Should I take supplements during IVF process? Get some logical answer

Does taking supplements help IVF patients?

Practically all women doing IVF are taking supplements of one sort or another, These are supposed to improve egg yield, egg quality and embryo implantation , thus helping to improve IVF pregnancy rates. I have come across women who take over 10 different supplements daily - and I wonder how they manage to swallow so many different tablets, syrups and capsules in a day, On second thoughts thought, it is not surprising, because the craving for a baby can make a woman move heaven and earth; which means taking umpteen supplements is not such a difficult task to accomplish. I have heard the following questions repeatedly from other women who are undergoing IVF treatment.

·         What supplements are you taking?

·         Can you recommend any supplement which can improve egg quality?

·         Is there any special diet which could help in increasing the chances of IVF success?

·         I wish I knew a magic supplement or diet which will make our much desired wishes come true.

·         Why do women undergoing IVF take so many supplements?

·         And how important is it to take these supplements during an IVF cycle?

·         Do these supplements really help?

·         Why do so may ART centers prescribe supplements for their patients before an IVF cycle?

·         Does this impact their success rates?

There are lots and lots of questions - and this blog is intended to answer some of these in a rational way.

Why did supplements gain importance in the field of IVF?

Women who are struggling to have a baby are desperate to find a solution for their problem and are ready to try anything which may help to make their dream come true. No one can pinpoint why a particular IVF cycle fails - and when there are no simple logical answers for the failure, anecdotal evidence and empirical therapies gain lots of importance in the field of IVF. Patient pressure and competition among IVF clinics have forced clinicians to give nonfactual solutions to these questions. When we are spending lots of money for IVF treatment, we want to give it our best shot. Taking supplements gives us a sense of satisfaction that we are doing our best to maximize the chance of success.

Which supplements are used by woman undergoing IVF?

There are list of supplements which are used by women who undergo IVF  like (Co-enzyme Q10, r-alpha lipoic acid, Pycogenol, Resveratrol, Melatonin, , Vitamin C, Vitamin E, Selenium, Zinc, Myo-inositol, Cinnamon extract, Apple cider vinegar, DHEA, Choline, L-arginine / L-ornithine, Prenatal vitamin, Vitamin D, Vitamin B complex, Folic acid, Biotin, Calcium, Omega 3, Low-dose Aspirin, Vitex , Royal jelly, Wheat grass, Flax-seed oil, Evening primrose oil, Nettle leaf and Red raspberry leaf tea, Probiotics and many many more

For what purposes are these supplements used?

·         For increasing egg quantity

·         For improving egg quality

·         For increasing endometrial thickness

·         For improving endometrial receptivity

How are the above mentioned supplements thought to help?

These supplements fall under the following categories:

1.       Anti-oxidants - (Co-enzyme Q10, r-alpha lipoic acid, Pycogenol, Resveratrol, Melatonin, , Vitamin C, Vitamin E, Selenium, Zinc)

2.       Insulin sensitizers (Myo-inositol, Cinnamon extract, Apple cider vinegar)

3.       PCOD mimetic (DHEA)

4.       Vitamins and minerals (Prenatal vitamin, Vitamin D, Vitamin B complex, Folic acid, Biotin, Calcium)

5.       Amino acids (L-arginine / L-ornithine)

6.       Blood thinner ( Low-dose Aspirin)

7.       Essential fatty acids (Omega 3, Flax-seed oil, Evening primrose oil)

8.       Miscellaneous (Vitex, Royal jelly, Wheat grass, Nettle leaf and Red raspberry leaf tea, Probiotics etc)

9.       Traditional ( home ) remedies

What are the alleged things of some of these supplements on the reproductive system?

Pycogenol is a strong anti-oxidant derived from the bark of pine tree. When did humans consume pine tree bark, It is also present in peanut skin and grape seed. It is thought to help with male fertility and there are several other health claims too. Since it is assumed that free radicals cause damage to eggs; this supplement has gained importance among women who undergo IVF.

Myo-inositol is also called Vitamin B8. It is naturally produced in many of our body tissues. The best sources are fruits, beans, nuts and grains. Humans generally consume about a gram of myo-inositol per day. Our kidneys produce 2 grams per day. There are many functions of it in our body but its positive effect on reproductive system is due to its action as an insulin-sensitizer. PCOD women with insulin-resistance are found to be deficient in myo-inositol (perhaps because they have a defective myo-inositol synthesis pathway). Since myo-inositol plays a vital role in insulin signaling, it is thought to benefit women with PCOD. Cinnamon extract, Apple cider - thought to function as insulin-sensitizers and hence might benefit women with PCOD.

Melatonin is touted as a strong anti-oxidant. The story of melatonin's use in reproductive biology started with its ability to inhibit ovulation. It was even used in phase III clinical trials to test its effectiveness as contraceptive.

Co-enzyme Q(10) is another strong antioxidant which occurs naturally in our body. It is present in abundance in mitochondria. It helps in the production of ATP molecules which acts as the "energy currency" of our cells. Since egg cell contains more mitochondria than any other cell type; and ageing egg cells have defective mitochondrial function .

Vitamin D is the new age wonder vitamin, Since the facility to test vitamin D levels in serum is widely available today, almost everyone is screened for their vitamin D levels, irrespective of their sun exposure status and age. The pity is that there are no proper studies to suggest what vitamin D concentration in serum is normal for a particular group of people. Even worse, a lack of this vitamin has been linked to every disease in the world - and use of this vitamin has been shown to prevent practically all the diseases under the sun. So why should reproductive biology leave this 'miracle' vitamin unused.

Are there any supplements which every woman undergoing IVF should take?

Yes, every woman who is trying to conceive should take folic acid. It is a supplement which is proven to prevent neural tube defects in the developing fetus. Folic acid prevents 70 % of neural tube defects. So make sure you take 400g of folic acid atleast 3 months before starting your IVF treatment. Women who have had a child with NTD and women who themselves have NTDs are also advised to take 5 mg folic acid daily. Myo-inositol was able to prevent folate-resistant NTDs in mice but in humans whether this is true is not known. Women who had child with NTD even after consuming enough folates could try taking a myo-inositol supplement too.

Can lack of a particular nutrient hinder my chances of conception?

There is no need for complicated research findings. Just look at the women around you. I come from a developing country in which there are so many women who live below the poverty line. Many survive on just rice or wheat. They can't afford meat, fresh fruits or vegetables on a daily basis. Do you think that their families are any smaller? Since they are poor and illiterate, they are married at a young age. They are extremely successful in expanding their family - actually most have a bunch of children. due to their lack of knowledge about contraception! If nutrients play such a pivotal role in conception, these women who live below the poverty line would never have any offspring. After seeing them I am tempted to conclude that excess nutrients and lack of physical work might play a role in accelerating reproductive ageing. It is a well-established fact that calorie restriction protects the reproductive system in mice from ageing. 

Supplements don't cause any harm, do they?

