What does the IVF process involve?

ivf process

The IVF Process At-A-Glance

In vitro fertilization (IVF) is a fertility treatment that involves combining eggs and sperm outside the body in a laboratory setting. Once an embryo or embryos form, they are then placed in the uterus. Below, we explain how in vitro fertilization is performed.

1. Preparing the Ovaries

Their natural activity is suppressed with an injectable medication in the month preceding the IVF cycle, in order to make them more responsive to stimulation.
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2. Ovarian Stimulation

The ovaries are stimulated over a 10 to 12 day period with injectable fertility medications to produce multiple mature eggs during the cycle.
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3. Egg Retrieval

Under sedation anesthesia, the eggs are aspirated through a needle attached to the ultrasound probe. The needle passes through the vaginal wall to reach the ovaries.
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4. Insemination and Fertilization

In standard IVF, the mature eggs are combined in the laboratory with a processed sperm sample from the husband or donor. For most patients, intra-cytoplasmic sperm injection (ICSI) is advisable: the fertilization rate is much better because one sperm is injected directly into each egg. This service is part of the IVF cycle fee.
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5. Embryo Culture and Development

The fertilized eggs are allowed to develop in the laboratory for at least 3 days, by which time healthy embryos would reach at least the 8-cell stage. If the embryos appear capable of developing further on their own before being placed into the uterus, they may be cultured for another 2 days for a Day-5 transfer – the best embryos will have developed into blastocysts, the stage at which the embryo migrates normally to the uterus from the fallopian tube in a conventional pregnancy.
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6. Embryo Transfer

Three to five days after egg retrieval, healthy embryos are placed into the uterus with a thin catheter introduced through the cervix. This is a simple, painless, non-surgical procedure.
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7. Luteal Support

After the transfer, progesterone (the natural pregnancy-maintaining hormone) is given by injection and/or vaginal suppositories to better prepare the lining of the uterus for a possible pregnancy. Estrogen tablets are also given to enhance progesterone action.
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8. Pregnancy Test

12-14 days after embryo transfer, a serum pregnancy test will determine if conception has occurred.
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Learn more about the IVF process at New York Fertility & IVF Surgery Associates below, or request an appointment today using the form on this page.

The IVF Process in Detail

Your IVF process begins in the month that precedes your IVF treatment cycle itself (i.e., from stimulation to embryo transfer). You may be asked to take a birth-control pill for better control of timing (especially if your cycles are highly irregular). The pill also helps prevent the development of ovarian cysts which would interfere with stimulation.

1. Preparing the Ovaries

During the last four days that you are taking the pill, you will start a daily injectable medication of leuprolide acetate (a generic name for Lupron) which you will continue until just before your eggs are retrieved for IVF (a total of about 21 days).

Patients who do not require pill regulation usually start Lupron seven days after ovulation in the pre-IVF cycle (determined by a progesterone level greater than 3 at mid-cycle). Example: If you are planning to have your IVF procedures done in January, you will begin to take Lupron after you ovulate in December.

About Lupron (leuprolide acetate)
Leuprolide is a synthetic analog of the hormone GnRH (gonadotropin-releasing hormone) produced in the hypothalamus of the brain. GnRH is the master reproductive hormone because it allows the entire reproductive process to take place when it is produced and released in the appropriate amount. Too much of it suppresses its function, and too little will not produce its effect. As the name implies, GnRH regulates the release of the gonadotropins FSH and LH from the pituitary.

Lupron and similar GnRH analogs are administered before IVF, increasing the daily GnRH present in your body in order to temporarily suppress its action, (i.e., suppress the release of FSH and LH). Since FSH and LH regulate the activity of your ovaries, their temporary suppression will also produce temporary inactivity in your ovaries.

This short period of ovarian inactivity or quiescence during the last days of your pre-IVF cycle will make them more responsive to stimulation by the FSH and LH contained in fertility medications that you will take during the IVF cycle.

Lupron is continued into the IVF cycle until just before egg retrieval, because during your stimulation, it will prevent the possibility of premature ovulation before your eggs can be retrieved in the IVF process. Lupron will prepare you for ovarian stimulation during the actual IVF cycle by suppressing the activity of your ovaries before your next cycle begins, so they will better respond to stimulation.

You will be taught by your doctor or one of our clinical coordinators how to inject yourself with Lupron and the other injectable medications you will be using.

Administering Lupron
Lupron is injected with a very thin, small needle that is injected just under the skin (subcutaneous, or sub-Q) on the surface of the thigh.

