In vitro fertilization (IVF), which literally means "fertilization in glass", is a treatment for infertility that has failed to respond to other medical and surgical interventions. The world's first IVF baby, Louise Brown, was born in 1978 in England. Since then, approximately 1,000,000 babies have been born as a result of IVF.
An IVF cycle has 6 phases: 1. Suppression 2. Stimulation 3. Retrieval 4. Fertilization 5. Transfer 6. Luteal Phase and Pregnancy
Pituitary Suppression -
In a natural menstrual cycle, hormones from the pituitary gland (LH & FSH) cause the growth of an egg within a fluid-filled space, or follicle, within the ovary. Although several follicles start to grow each month, in a natural cycle only one will become mature enough to ovulate following a surge of the hormone LH at midcycle.During the suppression cycle, you will be taking Lupron to prevent ovarian cysts and to block spontaneous ovulation during the stimulation cycle.
In contrast, during an IVF cycle it is desirable for several eggs to mature simultaneously. At the same time we do not want an LH surge to trigger early release of these eggs. We therefore use a medication known as a GnRH agonist to temporarily turn off your own LH and FSH secretion. This medication is usually started around day 22 of the menstrual cycle and continues through the stimulation phase. It is given daily, usually by nasal spray or occasionally by injection. Other GnRH agonist regimens or protocols may also be used in specific cases.
Below is what I found online about Lupron
Suppression Stage Lupron Depot (leuprolide acetate for depot suspension) is a GnRH agonist -- a hormone that works in two distinct phases. Phase one stimulates the ovaries causing them to produce more of the most potent of the three estrogens produced by women -- estradiol. In phase two the messenger hormones that tell the ovaries to produce estrogen decline dramatically. This causes a significant reduction in estrogen levels, and causes women to experience menopause-like side effects.
During the suppression stage of the IVF cycle, you take a GnRH Agonist (Lupron, Suprefact, Synarel etc.) to suppress your ovarian function.
The average length of time it takes to get suppressed is 10-12 days. .
The side effects from the suppression medication are similar to that of going into menopause. Some women are very sensitive to the effects of the medication while others experience hardly any changes. I may experience some of the following side effects below.
mood swings breast tenderness hot flashes headaches changes in sex drive
Leuprolide is an injectable, man-made hormone that is used for treating prostate cancer, endometriosis, central precocious puberty, and fibroids. It is similar to but stronger than human gonadotropin releasing hormone (GnRH).
GnRH is made in the hypothalamus (a part of the brain)and travels to the pituitary gland where it causes the production of luteinizing hormone (LH) and follicle stimulating hormone (FSH). LH and FSH are released by the pituitary into the blood and stimulate the production of testosterone by the testes in men and estrogens by the ovaries in women. The release of GnRH, LH and FSH is governed by negative feedback which means that when there is too much testosterone or estrogen being produced, the body sends a signal to the pituitary gland to reduce the production of GnRH which, in turn reduces the production of LH and FSH. This results in reduced production of testosterone and estrogen. When given continuously, leuprolide initially increases the production of LH and FSH as well as testosterone and estrogen; however, after a few weeks of continuous leuprolide, the levels of LH and FSH drop because the pituitary gland stops responding to GnRH and leuprolide. This leads to a decrease in the production of estrogen and testosterone.
Testosterone promotes the growth of prostate cancer. Therefore, leuprolide is used in treating prostate cancer to slow the growth of the cancer. In children with central precocious puberty (puberty caused at an early age because of too much LH and FSH) leuprolide, by suppressing LH and FSH, reduces the levels of estrogen and testosterone and allows for more normal timing of puberty. Estrogens promote the growth of fibroids (benign tumors of the uterus) and areas of endometriosis (abnormal uterine tissue that exists outside of the uterus). Leuprolide is used to reduce the production of estrogen and treat both fibroids and endometriosis.