It is important to understand that no one are not responsible for ensuring the safety of dietary supplements available in the market and it does not check their efficacy either. This means that there is no certainty that the claims of the manufacturers are true - and their safety is not guaranteed either. Remember that too much of a good thing can be bad. The field of supplements is not entirely black-and-white, and there are many grey areas left. Hence it is wise not to overdo anything when you do not know what effect they have on your reproductive system. When you get a particular nutrient through your diet how could take them in excess helps? Remember, more is not always better.

I am taking only herbal supplements and hence I can't suffer any side-effects.

It is a very Illogical on our part to assume that the so-called 'herbal' supplements are safe. The word 'natural' in supplements doesn't mean they are harmless. Even worse, many herbal supplements contain alkaloids or heavy metal contaminants which can cause serious damage to your vital organs. Some herbal supplements can interact with the medications you are taking and make them ineffective. Are you aware that even grape fruit juice can interfere with medications you are taking and can cause life-threatening complications? So please do not think that everything which is marketed as herbal or everything which occurs naturally is OK to take without a second thought, especially when there is no proof for the tall claims their manufacturers make.

What about supplements for improving sperm count and motility?

The simple answer is - nothing works! However, because this is not an answer which patients want to hear, they consume thousands of dollars worth of cleverly named supplements, to "boost" their sperm count and motility. They usually stop after they fail to see results in a few months - but this wasted therapeutic trial damages their confidence - and their bank balance!

Can supplements make my eggs younger or help my embryo to implant?

Our ovary is like an egg bank where the eggs are stored for years. As women age, their eggs in their ovary age too; ageing affects the genetic quality of the egg; and the quantity of eggs available in the ovary declines too. Unfortunately, we do not know the exact mechanism behind such changes, and hence we do not know how to prevent it. I wish there was a supplement which could make me and my eggs younger too!

Should I take supplements?

When all is said and done if taking supplements helps give you peace of mind that you are doing your best to make the IVF cycle a success, go ahead and take it. But before taking them, analyze critically what you might need, depending on your specific condition. If you have PCOD with insulin resistance, try an insulin sensitizer. But remember, insulin-sensitizers can never replace a sensible diet and a good exercise regimen in controlling PCOD. If you are a women with poor ovarian reserve try using DHEA. Women of advanced maternal age can try taking anti-oxidants. A multivitamin tablet is always a safe option - the extra vitamins will just make you produce expensive colorful urine.

The most important supplements as per my understanding is when patient undergoing IVF are need lots of love and pampering from your dear ones. Never obsess about other 'miraculous' supplements, they are not worth it. 

How many eggs am I donating & what are risks of being an egg donor?

Often, egg donors inquire about egg donation and expect that they will be donating just one of their eggs to an infertile couple. It just doesn’t work that way. When an egg donor is matched with a recipient, they are contracted to donate the eggs that they produce in a particular menstrual cycle. During that cycle, the physician that they are seeing intentionally increases the number of eggs that are produced. While a “normal” woman might release one or two eggs a month, those numbers would be cause to cancel an egg donor cycle prior to the retrieval. The number of eggs produced and donated in an egg donor cycle can range from about 8 to as many as 40 (although that is very, very rare). The average cycle results in a retrieval of between 15 and 20 eggs. The eggs are fertilized after retrieval, and often not all of them will successfully fertilize and develop. About 12 to 14 healthy embryos generally result from 20 eggs. Some of these embryos (possibly 2) will be transferred to the recipient or a gestational carrier, and the remainder frozen for future use.

Egg donation is generally very safe with no long-term risks.  Society in general, would not permit a young healthy woman to donate her eggs if the procedure was dangerous.  There, however, are some short-term risks associated with egg donation.   Knowing the warning signs and being educated about them will drastically help reduce these risks.

Pregnancy!

Yes, this is a real risk!  When you are in an egg donation cycle, you will be off all birth control and will be producing multiple eggs because of the stimulation medications. It sounds crazy, but pregnancy is possible. If you have unprotected intercourse during your cycle you can become pregnant.  This could occur if some of the eggs are released before your retrieval, or if not all of your mature eggs are retrieved.  You must abstain from intercourse or use effective barrier contraception. Remember - you are taking stimulation medications, the same ones a woman going through fertility treatment to get pregnant is taking.

Medication side effects

The fertility injections contain higher doses of the same hormones (follicle stimulating hormone (FSH), and luteinizing hormone (LH)) that the brain releases naturally to stimulate the ovaries to produce multiple eggs.  As the ovaries respond, it is actually a sign of a robust response if there is some bloating and cramping.  You can take Tylenol for the discomfort.  However, if the symptoms are severe you should call the office immediately.  This may be a sign of ovarian hyper-stimulation syndrome (OHSS), which is discussed later.

Both the birth control pills you are prescribed as well as the injectable medications (especially Lupron) you will be taking as an egg donor may cause you some side effects that are similar to premenstrual syndrome.  You may have hot flashes, vaginal dryness, fatigue, sleep problems, body aches, mood swings, breast tenderness, headache, slight bloating, etc.

Temporary weight gain

Donors can gain approximately 5 lb in weight due to increase in size of the ovaries and fluid retention.  This is temporary and should resolve completely with the next menses.

Does egg donation affect a donor’s future menses, fertility or when she will undergo menopause?

The simple answer is no!  When a woman starts getting her periods, there are approximately 300,000 eggs.  In her reproductive lifespan, a woman will ovulate around 400 times.  So, there are hundreds and thousands of “spare” eggs.  With each cycle, we will retrieve around 12 – 25 eggs.  Even with 6 such cycles (the maximum number permitted) the number of eggs retrieved will not affect future menses, fertility or menopause.   A recent study measured Anti-Mullerian Hormone levels (AMH) in donors who had undergone multiple cycles over a period of a couple of years.  AMH is a marker of the number of eggs that remain in the ovary.  These donors did not show any decrease in their AMH levels indicating that their fertility was not affected by the procedure.

Ovarian Hyper-stimulation Syndrome (OHSS)

Infrequently, some donors are exquisitely sensitive to regular doses of the stimulation medications.  This results in an exaggerated swelling of the ovaries and fluid collection in the abdomen and chest.  This is known as OHSS and occurs in less than 5% of all egg donors.  When mild, you may have abdominal pain, pressure, and swelling which should go away after your next period.  When moderate, you may require careful monitoring, bed rest, and pain medications.  When severe, which is rare but very serious, there is a possibility of serious medical complications such as blood clots, kidney failure, fluid build-up in the lungs, and shock.  Severe OHSS normally requires hospitalization.

If you have any abdominal discomfort, weight gain, headaches, severe nausea or vomiting etc., please contact the Clinic as soon as possible.  Egg donors are monitored very closely and it is important for us to be aware of how you are feeling.