  • Fourteen syringes and needles are provided with the Lupron kit, similar to the syringes used for insulin injections.
  • Because you start daily Lupron injections several days before your period begins, and will continue them during the IVF cycle itself until just before egg retrieval, you will need more than 14 syringes, so we always order an additional 10 syringes.

Although the Lupron kit is labeled a 2-week kit, you will have much more than you will actually need, because we prescribe a daily micro-dose of 0.05 ml rather than 0.5 ml. We have found that the micro-dose works just as well to suppress ovarian activity as the larger dose, which is more likely to cause side effects.

Side effects of Lupron
Side effects can be hot flushes, mild headaches, and/or vaginal spotting. These are all possible normal effects from this medication. Most patients do not experience any side effects.

In the unlikely event that you were pregnant at the time you start Lupron, you would discontinue it as soon as this is discovered so that your ovaries can resume normal functioning and produce pregnancy-supporting hormones.

You may expect to get your period within 5-10 days after you start Lupron.

  • If you do not get a period within 10 days, we will advise blood tests to determine whether and when you may expect to get your period and to rule out pregnancy.
  • He will advise you on your next step, depending on the blood results.

Antagonist alternative to Lupron protocol
Some patients may benefit from an antagonist protocol instead of Lupron to prevent premature ovulation. In this, all the IVF medications are taken during the IVF cycle, starting from Day 3 of the cycle. If the patient has no ovarian cysts and her Day 2 hormone levels are normal, ovarian stimulation is started on Day 3.

The patient will be monitored with blood and ultrasound after the first three days of stimulation to see when she should start with the antagonist (Cetrotide or Ganirelix), which is also an injectable medication available in pre-prepared syringes containing the single daily dose. The antagonist must be started when the estradiol level reaches 200 and/or one or two follicles reach an average diameter of 10mm. The antagonist will be taken along with the stimulation meds until just before egg retrieval.

2. Ovarian Stimulation

The ovaries are stimulated with injections of the natural hormones that cause ovulation in order to produce multiple follicles – each containing an egg – during the IVF cycle.

If the retrieved egg fertilizes normally and the resulting embryo develops appropriately in the 3-5 days before it is placed in your uterus, then poor ovarian reserve and poor sperm quality are not among the current factors causing your infertility. For the majority of IVF patients, however, ovarian stimulation – whether at a regular dose or minimal dose – is an essential part of the IVF process.

Once you get your period, your doctor will see you on Day 2 or Day 3 to draw blood for your baseline hormone levels and to assess your ovaries by ultrasound.

Before you can start stimulation, it is important to show that:

  • Your hormone levels are suppressed by Lupron; FSH and LH should have values <10; E2 should be <50.
  • You have no ovarian cysts larger than 15 mm, which can interfere with stimulation.
  • If you are 37 years or older, we will also want to see at least four follicles (sacs containing the egg cell) in the ovaries at the start of the cycle.

Most patients generally are able to proceed to stimulation at this time. In any case, we will tell you when to start the medications for stimulation and in what doses.

A typical stimulation protocol consists of daily injections of gonadotropin preparations over 10-12 days.

  • These gonadotropins are follicle-stimulating hormone (FSH) and luteinizing hormone (LH) produced by the pituitary gland in the brain.
  • In the natural cycle as well as in stimulated cycles, FSH mainly causes follicles to grow, and LH activates the egg for ovulation.

Natural cycle (unstimulated) IVF
Women who are poor responders by history or because of age, generally will not produce more than 1-2 eggs even at high stimulation doses. Provided their baseline cycle hormones are appropriate, an option for them is to try natural-cycle IVF which does not require any stimulation.

The option is not advisable for women with baseline FSH >10 and/or baseline estradiol >50, and a low level of anti-Mullerian hormone (AMH), because, regardless of the patient’s age, such values indicate decreased ovarian reserve (the pool of egg cells left in the woman’s ovaries are not just fewer in number, but also less responsive to natural or medication-induced stimulation for ovulation).

In natural-cycle IVF:

  • IVF is performed using the single egg that a woman normally produces in a natural cycle.
  • The chances of pregnancy are less than with stimulated IVF only because only one embryo can be obtained, whereas stimulated IVF.would result in more embryos given a chance to implant and produce
    a conception.
  • The benefit is that the patient does not incur the cost of stimulation medication, which is one of the major costs in an IVF procedure.

Natural cycle IVF can also indicate the quality of the eggs you are capable of ovulating at this particular time in your life. If the egg fails to fertilize or results in an embryo that develops poorly, this would be a direct indication of poor ovarian reserve. Your options would be to try stimulated IVF or donor egg IVF.

