In Vitro Fertilization (IVF)

FERTILITY TREATMENT

So you have tried “conventional” therapy for some time and have not been successful. You may have been treated with fertility drugs, undergone artificial insemination, or you may have had laparoscopy to treat scar tissue, fibroids or endometriosis. For one reason or another the egg and sperm are just not able to “meet “or implant in the uterus. The problem may be traced to tubal function, pelvic adhesions or scar tissue preventing release of the egg from the ovary. It is also possible that the sperm can not get into the egg because of low sperm count or structure or thickened egg shell. What can be done now?

What is IVF?

IVF is simply a process of fertilizing an egg with a sperm in the laboratory (in vitro) to form an embryo. The embryos are then transferred into the uterus to initiate a pregnancy.

What to expect before starting your IVF cycle

You may have already completed some of the required testing during your fertility evaluation. Your nurse will go over your file and will let you know what else may need to be done in preparation for IVF. The procedures or tests may include:

  • Hysterosalpingogram or HSG (tubal X rays) within the past 2 years.
  • High complexity semen analysis to assess sperm concentration, motility and morphology, and a semen culture to check for the presence of bacteria.
  • Sonohysterogram (Saline Infusion Sonography or SIS) to evaluate the uterine cavity to make sure there are no abnormalities, such as, uterine polyps or fibroids, which may interfere with embryo implantation.
  • Trial (“mock”) transfer will also be performed with your sonohysterogram. This is a “dress rehearsal” utilizing a soft embryo transfer catheter to make sure that there will be no problem transferring the embryos into the uterus during the IVF cycle.
  • Antral Follicle Count or AFC is an ultrasound evaluation to count the number of eggs present in your ovaries. This, together with other ovarian reserve markers (FSH and AMH) can help the doctor determine the dosage of hormone injections required to stimulate egg development. High AFC, high AMH and low FSH are usually predictive of good ovarian reserve

What is a Sonohysterogram or Saline Infusion Sonography (SIS)?

In this test, saline is injected in to the uterus while performing vaginal ultrasound to make sure that there are no uterine abnormalities (fibroids, polyps, scar tissue or uterine malformations) which may interfere with embryo implantation. The test takes only a few minutes to complete and is associated with little discomfort, if any

Abnormal test

Abnormal test: The uterine cavity has an irregular outline consistent with endometrial polyps (outlined in red and marked by white arrows).

Normal test

Normal test: The dark area within the uterus is the saline filling the uterine cavity. No abnormalities are seen

Trial transfer (mock transfer)

A trial transfer is performed together with the sonohysterogram.

The IVF Cycle

A typical IVF treatment consists of suppression and stimulation phases and takes about 6 weeks to complete. Your doctor will determine which stimulation protocol is best for you, taking into consideration your age, weight, and ovarian reserve assessment indicators, such as, day 3 FSH (Follicle Stimulating Hormone) level, Antral Follicle Count (AFC) and AMH (Anti Mullerian Hormone) level.

Stimulation Protocols

The most common stimulation protocols utilized for IVF are:

  • Long protocol – utilizing GnRH agonist such as Lupron; it is typically given after 14-21 days of oral contraceptive use (suppression cycle). The purpose of Lupron is to prevent ovarian cysts from occurring, and to block spontaneous ovulation during the stimulation cycle.
  • Microdose agonist protocol – In patients with high FSH levels, or previous poor response to stimulation with fertility hormone injections, the suppression phase of the treatment is omitted. The woman is treated instead with injectable hormones to stimulate ovulation beginning on day 2 or day 3 of the menstrual cycle in combination with low dose (microdose) Lupron.
  • Antagonist protocol – Here, Ganirelix or Cetrotide injections are given daily starting on day 6 of gonadotropin hormone injections or when the largest follicle is 14mm in size. Pretreatment with oral contraceptives may be used with this protocol at the discretion of the physician.

The Suppression Cycle

Typically involves oral contraceptive therapy for 14-21 days. During this time uterine evaluation and trial transfer can be performed before you begin the stimulation phase of the treatment. If uterine polyps or scar tissue are detected, minor surgery (hysteroscopy) can correct the uterine abnormality.

The Stimulation Cycle

Expect to take fertility hormone injections for about ten days. You will have several ultrasounds and blood tests to monitor the development of the eggs and the thickness of the uterine lining (endometrium).