Bleeding and Infection with Retrieval

During egg retrieval, a needle is inserted into your ovary and there may be bleeding.  Although it is very rare, it is possible to damage or puncture the bowel, bladder, or nearby blood vessels. Spotting is normal after your retrieval, but if you bleed heavily, immediately contacts the doctor. To prevent infection, donors receive an antibiotic intravenously.  A member of clinic staff will also contact the donor the morning after her retrieval to see how she is feeling.  Donors also come back to the clinic for a post-operative appointment two weeks after their retrieval for a check-up.

The Miracle of life at the age of 40; success fragrance beyond the challenges

I am Sulekha, 44 year old from Gujarat and the mother of a healthy beautiful sweet little 9 month old son. I was 42 when I started IVF treatment in Pahlajani Test Tube Baby Centre and became pregnant and 43 when I gave birth. Thanks to Dr. Neeraj Pahlajani for her immense support during my odd periods.

My personal experience is example of positive information about the IVF process to women over 35 after scouring the internet myself desperately looking for success stories of women my age undergoing IVF treatments. I was nervous and afraid and really wanted some inspiration yet; I couldn’t find what I needed. So spirituality was created and here I am, 20 odd months down the track giving you living proof that IVF over 40 years; my works and being a mother over 40 is most definitely achievable.

I was going through each step in the IVF process.  They offer a complete detailed process to run down of my IVF journey and the things I did, for my physical mental and emotional wellbeing to help the process along.  They are promise to do absolutely from the heart, aimed to give an honest perspective of the journey.

 To share my story with women going through the same process or women thinking about starting  IVF who are searching for inspiration, who want to connect with a success story to help them find the courage to begin has been a truly uplifting experience. I thank all the support staff of Pahlajani Test Tube Baby Centre and my family who supported my journey, who offered kind loving words and encouraged me to continue to share my story, to those of you who are still in the process, I send you my love. Try to keep positive and keep visualizing the outcome you want. It can happen for you, don’t give up, and keep the good energies flowing.

I am living proof that becoming a mother on IVF over 40 is possible. I am proof that the  process can be smooth and straight forward and am proof  also that the  journey no matter how emotional and challenging, can be a beautiful one with a happy ending.

I know that this is not always the case, I know there are women who experience a great many challenges, but when I began my journey and actually all the way through it, I needed to hear about successes as well as the challenges. I needed to read about women positive experiences.  I wanted to read positive uplifting information. So to all of you who have found their way to this blog I send you my love and my best wishes for the adventure ahead. Keep your thoughts positive, acknowledge your fears but don’t let them take over you and keep your heart open.

These I believe are keys to success in this journey.  To believe that you can and will be a mother, to have faith your process will work and to consistently visualize the outcome you want to see it in your mind’s eye clearly. This is the attitude to aspire to and my sincere blessings to all of you.

Life is fast these days and while I try to stay in the moment in order to appreciate the everyday miracles occurring from moment to moment I forget sometimes. I forget how amazing life really is and how truly blessed I am to be here. Thankfully life sends me little reminders and this clip was one of them. What a miracle the creation of life is and women bodies it’s really absolute masterpieces.

Is mock transfer is essential before actual embryo transfer, know the facts

Embryo transfer is a simple procedure that follows In Vitro Fertilization (IVF) and is often considered the simplest and final step of the in vitro fertilization process. The objective of embryo transfer is to facilitate conception following fertilization from the in vitro fertilization procedure. Embryo transfer is one of the rate-limiting steps in an IVF cycle and plays a pivotal role in determining IVF success. The day when our in-vitro embryos return back to us is one of the most exciting moments of an IVF cycle. We forget the all our struggles; we went through during the whole procedure; since the invention of IVF, major developments have been made in ovarian stimulation protocols; the way oocytes are collected; and in the IVF lab; but the embryo transfer method remains largely unchanged. When different individuals perform embryo transfer within the same ART programme, the pregnancy rate of each doctor varies widely. This shows the importance of the embryo transfer technique and how it determines IVF outcome. It is estimated that 30% of IVF cycles fail because of shortcomings in this crucial procedure.

There are many questions, what actually happens during an embryo transfer? Is it an easy procedure? Will it be painful? Can my embryos fall out of my uterus after the transfer? Come let us find the answers together

When does the embryo transfer procedure occur?

Embryos are generally transferred to the woman’s uterus at the 2-8 cell stage. Embryos may be transferred anytime between Day- 1 through day 6 after the retrieval of the egg, although it is usually between days 2 -4. Some clinics are now allowing the embryo to reach blastocysts stage before transferring, which occurs around day 5.

What is an embryo transfer (ET)?

Transferring one or more embryos into the uterine cavity of the recipient is called embryo transfer (ET).  It is the final and crucial step of an IVF process. The embryos in the IVF lab are grown usually until day 3 or day 5 in an incubator in a Petri dish. The qualities of embryos are graded by inspection under a microscope. The top quality embryo(s) are returned back to the uterus, where they belong! Even though more than 90% of patients who undergo IVF reach the embryo transfer stage, only a small percentage of them actually get pregnant. Unfortunately, not all the embryos which are transferred to the uterus become deeply desired babies!

What risks are there with embryo transfer?

There are minimal risks associated with the embryo transfer procedure. They include the loss of the embryos during transfer or implanting the embryos in the wrong place such as the fallopian tubes. Although some women experience mild cramping, the procedure is usually painless.

How is an ET performed?

During Embryo Transfer, the doctor puts you in the undignified Lithotomy position in the OR, and inspects your cervix with the help of a speculum. The sticky cervical mucus is cleared away using a moist cotton swab carefully. Then the cervix is washed with a sterile fluid. The best embryos are then loaded into the transfer catheter by the embryologist in the adjoining IVF lab. He does this under the microscope, and sucks up the embryos into the catheter by applying negative pressure with the help of a 1 ml syringe.  He brings the loaded catheter to your doctor, who performs the ET slowly by inserting the catheter into the uterine cavity through the cervix; and then expelling its contents by gently pushing the barrel of the syringe. This deposits the embryos into the cavity of your uterus. This method of transferring embryo(s) to the uterus is called transcervical embryo transfer. After transferring the embryos, the doctor hands over the catheter to the embryologist, who then examines it immediately under the microscope, to see whether there are any embryo(s) retained in the catheter. If this is the case, the retained embryo(s) are transferred back again to the recipient. An embryo transfer procedure is normally painless, and takes only few minutes to perform. You do not need anesthesia for this procedure. Most embryo transfers are easy but some embryo transfers can be difficult too; normally your husband is allowed to stay with you during the Embryo Transfer procedure, in order to hold your hand and provide you with emotional support, so that you remain stress-free and relaxed. 

Are there any instructions following the embryo transfer procedure?

Once embryos are transferred, there is nothing a patient can do to influence the outcome of her cycle. Currently, there is no documented evidence as to whether bed rest or continuing normal activities following the procedure make a difference in the outcome. Some physicians encourage the patients to rest for twenty four hours. Others suggest returning to normal activities as soon as possible. Some patients choose to rest because they think that by doing so they are improving their chances. Additional rest also gives them an opportunity to think about the potential baby. Other women elect to return to normal activities to help them avoid worrying about things that could go wrong. Together with counsel from the doctor, the state of your body and mind should help you decide your course of action.