About fertility medications
Fertility medications used for ovulation induction or ovarian stimulation are concentrated preparations of the natural hormones FSH and LH that can only be injected. They cannot be taken orally (by mouth) because the acidity in the stomach will break them down before they can act.

Fertility medications used to be obtained by concentrating FSH and LH from the urine of menopausal women, who produce high levels of these hormones. Pergonal and Metrodin belong to this first generation of commercial gonadotropin preparations.

Today, recombinant forms, like Gonal-F and Bravelle (obtained by replicating the biochemical components of FSH and LH), and highly purified concentrates, like Follistim, Humegon, and Repronex, are used.

  • Gonal-F, Bravelle, and Follistim are pure FSH preparations.
  • Menopur, Humegon, and Repronex contain both FSH and LH.

In our current protocol for ovarian stimulation:

  • Pure FSH (Gonal-F or Bravelle) is used for the first 4-5 days of stimulation
  • Menopur is added in the last few days.

Your daily dosages will depend on your response to the medications, as determined by:

  • Rising level of estrogen (E2)
  • Number of developing follicles
  • Rate of increase in both E2 and in follicle sizes

The fertility medications for stimulation are injected the same way as Lupron.

  • Gonal-F and Follistim are available in pre-loaded ready-to-inject syringes good for multiple doses, but they also come in single doses of 75 IU strength, like all the other brands.
  • In the usual single dose form, each dose comes as a powder in a vial, which has a companion vial containing the liquid to dilute the powder.
  • Your doctor or one of the coordinators will instruct you how to dilute the powder for your daily injection dose.

The purpose of these medications is to stimulate as many follicles as possible to produce a mature egg during this one cycle, in the hope that at least 8 mature eggs will eventually be retrieved from your ovaries.

What happens during ovarian stimulation
Follicles are egg-bearing sacs in the ovaries. In women of reproductive age, each ovary contains hundreds of thousands of follicles, but during a regular menstrual cycle (without stimulation), only a few will be ‘recruited’ — on the basis of their response to FSH — for development during the cycle, and only one of them will ovulate a mature egg.

The recruited follicles, called antral follicles, may be seen on ultrasound at the start of the cycle because they will be at least 5 mm in diameter. The number of antral follicles seen in a natural cycle is now considered a good predictor of response to stimulation. The egg itself is about one-tenth of a millimeter in diameter and is not visible on ultrasound.

Of these antral follicles, usually only one follicle – called the dominant follicle – will develop enough to mature the egg which will be ovulated in a natural cycle.

  • Just before ovulation, the dominant follicle will measure about 2 cms in diameter.
  • The dominant follicle did better than all the other antral follicles in utilizing available FSH and LH in order to produce a mature egg.
  • The other antral follicles will simply be absorbed into regular ovarian tissue without further reproductive function.

With stimulation, multiple follicles will respond to the FSH and LH provided by the medications.

  • Several follicles – up to 30 in some patients who have polycystic ovary syndrome – will grow simultaneously, although not always at the same rate.
  • Generally, we like to see at least 8 developing follicles.
  • At the time of egg retrieval, only those follicles which have a diameter of 18 mm or more are likely to contain a mature egg.

Within the follicle, the egg cell is surrounded by granulosa cells which produce the follicular fluid with the nutrients that support the development of the egg from recruitment until maturation and the ovarian hormones estrogen and progesterone. During stimulation, the dominant hormone produced is estradiol (E2), the primary form of estrogen in non-pregnant women. This is the hormone that is measured daily during your stimulation for IVF.

Your daily stimulation dose of gonadotropin is based on predicting how your ovaries will respond and usually varies from one vial (75 IU) to six vials (450 IU) a day. Women who are very sensitive to the medication need only a small amount of gonadotropin, while those who are resistant require more. A patient who does not respond well even with six vials a day of gonadotropins should consider natural-cycle IVF after she fails to get pregnant with high-dose stimulation, provided her baseline FSH. E2 and AMH are appropriate.

The medications are usually administered for a period of 10-12 days, during which you will be seen at least 4-6 times after your baseline visit to monitor your response to the medication and adjust your dose if necessary.

Monitoring your response to ovarian stimulation
Your response is measured by a blood test to determine the level of estradiol, E2, which is a measure of follicle activity. In addition, an ultrasound will be used to follow the number and size of developing follicles.

Generally, after the baseline visit, you will next be seen 2-3 days after you start the medications for stimulation. After that, you may be seen every two days, depending on how appropriately you are responding. Women who have polycystic ovary syndrome (PCOS) may be seen more often, especially in the early days of stimulation, because they tend to over-respond to the medication, and we can adjust their dosage down as needed.