  • Day 2-3 of cycle - You will have an estradiol level and a vaginal ultrasound, before you are cleared to start treatment, to make sure your ovaries contain no cysts which can interfere with proper egg development. You will continue with Lupron injections until the day before your retrieval.
  • Gonadotropin injections; you will be given daily hormone injections for about 8-10 days to stimulate your ovaries to produce multiple eggs.
  • Day 4 of hormone injections - An estrogen blood level is measured and the medication dose is adjusted accordingly.
  • Day 6 of hormone injections – begin a series of Estrogen level measurements and ultrasound evaluations of the number and size of your follicles (Fig. 2). The eggs are microscopic and invisible on ultrasound. We can tell, however, by the size of the follicles, whether the eggs are “mature” and ready for harvesting (retrieval).
  • The ultrasound examination also evaluates the thickness (solid white line) and pattern of the lining of the uterus (Fig.3). The lining of the uterine cavity should be at least 8mm thick with a trilaminar (three lines) appearance. This indicates that the uterus has been optimally prepared for embryo implantation.

fig. 1

fig. 2

fig. 3

The HCG injection

The HCG injection is given when the follicles (containing the eggs), reach 18-20 millimeter in size and the uterine lining is at least 8mm thick. The egg retrieval will take place about 35 hours later.

The Egg Retrieval

Egg Retrieval

Egg Retrieval

  • The eggs are removed from the ovaries by a minor transvaginal ultrasound surgical technique, performed in our in-office operating room suite. This takes about 15 min. to complete and is done using intravenous sedation administered by our board-certified anesthesiologist. Our operating room is certified by the American Association for the Accreditation of Ambulatory Surgical Facilities (AAAASF).
  • You will be going home about 30 minutes later, but plan on taking the rest of the day off.
  • After the retrieval you will be receiving daily progesterone treatment (injections or suppositories) until your pregnancy test 2 weeks after the retrieval. You may also be given Tetracycline (antibiotic) and Medrol (steroidal anti inflammatory) for 4 days to help the embryos implant.

Fertilization in the laboratory

The sperm

The Eggs

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 conventional fertilization, the sperm and egg are placed in culture media in a round dish. Typically, only one sperm penetrates the egg to initiate fertilization. When there are sperm abnormalities and the sperm cannot penetrate the egg, the embryologist can inject one sperm directly into each egg. This procedure is called Intracytoplasmic Sperm Injection or ICSI.

ICSI (Intracytoplasmic Sperm Injection)

The eggs will be checked 24 hours later to see how many of them were fertilized. You will receive daily briefing from the IVF nurse coordinator, informing you of the embryos development.

Utilizing ICSI or Intracytoplasmic Sperm Injection, a single sperm for each egg is all that is needed. Using microscopic techniques (micromanipulation) a single sperm is drawn into a very thin-tipped glass pipette. The tip of the pipette is inserted into the egg through the egg shell (zona pellucida) and the sperm is injected into the egg. This process is repeated for each egg. The eggs are returned to the incubator and are checked 24 hours later to see how many fertilized. About 70 – 80% of the injected eggs will fertilize normally to form a zygote.

Is ICSI for me?

When undergoing IVF you may be a candidate for ICSI:

  • If your partner has male factor.
  • If there was a poor rate of egg fertilization during your previous IVF cycle.
  • If only few eggs are retrieved.
  • Many centers routinely perform ICSI procedures on all the eggs. Some centers prefer “partial” ICSI during the first IVF cycle, when there is no male factor involved. Here, only half of the eggs are injected (ICSI), and the remaining eggs are allowed to fertilize conventionally (no ICSI). If there is normal fertilization in the non ICSI group of eggs, then ICSI may not be necessary. This significantly lowers the cost of treatment if you were to require another round of IVF. Keep in mind that Mother Nature may do a better job than the embryologist in selecting sperm to fertilize your eggs.

Embryo Culture

The eggs and sperm are placed in a dish containing culture media rich in nutrients essential for embryonic development. The dishes containing the eggs and sperm are placed in embryo incubators. A computer controlled system precisely regulates temperature, oxygen and CO2 levels within the incubators conducive for embryonic growth.

The eggs will be checked 24 hours later to see how many of them were fertilized. You will receive daily briefing from the IVF nurse coordinator, informing you of the embryos development.

Zygote Stage

The fertilized egg, as it appears 16-18 hours as after fertilization, showing the male and female genetic material (pronuclei) 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.

8 cell stage (Day 3)

As it appears 72-80 hours after fertilization. Generally, 2 embryos will be transferred into the uterine cavity. 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%.