Stimulation Phase
During this very important phase of the IVF cycle, patients receive daily (occasionally twice daily) injections of gonadotropins – hormones, which stimulate the ovaries to produce multiple eggs. The common names for these gonadotropins are Follistim and Repronex. The “stim” phase of the cycle lasts on average 10 days, but can vary from 8 to 12 days, are necessary. At each visit blood will be drawn to study the change in the hormones and a vaginal ultrasound will be performed to note the progression of the ovarian follicles.
The staff will make frequent reference about follicles – their number and size. Within each follicle is an egg. The egg is very small and cannot be seen on ultrasound. The fluid filled follicle surrounding the egg, however, is much larger and because fluid stands out on ultrasound, it is very easy for us to locate, count and measure the size of each follicle. Most importantly, the size of the follicle correlates with the maturity of the egg! The larger the follicle, the nearer the egg to being ripe and ready for harvest (a procedure we refer to as follicle aspiration, or retrieval). The egg within a follicle is usually mature – and ready for harvest- when the follicle measures between 16 and 20 millimeters.
Just before stimulation begins the follicles are usually small and often not visible and Estradiol (estrogen) levels are low. Large follicles (greater than 12mm) or elevated Estradiol levels at the start of stimulation usually indicates that a woman is not truly at day 3, and often necessitates postponing the cycle. A suppression check (a blood test and an ultrasound) is done in the days prior to the start of stimulation to ensure that all is ready. As stimulation progresses through the early stages (the first 5 days) the follicles usually show only minimal growth, but estrogen levels (measured as Estradiol) start to increase.
Soon thereafter, the follicles start to grow and once they reach about 12 to 14mm, they will grow fairly predictably at a rate of 2mm per day. During this phase of growth you will be monitored closely, sometimes as often as daily. The Doctor reviews lab results and follicle sizes after each visit. The nurse also calls all of their patients later in the day to update them on any medication changes that need to be made. Frequently, the combined results of the ultrasound and the lab work will necessitate either slowing the cycle down (decreasing the dose of medication) or speeding it up (increasing the medication).
One of the problems in the early days of IVF was that dramatic rise in Estradiol would cause the eggs to “ovulate”, that is, to be released from the ovary. Once released, the egg can no longer be retrieved, and entire cycles were ruined. When Lupron became available, daily injections of this medication were found to suppress the tendency toward premature ovulation, thus allowing longer cycles and better quality eggs. For years, Lupron has been an essential part of the stimulation phase of IVF.
Ovarian Stimulation After about 2 weeks of pre-treatment with the GnRH agonist, we add daily injections of FSH & LH (known as Pergonal, Puregon or Gonal F). The injections continue for about 12-14 days. The amount of FSH & LH used is somewhat higher than you would produce on your own. This is what stimulates the growth of several follicles, instead of just one. The response of the ovaries is monitored with frequent blood tests and ultrasounds. These are done between 8:00 and 9:00 each morning. Most women learn to give their own injections in order to reduce the number of clinic visits. You will be taking fertility shots for about ten days to stimulate multiple eggs to develop. You will continue to take Lupron all this time and you can expect several ultrasounds and blood tests to monitor the development of the eggs. Women can respond differently to the fertility drug injections and may need adjustment in the amount of medications taken.
Follistim AQ Cartridge acts like naturally produced follicle-stimulating hormone (FSH), the hormone that stimulates the ovaries. It binds to the surface of the immature follicle to trigger a series of events that lead to the growth of the follicle and the maturation of the egg. Follistim® AQ Cartridge (or other drugs containing FSH) will not induce ovulation. For ovulation to occur, a second hormone called Pregnyl® (chorionic gonadotropin for injection, USP) is administered. Pregnyl® acts like luteinizing hormone (LH) to induce ovulation and release the mature egg from the follicle.
Follistim AQ Cartridge is administered as a subcutaneous injection (under the skin) using the Follistim Pen. You load a pre-mixed, pre-filled Follistim AQ Cartridge containing the medication into the Follistim Pen, dial up your exact dose and give yourself an injection.