For women with regular cycles, the first 4-5 days of stimulation are generally ‘slow’ in terms of E2 and follicle sizes. But once the follicles reach 10mm in diameter, they should start growing at the rate of 2mm every day, especially if your E2 starts to rise above 200.

The last step before egg retrieval
When 2 or more follicles are 18mm in average diameter, you will be ready for HCG (human chorionic gonadotropin), another hormone injection which helps to mature the egg cells before they are taken out, or with a 1ml dose of Lupron. Lupron rather than HCG is the preferred trigger for patients who have very high estradiol levels or more than 20 developing follicles in order to avoid the development of ovarian hyperstimulation syndrome (to be discussed later).

  • HCG is the hormone produced by the embryo or fetus. Its structure is similar to LH and can, therefore, act like LH does in the natural cycle to complete maturation of the egg. LH itself is not given in order to prevent premature ovulation.
  • HCG is injected intramuscularly into the fleshy part of the buttocks) about 32-36 hours before egg retrieval. Lupron is injected subcutaneously.
  • We will tell you what time to take this injection. It is very important that you take it at the right time.

After the HCG or Lupron injection, you will not take any more medication until after egg retrieval.

Like the medications you used for stimulation, HCG also comes as a powder with a vial of liquid.

  • Using the same kind of syringe and needle you use to prepare your Gonal-F, Bravelle or Menopur, you will only need 1 cc of the liquid to inject into the powder.
  • After all the powder has dissolved, you will take the liquid back into the syringe. Unless we instruct otherwise, you will use the whole preparation.
  •  You will inject yourself with the same needle in the buttocks, but into the muscle (about ¼ inch of the needle should go in).

Lupron comes in a pre-diluted form, and you only need to draw 1 ml into the syringe and inject it subcutaneously on the front of the thigh.

For an egg retrieval that is scheduled at 9 a.m. on a Wednesday, for instance, you will inject the HCG or Lupron sometime between 7pm and 9 pm on the preceding Saturday (34-36 hours before the retrieval).

Before egg retrieval – preparing for anesthesia
For your comfort and to minimize your anxieties about the procedure, sedation anesthesia is administered for egg retrieval. This requires that the patient must not eat or drink anything (not even water) for at least 8 hours before the procedure. If you have a morning retrieval, you may have a big dinner, and then, you must not eat or drink anything from midnight onwards.

If you have an afternoon or early evening retrieval, you may have a big breakfast, and then, you must not eat or drink anything starting eight hours before your scheduled retrieval.

Failure to observe this simple rule will result in cancellation of your procedure for your own safety.

  • The anesthesiologist will not administer anesthesia to any patient who has not observed this rule.
  • The risk is that during the procedure, you could cough up food or drink that can get into your airways.

3. Egg Retrieval

Egg retrieval is a non-surgical procedure done under sedation anesthesia in a state-licensed IVF facility.

What happens during egg retrieval

  • A board-certified anesthesiologist administers the anesthesia and monitors you throughout the procedure and afterward.
  • An aspiration needle is attached to the ultrasound probe and the fertility doctor guides the needle through the vaginal wall under ultrasound guidance in order to puncture the follicles that contain the eggs.
  • The needle is connected to a suction system to draw out the egg-containing fluid directly into a test tube.
  • The embryologist immediately examines this fluid under the microscope.
  • He will identify the egg and transfer it to a lab dish that contains culture medium.
  • This medium is similar to the fluid found inside the fallopian tube (where natural fertilization takes place).

Retrieval usually takes about half an hour – or even less, if there are only a few follicles to be aspirated. Just before your procedure, your husband or partner will be asked to produce a semen sample to be processed by the embryologist.

If you are using donor sperm – make sure the sample is delivered to you the day before the retrieval. It will come in a small transporter tank with enough liquid nitrogen in it to keep the sample properly frozen for a few days. Do not open the transporter tank. When you come for the retrieval – bring the sealed tank and all the paperwork that came with it.

Egg retrieval complications
Complications during and after egg retrieval are rare.

  • Internal bleeding after the ovarian punctures is the primary concern.
  • We will always check with ultrasound that this is not happening.
  • He also will make sure you are completely ‘dry’ (no bleeding even in the vagina from the punctures) before you get off the table.

You will then be transferred to a recovery area, where you will lie down or in an EasyChair for observation until you no longer feel the effects of anesthesia and can get up and walk.

