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 laparoscopic surgery for 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, egg quality or pelvic inflammation. It is also possible that the sperm can not get into the egg because of low sperm count and motility or thickened egg shell. What can be done now?

What is IVF?

IVF is 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 and a live birth.

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:

  1. Hysterosalpingogram or HSG (tubal X rays) within the past 2 years. When the tubes are found to be blocked at their ends (Hydrosalpinx), inflammatory secretions within the fallopian tubes may be find their way into the uterine cavity and adversely affect embryo implantation. Removal of the tubes is therefore recommended before embryo transfer.
  2. High complexity semen analysis to assess sperm concentration, motility and morphology, and a semen culture to check for the presence of bacteria.
  3. 3-D 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.
  4. 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.
  5. Ovarian reserve assessment. 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, estrogen 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.

The IVF Cycle

A typical IVF treatment takes about 4 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.

Ovarian stimulation Phase

Ovarian Stimulation Phase

The most common stimulation protocol for IVF utilizes an Antagonist such as Cetrotide or Ganirelix to suppress your pituitary and prevent premature spontaneous ovulation.
Ovarian stimulation typically begins of day 3 of your menstrual cycle. You will be taking fertiity hormone injections for approximately 10 days resulting in development of multiple follicles .
Follicle development and endometrial thickness will be monitored by ultrasound and blood tests. Daily antagonist injections will be initiated on day 6 of ovarian stimulation.

Ovulation Trigger

HCG or Lupron will be administered to trigger ovulation after 10 days of ovarian stimulation when the leading follicles containing the eggs reach a diameter of 20 mm. Lupron trigger is gradually replacing the Hcg trigger to minimize the risk of Ovarian Hyperstimulation Syndromm(OHSS).

The Egg Retrieval

The eggs are removed from the ovaries by a minor transvaginal ultrasound guided 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 egg retrieval you will be given medications to suppress your ovary. Expect to begin your menses in 10-14 days. Meanwhile all of your embryos will making it to day 5-6 in the laboratory will be frozen and transferred during next cycle.

After the Retrieval

We do not transfer fresh embryos so all embryos are frozen at the blastocyst stage. The frozen embryos will be thawed and transferred in the subsequent cycle.

This is done for the following reasons:

  1. The lining of the uterus (endometrium) is stimulated with estrogen level exceeding 10 times the natural estrogen production during natural or unstimulated cycle. The end result is that the uterine lining may be overdeveloped in comparison with the embryo and may adversely affect implantation.
  2. Patients may experience significant discomfort after the retrieval, so transferring embryos under such conditions may be stressful to the patient and affect implantation.

The IVF Laboratory

IVF Lab
IVF Lab

Fertilization In The Laboratory

The sperm

The sperm

The egg

The egg

The incubator

The incubator

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 a single sperm directly into each egg. This procedure is called Intracytoplasmic Sperm Injection or ICSI.

ICSI (Intracytoplasmic Sperm Injection)

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.

Microscope for ICSI

Microscope for ICSI

The ICSI process

The ICSI process

Embryo Development in the Laboratory

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.

Stages of Embryo development in the Laboratory

Zygote Stage

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 and abnormal development of the embryo.

8 Cell Stage (Day 3)

8 Cell Stage (Day 3)

As it appears 72-80 hours after fertilization. At BocaFertility transfer of two blastocysts on day 5 results in an overall delivery rate exceeding 50%.

Blastocyst Stage (Day 5-6)

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. In good prognosis patients (under 35 with good quality embryos) – a single embryo transfer (SET) may be considered.

Preimplantation Genetic Testing (PGT)

PGT 1
PGT 2

PGT is a genetic test performed on embryos produced during IVF. The test involve biopsy of embryos at the blastocyst stage corresponding to day 5-6 of embryo development in the laboratory. The biopsy utilizes sophisticated microscopic laser technology to remove peripheral cells, called trophectoderm, which are destined to become the placenta. The cells destined to become the fetus are not disturbed. Determining the genetic health of the embryos help select a healthy normal embryo for transfer into the uterus.

There are two types of embryo genetic tests:

  1. PGT-A (Preimplantation Genetic Testing for Aneuploidy) is a diagnostic test for screening the 23 pairs of chromosomes in IVF embryos to identify those with correct number of chromosomes (called euploid embryos). Embryos with incorrect number of chromosomes (aneuploid embryos) are less likely to result in successful pregnancy and not suitable for transfer.
  2. PGT-M (Preimplantation Genetic Testing for Monogenic or single gene defect). The test performed on IVF embryos to reduce the chance of having an affected child with a specific genetic disease, such as Cystic fibrosis.

Currently, routine screening all embryos (PGT-A) has not been proven to be of benefit in all patients. Concerns about routine embryo biopsy include:

  1. Risk of false positive results.
  2. It is estimated that 20-30% of embryos that might have implanted are lost as a result of the biopsy.
  3. The biopsy procedure adds to the cost of IVF and may result in lower cumulative pregnancy rate.
  4. The test is probably unnecessary in young women (under age 35) undergoing IVF, in women with limited number of eggs and in women over 40.

Preimplantation Genetic Testing is useful:

  1. For detection of a specific single genetic disorder, decreasing the risk of having an affected child.
  2. Recurrent Pregnancy Loss (RPL) attributed to incorrect number of fetal chromosomes, such as Down’s syndrome.
  3. Sex selection.

New promising non-invasive tests are currently being developed to avoid the risk of embryo biopsy. Here, DNA released by the growing embryo into the surrounding culture media in the petrie dish is tested to determine the genetic health of the embryo. The test avoids potential embryo injury as aresult of the embryo biopsy.

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 in the blastocyst stage of embryo development before embryo transfer or in preparation for embryo biopsy.

The Frozen Embryo Transfer Cycle (FET).

With your period after the egg retrieval you will begin taking Estrogen patches for about 2 weeks to prepare the lining of the uterus (endometrium) for embryo transfer. Blood estrogen level and ultrasound will be schedule to monitor your response to treatment. When your uterine lining is at least 7-8 mm, intramuscular progesterone shots will be administered for 5-6 days. The lining of the uterus is ready to receive the embryos. The embryos frozen on day 5-6 of development will now be thawed and loaded into a catheter in preparation for transfer.

The doctor will discuss with you the number of embryos to be transferred. In general only one is embryo is transferred in good prognosis patients (under age 35). Currently, our average number of embryos transferred per patient is 1.2.

You will be asked to sign consent forms for embryo transfer. Prior to the transfer you will be given valium to make you feel relaxed and decrease uterine contractions.. You will be given a photo of the embryos being transferred for your records.

The Embryo Transfer

The Embryo Transfer

You will be provided with a wrist band listing your name, birth date and last 4 digits of your social security. The staff will perform a brief time out to identify you and your embryos before proceeding with the transfer. The embryo transfer is not painful and takes only a moment to accomplish. A speculum will be placed in your vagina and the cervix will be cleansed with culture media. Abdominal ultrasound guided embryo transfer is then performed and you will be able to see the ultrasound imaging displayed on a large screen. The soft catheter preloaded with the embryo is carefully advanced into the uterine cavity and the embryo is gently deposited in the center of the cavity. The embryo within the center of endometrial cavity can be easily visualized (arrow).

For those interested in acupuncture, arrangements can be made ahead of transfer. Following the transfer, you will rest for 5-10 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.

Your pregnancy test will be performed 9 days after the embryo transfer.