What is IVF?

From the fertility booklet The A.R.T. of Fertility: A patient guide
By the Fertility & IVF Center of Miami

An understanding of natural conception is important in order to understand in-vitro-fertilization (IVF). Normally, a woman will produce a mature egg each month. The egg (oocyte) is released from the ovary at the time of ovulation and transported to the fallopian tube. Usually, it is in the fallopian tube that it will encounter sperm and be fertilized. The fertilized egg develops into an embryo that will travel to the womb where it attaches and grows.

In IVF, the egg is collected directly from the ovary before ovulation and is fertilized with sperm in the laboratory. The fertilized egg will be incubated for a period of 3 to 5 days. The resulting embryo is then transferred into the uterus (womb) passing through a small canal, called the cervix, which can be accessed through the vagina.

There are also variations in the timing and method of transfer that may be appropriate for certain patients. How is IVF performed? The following are step-by-step descriptions of the IVF process.

Down-regulation

In order to begin the egg production (follicular recruitment) the pituitary gland, which controls the ovary, must be "quieted", so as not to "interfere" with the fertility drugs. There are two types of medications used for this purpose: GnRH (Gonadotropin Releasing Hormone) agonists and GnRH antagonists.

GnRH agonist

Lupron is an injectable drug that creates this state of suppression, medically termed "down-regulation". Lupron's immediate action is to stimulate the pituitary gland to release hormones that regulate the ovary, called follicle stimulating hormone (FSH) and luteinizing hormone (LH). With continued use of Lupron, the pituitary exhausts itself and a state of suppression is created.

Patients start daily injections of Lupron about 7 to 10 days before their expected period. To avoid an unexpected pregnancy while taking Lupron, it is very important to abstain from intercourse or use protection.

To avoid an unexpected pregnancy while taking Lupron, it is very important to abstain from intercourse or use protection the month before starting medications. You can discuss issues regarding abstinence with your physician.

In some patients, Lupron may be started on the second day of their period, to take advantage of the initial release of FSH and LH, in a technique called "Flare up". In both techniques, Lupron is continued daily in conjunction with gonadotropins until the follicular recruitment phase is over.

The cycle of IVF treatment begins with the onset of the menstrual flow. Patients attend the office for a baseline ultrasound and blood work. The ultrasound evaluation ensures the absence of cysts in the ovaries, and the blood work verifies low levels of the hormone estradiol. These results indicate to the physician that Lupron has achieved its goal of down-regulation.

GnRH antagonists

An alternative method of down-regulation involves the use of GnRH antagonists (Antagon or Cetrotide) . Shortly after the initial injection of Antagon or Cetrotide, a state of down-regulation is immediately achieved, in contrast with Lupron which takes several days to produce this effect. Therefore, GnRH antagonists are started after initiating stimulation of the ovaries with fertility drugs, rather than prior to menses. The purpose is to block the potential premature release of LH, which precipitates ovulation, thus allowing the gonadotropins to continue to stimulate the follicles to grow. Often, an oral contraceptive is utilized in the cycle prior to initiating a GnRH antagonist.

Follicular Recruitment

Eggs develop within a small sac of fluid within the ovary, called a follicle. While eggs are so small that cannot be seen without a microscope, follicles are easily visualized with the use of ultrasound imaging.

Once down-regulation has been ascertained, daily injections of gonadotropins will begin to start follicular recruitment. Examples of human-derived gonadotropins are Pergonal, Fertinex, Repronex, and Humegon; they contain a mixture of FSH and LH. A synthetic form containing pure FSH is most often used called Gonal-F or Follistim. Follicles respond to FSH by growing and producing the hormone estradiol. Typically, patients use daily injections of gonadotropins for approximately 10 to 12 days.

The goal of fertility drugs is to recruit as optimal a number of eggs as possible without over-stimulation of the ovaries. Therefore, careful monitoring of the patient's response to the medications is required. Monitoring involves ultrasounds performed through the vagina to visualize the number and size of the follicles. Blood is also drawn to assess the level of estradiol. This information allows the physician to modify the medication dosage, if needed, and to determine the extent of stimulation. Such monitoring visits start on the fourth or fifth day of gonadotropin injections, and continue throughout the course of medications.

