at 16 -18 hours after insemination. When this occurs, a procedure called “Rescue ICSI” may be performed. Using ICSI in this way generally results in poor outcomes and is used only as a last resort to salvage an IVF cycle.
In some situations, Dr. Manara will also use a process known as assisted hatching. This process again requires the use of the high-powered microscope equipped with micro-manipulators. Assisted hatching involves weakening the outer membrane that surrounds the egg through the use of a laser or chemical agent. There is some evidence that this procedure will improve the implantation rates for patients older than 35. It may also be used when patients’ embryos are found to have a particularly thick outer membrane (zona pellucida) or when there has been repeated IVF failure.
This last part of the IVF treatment cycle involves placement of the embryos directly into the uterus. It is vitally important that this part of the treatment be carried out gently and quickly. In our program we incorporate the use of ultrasound guidance to assure accurate placement of the embryos and help identify the pathway into the uterus. The procedure is usually done with a full bladder and patients are asked to remain supine for about 10-15 minutes following placement of the embryos. Except for the discomfort of a full bladder, this procedure is painless.
The number of embryos transferred is highly individualized for each patient, taking into consideration the patient’s age and the quality of the embryos. At this time embryo quality is determined by carefully monitoring the embryos while they remain in the laboratory. Some of the important indicators of embryo quality are number of cells, symmetry of the embryo, presence or absence of cell fragments within the embryo, timely progression to the blastocyst stage of development, and thickness of the outer membrane of the embryo (zona pellucida).
At our New Jersey practice, we transfer embryos on the third or fifth day following removal of the eggs. The decision to transfer embryos on day 3 or day 5 is made based upon the quality and number of embryos available. Generally, if 4 high-quality embryos are available on day 3, they are kept in our incubators for two additional days, allowing them to develop into blastyocysts before transfer to the uterus. There is a distinct advantage in allowing the embryos to continue their growth. The highest quality embryos in the group will distinguish themselves from the others by their microscopic development. Blastocysts are graded based upon the appearance of the outer cell layer (trophoblast), the cavity (blastocoel), and the embryo itself (inner cell mass). Transferring the highest quality blastocysts will yield the highest live birth rate. Blastocyst implantation rates are so good that many programs today are encouraging patients to consider single embryo transfer to further reduce the chances of multifetal gestation. Studies have shown that choosing to transfer one blastocyst practically eliminates the chance of twins while reducing the overall pregnancy rate by only approximately 10%. The final decision concerning the number of embryos to transfer can be considered in general terms leading up to the actual transfer date. Often the final decision must be left until the actual day of transfer in order to incorporate embryo quality into the decision making process. One disadvantage of transferring blastocysts is that there is an increased chance of identical twins which some studies have indicated is about 1%. There is also some risk associated with keeping embryos in culture for the additional two days. The embryos may fail to continue developing and therefore may not be eligible for transfer to the uterus on the 5th day as planned. Fortunately, by exercising good judgment concerning which embryos should be allowed to continue in the laboratory past day 3, this rarely occurs.
Luteal Phase Support
Because many of the cells that produce estrogen and progesterone are removed with the eggs at the time of egg retrieval, it is important to replace these hormones in preparation for embryo attachment. Also, the agents used to prevent the eggs from releasing early (Lupron or Ganirelix) may impair the production of these hormones during this important phase of treatment. Therefore, supplementation with these hormones is standard in our practice following removal of the eggs. This support will continue through the early weeks of pregnancy to further support embryo implantation. We have found that the best route for delivering these hormones to the target tissue (endometrium) is by absorption through the vaginal mucous membranes. These medications are administered in the form of vaginal gel or tablets. Recent studies have indicated that an intra-muscular injection of these hormones is not necessary.
Cryopresevation of Extra Embryos
Many women going through IVF treatment will have more embryos available for transfer than is safe or advisable. In these instances, if embryo quality is good, it is advisable to freeze these embryos for future use. They may be transferred in the immediate cycle following a failed fresh embryo transfer, or they may be transferred years later when the couple is ready for another child. All indications are that as long as the embryos are maintained properly in the cryopreserved state, their potential to successfully implant is not hampered by the passage of time. It is important to realize that frozen embryo transfer success rates are significantly lower than fresh embryo transfer rates. However, the technology of cryopreservation has made significant advances in recent years and frozen/thawed embryo transfer success rates are improving. Because only high-quality embryos are selected for freezing in our program, the success rate for frozen embryo transfers is approximately 30%. The data available to date does not indicate that the risk of birth defects is any greater from frozen embryos than from fresh embryos.
More Information on In Vitro Fertilization
In vitro fertilization is one of the most advanced responses to male factor and unexplained infertility. Contact our Voorhees, New Jersey practice today to schedule and consultation and learn more about the in vitro fertilization process.