In Vitro Fertilization (IVF)

What is IVF? 

In vitro fertilization literally means “fertilization in glass”.  Fertilization takes place outside the body, in a test tube or petri dish in the laboratory.  The IVF process involves surgically removing eggs from a woman’s ovaries, fertilizing them with her partner’s sperm in the laboratory to produce embryos, culturing the embryos for 3 – 5 days, and transferring the resulting embryos back into the woman’s uterus.

Each cycle of treatment commences with a planning appointment with one of the IVF nurses to arrange a detailed calendar.  A few days after your menstrual cycle is to begin, you will begin taking progestogen and/or Lupron for at least 14 days.  These medications allow us to suppress your natural cycle and allow precise timing of the IVF cycle. Ovarian stimulation will begin within a few days following the menstrual period.

Controlled Ovarian Supra-ovulation:  Following the menstrual period, you will begin daily FSH injections. FSH (follicle stimulating hormone) is a medication that stimulates the ovary to produce numerous follicles, each containing an egg. During this time you will also continue taking Lupron to prevent ovulation prior to surgical retrieval.

While taking FSH, you will make several visits to our office for monitoring of your ovarian response by transvaginal ultrasound and by blood tests that measure your estrogen level.  If you are not responding well to the FSH, this monitoring allows adjustment of the FSH dose.  Typically, after 8 – 13 days of FSH, depending on your own response, enough follicles will reach the mature range.  At that point, you will be instructed to take in intramuscular injection of hCG to induce the final maturational changes in the eggs and prepare them for retrieval approximately 36 hours later.

Egg Retrieval:  You will be instructed to report to our facility on the morning of the retrieval at a specific time, accompanied by your partner.  You must not eat or drink anything after midnight the night before, because you will receive intra-venous sedation by an anesthetist to ensure that you remain relaxed during the procedure. Once you are sedated, your eggs will be retrieved by a process called transvaginal egg retrieval.  The vaginal transducer is inserted into your vagina, and follicular fluid containing the eggs is aspirated from the ovary with a needle inserted through the vaginal wall under the guidance of ultrasound. The retrieval procedure usually lasts about 25 to 45 minutes, and you will be discharged home when the sedation wears off, approximately 1 – 2 hours later.  You must have someone else to drive you home and you will need to relax the remainder of the day.

Your partner will be asked to provide a semen specimen before or immediately after the time of your retrieval.  This sperm will be placed with the retrieved eggs for fertilization in the embryology laboratory.

Insemination of Eggs and Embryo Culture: The follicular fluid aspirated during the retrieval is immediately passed through a window to the embryologist in an adjacent laboratory.  There the eggs are extracted from the fluid, examined, graded, and placed in a glass dish.  The embryologist combines the eggs with the sperm that your partner collected that morning, and examines the eggs the next day for evidence of fertilization.  The eggs that have fertilized will be allowed to develop for 3 – 5 days under controlled laboratory conditions before they are placed inside the woman's uterus. If the embryologist recognizes embryos of exceptional quality on Day 3, he may suggest to the physician that the embryos continue to develop to Day 5 so that blastocysts may be transferred.   Because blastocysts are in an advanced stage of embryo development, the physician can transfer fewer and reduce the incidence of multiple births. He will discuss the number to be transferred with you prior to the actual transfer.

Embryo/Blastocyst Transfer:  Embryo transfer involves passing a fine tube (catheter) through the cervix.  There is only minimal discomfort when passing the vaginal speculum and catheter, which has to stay in place a few minutes.  Thus, it usually requires no anesthesia, and you can return home soon afterward and to normal activity with 4 – 5 days.  You will return to the office 10 days after the embryo transfer for a pregnancy test.  Some couples may wish to have excess embryos or blastocysts cryopreserved for future use.