  • You may have something to eat and drink. If you prefer, you may bring a light snack from home.
  • We advise chocolate or rice pudding for a quick carbohydrate boost that is soothing, filling and refreshing, though you can always eat more if you prefer.

Some pelvic soreness and even cramping are common after egg retrieval, as well as some spotting from the needle punctures on the vaginal wall.

  • The pain or discomfort is usually mild and tolerable and does not last long.
  • If necessary, you may take Tylenol.
  • If you experience more discomfort than usual while you are in recovery, the doctor may examine you once again with ultrasound to make sure there is no internal bleeding.

Usually, you will be ready to go home within an hour after egg retrieval – once the anesthesia effects have fully worn off.

  • With most patients, these effects are gone within half an hour.
  • Once you feel well enough to sit up and walk, you may go home, but only in the company of an adult who can drive you home or take you in a cab.

Before you leave, the doctor or the nurse will review instructions with you, which will also be on an instruction sheet that you will take home. Generally, you will start taking your post-retrieval medications as soon as you get them from your pharmacy.

Most patients are able to go to work the following day without any problem. Unless you develop any problem, you will not have to be seen again until the day of embryo transfer.

4. Insemination and Fertilization

In the laboratory, the mature eggs that have been aspirated are isolated from the follicular fluid.

  • The embryologist removes the cells that normally surround an aspirated egg
  • The ‘cleaned’ eggs are placed into a laboratory dish containing culture medium until they are ready for insemination (the process of bringing the egg and sperm together)

In conventional IVF, insemination consists in putting each egg into a droplet of medium containing 100,000-500,000 sperm cells, in the hope that at least one sperm will penetrate and fertilize the egg.

However, in the past 10 years, because of its high fertilization rate compared to conventional IVF, it has become common to inseminate the retrieved eggs through intra-cytoplasmic sperm injection (ICSI), in which a single sperm cell is injected into each egg. Unlike most IVF programs, we do not charge extra for ICSI.

ICSI was originally devised for patients with:

  • A known male factor
  • History of previous fertilization failures
  • History of multiple IVF failures
  • A patient older than 37
  • A patient who has not conceived for more than 3 years despite open tubes and normal semen analysis

5. Embryo Culture and Development

A healthy egg cell (oocyte) will generally show fertilization 18 hours after it has been inseminated – conventionally or through ICSI. The embryologist confirms fertilization by the presence of two pronuclei (PN) within the egg – the nucleus of the egg has been joined by the nucleus of the sperm.

Over the next few hours, the male and female pronuclei will merge into one, bringing together the chromosomes from both nuclei, resulting in a fertilized egg (zygote). Because fertilization can only be ‘seen’ 18 hours after insemination, the earliest time we can inform you how many eggs fertilized would be the day after your egg retrieval. Embryo transfer will be done 3-5 days after the retrieval, depending on how the embryos develop.

In the zygote (fertilized egg), the chromosomes from the male and female pronuclei will ‘mix and re-match’ to form a completely new entity, which is your potential child.

  • The zygote splits into two (first cell division), giving rise to the 2-cell pre-embryo.
  • Each cell will split up in turn (1 to 2, 2 into 4, 4 into 8).
  • On the third day after egg retrieval, a healthy zygote becomes an embryo of at least 8 cells.
  • The 8-cell embryo is generally the earliest stage at which embryo transfer is done.

From this point on, the embryo will be growing rapidly – with many cell divisions occurring every day. Theoretically, the total number of cells will double with every cell division cycle.

But things will not always happen in a textbook way:

  • Some or all of the eggs may not fertilize.
    • Conventional IVF can sometimes result in zero fertilization – none of the eggs fertilize – if there is a male factor and/or the egg quality is not good.
  • With ICSI, zero fertilization is uncommon if there is more than one mature egg. If the embryologist thinks it is feasible, eggs that have not fertilized when they are checked the day after retrieval may be re-inseminated, conventionally or by ICSI.
    • Most Day-2 inseminations are not successful, but if fertilization occurs, any resulting embryos with acceptable quality will be transferred.
  • Some fertilized eggs may not divide, or some zygotes may undergo one or two cell divisions and then stop dividing (embryonic arrest).
    • Such embryos will be discarded along with the unfertilized eggs.
  • Some embryos may develop slower than the time-appropriate rate, usually due to a delay in the first cell division. This is not uncommon.
    • However, even embryos that are only at 6-cells or 4-cells on Day-3 post retrieval may be transferred if they are not fragmented. Pregnancies have occurred even when no 8-cell embryos were transferred.