Again, there is no documented evidence showing that physical activity has any impact upon embryo implantation or conception. Conception is a natural event that depends primarily upon the genetic quality of the eggs.

How many embryos should be transferred?

The number of embryos that should be transferred during any single IVF cycle is subject to debate. Medical experts and writers seem to agree that transferring no more than four embryos per IVF cycle will yield optimal results. Transferring more than four is believed to result in excess numbers of multiple pregnancies leading to the increase of other complications; transferring four embryos instead of only one or two increases the probability of pregnancy but with the risk that all four embryos could implant.

Are there any variations in the transcervical embryo transfer method?

Transcervical embryo transfer is performed in two ways – without ultrasound guidance and with ultrasound guidance.

In the traditional ‘clinical touch’ method, the catheter is positioned blindly in the desired position, by relying on the clinician’s tactile senses. In other words the ‘clinical touch’ embryo transfer method relies on the experience of the person who transfers the embryo; During ultrasound-guided embryo transfer, the clinician is able to find the appropriate position for placing the catheter and releasing the embryos using the ultrasound scan image. During ultrasound-guided embryo transfer, you need to have a full bladder, so that the uterus can be viewed clearly; It does create a lot of discomfort for the patient because the embryo transfer procedure can cause pressure on the already full urinary bladder; the uterus should not be disturbed during the transfer in order to avoid uterine contractions - if the uterus contracts, there is a danger of the embryo being expelled from the cavity.

Is ultrasound-guided embryo transfer better than ‘clinical touch’ method?

This is a passionately debated topic. There are studies which reported that ultrasound-guided embryo transfer significantly enhanced embryo implantation rates; and there are studies which found no difference if the ET was done by an experienced clinician in the absence of ultrasound guidance. This is a decision which is best made by your doctor, based on what works best for him; for junior doctors, an ultrasound guided transfer seems better, as they learn how to master this procedure.

What are trial transfers or mock embryo transfer?

Trial transfers or dummy transfers are performed before the actual embryo transfer. They can be done just before the ET; or during the ovum pick-up; or prior to the start of the IVF cycle. During a trial transfer the doctor inserts an empty catheter into the uterine cavity, to find the easiest passage to the cavity; and to measure the length of the uterus and the cervical canal. This allows him to measure how deep he has to insert the catheter, so that he can place the embryo at the appropriate position inside the uterus, without disturbing the fundus. Most embryo transfers can be performed easily, but there are some women where the doctor finds it technically difficult to negotiate the catheter through the cervix. In such a situation, their cervix has to be dilated to widen the cervical canal, so that the embryo transfer catheter passes easily through the cervix. There are women where the doctor needs to use a tenaculum to straighten the uterine axis and sometimes the uterus is so tilted that the passage of the catheter from the internal opening of the cervical canal into the uterus is difficult. Sometimes pulling on the tenaculum alone cannot do the job, especially if the uterus is acutely angulated in relation to the cervical canal. Then it may be necessary to curve the catheter, so it conforms to the curve of the uterus. In these patients, using specially designed catheter sets allows the doctor more freedom in gently guiding the catheter through the cervix. 

What factors play a role in affecting embryo transfer results?

The embryo transfer should be smooth and trauma-free. Many studies have shown that the pregnancy rate after embryo transfer is better if it is performed by an experienced physician, as compared to a newbie.

·         Placement of the embryo: Placing the embryo 2 cm from the uterine fundus (the upper rounded extremity of the uterus, above the openings of the fallopian tubes) helps in enhancing embryo implantation. This is the region which is thought to possess maximum implantation capacity.

·         Uterus contraction: When the cervix is handled roughly or if the catheter touches the uterine fundus, the uterus can contract. This can expel the embryos from the uterine cavity into the fallopian tubes or cervical canal, and compromising IVF success.

·         Cervical mucus: Carefully removing the cervical mucus without causing trauma to the cervix improves IVF outcome. The cervical mucus can plug the catheter tip , thus preventing the deposition of the embryo in the uterus. It can also be a source of introducing bacterial contamination into the otherwise sterile uterine cavity.

·         Catheter choice: Soft catheters have a better IVF outcome because they avoid trauma to the uterine wall.

·         After the doctor has done the transfer, the embryologist checks it under the microscope. The presence of blood in the catheter suggests that the transfer was technically difficult – and this may reduce pregnancy rates.

·         Trapped embryos:  Sometimes the embryos remain trapped with the catheter, even through the doctor has plunged the barrel of the syringe completely. When the embryologist identifies the trapped embryos in his petri dish, he simple reloads them again into a new catheter, and the doctor can then re-transfer them. This does not seem to affect pregnancy rates. 

Why are some embryo transfers difficult to perform? 

Some embryo transfers are difficult to perform because of the following problems in patients:

1.    Cervical stenosis (narrowing) or anatomical distortion of the cervical canal and uterus

2.    Acute Utero-Cervical Angulations

If a physician has several years of experience in doing IVF, then most embryo transfers are like a cakewalk. But in some women, the embryo transfer can become an arduous adventure because of the difficulty encountered in traversing the cervix. This is commoner in women of Indian and African origin, where pelvic inflammatory disease (PID) and cervical infections are more prevalent. There can also be anatomical distortion of the cervical canal and uterus because of previous surgery. These conditions might lead to a traumatic embryo transfer; or the embryo transfer cannot be performed at all. The presence of an acute curvature between uterus and cervical canal can also make the embryo transfer hard to perform.

How to avoid difficult embryo transfers?

Performing mock transfers before the actual embryo transfer helps in identifying the problem before hand, and can help the doctor to take precautionary measure. For example patients with cervical stenosis can undergo a process called cervical dilation to widen the cervical canal. This might help in the atraumatic passage of the ET catheter into the uterine cavity. But there are some patients in which transcervical embryo transfer becomes impossible! In such rare cases, there are other techniques which could be used to transfer the embryo to the uterus. 

What are the methods which bypass the transcervical route for embryo transfer?

Trans-myometrial embryo transfer (TET)

In this method, using a special set, two needles (one inside of the other) are passed through the vagina into the uterus wall, under ultrasound guidance, until the needle tip reaches the edge of the endometrial lining. The inner needle is then removed and a thin catheter is inserted inside the outer needle, which carries the embryo into the cavity. The embryos are then released in the endometrium. But the success rate with such embryo transfers are less when compared to transcervical embryo transfers.

Zygote Intra Fallopian Transfer (ZIFT)

ZIFT stands for zygote intra fallopian transfer. During ZIFT, cleavage stage embryos are transferred into the fallopian tubes, instead of the uterus, using laparoscopy. ZIFT is a very good option for women who cannot have a transcervical embryo transfer, but who have at least one normal fallopian tube. Since cleavage stage embryos belong to the fallopian tube and not to the uterus, ZIFT has a higher pregnancy rate than conventional ET. Most clinics are not able to offer the option of doing a ZIFT, because of the lack of surgical skills and anesthesia facilities. If your embryo transfers are difficult, then find a clinic which offers this option!