Follistim AQ Cartridge is usually administered once daily. The recommended daily dose is 75 IU or lower for patients undergoing ovulation induction, with a maximum daily dose of 175 IU. A 150 to 225 IU starting dose, with a maximum daily dose of 450 IU, is recommended for the first 5 days of treatment for patients undergoing controlled ovarian hyperstimulation for IVF.
Before beginning therapy, your doctor will explain the standard tests and monitoring procedures that he or she will use to track your progress. It is very important that you keep all your appointments during therapy since infertility treatments require precise timing of hormone injections and induction of ovulation. Delays may lead to cancellation of the treatment cycle or complications.
Your doctor will monitor your progress in two ways:
1. By measuring your blood levels of estrogen. As the follicles grow and respond to Follistim® AQ Cartridge, they release estrogen. A rise in your serum estrogen levels indicates that the follicles are developing. 2. By performing ultrasound scanning or ultrasonography. Ultrasound scanning allows your doctor to see the developing follicles and assess their stage of maturation. These monitoring techniques decrease the chance of complications and multiple births.
The following side effects have been reported in clinical studies with Follistim® AQ Cartridge: abdominal pain, flatulence, nausea, breast pain, injection site reaction, enlarged abdomen, back pain, constipation, headache, ovarian pain, ovarian hyperstimulation syndrome (OHSS), sinusitis, and upper respiratory tract infection.
Repronex
Each vial/ampule contains 75iu of equal amounts of human FSH (follicle stimulation hormone) and LH (luetinizing hormone) Purpose
Promotes both growth and maturation of developing follicles. Side Effects
With careful monitoring of blood hormone levels and follicle growth by ultrasound, side effects are minimal but can include the following:
Headache Mild to moderate ovarian enlargement Abdominal bloating or discomfort Temporary weight gain Nausea Insomnia Changes in mood
HCG Injection (Trigger Shot)
Ovidrel
This medication is given when the follicles (eggs) reach about 20 millimeter in size. The egg retrieval is scheduled about 34 to 36 hours after the HCG injection
Egg Retrieval
Once the blood tests and ultrasounds indicate a reasonable size and number of follicles, an injection of hCG is given. This hormone causes the final maturation of the egg and loosening of the egg from the wall of the follicle. The egg retrieval occurs on the second morning after this final injection (34-36 hours later).
The egg retrieval is performed by an ultrasound guided needle puncture through the top of the vagina. Local anesthetic (freezing) is placed in the top of the vagina. A short-acting intravenous medication is given for pain control. Relaxation techniques can also be helpful. Your partner is encouraged to be with you during the egg retrieval. The fluid is drained from each follicle and examined under a microscope. Not every follicle contains an egg, but at least half of the large follicles will usually yield eggs.
The eggs are removed from the ovaries by transvaginal ultrasound technique. This minor surgical procedure is performed in our certified in-office operating room suite. The procedure takes about 15 min. and is performed under intravenous sedation given by our board-certified anesthesiologist. You will be going home about 30 minutes later. You may feel tired afterwards, so plan on taking the rest of the day off.
Fertilization
The sperm sample is washed and concentrated, then added to the eggs a few hours after retrieval. The eggs are examined the next day for signs of fertilization. Not all of the eggs will fertilize, but we expect about 70-80% of the eggs to fertilize if the sperm sample looks normal. The fertilized eggs are kept in the incubator for an additional 48 hours. Not every follicle will contain an egg, not every egg will fertilize, and not every egg that fertilizes will go on to form a good quality embryo.
Now that your eggs have been removed from your ovaries, the next step is for the embryologist to prepare your eggs and your husband’s sperm for fertilization. In cases where the sperm cannot penetrate the egg because of low sperm count, abnormally shaped sperm or low motility, the embryologist will inject one sperm directly into each egg. This procedure is called Intracytoplasmic Sperm Injection or ICSI.
