IN VITRO FERTILIZATION EMBRYO TRANSFER (IVF ET)

What is IVF / In Vitro Fertilization?

IVF is an option for couples who are unable to conceive naturally because of problems involving

• The fallopian tubes (tubal factor)
• low sperm count or poor sperm quality (male factor)
• pelvic adhesions (pelvic factor)
severe endometriosis

IVF is also an option for
Unexplained infertility (no identifiable cause)
Women older than 38
Women who have fail to conceive through ovulation induction
and/or insemination
Younger women unable to conceive after trying for over 5 years

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Preparing for IVF: Initial Evaluation

By considering your age, reproductive history and the underlying cause/causes for your infertility, Dr. Brandeis will advise you early on, sometimes even at your first visit

• Whether you are a candidate for IVF, and
• Your realistic chances for success.

At your first meeting Dr. Brandeis will advise tests and procedures that are necessary to establish your fertility status:

• Baseline hormone levels taken on Day 3 of a natural cycle
• Baseline pelvic sonogram to document information about your ovaries and uterus
• Hysterosalpingogram to document the status of your fallopian tubes and uterine    cavity
• Semen analysis with strict morphology

If the tests confirm that you are a candidate for IVF, and show no abnormalities that should be treated before conceiving, then you would be ready to proceed to IVF immediately.

Dr. Brandeis will explain the IVF process to you (or review it, if you have already done it before) and answer your questions.

If you have insurance coverage, we will verify that your plan covers IVF (including the medications for it).

If you have no insurance coverage, then our coordinator will speak to you about our self-pay plan as presented on the Affordable Fertility Treatment page of this website.

Payment by cash, certified check or money order will be expected at the time you start your first medication. [Understanding our fees]

Whether you are self-pay or an insurance patient our coordinator will explain to you the medications you will be needing for the actual IVF cycle and place the orders for you with a fertility pharmacy that will deliver to your home or office.

Our coordinator will explain to you the medications you will be needing for the actual IVF cycle and place the orders for you with a fertility pharmacy that will deliver to your home or office.

We can also provide you with the name and telephone numbers of such specialty pharmacies. As a convenience, they offer next-day delivery, free of charge, anywhere in the United States.

Most fertility medications used for ovarian stimulation in IVF are injectables meant for self-injection by the patient. Dr. Brandeis or the clinical coordinator will explain and demonstrate to you how to inject yourself with these medications.

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The IVF Process at a glance

• Preparing the ovaries
Their natural activity is suppressed with an injectable medication in the month preceding the IVF cycle, to make them more responsive to stimulation.
• Ovarian stimulation
The ovaries are stimulated over a 10-day period with    injectable fertility medications to produce multiple mature eggs during the cycle.
• 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.
• Insemination and fertilization
In standard IVF, the mature eggs are combined in the laboratory with a processed sperm sample from the husband or donor. In  many cases, ICSI (intra-cytoplasmic sperm injection) is advisable: the fertilization rate is much better because one sperm is injected directly into each egg.
• 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.
• Embryo transfer
Healthy embryos are placed into the uterus with a thin catheter introduced through the cervix. This is a simple, painless, non-surgical procedure.
• 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 may also be given to enhance progesterone action.
• Pregnancy test
12-14 days after embryo transfer, a serum pregnancy test will determine if conception has occurred.

We will now discuss these phases one by one.

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Preparing The Ovaries: Pre-IVF Cycle

Your IVF process begins in the month that precedes your IVF treatment cycle (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.

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

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Patients start Lupron 7 days after ovulation (determined through 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.

The 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 Dr. Brandeis or one of our clinical coordinators how to inject yourself with Lupron and the other injectable medications you will be using.

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 Dr. Brandeis prescribes a 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 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, Dr. Brandeis 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.

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Ovarian Stimulation

For IVF, the ovaries are usually stimulated to produce multiple follicles - each containing an egg - during the IVF cycle.

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.

• An option for them is to try natural-cycle IVF which does not require any    stimulation.
• IVF is performed using the single egg that a woman normally produces in a    natural cycle.
• The chances for pregnancy are almost just as good as with stimulation.
• The benefit is that the patient does incur the cost of stimulation medication, which    is one of the major costs in an IVF procedure.

For the majority of IVF patients, however, ovarian stimulation - whether at regular dose or minimal dose - is an essential part of the IVF process.

Once you get your period, Dr. Brandeis 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, Dr. Brandeis will also want to see at least four follicles (sacs containing the egg cell) in the ovaries.

Most patients generally are able to proceed to stimulation at this time.

In any case, Dr. Brandeis will tell you when to start the medications for stimulation and in what doses.