Blastocyst stage (day 5-6)

The embryo as it appears five days after fertilization. The embryo is beginning to hatch out of its soft shell (white arrow) and is ready to implant. 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. In selected good prognosis patients (under 35 with good quality embryos) – a single embryo transfer (SET) may be considered

Preimplantation Genetic Diagnosis (PGD)

PGD is a diagnostic test for the detection of chromosomal abnormalities or single gene defects in the embryo. PGD is utilized most often in patients with genetic abnormalities, such as hemophilia or Cystic Fibrosis (CF), as a way to prevent transmitting the abnormal gene to their children. New technological advances allow for rapid detection of chromosomal or single gene defects in the embryos by doing the embryo biopsy at the blastocyst stage. The biopsy utilizes sophisticated microscopic laser technology to remove peripheral cells, called trophectoderm, which are destined to become the placenta. The cells are then analyzed by Comparative Genomic Hybridization (GGH). The cells destined to become the fetus are not disturbed. Only those embryos which are found to be normal are transferred into the uterus. The abnormal embryos are discarded. Any remaining normal embryos may be frozen for transfer at a later date. Currently, this procedure has not yet been proven to be of benefit for patients with repeated IVF failures, older patients or patients with recurrent miscarriages. Once this technology becomes more cost effective, all embryos may be routinely biopsied to avoid transfer of abnormal embryos.

What is Laser Assisted Hatching (LAH)?

Assisted hatching is a procedure, performed by the embryologist, to create a small hole in the envelope of the embryo utilizing high powered microscopy and a sophisticated laser beam. This is typically done on the fourth day (4-8 cell stage) or sixth day (blastocyst stage) of embryo development. At our center, Laser Assisted Hatching (LAH) may be performed for the following reasons:

  • Poor embryo quality
  • Previous failed IVF cycles
  • Patients older than 38
  • Diminished Ovarian Reserve (high FSH, low AMH or low number of eggs).
  • To prepare the embryos for biopsy. Assisted hatching is performed on day 3 of embryo development in preparation for biopsy 2 days later (blastocyst stage). Embryo biopsy is often performed to make sure that the embryo is chromosomally normal before it is transferred back into the uterus or frozen for future use.

Before Embryo Transfer

  • The doctor will discuss with you the number of embryos to be transferred. In general only one or two embryos are transferred 5 days after retrieval. Currently, our average number of embryos transferred per patient is 1.5.
  • We generally do not transfer embryos on day 3 because not all day 3 embryos will develop into blastocysts. Transition into blastocyst stage is a necessary step for successful embryo implantation. Typically, only 50% of good quality day 3 embryos will go on to develop into blastocysts. Therefore, we would rather follow the embryos to day 5 and see if they can make the transition to blastocyst. In our experience, blastocysts have better potential for implantation.
  • If less than 3 embryos are available on day 3, there is a small risk that no embryos will develop into blastocysts resulting in no embryo transfer. This result should be considered an early negative pregnancy test.
  • You will be asked to sign consent forms for embryo transfer and for freezing any remaining embryos.
  • Prior to the transfer you will be given valium to make you feel relaxed.
  • You will be given a photo of the embryos being transferred for your records.

The Embryo Transfer

Preimplantation Genetic Diagnosis (PGD)

A speculum will be placed in your vagina. The cervix will be cleansed with culture media 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. We do our transfers with your bladder empty to make it more comfortable for you. For those interested in acupuncture, arrangements can be made ahead of transfer.

Following the transfer, you will rest for 30-60 minutes before leaving the office. We recommend that you continue to take it easy at home for the next 24 hours, but it is not necessary to confine yourself to bed rest.

After the Embryo Transfer

  • Your pregnancy test (beta HCG) will be performed two weeks after your retrieval and you will be notified of the result within 1-2 hours. A positive result means that an embryo implanted and you will be instructed to continue with progesterone treatment (injections or vaginal suppositories) until the 12th week of pregnancy.
  • The HCG level should double every 48 hours or so in early pregnancy. A less than ideal rise in HCG level can sometimes indicate a possible miscarriage or tubal pregnancy. Therefore, your doctor may order the test every 2-3 days to make sure that the level rises appropriately.
  • You will be scheduled for an ultrasound about 4 weeks after your retrieval. The ultrasound will show how many embryos implanted, and display the baby’s heart rate pattern. The pictures below demonstrate a single intrauterine pregnancy at 9 weeks on the left and the baby’s heart rate on the right.

  • You will be referred to your obstetrician who will be taking care of you for the remainder of your pregnancy.

How Successful is Donor Egg IVF?

BocaFertility has a successful donor egg IVF program achieving a delivery rate above 60%.

To learn more about our donor egg IVF program call us at 1.844.207.0044