Assissted Hatching
Just prior to implantation, the developing embryo must "hatch" out of its outer shell (zona pellucida). Some embryos seem to have a thicker shell that may decrease their ability to implant. This may be due to the age of the woman or other unknown reasons.
Assisted hatching is done just prior to embryo transfer, usually on the morning of the third day after egg retrieval. The embryos have usually grown to six or eight cells at this stage. A fine needle is used to puncture the zona pellucida. There is little or no risk of damaging the embryo during the hatching procedure.
Assisted Hatching is done in situations where it is expected to have a thickened zona pellucida, or have had difficulties achieving implantation, such as:
o When the woman is 38 years or older o When we are using cryopreserved (frozen/thawed) embryos
With assisted embryo hatching a small opening is created in the outer shell of the embryo just prior to embryo replacement.
Embryo culture
Once fertilization occurs, the embryologist will monitor the fertilized eggs for three to five days to make sure that they develop normally.
Stages of embryo development in the laboratory
1. Zygote - the fertilized egg, as it appears 16-18 hours as after fertilization, showing the male and female genetic material (pro nuclei) is called a zygote. Sometimes more than one sperm can penetrate the egg resulting in an abnormal zygote which will not be transferred into the uterus.
2. 8 cell stage embryo - as it appears 72-80 hours after fertilization. Generally, 2 embryos will be transferred into the uterine cavitry. If more than 3 such embryos are available, your doctor may choose to allow them to grow two more days in the laboratory to a blastocyst stage. At BocaFertility transfer of two blastocysts on day 5 results in an overall delivery rate exceeding 50%.
3. Blastocyst - the embryo as it appears five days after fertilization. Since implantation rate for blastocysts is significantly higher than day 3 embryos, only 2 blastocysts need to be transferred minimizing the risk of multiple pregnancies.
Embryo Transfer
Three days following egg retrieval, the fertilized eggs (embryos) are transferred to the uterus using a fine plastic tube (transfer catheter). The exact number transferred will depend on a woman's age and embryo quality. This procedure takes only a few minutes and is usually not uncomfortable. Everyone involved with IVF treatment will be offered the option of cryopreservation. Many couples, however, will not have enough extra embryos suitable for freezing. The best quality embryos (those most likely to result in pregnancy) are usually transferred in the treatment cycle. To be selected for freezing, embryos must not show any signs of fragmentation (cell breakdown) or abnormal development. Obviously, not all embryos will meet these criteria.
The doctor will discuss with you the number of embryos to be implanted. At BocaFertility we usually transfer the embryos on day 5 at the blastocyst stage. The advantage of blastocyst transfer is that only 2 embryos need to be transferred to achieve a very good pregnancy rate, minimizing the risk of multiple pregnancies. Prior to the transfer you will be given valium to make you feel relaxed. You will be given a photo of the embryos transferred for your record.
A speculum will be placed in your vagina and the embryos will be gently transferred into a predetermined site within your womb using a very soft catheter. The transfer of the embryos is not painful and takes only a moment to accomplish.
Following the transfer of embryos, you can expect to rest for a few minutes some offices is about an hour before leaving the office. Many offices recommend that you continue to relax at home for the next 24 hours.
Luteal Phase and Pregnancy
You will be encouraged to limit your activity for 24 hours after the embryo transfer. Your activity can be gradually increased over the next few days to non-strenuous, non-aerobic activity. Many women return to work after a few days if their jobs are not strenuous. After a 16-days, a blood test will determine whether a pregnancy occurred.
Pregnancy test Your pregnancy test will be scheduled two weeks after your retrieval and you will be notified of the result within 1-2 hours. A positive result indicates that an embryo implanted and you will be scheduled for an ultrasound about 2 weeks later. The ultrasound allows the doctor to document the number of embryos implanted and to check the baby’s heart rate. At this time you can expect to be referred to your obstetrician who will be taking care of you for the remainder of your pregnancy.