E-SET (Elective Single Embryo Transfer)

Elective single embryo transfer (e-SET) is becoming popular for women who are young and have good ovarian reserve. While transferring multiple embryos improves the pregnancy rate, it also increases the risk of multiple gestations. Children who are a result of multiple pregnancies have an increased risk of health problems, because of the increased risk of preterm delivery and low birth weight. With the advent of better embryo selection strategies such as comprehensive chromosome screening (CCS), single embryo transfer may become the norm in the future.

IVF - the hope comes true for infertile couples

Sperm Collection and Preparation

On the day of egg collection, the husband gives a sperm sample. The semen specimen should be obtained following a 3-4 day abstinence from sexual activity and masturbation is the preferred method of collection. A shorter or longer period of time or the use of a different method of collection may affect semen parameters. After collection the semen sample is delivered to the lab where it is properly prepared for IVF. The purpose of the preparation is to isolate the motile spermatozoa from other elements of the semen and activate them in order to be capable to fertilize the mature oocytes.

It should be noticed that masturbation, especially at the clinic, is sometimes difficult and stressful for men on the day of egg collection. Therefore men could bring the semen sample from home or can freeze a sample several days before the day of oocyte retrieval (fresh samples are always preferred). In cases of men with azoospermia, spermatozoa are retrieved directly from the testis (surgical sperm retrieval).

Egg Retrieval

The ability to collect mature eggs from a woman's ovaries for fertilization outside of the body has revolutionized fertility treatment. Originally developed as a way to help women whose fallopian tubes were irreparably blocked, IVF now allows couples who suffer from a wide range of fertility problems to successfully conceive. In vitro fertilization begins with ovulation induction, a process of stimulating and monitoring the ovaries. Once it is determined that the ovarian follicles are the right size and the eggs ready to be collected, a dose of human chorionic gonadotropin (hCG) is administered to trigger the final maturation process and egg retrieval will take place approximately 36 hours later. Prior to the procedure, anesthesia will be given. In most cases, egg retrieval is performed under moderate sedation (aka MAC), allowing the patient to be asleep for the procedure. The actual technique used to collect eggs for in vitro fertilization is known as an ultrasound-guided transvaginal aspiration.

While an ultrasound probe is used to provide a visual image of the ovary and the surrounding structures, a very fine needle is inserted through the upper wall of the vagina and into the ovary. Through magnification of the ultrasound image, the physician can locate the individual follicles that contain mature eggs and apply gentle suction to remove the contents of each one, which is known as aspiration. The fluid and egg from each follicle are collected into an individual container, which will then be taken to the lab for examination and preparation for fertilization. The procedure is performed on both ovaries, usually taking between 10 and 15 minutes to complete. Once the egg retrieval process is finished, the patient will remain under observation for one or two hours before being sent home. Patients may experience some discomfort after egg retrieval and are encouraged to rest as much as possible. Mild soreness, cramping, and light spotting are normal.

Vigorous exercise and other strenuous activities should be avoided. Specific instructions will be provided prior to the procedure and should be followed carefully. Progesterone, a hormone that would normally be released by the follicle after ovulation, is vital to the support of early pregnancy. Because aspiration of the follicles can interrupt the normal hormonal process and prevent adequate amounts of progesterone from being produced, the patient will generally be given supplemental progesterone from the time of egg retrieval through the end of the cycle.

The whole process is performed under mild sedation with a recovery period of approximately an hour. However, it is important to notice that for safety reasons, women scheduled for egg retrieval must be at the clinic at least 30 minutes before the procedure in order to have a cardiograph and talk to the anesthesiologist about allergies, any medication they are taking and any other health problems they may have. Last but not least, women programmed for this procedure shouldn’t eat or drink anything from the previous night.

Oocyte Fertilization

Several hours after egg retrieval and semen preparation, fertilization occurs. More specifically at a conventional IVF cycle the mature oocytes are placed in 4-well dishes of culture medium containing processed sperm. One of the spermatozoa will penetrate and fertilize the oocyte. In cases of severe male infertility, other laboratory techniques are required following egg retrieval. Fertilization may be assisted by intracytoplasmic sperm injection (ICSI), a micromanipulation technique which involves the injection of a sperm directly into the egg. The eggs are then incubated in the lab overnight.

The next morning, 16-18 hours after the time of fertilization, fertilization check is performed by the embryologists. The first signs of normal fertilization are shown by the presence of two pronuclei (small round structures) within the egg. The fertilization rate is usually between 50 and 100%. The maturity of the oocytes, semen parameters, handling procedures and culture systems are some factors that are responsible for the variance in the fertilization rate.

Embryo culture, selection and transfer

The earliest stages of human development, until day five or six after fertilization, normally occur in the woman’s fallopian tube. However, after in vitro fertilization (IVF), much of this period of early development occurs in the laboratory. The conditions under which the embryos are “cultured” have been carefully formulated to provide an environment that as closely as possible that of the fallopian tube. Recently, commercially prepared culture media have become available. These media support embryo development in the laboratory for up to six days. By allowing the embryo to reach the blastocyst stage, we can make a more stringent selection of those to be transferred during an IVF cycle; as a result, these systems may be preferable for patients who would prefer or benefit from a one- or two-embryo transfer.

Once the embryos have been created in the laboratory, they are placed into the uterus. At this point, in order for pregnancy to occur, an embryo must implant into the uterine lining. For many patients, the two-week wait between the embryo transfer procedure and the initial pregnancy test is the most difficult stage of the process. While the embryos are developing in the laboratory, they are monitored for rate of growth, size, form, and signs of irregularity. Based on this data, the embryos are graded by quality, which helps us to estimate which are most likely to successfully implant and continue to develop. Typically, the embryos of the highest grade are selected for the first IVF transfer. Embryos with significant abnormalities are not suitable for transfer and will be discarded. In most instances, no more than two or three embryos will be transferred during any given IVF cycle. This number allows the best chances for implantation while still keeping the risk of a multiple pregnancy to a minimum. In some cases, depending on age and other factors, our physicians recommend electing a single embryo transfer. Any additional embryos that are created will be cryopreserved for later transfer. The embryo transfer procedure will be scheduled for three to five days after the egg retrieval. In IVF cycles where frozen embryos are to be used, the patient will be closely monitored via ultrasound and the embryos will be placed about two days after ovulation takes place.