A typical stimulation protocol consists of daily injections of human gonadotropins 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

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About Fertility Medications

Fertility medications used for ovulation induction or ovarian stimulation are concentrated preparations of 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.
• Humegon and Repronex contain both FSH and LH.

In our current protocol for ovarian stimulation

• Pure FSH (Bravelle or Gonal-F) is used for the first 4-5 days of stimulation
• Repronex 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.
• Each dose comes as a powder in a vial, which has a companion vial containing the    liquid to dilute the powder.
• Dr. Brandeis or one of the coordinators will instruct you how to dilute the powder    for your daily injection dose.

The object 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.

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About Follicles

Follicles are egg-bearing sacs in the ovaries. Each ovary contains hundreds of thousands of follicles, but during a regular menstrual cycle (without stimulation), only a few will be 'recruited' - through their response to FSH - for development, 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 - 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 till maturation.
• the ovarian hormones estrogen and progesterone.
• During stimulation, the dominant hormone produced is
   estradiol (E2), the primary form of estrogen in non-pregnant
   women.

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 (600 IU) a day.

Women who are very sensitive to the medication need only a small amount of gonadotropins, 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.

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

Your response is measured by

• Blood test to determine the level of estradiol, E2, which is a
   measure of follicle activity; and
• Ultrasound to follow the number and size of developing
   follicles

Generally, after the baseline visit, you will be seen next 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 PCOS may be seen more often, especially in the early days of    stimulation, because they tend to over-respond to the medication, and Dr.    Brandeis can adjust their dosage down as needed.

NOTE:
Early in the cycle, your husband or partner may be asked to provide a sperm sample to be frozen and stored as an emergency back-up in case he is unable to produce a sample on the day of egg retrieval.

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.

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.

• HCG is the hormone produced by 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 intra-muscularly into the fleshy part of the buttocks) about 32-34 hours before egg retrieval.

• Dr. Brandeis will tell you what time to take this injection. It is very important that you take it at the right time.

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 Repronex, 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 Dr. Brandeis instructs 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).

At present, because our egg retrievals are done in the late afternoon or early evening, the HCG injection is usually taken around 2 p.m. the day before egg retrieval, which is done the evening of the next day.

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About Ovarian Hyperstimulation

Apart from the usual risks associated with anesthesia, the main risk in IVF is ovarian hyperstimulation syndrome (OHSS).

This occurs in about 1-3% of patients - if too many follicles develop in response to stimulation. Patients with PCOS are more likely to hyper-stimulate with medication, that is why their response is closely monitored.

OHSS symptoms are usually not observed until after embryo transfer. OHSS is very manageable provided it is promptly recognized and its signs are closely observed.

However, before egg retrieval

• An E2 level is above 4000 before HCG, and
• The presence of many small and intermediate-size follicles (10-15 mm) just    before HCG would indicate you are at risk for OHSS.

Dr. Brandeis will advise you not to proceed with embryo transfer during the cycle.

• He may not give you the full dose of HCG (10,000 IU), but only half.
• Your eggs will still be retrieved, but Dr. Brandeis will also try to aspirate most if    not all of the smaller follicles.
• The mature eggs retrieved will be fertilized in the laboratory with your partner's    sperm.
• The resulting embryos will be allowed to grow 3-5 days, and they will then be    frozen for transfer at a later cycle.
   [See Embryo freezing and frozen-embryo transfer (FET) cycle]
• The E2 level generally drops after egg retrieval. This decrease, together with the    fact that most of your follicles have been aspirated, will generally prevent OHSS    from developing.

If OHSS does occur in patients who undergo embryo transfer, signs will first appear in the week following the transfer.

Often, the first signs are one or all of the following:
• Abdominal distention and increase in waist size
• Weight gain
• Enlarged ovaries (sometimes painful)
• Nausea.
• Some patients also complain of
   • shortness of breath
   • decreased urine flow

If these signs and symptoms occur, call us.

Dr. Brandeis will see you for blood studies and ultrasound,
and advise you what to look out for in the next few days.

Generally, OHSS signs resolve spontaneously after 3-5 days, but careful observation is needed.

In highly infrequent cases, hospitalization may be necessary for appropriate monitoring.

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Precautions Before Anesthesia

For your comfort and to minimize your anxieties about the procedure, we use sedation anesthesia for egg retrieval.

If your retrieval will take place in the early evening

• You are advised to have a big breakfast around 7-8 a.m. on the day of egg    retrieval.
• But from 12 noon onwards, you must not eat or drink anything until after the eggs    are retrieved.

• 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.

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Oocyte - Egg Retrieval

Egg retrieval is a non-surgical procedure done in the office under sedation anesthesia for your comfort.

