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In Vitro Fertilization (IVF)

IVF is an intricate process, which requires several weeks of preperation. The 6-step process can be summarized as follows:

6 IVF Steps
1. Preparation for IVF

During the treatment cycle, there are certain activities and medications that could decrease the chance of conception and thus should be avoided. The following is a list of the some of the recommendations that should be followed in order to maximize pregnancy rates:

  • Smoking is contraindicated during pregnancy and should be avoided before and during treatment.
  • The use of alcohol should be avoided during pregnancy as well as during the treatment cycle.
  • Recreational drugs are contraindicated.
  • The consumption of caffeinated products and beverages should be no more than one a day.
  • Prenatal vitamins should be taken on a daily basis before the treatment is begun. This is to decrease the chance of birth defects in the baby, specifically neural tube defects (for example spina bifida).
  • The use of all prescription and over-the-counter medications (including herbal remedies) should be discussed with Dr. Hosseinzadeh before starting your treatment cycle.
  • Ingestion of aspirin or aspirin-like products (for example Motrin®, Advil®, ibuprofen, Aleve®, Anaprox®, naproxen, etc.) should be avoided during treatment. Tylenol® is safe to take during pregnancy. In some circumstances, you may be required to take low dose aspirin (81 mg).
  • Prior to starting the treatment cycle, you will be required to submit to all necessary blood and urine tests including but not limited to testing for HIV, hepatitis, RPR and blood type.
  • You will also be required to provide a genetic history and consent to any genetic testing that Dr. Hosseinzadeh may deem necessary.
  • Ingestion of some fish can affect the development of the nervous system of a fetus. This is due to the mercury content of the fish. It is recommended that you should avoid eating fish with a higher mercury content such as shark, swordfish, king mackerel, tilefish and canned tuna fish. It is also recommended that you limit the intake of other fish to 12 ounces per week.

2. Controlled Ovarian Stimulation

During a woman’s natural menstrual cycle, usually one mature egg develops. This is housed in a small cystic structure called a follicle. The follicle stimulating hormone (FSH) is the primary hormone responsible for the growth of the follicle. FSH is released from the pituitary gland within the brain. As the follicle grows, it produces a hormone called estradiol, which is an estrogen. When the follicle reaches a mature size, a large amount of luteinizing hormone (LH) is released from the pituitary gland. The purpose of this LH surge is to help mature the egg and leads to ovulation approximately 36 to 40 hours later. The goal of IVF is to develop multiple follicles, which will lead to the retrieval of multiple eggs thereby increasing the potential number of fertilized eggs or embryos. The pregnancy rates increase with increased number of embryos transferred.During the process of controlled ovarian stimulation, the response to the medications used will be determined by transvaginal ultrasound and periodic blood hormone tests. The monitoring helps Dr. Hosseinzadeh to determine the appropriate dose of the medications and the timing of the egg retrieval. Vaginal ultrasound uses sound waves and is usually painless. The blood hormone testing may be associated with mild discomfort and possible redness, bruising, bleeding and rarely infection. Monitoring may be required as often as once a day to document follicular development.

Various protocols will be used to achieve controlled ovarian stimulation. Dr. Hosseinzadeh will determine the protocol that best suits you. There are several medications that can be used for the ovarian stimulation.

Learn more about medications here.

 

Side Effects

Although the medications listed in the medications section above are usually well tolerated, they can cause various side effects including but not limited to nausea, vomiting, irritability, mood swings, hot flashes, night sweats, sleeplessness, headaches, dizziness, joint problems, weight gain, weight loss, as well as visual difficulties. These side effects are generally temporary. Rarely allergic reactions can also occur. Other more serious side effects include:

Ovarian Hyperstimulation Syndrome (OHSS):

    This syndrome is characterized by the development of multiple ovarian cysts. The cysts are the follicles that fill up with fluid after the egg retrieval and result in ovarian enlargement. The typical presentation is lower abdominal discomfort, bloating and distention. The symptoms generally occur one to two weeks after the egg retrieval and resolve within one to two weeks without intervention. During this time, we usually recommend a period of reduced activity and possibly bed rest. It is known that if you get pregnant in a cycle that is complicated by OHSS, the symptoms are usually more severe and it takes longer for the symptoms to resolve. In rare cases the syndrome can be severe with accumulation of fluid in the abdominal and/or the chest cavities. In this case the ovaries are even further enlarged and patients present with severe abdominal pain, bloating, weight gain, shortness of breath, nausea, vomiting and decreased urinary output. In extremely rare circumstances this can lead to the formation of blood clots in the legs (deep vein thrombosis), and lungs (pulmonary embolus). Such complications may require hospitalization. It is imperative that you contact Dr. Hosseinzadeh should you develop any of these symptoms. If Dr. Hosseinzadeh judges that you are at an increased risk for developing OHSS, your cycle will be cancelled or your eggs will be retrieved, fertilized, and the resulting embryos will be frozen. The embryos will not be transferred in that cycle. Once the OHSS has subsided, your embryos will be transferred in a subsequent frozen embryo transfer cycle thereby eliminating the risk for developing OHSS.