This stage of in vitro fertilization treatment involves threading a thin catheter through the opening in the cervix, through which the embryos are gently deposited into the uterus. There is very little discomfort during this part of treatment and anesthesia is not necessary. After the transfer procedure, our IVF patients are advised to take it easy for the next few days. Physical activity should be limited and strenuous exercise should be avoided. Although there is little that can be done at this point that will affect the chances of successful implantation, eating well, getting enough sleep, and minimizing stress will go a long way toward the health and wellbeing of the patient. The process of implantation is complex and unpredictable. First, the embryo must escape, or hatch, from the zona Pellucida. Even if the embryos are transferred on day three, this will not occur until after the embryos have reached the blastocyst stage on day five or six. Once an embryo has hatched, it must attach to the endometrium, or uterine lining, and gradually become imbedded in it. Once an embryo has completed this process, pregnancy is achieved and the in vitro fertilization cycle is a success.

Approximately fourteen days after the embryo transfer procedure, a blood test will be conducted to measure the amount of human chorionic gonadotropin (HCG) in the patient's system. This hormone is released only after implantation and is an accurate indicator of pregnancy. However, because HCG is sometimes used during the ovulation induction process to trigger the final maturation of the oocytes, small amounts may exist even if the patient is not pregnant. For this reason, at-home pregnancy tests that detect the presence of HCG but do not measure the quantity are not considered accurate for women undergoing in vitro fertilization. Elevated levels of HCG indicate that implantation has occurred and the patient is pregnant. If pregnancy is detected, the patient will then undergo an ultrasound examination to confirm the findings, determine how many embryos have implanted, and ensure that everything is progressing normally.

If pregnancy has occurred, progesterone treatments will be continued for a period of time and then be gradually reduced as the patient's body takes over normal hormone production. The patient will continue to visit our IVF Centre for blood work and ultrasounds during the early weeks of pregnancy to ensure that everything is proceeding as it should. Once we are able to detect the fetal heartbeat, the patient will be referred to an OB-GYN (if she does not have one already), who will handle the remainder of the patient's prenatal care. A high-risk obstetrician is only necessary if certain medical problems are a factor.

If pregnancy has not occurred, progesterone supplements will be ceased and the cycle will come to an end. If the couple has opted to try another in vitro fertilization cycle, we may recommend waiting one or even two complete menstrual cycles before resuming treatment. This allows the body to rest and gives us a chance to examine our treatment strategy and possibly change our approach in future cycles. In subsequent IVF cycles, the ovulation induction phase may not be necessary if frozen embryos are available for transfer.

Complications & Risk Factors after Embryo Transfer

Assisted reproduction technique (ART) is an efficacious treatment in sub fertile couples. So far little attention has been paid to the safety of ART, i.e. to its adverse events and complications; the consensus meeting on Risks and Complications in ART.

Multiple pregnancies

If 25% of all pregnancies after IVF/ICSI are twin pregnancies, 40% of all babies born after ART are born as part of a twin pair. Many physicians and patient couples underestimate the negative consequences of twin pregnancies. Perinatal as well as maternal mortality and morbidity are increased in multiple pregnancies as compared with singleton Pregnancies due to a higher rate of prematurity and low birth weights in the children; and due to pregnancy complications in the mothers. Furthermore, parents of multiple births have more stress, and siblings of multiples are more likely to have behavior problems.

Long-term effects of ART on women

Hormonal and reproductive factors are involved in the etiology of breast cancer and cancers of the female genital tract. Therefore, the effect of fertility drugs on the risk of these

Cancers has been investigated. Many studies have not been able to reach solid conclusions due to low statistical power, lack of control for important confounders (such as cause of sub fertility and parity) and short duration of follow-up.

Effects of ART on offspring

Much concern has been expressed about the health of children born after ART. In particular, the risk of boys born to couples with male factor sub fertility has drawn attention, since in a substantial number of male factor sub fertility cases, a genetic cause can be suspected.

Patient selection and counseling for eSET (elective single-embryo transfer)

It was agreed that the essential aim of IVF/ICSI is the birth of one single healthy child, with a twin pregnancy being regarded as a complication. The chances of having a single healthy child after eSET have increased, and equal the spontaneous pregnancy rate in a normally fertile couple.

Women who can get pregnant without fertility drugs or medical procedures usually have only one baby. Women who need fertility treatment are at higher risk to get pregnant with twins, and rarely with triplets or more. This is called multiple gestations. Multiple gestations can increase the risk of pregnancy for the mother and for all the babies. Multiple gestations are risky for the babies. Because there are too many babies in the womb, you may have a miscarriage. A miscarriage occurs when your pregnancy ends without the birth of any infants that can survive, before the 20^th week of pregnancy. Or you could have a premature delivery when the babies may be born too early (but after 20 weeks of pregnancy) and have problems with lungs, stomach, or intestinal tract. They may have bleeding in the brain, which can cause problems with the baby's brain, nervous system, and hamper its development. If the babies are born very early, they will probably be very small and may even die.  Twins, triplets, and other multiples are more likely to have problems with their brain development and nerves if they are born early. One of the more common problems is cerebral palsy, a condition that affects movement. Other problems associated with multiple births may not present for many years after delivery

Embryo transfer and elective single embryo transfer have become popular topics as more couples turn to fertility treatments to conceive. Our Fertility doctor takes your age and in vitro fertilization (IVF) prognosis into account when performing embryo transfer. Pahlajani Test Tube Baby has a clear guidelines offer you the best chances for a healthy pregnancy and delivery. Do you have a good prognosis for IVF? A good, or favorable, IVF prognosis applies to women who:

» Are in their first IVF cycle

» Have healthy embryos or multiple frozen embryos

» Have already had success with IVF

If you are under 35, and have a favorable prognosis for IVF, you are more likely to conceive with a single embryo transfer. If you're over 35 and have a good IVF prognosis, our doctor may prefer to transfer more than one embryo.

» Under 35: 1-2 embryos

» 35 to 37: 2 embryos

» 38 to 40: 2 to 3 embryos

» 41 to 42: 3 to 5 embryos

Becoming pregnant with multiples increases the risk of complications for you and your babies. Single embryo transfer can help you avoid these risks. The most common complications associated with multiples are increased rates of preterm labor and preterm delivery. Preterm delivery can cause a host of problems for the infant, including:

» Respiratory, growth, and digestive problems

» Long-term learning and developmental difficulties

» Low birth weight

Complications for mom are also increased with multiple gestations. Here are some of the increased health risks for moms of multiples:

» C-section

» Emotional stress

» Gestational diabetes

» High blood pressure and preeclampsia

» Increased cost for medical care

» Increased risk of miscarriage

This is why doctors prefer single embryo transfer, or transferring a lower number of embryos during IVF, when possible.

Investigation and Clinical Approach of Recurrent Implantation Failure

Recurrent implantation failure (RIF) derives from the practice of IVF. The ability to identify implantation failure after the transfer of embryos raised the possibility that there exists a patho-physiological state leading to repeated implantation failure. RIF can be defined as the repeated lack of implantation after the transfer of embryos. Prior to IVF, treatment resulted either in a pregnancy or not. IVF added the ability to further compartmentalize the treatment process so that it became possible to know when an embryo was transferred and if an implantation occurred. Hence RIF became a possible clinically identifiable phenomenon. The relevance of defining such a problem lies in the ability to diagnose patho-physiological conditions, which might be amenable to treatment and thus increase the implantation rate thereby increasing a couple’s chance of conception.

