Every cycle of ART involves multiple steps, and each occurs at a specific time during a six-week period. The procedure begins around the time of ovulation in the month proceeding the ART cycle. Each patient will require a personal calendar for her individual schedule. The following is provided only as a general guide. Remember that you will be following an individual protocol designed specifically for you. This may differ from the protocol recommended to your friends or other women.
Cycle Preceding ART Cycle
1. Initiation of oral contraceptives or documentation of ovulation (mid-luteal)
2. Initiation of Lupron or other GnRH analog therapy
ART Cycle
1. Baseline pelvic ultrasound on cycle day 2
2. Ovarian stimulation with gonadotropins (e.g. Humegon®, Pergonal®, Metrodin®, Repronex®, Follistim®, Gonal-F®, and/or Fertinex®)
3. Monitoring follicle development with ultrasound and serum hormone levels
4. hCG administration (Profasi®, Pregnyl®, and Ovidrel®)
5. Transvaginal oocyte retrieval
6. Embryo transfer
7 Progesterone supplementation
8. Hormonal studies and pregnancy test
9. Follow-up consultation
Step 1 - Initiation of Oral Contraceptives
Some of you will receive oral contraceptives in the cycle prior to the ART cycle. This ensures that GnRH analog therapy will start at the proper time if you have irregular cycles. There is also evidence that oral contraceptive can help prevent ovarian cysts, which sometime develop during GnRH analog therapy. You will usually begin a pack of oral contraceptives on the Sunday after your normal period begins. Alternatively, we may prescribe Provera® or progesterone for patients who ovulate irregularly or not at all.
Step 2 - GnRH Analog Administration
You will begin treatment with a GnRH analog on the sixteenth day of oral contraceptive pills or the sixth day of Provera® progesterone, although this may vary. You do not need a pregnancy test before you start the GnRH analog.
We will instruct you to reduce the dosage of GnRH analog by one-half on the day you begin ovarian stimulation. You will use the GnRH analog until the day of hCG (human chorionic gonadotropin) administration.
We sometimes treat patients with a different dosage or schedule of GnRH analog. For example, the GnRH analog is begun during the cycle preceding stimulation in the "mid-luteal" protocol, after the start of menses in the "flare" or "micro-flare" protocol, or after six or so days of stimulation in the "GnRH antagonist" protocol. Your physician will advise you if these variations apply to you.
Step 3 - Baseline Pelvic Ultrasound
Around the time of your expected period, we will perform an ultrasound scan to examine the ovaries. If we detect a cyst, we may withhold therapy until the cysts resolve spontaneously (usually in about a week). Occasionally, we recommend cyst aspiration (drainage). This is a procedure in which your doctor inserts a fine need1e connected to a syringe, guided by ultrasound, into the cyst. We may also perform a serum estradiol measurement to confirm ovarian suppression.
Step 4 - Ovarian Stimulation
In general, we start ovarian stimulation after menstrual bleeding begins if the baseline ultrasound shows no significant cysts. We use several similar medications to stimulate follicle (egg) development. Humegon®, Pergonal®, and Repronex® are injected intramuscu1arly (into a large muscle under the skin). Lupron® and the GnRH antagonists, Gonal-F®, Repronex® and Follistim® may be injected just under the skin using a smaller needle.
Step 5 - Monitoring of Follicle Development
We monitor follicle development with a combination of vaginal ultrasound and hormone measurements (blood tests). We must perform these tests frequently during the ART cycle to ensure that you take the proper dosage of medication. We usually see patients every one to three days for an ultrasound and an estradiol level. This allows us to adjust the dose of medication in an effort to improve follicular development. When the largest follicle reaches 18 mm, we usually schedule daily visits for ultrasound exams and serum estradiol tests. The amount of medication we prescribe each afternoon depends upon the results of the blood tests and ultrasound exams. Typically, the lab results from the blood samples are not available until after 2:00 p.m. Patients must be available in the afternoon so that we can confirm the dosage of medication for that day.
Step 6 - Final Oocyte Maturation and hCG Administration
Human chorionic gonadotropin (hCG) is a hormonal drug that stimulates the final maturation of the oocytes. Determining the proper day for hCG administration is critical. If it is administered too early, few, if any, oocytes will be mature. If it is administered too late, the eggs within the follicles may be postmature (atretic) and will not fertilize. Optimal oocyte maturity occurs when we administer the hCG at the time when more than two follicles measure at least 20 mm and serum estradiol is greater than 500 pg/mL. The drug is given as a single intramuscular injection. The time of the injection is based on the time at which we schedule the egg retrieval.
Step 7 - Transvaginal Oocyte Retrieval
Oocyte retrieval is performed about 35 hours after hCG has been administered. An anesthesiologist usually administers intravenous medications (sedatives and pain relievers) in order to minimize the discomfort that may occur during the procedure. Side effects from these medications are much less common than with general anesthesia. Most patients sleep through the procedure but breath without assistance. A team member will discuss anesthetic options with you prior to your retrieval.