Ovarian Torsion (twisting of the ovary):

    In rare cases, due to the fluid filled cysts in the ovary, the ovary can twist on itself and in the process compromise its blood supply. Surgical intervention may be required to untwist the ovary and occasionally it may become necessary to remove the ovary. It is important that you contact Dr. Hosseinzadeh if you should develop abdominal pain.

Ovarian Cancer:

    Limited studies have shown a higher correlation than normal of ovarian cancer in patients who have used ovulation induction drugs such as clomiphene citrate and gonadotropins. However, to date, no cause and effect correlation has been clearly established.

3. Egg Retrieval

The egg retrieval is performed under transvaginal ultrasound guidance in our own fully accredited surgical suites located in our office. A board certified anesthesiologist is also present to administer intravenous sedation and in rare circumstances general anesthesia may be required. This will be discussed with you on a case-by-case basis.For the egg retrieval, the patient is placed in the same position as if she was having a pelvic exam. Following the administration of sedation, the vagina is cleansed with a saline solution. The vaginal probe ultrasound is then inserted into the vagina, and under ultrasound guidance, a needle is passed through the vaginal wall into each follicle to harvest the follicular fluid, which contains the microscopic egg. The follicular fluid is handed off to the embryologist who will scan the follicular fluid under a microscope to look for the presence of eggs. The IVF lab is located adjacent to our operating room. The procedure typically lasts less than 30 minutes. Following this you will be recovered in our own recovery room until you are ready to go home.

Instructions prior to the egg retrieval:

  • It is mandatory that you do not eat or drink after midnight the night prior to the egg retrieval. You can brush your teeth the morning of egg retrieval.
  • Do not wear any jewelry or any perfume. Notify the anesthesiologist if you are wearing any dentures.
  • Wear comfortable clothing.
  • Make sure to be at FISD at least 45 minutes before your appointment.

Instructions for after the egg retrieval:

  • Due to the anesthesia, you will be unable to drive after the procedure and must be accompanied home by a responsible adult.
  • Eat or drink anything you would like as tolerated. Some nausea is common for a few hours.
  • Expect some mild lower abdominal cramping as well as vaginal spotting after the procedure.
  • You should limit your activity for the remainder of the day following the egg retrieval. Do not exercise.
  • You should refrain from intercourse.
  • Do not use a hot tub or bathtub. You may shower.

Call Dr. Hosseinzadeh immediately if you have any of the following symptoms:

  • Fever (>101 F or 38.0 C).
  • Bleeding (i.e. soaking a pad every 1-2 hours).
  • Severe abdominal pain and tenderness.
  • Difficulty breathing.

4. The IVF Lab

Intracytoplasmic Sperm Injection (ICSI)

Your partner will be asked to provide us with a semen sample around the time of the egg retrieval. Sperm can be frozen prior to the egg retrieval if the male partner may not be available on the day of the egg retrieval or if there has been difficulty in the past with the production of the sperm sample. Donor sperm can also be used. The semen is then washed and prepared to inseminate the eggs 3-4 hours later.There are two methods to the insemination of the eggs:

  1. Standard Insemination: This is traditionally performed in cases where the semen parameters are adequate. After the sperm sample has been processed, the sperm and eggs are placed in a dish with a special culture media and then placed in the incubator of the laboratory overnight to allow for fertilization. The next morning the eggs are examined to determine whether fertilization has taken place.
  1. Intracytoplasmic Sperm Injection (ICSI): In this procedure the sperm is isolated and inserted directly into a mature egg to increase the likelihood of fertilization. Prior to this procedure being performed, the eggs are treated in a solution containing hyaluronidase (an enzyme which removes the cumulus cells surrounding the egg). The egg is held in place by an egg-holding pipette while the needle (micro pipette) is introduced through the zona pellucida, or shell, of the egg in order to inject a single sperm directly into the egg. Following incubation overnight, the eggs are examined to assess whether fertilization has taken place.

Some of the patients who would benefit from ICSI include:

  • A previous semen analysis demonstrating poor parameters.
  • Sperm that has been surgically obtained from the testicle or the vas deferens.
  • Prior poor fertilization in an IVF cycle.
  • Use of frozen sperm.

On average, approximately 75% of eggs will fertilize following either standard insemination or the ICSI procedure.

Laser Assisted Hatching (AH)

The embryo is surrounded by a protein shell called the zona pellucida. A portion of this shell must dissolve for the embryonic cells to escape or “hatch.” Only after “hatching” can the embryo then attach, or implant to the lining of the uterus in order to establish a pregnancy. Possible reasons for implantation failure could include the inability of the embryo to “hatch” out of its shell.

How is this done?