6. Embryo Transfer

Three to five days after egg retrieval, you will be seen again for the embryo transfer. Because the procedure does not require anesthesia, you may eat anything beforehand. However, you will be asked to start drinking water about half an hour before your scheduled procedure. This is necessary because the embryo transfer will be guided by abdominal ultrasound which requires a full bladder for best visualization of the uterus.

Just before the transfer, the doctor will discuss with you and your husband (or partner) the number and quality of the embryos available for transfer.

What happens during embryo transfer

  • Unless you have a tight or scarred cervix (from prior procedures such as colposcopy), embryo transfer is done without anesthesia.
  • The procedure is very much like an insemination, except that embryos, instead of sperm, are being introduced into your uterus.
  • The embryos in a small amount of culture medium are loaded into a thin catheter (plastic tube) attached to a syringe.
  • The doctor introduces the catheter into the cervix under ultrasound guidance, so that its tip is about 1 cm from the top of the uterus – at the level where the fallopian tubes enter the uterus. He injects the embryos into the uterus at that point.
  • Once the embryos have been released, the catheter is held in place for about 30 seconds, then gently withdrawn.
  • It is taken back to the laboratory by the embryologist who inspects it under the microscope to make sure all the embryos have been released.
  • If there is any retained embryo or embryos, these are re-loaded into a fresh catheter and a second transfer is done immediately. This should have no effect on your chances of pregnancy.
  • Once all of the embryos have been deposited in the uterus, we will remove all instruments and you will stay on the table for an appropriate period of time.
  • If you need to urinate right away, you will be given a bedpan so you do not have to get up.
  • Normally, you will be able to go home after about half an hour. You will be given instructions on what to do in the next two weeks. The instructions are also contained in a written sheet which you will take home with you.

We advise all of our IVF patients to rest at home in bed or in a comfortable chair for at least 3 days after embryo transfer. You should also avoid stress and physical exertion for the next two weeks. If your job requires lifting, walking up and down stairs or other strenuous activity, then we may recommend that you stay home for two weeks.

We will provide you with an excuse note for the appropriate time that you may need to stay home. The note will not indicate what procedures you underwent nor what you are being treated for.

When to perform embryo transfer
The decision on when to do the embryo transfer is based on several considerations discussed by us and the couple.

With the present state of ART, embryo ‘quality’ is usually assessed on the basis of:

  • Whether the cells develop and divide on schedule (8 cells by Day-3 after retrieval)
  • How the embryos look under the microscope
  • Are the individual cells more or less uniform in size?
  • Is there any fragmentation; and if so, is the degree within acceptable limits?

Pre-implantation genetic diagnosis (PGD), which looks at the chromosomes in the embryo, will show chromosome abnormalities, but this is not routinely indicated to check embryo quality. Please note, however, that some IVF patients do get pregnant even with embryos that failed to show appropriate development or uniform cell size and/or had some degree of fragmentation.

For some patients, embryo transfer may be done on Day 4 or Day 5, when the embryos are further advanced in development.

Morula stage
Healthy embryos reach the compacted morula stage on Day 4 post-retrieval. The cells have now become so numerous that the embryo looks like a blackberry (morula is the Latin word for blackberry) with at least 64 cells.

Blastocyst stage
By Day 5, a healthy embryo will be at the blastocyst stage, with at least 128 cells. In natural conception, the embryo normally reaches the uterus from the fallopian tube about 5 days after fertilization – when the embryo is at the blastocyst stage. Therefore, theoretically, embryo transfer at the blastocyst stage may result in a higher IVF success rate.

In general

  • Good embryos which develop according to schedule and appear normal in appearance under the microscope may be allowed to become blastocysts before transfer.
  • If the embryos are of lesser quality, one must consider the advantage and the disadvantage of aiming for a blastocyst transfer anyway.
  • Plus: It is a good sign of embryo quality if the embryo reaches blastocyst stage by Day 5.
  • Minus: Embryos that do not progress to blastocyst or even to morula stage by Day 5 may have benefited from a Day-3 transfer. The uterus is still the best incubator for embryos because it produces natural nutrients for the embryo.

In donor egg IVF, embryo transfer is generally done on Day-5, because a young donor with healthy eggs is likely to produce good-quality embryos that will benefit from being transferred at the blastocyst stage.

Two other decisions must be made with the couple about embryo transfers:

Both depend on embryo quality primarily. These considerations will be discussed with the couple before proceeding to the transfer.

How many embryos to transfer
This is very patient-dependent. Theoretically, more embryos transferred at one time means greater chances for at least one of them to implant. However, this can also lead to multiple gestations (conceiving more than one child in the same cycle).