Once you are comfortable and relaxed, your physician will place the ultrasound transducer into the vagina. A guide attached to the transducer leads the needle through the wall of the vagina and into each follicle in the ovaries. Your physician will collect the oocytes and follicular fluid into a test tube for transport to the Embryology lab. The laboratory staff will examine the oocytes microscopically.
After the retrieval, you will be taken to a recovery room where you will be observed for 1-2 hours while the intravenous medications wear off. When you are fully awake, your vital signs are stable, and you have urinated, you will be released to go home. You may have some vaginal spotting and lower abdominal discomfort for several days following this procedure. Generally, patients feel completely recovered within 1-2 days. You should notify your physician immediately if you develop severe pain, heavy bleeding, or fever after the retrieval.
The number of oocytes retrieved is related to the number of ovaries present, their accessibility, and the number of follicles that develop in response to stimulation. Ultrasound provides only an approximation of the number of oocytes that one can expect to recover. On the average, 8-15 oocytes are retrieved per patient. More than 95% of retrievals result in the recovery of at least one oocyte.
Step 8 - Insemination of Oocytes
The Embryology laboratory staff examines the fluid aspirated from follicles for the presence of oocytes. We routinely aspirate all mature follicles in order to obtain as many oocytes as possible. Not every follicle contains an oocyte, and rarely, a follicle may contain more than one.
It is important to determine the maturity of the oocytes in order to time the insemination properly. The oocyte can only be fertilized during a short interval of about 12-24 hours. If the oocyte is either immature or postmature (too old), it may not be capab1e of fertilization or normal development. If immature oocytes are obtained at retrieval, they can sometimes be matured in the laboratory prior to insemination. Normal pregnancies have occurred with such oocytes.
Semen is usually collected by masturbation the morning of the retrieval. The staff will instruct you regarding time of collection and transportation to the office. On rare occasions, the laboratory staff may request a second semen sample . You must notify the staff beforehand if you are planning to leave town or will otherwise be unavailable after the first collection. We recognize the pressure that semen collection may generate under these circumstances. In many cases, some flexibility in the timing and even in the method of collection is possible. We also recommend semen cryopreservation (freezing) before oocyte retrieval as a backup or sometimes as the primary sperm source.
The laboratory staff prepares the semen specimen for insemination using techniques designed to separate the sperm from other material present in the ejaculate. As a result of this process, we select the most active sperm to inseminate the oocyte. We usually place about 10,000 sperm in a culture dish with each oocyte. The dish is placed into an incubator which maintains a specific temperature, pH, level of humidity, and concentration of carbon dioxide. After 12-20 hours, the laboratory staff may detect evidence of fertilization under the microscope. In our laboratory, approximately 70% of oocytes fertilize. This figure may be much lower for patients with severe male factor. It is extremely uncommon for couples without male factor infertility to experience complete lack of fertilization in IVF-ET.
Cycle Preceding ART Cycle
1. Initiation of oral contraceptives or documentation of ovulation (mid-luteal)
2. Initiation of Lupron or other GnRH analog therapy
ART Cycle
1. Baseline pelvic ultrasound on cycle day 2
2. Ovarian stimulation with gonadotropins (e.g. Humegon®, Pergonal®, Metrodin®, Repronex®, Follistim®, Gonal-F®, and/or Fertinex®)
3. Monitoring follicle development with ultrasound and serum hormone levels
4. hCG administration (Profasi®, Pregnyl®, and Ovidrel®)
5. Transvaginal oocyte retrieval
6. Embryo transfer
7 Progesterone supplementation
8. Hormonal studies and pregnancy test
9. Follow-up consultation
Step 1 - Initiation of Oral Contraceptives
Some of you will receive oral contraceptives in the cycle prior to the ART cycle. This ensures that GnRH analog therapy will start at the proper time if you have irregular cycles. There is also evidence that oral contraceptive can help prevent ovarian cysts, which sometime develop during GnRH analog therapy. You will usually begin a pack of oral contraceptives on the Sunday after your normal period begins. Alternatively, we may prescribe Provera® or progesterone for patients who ovulate irregularly or not at all.
Step 2 - GnRH Analog Administration
You will begin treatment with a GnRH analog on the sixteenth day of oral contraceptive pills or the sixth day of Provera® progesterone, although this may vary. You do not need a pregnancy test before you start the GnRH analog.
We will instruct you to reduce the dosage of GnRH analog by one-half on the day you begin ovarian stimulation. You will use the GnRH analog until the day of hCG (human chorionic gonadotropin) administration.
We sometimes treat patients with a different dosage or schedule of GnRH analog. For example, the GnRH analog is begun during the cycle preceding stimulation in the "mid-luteal" protocol, after the start of menses in the "flare" or "micro-flare" protocol, or after six or so days of stimulation in the "GnRH antagonist" protocol. Your physician will advise you if these variations apply to you.
Step 3 - Baseline Pelvic Ultrasound
Around the time of your expected period, we will perform an ultrasound scan to examine the ovaries. If we detect a cyst, we may withhold therapy until the cysts resolve spontaneously (usually in about a week). Occasionally, we recommend cyst aspiration (drainage). This is a procedure in which your doctor inserts a fine need1e connected to a syringe, guided by ultrasound, into the cyst. We may also perform a serum estradiol measurement to confirm ovarian suppression.