Once the doctor determines that the follicles have grown sufficiently and estradiol levels are appropriate, Lupron and gonadotropin injections will stop. In preparation for egg harvest, the patient receives a single injection of a hormone called hCG (human chorionic gonadotropin), also called Ovidrel, Profasi, or Pregnyl. This injection is given at a specific hour since egg retrieval must be coordinated approximately 36 hours later.

Egg harvesting

Egg harvesting or retrieval is performed under sedation in a special suite in the Center . An anesthesiologist is present during the procedure to administer anesthesia into the patient's vein, similar to that which a dentist might use for wisdom teeth extraction. Once the patient is asleep, a needle, guided by an ultrasound, is inserted in the back of the vagina and into the ovary. All the visible follicles are aspirated, and the fluid obtained is taken to the laboratory. It is in the laboratory, that the embryologist will examine the follicular fluid to locate the eggs, and place them in the incubator. After the procedure, the couple is informed of the number of eggs retrieved. Recovery from the sedatives usually takes approximately one hour depending on the individual.

That same morning of the procedure, the male partner will provide the semen sample. He prepares by keeping a period of abstinence of at least 2 days but no more than 5 days. He provides the sample in the privacy of specially designed rooms in the Center furbished with printed material and movies. Once the semen sample is collected, it is analyzed, washed, concentrated, and later mixed with the eggs.

The interior of the uterus (endometrial lining) is prepared for the embryo transfer using Progesterone injections. Progesterone is a steroid hormone that prepares and maintains the endometrial lining in optimal condition to receive an embryo, and support a pregnancy. The daily injections of Progesterone begin in the evening the next day following the egg retrieval and continue until the 10th or 12th week of pregnancy.

Fertilization and Incubation

The following day ("day 1"), the embryologist examines the eggs under a microscope to verify that fertilization has taken place. Some eggs may not have fertilized. The fertilized eggs are kept in a special fluid called culture media. They will remain undisturbed in the incubator where they grow and divide into many cells. On "day 3" (three days following the retrieval of the eggs), the embryologist will examine the embryos and check the degree of development. This information will help the embryologist and the physician determine whether to transfer the embryos that same day, or wait two additional days until the embryos reach the blastocyst stage.

Embryo transfer
The embryo transfer takes place in a comfortable room while the patient lies on a special bed with stirrups. Anesthesia is not needed since only temporary, mild period-like cramping or no discomfort might be experienced. The partner or a family member can keep the patient company during the procedure. Use of strong perfumes should be avoided since it might be toxic to the embryos.

The morning of the transfer the embryologist and the doctor discuss with the patient the status of the embryos: the number of developed embryos, their quality, and number of cells of each one. A photograph of the embryos might be provided. At this point, the physician makes a final recommendation based on the patient's past history, age, status of the embryos, and the patient wishes regarding selective reduction. Then the couple and the doctor make a joint decision regarding the number of embryos to be transferred.

Prior to the transfer an ultrasound is performed through the vagina to chart the position of the uterus and measure the length of the cervix and the endometrial cavity.

The doctor begins the transfer by placing a speculum in the vagina to help him/her visualize and thoroughly cleanse the cervix. First, a very thin catheter or tube is introduced through the cervix and into the uterus to assess any difficulties placing the catheter. This trial gives the doctor an opportunity to choose a technique for the smoothest transfer. Once the trial is completed, the embryos are brought from the laboratory inside a similar catheter and then placed gently inside the uterus.

Following the transfer, the patient lies for approximately one hour and then is sent home to rest. Intense activities, strenuous exercises, extreme temperatures and intercourse should be avoided until pregnancy tests results are known. Two weeks following the retrieval of the eggs a blood pregnancy test is performed. If pregnant, the patient continues Progesterone injections and returns for a pregnancy ultrasound two and a half weeks later. Once the ultrasound confirms a pregnancy inside the uterus, the patient is then referred back to their obstetrician for continued care and delivery.



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