• A board-certified anesthesiologist administers the anesthesia and monitors you    throughout the procedure and afterwards.
• An aspiration needle is attached to the ultrasound probe and Dr. Brandeis 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. Do not open the transporter tank. When you come to our office for the retrieval - bring the sealed tank and all the paperwork that came with it.]

Complications during and after egg retrieval are rare.

• Internal bleeding after the ovarian punctures is the primary concern.
• Dr. Brandeis 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.

Once you are in Recovery

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

Some pelvic soreness and even cramping are common after egg retrieval, as well as some spotting from the needle puncture site.

• 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, Dr. Brandeis 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, the effects of anesthesia wear off 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, Dr. Brandeis 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 the night that you get home from the procedure, or the following morning.

Most patients are able to go to work the following day without any problem.

We will not need to see you again until the day of embryo transfer -
unless you develop any problem.

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Insemination and Fertilization

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

• The embryologist removes the cells that normally surround an aspirated egg, then
• 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, insemination is done through ICSI (intra-cytoplasmic sperm injection) in case of

• 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

In ICSI, one sperm is directly injected into each mature egg that is retrieved. This results in much better fertilization than conventional IVF, especially in the above-cited cases.

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About Fertilization and Embryo 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 pro-nuclei (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 pro-nuclei 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 evening following your egg retrieval. Dr. Brandeis himself will call to notify you about this.

In the zygote (fertilized egg), the chromosomes from the male and female pro-nuclei will 'mix and re-match' to form a completely new entity

• Your potential child.
• The zygote then 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

Unfortunately, most Day-2 inseminations are not successful. 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).
- Along with the unfertilized eggs, these will be discarded.

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.

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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 are advised 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, Dr. Brandeis will discuss with you and your husband the number and quality of the embryos available for 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.
• Dr. Brandeis 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 for pregnancy.
• Once all of the embryos have been deposited in the uterus, Dr. Brandeis 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 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 Dr. Brandeis may recommend that you stay home for two weeks.

Dr. Brandeis 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 that require staying home afterwards.

OTHER IMPORTANT CONSIDERATIONS REGARDING EMBRYO TRANSFER

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When to transfer

Day-3? Day-4? Day-5?

The decision on when to do the embryo transfer is based on several considerations discussed by Dr. Brandeis with 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 farther 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:

• How many embryos to place into the uterus?
• Whether to do assisted hatching?

Both depend on embryo quality primarily.

These considerations will be discussed with the couple by Dr. Brandeis before proceeding to the transfer.

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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 gestation (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 by transferring more embryos to       increase the chances for pregnancy?
   • Will you want to avoid a multiple gestation 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 gestation (conceiving more than one child in one IVF cycle).

However, these guidelines do not

• Distinguish between Day-3 embryos and Day-5 blastocysts
• Account for the generally non-uniform characteristics of embryos from the same    patient in the same cycle.

However, in donor egg IVF, if the embryos develop into excellent-appearing blastocysts by Day 5, Dr. Brandeis 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.

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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).

If assisted hatching (AH) is necessary or advisable, it is done just before the embryos are loaded into the transfer catheter.

• Hatching 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 micro-injecting a tiny amount of an acidic substance that    dissolves the shell only at the point where it is injected.
• Hatching can now be done with laser. At the Brandeis Center, we are considering    a study to determine whether there is an advantage to laser-assisted hatching.

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When to freeze embryos

Couples using donated eggs have this option if there are extra good 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.

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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. 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 naturally found in the blood
• Cell adhesion factors that have not yet been fully characterized.

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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

Dr. Brandeis may see you to check the lining of the uterus and your progesterone level.

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Pregnancy testing

Fourteen days after embryo transfer, you may see us or go to a laboratory near you for your first pregnancy test.

Your blood will 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)and
• Progesterone (a level of >20 is desirable, but women on luteal medications will   usually show an even higher level, especially if they have conceived.

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If your pregnancy test is negative

You May
• Stop all medications
• 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.
• Schedule a re-consultation with Dr. Brandeis the following Saturday or Sunday. He will
       • Review the cycle with you
       • Discuss what the possible problems could have been
       • Discuss future alternatives.

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PREGNANCY: THE FIRST FEW WEEKS

If the first blood test 14 days after embryo transfer shows you are pregnant, Dr. Brandeis 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, Dr. Brandeis 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.
   • Dr. Brandeis advises 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, Dr. Brandeis will advise you to schedule a visit with the obstetrician of your choice. Let us know who you will be seeing - so Dr. Brandeis 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 Dr. Brandeis 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.

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Is an ectopic pregnancy possible with 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.

Dr. Brandeis will advise serial ultrasound with a radiologist over a period of 1-2 weeks will be advised to see whether the embryo has in fact implanted in the tube.

If an ectopic pregnancy is confirmed, Dr. Brandeis 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.

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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.

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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.

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