Many practical procedural problems exist when trying to define implantation failure. One limitation when defining implantation and implantation failure is that at present, implantation can only be determined by a rising quantitative hCG level which occurs a number of days after implantation has actually occurred or failed. There remains a time-frame which cannot be further compartmentalized and thus limits the ability to precisely define the cause of implantation failure. Thus, for practical purposes, implantation is defined as a rise in the quantitative hGC level determined at some point after embryo transfer. The most accurate way to determine this would be to do daily serum HCG levels starting after embryo transfer. But again practicality dictates that the first level is drawn at some point after embryo transfer and for many programs this is usually 10–14 days after hCG is given.

The timing of when the first hCG determination is performed will affect the implantation rate. The earlier the first hCG determination is done, the lower the failed implantation rate will be since some pregnancy losses will occur prior to the hCG determination for those programs measuring it later in the cycle. Any definition of RIF requires a standardization of the time from embryo transfer to the time used to determine a positive hCG level. The definition also needs to establish what will be considered a pregnancy when using hCG. For example, will any value above the threshold value be considered evidence of implantation or will there need to be rising hCG levels? Finally, the day of embryo transfer needs to be established. For example, suppose there was a preventable cause of failed implantation that occurred at the morula stage. Programs transferring day three embryos would have a higher failed implantation rate than those programs transferring blastocyst embryos.

The accuracy of a clinical definition is to a large extent determined by the simplicity or, conversely the complexity, of the problem. A physiologic process that has a single factor is easy to define in its entirety. A pathological process that alters the physiology of the process in question may be caused by a single factor and, if measurable, the definition of the disease process is simple and accurate. The thesis of this manuscript has two prongs. First, implantation is extremely complex and highly redundant. Continuation of the species is evolutionarily a high priority. Therefore, the evolutionary process has preserved the ability to implant through accruing a number of individual processes, many of which are, in and of themselves, not necessary, but collectively contribute to a maximum chance for implantation. Second, because of the complexity and redundancy of implantation, assigning etiologies for implantation failure and RIF will be difficult.

There are some processes involved in implantation which are simple and absolutely required for implantation to occur. But there are many processes which are not necessary but contribute to implantation. Therefore, the problem with implantation failure as well as RIF is not in defining the problem, which is self-evident, but in assigning causality to the phenomenon. Some causes of IF and RIF will be a single factor. Their identification and their contribution will be easier to discern. However, implantation failure and RIF may be a result of a threshold phenomenon whereby there are a multitude of factors required for maximum implantation efficiency. A failure of any one of these factors might, or might not, reduce the overall implantation rate. But to reach a state whereby implantation failures, or implantation fails repeatedly, might require errors in a number of factors and might not be the same factors for each case of IF or RIF. The identification of this problem becomes complex and very difficult to approach experimentally.

Any deviation from or interruption of the normal structure or function of any part, organ, or system, or combination thereof, of the body that is manifested by a characteristic set of symptoms or signs, and whose etiology, pathology, and prognosis maybe known or unknown. Implantation failure and especially to recurrent implantation failure demonstrates just how difficult it becomes to define a disease. There are two ways of approaching a definition for a normal implantation rate: evaluate spontaneous pregnancy rates in fertile couples, or evaluate implantation rates when using donor oocytes. There are many factors intervening when couples have intercourse which could result in a less than perfect system so that more than 50% of the cycles do not result in a pregnancy. Therefore, using the natural pregnancy rate in maximally fertile women does not provide the best definition of a normal implantation rate.

IVF provides a more definable system since it involves oocyte, sperm and, endometrium. For this more defined system, the relevant statistic is not normal implantation rate but rather, the maximum implantation rate. Any deviation from this maximum implantation rate would represent a compromise that is, by definition, a disease. Identifying the maximum implantation rate requires evaluating implantation rates obtained through the use of normal oocytes, sperm, and endometrium when the IVF procedure is done by the technically most adept IVF units. This condition is frequently met for women using donor oocytes for age-related ovarian failure. The implantation rate for the double embryo transfer patients was equally high at 56%. It would appear that the maximum implantation rate for IVF is between 40% and 60%. For IVF programs with substantially lower implantation rates, the problem may be technical related to either the clinical or laboratory components of the program. Until a program’s implantation rates meet industry standards, evaluating the patient for problems with implantation failure will be premature.

Defining the term “recurrent” is very challenging, analogous to defining infertility or recurrent pregnancy loss. A problem when using pregnancy rates based upon number of transfer cycles relates to the variability of the number of embryos transferred on any given cycle, the quality of the embryos transferred, and the day of embryo transfer. Defining recurrent implantation failure as three unsuccessful IVF attempts actually defines RIF in terms of failed IVF cycles and does not address the issue of implantation rates. Some patients may have a large number of poor quality embryos transferred for a given IVF cycle; whereas, others may have only one or two embryos transferred. Thus, defining RIF in terms of pregnancy rate does not allow an evaluation of the implantation rates. Also, the day of transfer greatly impacts the pregnancy rate since blastocyst embryos have a higher implantation rate than day three embryos.

Therefore, time to pregnancy should be shorter for cycles with blastocyst transfers and especially if many blastocysts are transferred on a given cycle. For example, transferring three blastocyst embryos should result in a pregnancy sooner than transferring only a single blastocyst embryo. The definition of RIF would be fewer transfer cycles for multiple optimal embryos transferred per cycle than for either poorer quality embryos, high quality embryos transferred on day three, or fewer blastocyst embryos per cycle. Age also has an impact on the pregnancy rate and is a known factor for implantation failure. Thus, defining recurrent differs depending upon the age of the population studied. Finally, the choice of the number “three” deserves some attention. For three to be the operational number of IVF cycles, there needs to be some correlation with that number and the incidence of implantation failure. For example, the cycle fecundity needs to decline after three cycles of IVF if RIF is defined by the number of cycles for transfer. Where there is no implantation failure, the cycle fecundity rate remains constant. The cycle fecundity rates of 36.2% for each of the first four cycles of donor oocyte embryo transfers.

However, cumulative pregnancy rates for IVF have demonstrated a decline in cycle fecundity with successive failed IVF cycles. A clinical pregnancy rate of 19.0% for the first IVF cycle, 17.4 for the second, 11.8 for the third, 10.8 for the fourth, and less than 6% for the next three successive cycles of IVF. Defining RIF after three cycles of IVF with this data is problematic given the fact that is seems the number should be either two or four cycles of IVF. Furthermore, notes an even more dramatic decline in pregnancy rates with successive IVF cycles where the embryos transferred were blastocyst embryos. The cycle fecundity rates were 36% for the first transfer, 19% for the second, and 9% for the third. Given this data, RIF may need to be defined as failed two or even one cycle of transfers with blastocyst embryos.