Assisted hatching is a procedure where an artificial opening is made in the zona pellucida of the embryo. The goal of this is to assist the embryo in breaking out of its shell to facilitate implantation to the uterine lining. Assisted hatching has traditionally been performed by acid digestion of the zona pellucida. At Fertility Institute of San Diego, we use the latest cutting-edge laser to provide our patients with what we believe is the fastest, safest and most uniform method of performing assisted hatching. This involves using a laser to make a tiny hole in the zona pellucida and takes only a few seconds per embryo thereby minimizing the time they are out of the incubator. It also does not expose the embryos to the potential deleterious effect of the acid digestion.

Who would benefit from AH?

Some of the patients who would benefit from assisted hatching include:

  • Women 38 years or older.
  • Patients with elevated day 3 FSH (follicle stimulating hormone) level.
  • Patients with poor egg quality.
  • Patients with poor embryo quality as evidenced by slow growth or excessive fragmentation.
  • Patients with previous failed IVF cycles.
  • Patients undergoing FET (frozen embryo transfer).

What are the risks of AH?

Present research suggests that the risks to the embryos are minimal with this method of assisted hatching. There appears to be an increased risk of monozygotic twinning (MZT), where the embryo splits resulting in a set of identical twins.

Embryo Cryopreservation

Freezing (or cryopreservation) of embryos is a common procedure. Since in a typical IVF cycle, multiple embryos are created and only one or 2 embryos are transferred into the uterus, there is sometimes a surplus of embryos. These embryos, if viable and of adequate quality, can be frozen for future use in a frozen embryo transfer (FET) cycle.

A FET offers significant cost savings in comparison to a fresh IVF cycle as the medications used to prepare the lining of the uterus are relatively inexpensive and the patient does not have to undergo an egg retrieval, which requires it to be performed in an operating room in the presence of an anesthesiologist. Furthermore, the availability of cryopreservation permits patients to transfer fewer embryos during a fresh cycle, reducing the risk of high-order multiple gestations (triplets or greater). Other possible reasons for cryopreservation of embryos include freezing all embryos in the initial cycle to prevent severe ovarian hyperstimulation syndrome (OHSS), or if a couple is concerned that their future fertility potential might be reduced due to necessary medical treatment (e.g., cancer therapy or surgery).

Overall pregnancy rates at the national level with frozen embryos are lower than with fresh embryos. This, at least in part, results from the routine selection of the best-looking embryos for fresh transfer, reserving the ‘second-best’ for freezing. There is some evidence that pregnancy rates are similar when there is no such selection.

5. Embryo Transfer

If fertilization occurs normally, the growth of the embryos is monitored in the laboratory. The embryo transfer is usually performed 2 to 6 days following the egg retrieval. In cases where there are only a limited number of embryos, it is better to transfer the embryos into the uterus sooner. Traditionally though, embryo transfer is performed three days after the egg retrieval, at the 4 to 8 cell stage, or 5 or 6 days after the egg retrieval at the blastocyst stage.

On the day of the embryo transfer, Dr. Hosseinzadeh will review the status of your embryos and make a decision regarding the number of embryos to be transferred. Increasing the number of embryos transferred not only increases pregnancy rates but also increases the risk of multiple pregnancies (twins, triplets). Prior to the embryo transfer, you will be given Valium, which is a muscle relaxant. The purpose of this is to relax the uterus, which is composed of muscle. In order to perform the embryo transfer, the patient is placed in the same position as for a pelvic exam The embryo transfer is usually performed under ultrasound guidance. This can be done by either using transvaginal ultrasound or trans abdominal ultrasound guidance. The trans abdominal approach requires you to have a full bladder. A speculum is placed inside the vagina. The cervix and the vagina are then thoroughly rinsed. Once the embryos have been loaded into a special catheter, the catheter is introduced through the cervix and into the uterine cavity. The embryos are then injected into the top of the uterus. Following this, the catheter will be examined by the embryologist to ensure that none of the embryos are retained in the catheter.

The procedure usually takes about 10 to 15 minutes and does not require anesthesia. There is no need to abstain from eating or drinking before your embryo transfer. We ask that you abstain from wearing any perfume, deodorant or scented lotions on the day of the embryo transfer. You will not be able to drive home because of the Valium. You will be asked to decrease your activity for a few days after the embryo transfer.

6. Hormonal Support of the Uterine Lining

Following the egg retrieval, the hormone progesterone is required to prepare the lining of the uterus for implantation. Progesterone is naturally produced from the ovary following ovulation. Various forms of natural progesterone will be administered following the egg retrieval. The most common route of administration is that by intramuscular injection. Other medications including, but not limited to, estrogen will also be given in the luteal phase of the cycle.

The pregnancy test, measurement of the beta-HCG hormone, will be scheduled on a given day. If this is positive, a repeat pregnancy test will be performed two to three days later. The beta-HCG hormone level will be followed until it is high enough to schedule a transvaginal pregnancy ultrasound. During the early part of your pregnancy, you will be asked to continue with the progesterone and estrogen injections. You may also be asked to see a perinatologist (an obstetrician who deals with high risk pregnancy) for a special ultrasound to assess the risk of chromosomal abnormalities in the fetus.

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