Embryo Cryopreservation and Storage

After controlled ovarian hyperstimulation and fresh embryo transfer, 60% of stimulated IVF cycles will produce excess viable embryos, which are available for cryopreservation. Cryopreserved or frozen embryos can be thawed and transferred back into the uterus, during a subsequent frozen embryo transfer cycle. This allows for higher overall pregnancy rates per attempted IVF cycle. The indications for embryo cryopreservation include: >> Storing excess embryos for future use after a fresh embryo transfer   >> Eliminating the risk of OHSS in a fresh embryo transfer cycle at very high risk of OHSS.   >> Uterine conditions that are unfavorable for fresh embryo transfer after retrieval (e.g., uterine bleeding, polyps, leiomyomas, severe cervical stenosis, or a thin endometrial lining).   Cryopreservation techniques attempt to minimize cell damage to embryos during the freezing and thawing process with the aid of cryoprotectants. Embryos are frozen at a slow rate with the cryoprotectant. A gradient is induced that allows intracellular water to leave the cell. The embryo is dehydrated to avoid the formation of cytotoxic intracellular ice crystals. Once they are frozen, the embryos are loaded into cryostraws and stored in liquid nitrogen at -196°C. When embryos are needed for transfer, they are thawed rapidly to avoid formation of intracellular ice crystals. Typically, cryopreservation results in an 80% survival rate after thawing frozen embryos. Patients should be extensively counseled prior to oocyte retrieval with regard to cryopreserving excess embryos. Informed consent is obtained as outlined in the ASRM committee opinion on elements to be considered in obtaining informed consent for ART.

 

When is IVF indicated?

• In women with blocked, damaged or absent fallopian tubes

• In cases of prolonged unexplained infertility which has not responded to other forms of infertility

• In women with severe endometriosis who have not been successful using other infertility

• In women whose partners have male factors, including severe oligospermia (low sperm count)

• In women with premature menopause, using donor eggs and their partner’s sperm

 What is ICSI and when is it indicated?

ICSI, or Intracytoplasmic Sperm Injection, is the most widely used specialized insemination technique.  It is a newer advancement in reproductive technology in which procedures are performed on eggs under a specially constructed microscope in a process known as micromanipulation. ICSI enables fertilization in cases of very low sperm counts, of non-motile sperm, of severe sperm abnormalities, and in cases in which sperm have poor penetration ability.  It may also be indicated in couples who had no fertilization in previous IVF attempts.

The technique involves injecting a single sperm directly into the egg. After injection of the sperm, the eggs are incubated for 16-18 hours, and then examined for evidence that fertilization has occurred. The resulting embryos can then either be transferred back to the woman's uterus using standard IVF techniques (or to the fallopian tubes using ZIFT), or can be frozen for transfer at a later time.

What is Assisted Zona hatching (AZH) and when is it indicated?

Assisted zona hatching (AZH) is a technique used to, potentially, improve implantation rates. Once an egg has been fertilized (by either conventional IVF or ICSI), the embryo is then assessed to determine its quality. Part of this assessment is measurement of the shell thickness (zona pellucida) around the embryo. If the zona pellucida is thicker than normal, this is an indication for assisted hatching.

At the Center for Reproductive Health, using micromanipulation techniques, we use a small amount of acid to create a small defect (hole) in the zona pellucida itself. In theory, this small hole in the shell of the embryo allows the embryo reaching the blastocyst stage to, break out of it's shell easier to allow for better implantation rates.

Some embryos may have a normal or thin zona pellucida that is extremely tough or hard to hatch. One cannot determine how hard the zona is until the assisted hatching procedure is actually performed.  Indications for assisted hatching include:

>>	Thick zona pellucida measured via IVF
>>	An elevated FSH level
>> >>	Age greater than 38 years Previously failed IVF embryo transfers without assisted hatching

Occasionally embryo quality can be improved by removing fragmented debris through the hole created by the assisted hatching procedure. We have had very good success rates when assisted hatching is used.

IVF SUMMARY POINTS >> IVF was initially developed to treat tubal factor infertility but now represents the final therapy for many infertile couples, regardless of the etiology.   >> There is a significant maternal age-related decline in IVF pregnancy and delivery rate, which should be taken into account when discussing infertility therapies. Unless egg quality can be improved with specific technology the outcome of IVF in these patients is inadequate.   >> Day 3 FSH ± estradiol, clomiphene, and GnRH challenge tests are more accurate predictors of IVF success than simply maternal age.   >> IVF with ICSI has allowed procreation in men with severe oligospermia and in azoospermic men after retrieval of sperm from the epididymis and testes.   >> Careful consideration should be given to transferring the fewest number of embryos possible without jeopardizing the outcome of an IVF cycle.   >> Donor oocyte IVF is very successful for women with ovarian failure, poor untreatable oocyte reserve, advanced maternal age, and genetic disorders.   >> The chance of successfully establishing a pregnancy following IVF increases significantly when more than one embryo is replaced into the uterus. In order to maximize the number of embryos available for replacement, regimes for superovulation have been developed to enable the recovery of multiple oocytes.

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