Besides embryo quality, one must consider:

  • The patient’s age and reproductive history
  • The couple’s wishes
  • Will you take a chance on a multiple gestation pregnancy by transferring more embryos to increase the chances of pregnancy?
  • Will you want to avoid multiple gestations at all?

In 2004, the American Society of Reproductive Medicine and the Society for Assisted Reproductive Technology issued guidelines suggesting how many embryos to transfer in order to avoid multiple gestations (conceiving more than one child in one IVF cycle).

AGE EMBRYOS TO TRANSFER CONDITIONS
< 35 a) No more than 2
b) Consider just 1
  • First IVF cycle
  • Previous IVF pregnancy
  • High-quality surplus embryos to freeze
35 - 37 a) 2
  • Patients with favorable prognosis
b) No more than 3
  • All others
38 - 40 a) No more than 3
  • Patients with favorable prognosis
b) No more than 4
  • All others
> 40 No more than 5
Age Independent Additional, depending on prognosis
  • Multiple failed IVF cycles
  • Unfavorable prognosis by history
Defined by age of donor
  • Donor egg IVF

However, these guidelines do not distinguish between Day-3 embryos and Day-5 blastocysts nor do they account for the generally non-uniform characteristics of embryos from the same patient in the same cycle.

If your embryos develop into excellent-appearing blastocysts by Day 5, we will recommend transferring no more than 2 blastocysts. Any other remaining embryos suitable for freezing can be frozen for your future use, without having to go through the entire process again – you would simply undergo a frozen embryo transfer (FET) cycle just like a regular patient whose embryos come from her own eggs.

When to do assisted hatching
Assisted hatching is advisable when:

  • The zona pellucida (protein shell enclosing the embryo) is thick.
  • The patient is older than 37 and/or has a history of high FSH.
  • The patient has had previous IVF failures.
  • Frozen embryos are thawed for transfer (freezing hardens the zona).

Assisted hatching is done just before the embryos are loaded into the transfer catheter. It involves creating a tiny hole in the protective covering of the embryo – this will make it easier for it to hatch from this shell at the time of implantation into the lining of the uterus. The ‘hole’ is created by microinjecting a tiny amount of an acidic substance that dissolves the shell only at the point where it is injected.

You do not need to pay anything extra for assisted hatching.

When to freeze embryos
Couples using donated eggs have this option if there are extra viable embryos left after the couple has decided how many embryos to transfer.

  • If pregnancy does not occur in the cycle using ‘fresh’ embryos, freezing extra embryos will enable you to have an embryo transfer at a later date without having to undergo the whole process again, except for the embryo transfer.
  • If you do get pregnant, the frozen embryos are available if want to have another child, but a monthly storage fee will be charged after the first year of free storage.

What happens after embryo transfer
Except for the anxiety of waiting for the outcome of the IVF process, most patients will have an unremarkable two weeks until the first pregnancy test. However, patients who are susceptible to OHSS will usually manifest some signs and symptoms in the week following embryo transfer. Even patients not likely to develop OHSS may continue to feel heaviness or cramping in the pelvis for several days after egg retrieval, usually because the ovaries are still enlarged from stimulation.

Call us if:

  • The discomfort is significant
  • You feel nauseated or bloated
  • You gain more than 10 pounds in 3 days
  • You develop a fever
  • You have any questions

Seven days after embryo transfer, we may see you to check the lining of the uterus and your progesterone level.

7. Luteal Support

In the two weeks following embryo transfer, the embryo continues to develop and implant itself in the lining of the uterus. This corresponds to the period following ovulation (and possible conception) in a natural cycle and is called the luteal phase.

During this time, you will be taking progesterone and estrogen preparations to thicken the uterine lining so it is more receptive and better able to support embryo implantation. The lining produces special nutrients and cell adhesion molecules that will allow an embryo to continue developing and implant itself in the uterus.

Implantation is when the embryo attaches itself to the lining of the uterus, and some of its cells penetrate into it. The interaction between the embryonic cells and the uterine cells will give rise to the placenta, the structure through which the mother’s system interacts with the fetus during the pregnancy.

The placenta:

  • Allows fetal blood to absorb nutrients from the mother’s blood.
  • Produces the pregnancy-supporting hormone progesterone starting 8 weeks after conception.
  • Produces human chorionic gonadotropin (HCG), whose level is a measure of the progress of pregnancy in the first 12 weeks.