Step 4 - Ovarian Stimulation
In general, we start ovarian stimulation after menstrual bleeding begins if the baseline ultrasound shows no significant cysts. We use several similar medications to stimulate follicle (egg) development. Humegon®, Pergonal®, and Repronex® are injected intramuscu1arly (into a large muscle under the skin). Lupron® and the GnRH antagonists, Gonal-F®, Repronex® and Follistim® may be injected just under the skin using a smaller needle.
Step 5 - Monitoring of Follicle Development
We monitor follicle development with a combination of vaginal ultrasound and hormone measurements (blood tests). We must perform these tests frequently during the ART cycle to ensure that you take the proper dosage of medication. We usually see patients every one to three days for an ultrasound and an estradiol level. This allows us to adjust the dose of medication in an effort to improve follicular development. When the largest follicle reaches 18 mm, we usually schedule daily visits for ultrasound exams and serum estradiol tests. The amount of medication we prescribe each afternoon depends upon the results of the blood tests and ultrasound exams. Typically, the lab results from the blood samples are not available until after 2:00 p.m. Patients must be available in the afternoon so that we can confirm the dosage of medication for that day.
Step 6 - Final Oocyte Maturation and hCG Administration
Human chorionic gonadotropin (hCG) is a hormonal drug that stimulates the final maturation of the oocytes. Determining the proper day for hCG administration is critical. If it is administered too early, few, if any, oocytes will be mature. If it is administered too late, the eggs within the follicles may be postmature (atretic) and will not fertilize. Optimal oocyte maturity occurs when we administer the hCG at the time when more than two follicles measure at least 20 mm and serum estradiol is greater than 500 pg/mL. The drug is given as a single intramuscular injection. The time of the injection is based on the time at which we schedule the egg retrieval.
Step 7 - Transvaginal Oocyte Retrieval
Oocyte retrieval is performed about 35 hours after hCG has been administered. An anesthesiologist usually administers intravenous medications (sedatives and pain relievers) in order to minimize the discomfort that may occur during the procedure. Side effects from these medications are much less common than with general anesthesia. Most patients sleep through the procedure but breath without assistance. A team member will discuss anesthetic options with you prior to your retrieval.
Once you are comfortable and relaxed, your physician will place the ultrasound transducer into the vagina. A guide attached to the transducer leads the needle through the wall of the vagina and into each follicle in the ovaries. Your physician will collect the oocytes and follicular fluid into a test tube for transport to the Embryology lab. The laboratory staff will examine the oocytes microscopically.
After the retrieval, you will be taken to a recovery room where you will be observed for 1-2 hours while the intravenous medications wear off. When you are fully awake, your vital signs are stable, and you have urinated, you will be released to go home. You may have some vaginal spotting and lower abdominal discomfort for several days following this procedure. Generally, patients feel completely recovered within 1-2 days. You should notify your physician immediately if you develop severe pain, heavy bleeding, or fever after the retrieval.
The number of oocytes retrieved is related to the number of ovaries present, their accessibility, and the number of follicles that develop in response to stimulation. Ultrasound provides only an approximation of the number of oocytes that one can expect to recover. On the average, 8-15 oocytes are retrieved per patient. More than 95% of retrievals result in the recovery of at least one oocyte.
Step 8 - Insemination of Oocytes
The Embryology laboratory staff examines the fluid aspirated from follicles for the presence of oocytes. We routinely aspirate all mature follicles in order to obtain as many oocytes as possible. Not every follicle contains an oocyte, and rarely, a follicle may contain more than one.
It is important to determine the maturity of the oocytes in order to time the insemination properly. The oocyte can only be fertilized during a short interval of about 12-24 hours. If the oocyte is either immature or postmature (too old), it may not be capab1e of fertilization or normal development. If immature oocytes are obtained at retrieval, they can sometimes be matured in the laboratory prior to insemination. Normal pregnancies have occurred with such oocytes.
Semen is usually collected by masturbation the morning of the retrieval. The staff will instruct you regarding time of collection and transportation to the office. On rare occasions, the laboratory staff may request a second semen sample . You must notify the staff beforehand if you are planning to leave town or will otherwise be unavailable after the first collection. We recognize the pressure that semen collection may generate under these circumstances. In many cases, some flexibility in the timing and even in the method of collection is possible. We also recommend semen cryopreservation (freezing) before oocyte retrieval as a backup or sometimes as the primary sperm source.
The laboratory staff prepares the semen specimen for insemination using techniques designed to separate the sperm from other material present in the ejaculate. As a result of this process, we select the most active sperm to inseminate the oocyte. We usually place about 10,000 sperm in a culture dish with each oocyte. The dish is placed into an incubator which maintains a specific temperature, pH, level of humidity, and concentration of carbon dioxide. After 12-20 hours, the laboratory staff may detect evidence of fertilization under the microscope. In our laboratory, approximately 70% of oocytes fertilize. This figure may be much lower for patients with severe male factor. It is extremely uncommon for couples without male factor infertility to experience complete lack of fertilization in IVF-ET.