Whether one or more of your embryos will implant depends upon:

  • Embryo health and quality
  • Appropriateness of the uterine lining
  • Immunologic factors, such as the presence and quantity of natural killer cells (NK cells) that are found in the blood
  • Cell adhesion factors that have not yet been fully characterized

Progesterone, a natural hormone, helps the lining of the uterus develop and support the pregnancy. Supplemental progesterone is given by vaginal suppository and by injection. Most patients will develop a thicker lining if, in addition to progesterone, supplemental estrogen is taken in the form of tablets (Estrace 2mg or generic equivalent) taken twice a day. Progesterone and estrogen are taken daily after egg retrieval and continued at least until the first pregnancy test (14 days after embryo transfer).

Although the FDA requires the drug manufacturer to include warnings about adverse effects of progesterone in early pregnancy, long experience with IVF shows that progesterone has proven beneficial effects on pregnancy. For more than three decades now, progesterone has been universally prescribed for luteal support after fertility treatments, even for patients who use fertility drugs, with or without insemination.

8. Pregnancy Test

Fourteen days after embryo transfer, you may see us or go to a laboratory near you for your first pregnancy test. Your blood will be tested for:

  • HCG, the hormone made by the trophoblast cells of the embryo (a value of >50 at this time indicates that the embryo has implanted)
  • Progesterone (a level of >20 is desirable, but women on luteal medications will usually show an even higher level, especially if the treatment has resulted in a conception)

If your pregnancy test is negative
Should your pregnancy test come back negative, you may stop all medications. You should expect to get your period in 2 to 5 days. If you do not get your period within 5 days of discontinuing the medication, call us to schedule a re-consultation with us the following Saturday or Sunday. During this consultation, he will review the cycle with you, discuss what possible problems could have occurred, and discuss future alternatives.

During the first few weeks of pregnancy
If the first blood test 14 days after embryo transfer shows you are pregnant, we will advise you to repeat the test within 2-3 days, depending on the initial value.

  • Generally, if more than one embryo has implanted, this first level is >100.
  • If your level is <50, we may recommend that you repeat it the following day to make sure it is rising.
  • If your HCG level rises appropriately, then you are most likely pregnant.
  • We advise blood tests every 3 days the first two weeks, then at least once a week until your 12th week of pregnancy.

If your HCG level continues to rise appropriately, we will advise you to schedule a visit with the obstetrician of your choice. Let us know who you will be seeing so we can speak directly with the OB and urge that you must be:

  • Seen as soon as possible
  • Treated like a high-risk patient because of your infertility history
  • Monitored with blood tests and ultrasound more frequently and regularly than normal patients

If your pregnancy is going well, your ovaries will be able to make the progesterone you need to support the pregnancy in its first 8 weeks. Your obstetrician will be able to tell based on serial progesterone values.

If you continue to make progesterone appropriately, then you may stop progesterone supplementation, but we would still advise regular monitoring.

You will be considered clinically pregnant only after ultrasound shows the presence of a gestational sac or sacs inside the uterus. This can usually be seen during the third week after embryo transfer, at which time we will know how many embryos have implanted.

A heartbeat is your best confirmation
By the 4th week after embryo transfer, ultrasound will be able to detect a heartbeat in the gestational sac. For purposes of IVF data reporting, it is this ultrasound that dates your clinical pregnancy. Subsequent ultrasounds through your obstetrician will continue to monitor the development of the fetus.

Ectopic pregnancy and IVF
Occasionally, some IVF patients may have an ectopic pregnancy – when the conceptus implants in one of the fallopian tubes instead of within the uterus. This is more likely if one or both of your fallopian tubes are not blocked at the point where they join the uterus.

An ectopic pregnancy is suspected if ultrasound in the third week after embryo transfer does not show a gestational sac, although your HCG level has been rising. We will advise serial ultrasound with a radiologist over a period of 1-2 weeks to confirm that there is no gestational sac in the uterus and whether the embryo has in fact implanted in the tube.

If an ectopic pregnancy is confirmed, we will discuss treatment with you.

  • At this early stage, it will generally involve a medication called Methotrexate (MTX) injected once or twice. MTX results in ‘dissolving’ the ectopic pregnancy.
  • An ectopic pregnancy that is discovered late, when the pregnancy mass has grown or when the pregnancy value is already high, may require surgical removal.

Possible concerns in early pregnancy
You may experience spotting, minor bleeding, and even some mild cramping in these first few weeks. This is quite common. But as long as the cramping is not severe and/or bleeding is not heavy or accompanied by blood clots, it is usually not a cause for alarm.

If the bleeding becomes heavy, similar to menstrual bleeding or heavier, or if the cramping or pelvic pain is significant, call your obstetrician right away.

Thank you. We will get back to you as soon as possible.