A second method of defining RIF uses the number of embryos transferred. All consecutive pregnancies from a large IVF program were analyzed to determine the total number of embryos that had been transferred to achieve each pregnancy. The number to achieve 80% of the pregnancies was 8 and for 95% of the pregnancies it was 12. Arbitrarily defining normal at the 95 percentile, RIF was defined as having failed to achieve a viable pregnancy if more than 12 embryos had been transferred. The patients participating in this study were all infertility patients and, thus, the pregnancy rates were not maximal as they might have been had donor oocyte recipient patients been used. The pregnancy rates and implantation rates were below what they are today, and these pregnancies were achieved using day three transfers, not blastocyst transfers. Therefore, the number used to define RIF would be lower today and depend upon whether day three or blastocyst transfers were being considered.

Any definition of RIF will be found wanting given the complexity and redundancy of the implantation process. However, a working definition of RIF can be based upon the number of embryos transferred. The definition will depend upon the stage of embryo development. The actual number will vary by center and can best be calculated by using pregnancies delivered in patients using donor oocytes. The definition of RIF used in our program requires the transfer of =8, 8-cell stage embryos or =5 blastocyst embryos. Evidence of implantation is accepted when there is a rise in hCG for hCG measurements made 12 and 14 days after the hCG injection that is given to trigger the time of retrieval.

Implantation Bleeding after Embryo Transfer

Embryo transfer is the most critical step in the IVF procedure. You can have the best quality embryos, but if they are not placed into the uterus correctly, then pregnancy will not occur. That is why transfer technique is so important. Pregnancy rates can vary by Physicians, and this is all because of transfer technique. Once the disparities between transfer techniques were corrected and integrated, the pregnancy rates became consistent. For this reason, you want to seek out a Physician who has a lot of experience with embryos transfers and comparable good pregnancy rates. So, if you were paying much more money for an IVF cycle, would ask for a more experienced doctor to do the transfer.

After we discharge our patients from implantation unit, we send them home with instructions to go about the rest of the day and ensuing two weeks with normal, reduced activity. There is no need to be on bed rest. All our patients have different medication protocols that they go home with. Often referred to as the two week wait so we have now come to the end of the IVF procedure and the maximum that our technology can help a person to achieve a pregnancy. We are at the point where we have to wait and see. If a day-3 transfer was done, it will take approximately 7 days for the remainder of the process to be completed and for the pregnancy test to be positive. For that reason, it is refer to pregnancy tests at 8 or 9 days post transfer. For a blastocyst transfer, you only need three more days to get a positive pregnancy test.

Pregnancy occurs when the egg is released by the ovaries, fertilized by sperm to form a Zygote fertilized eggs. This process occurs in the fallopian tubes, the Zygote travels to the uterus and during this period, it was further divided to form a blastocyst, which can be described as a ball of cells with sheath. Once the blastocyst reaches the uterus, it gets out from the protective outer layer and glued on the inside lining of the uterus (endometrium). Through this entanglement, blastocyst formed a relationship with the mother's blood vessels, to receive the oxygen and nutrients needed for growth.The blastocyst can cause a slight amount of bleeding, such as penetrating the endometrium and will be attached to the uterus. This blood coming out from the uterus through the vagina, and this incident is called implantation bleeding, which is considered as one of the signs of early pregnancy. Although it is a sign of pregnancy, absence does not mean that there is no pregnancy, no. In other words, every pregnant woman is not likely to experience bleeding, because it is not necessary to cause bleeding while the blastocyst implanting itself in the uterine wall. It is said that only a third of women experience this condition. The basic idea about the signs and symptoms of implantation bleeding and the time of the occurrence may be useful in recognizing the condition.

This usually happens right before the estimated date of the menses. The average menstrual date is calculated as the 14 day from the date of ovulation (the cycle can vary between women) and the implantation bleeding occurs between six to twelve days after ovulation. In other words, this bleeding usually occurs on the third or fourth week of the date of the last menstrual period. Eggs that have been fertilized or Zygote takes approximately five to six days to travel from the fallopian tubes toward the uterus. After that, it will be attached to the endometrium. Thus, implantation bleeding is said to occur in nine to twelve days of ovulation. But in some cases, it may occur as early as six days as well. So, the time frame for the occurrence of implantation bleeding is usually given as 6 to 12 days after ovulation. Even the time taken by the blood to come out of the womb may affect the time of implantation bleeding.

As mentioned above, this type of bleeding is caused by small amounts of blood that is released from the blastocyst attachment locations on the endometrium. First of all, you must understand that implantation bleeding is not likely to occur in women. It may happen that the endometrium does not bleed at all, while the blastocyst will be attached. Even the amount of bleeding can vary from one woman to another. So, the first and foremost sign of bleeding implantation bleed itself. The vaginal discharge may be too minimal or spotty in some women, whereas in some others may be a little heavier. However, in this case the type of bleeding, blood will be pink or Brown, like old blood (it takes some time for the blood to come out of the womb). Commonly, implantation bleeding is not associated with any symptoms, but some women may experience minor cramps in uterus and increased basal body temperature (the lowest temperature attained by the body during rest, usually while a sleep).In addition to the implantation bleeding and other symptoms of pregnancy include nausea or vomiting, tender and swollen breasts, frequent urination, fatigue, flatulence and increased sensitivity to odors. If these symptoms develop after implantation bleeding along with the late period; they may indicate pregnancy. However, confirmation of the pregnancy is done with a blood test and urine as well as obstetrical ultrasound. If implantation bleeding is accompanied by pain, you should consult with your obstetrician.

Blood contaminates the endometrial cavity at the time of the transfer, this will kill the embryos and pregnancy will not occur. The catheter must be placed as gently and a traumatically as possible. That is an absolute requirement. The endometrium, which is now in its fullest growth state, thickened from estrogen stimulation, can be easily scraped and these cause bleeding. You should not worry if brown blood or discharge occurs at the time of transfer, it will usually manifest within the first day or so after the transfer, but not into the mid-Luteal phase or later. That type of bleeding would be from a different source. There are situations, however, when bleeding can occur but not be ominous. Sometimes a woman's cervix will bleed easily from being scraped by the speculum or irrigation or wiping. This external bleeding will not affect the endometrial cavity as long as the transfer catheter is not exposed to the blood. For example, I do not let the catheter get exposed until the introducer is well into the cervical canal, near the internal cervical, to begin advancing the catheter. Bleeding that occurs later in the luteal phase, days after the transfer, is very common if vaginal progesterone is used. 

For some patients, because used both vaginal and injectable progesterone by the experts, it is almost 90%, but the bleeding tends to occur near the time of the pregnancy test or soon thereafter. This is probably caused by some erosion occurring on the external cervix. The exact cause, however, is not clearly understood. It is usually light spotting and can be anywhere from red to brown. Red is newer blood and brown is old blood. Patients not to worry about this; the only bleeding that patient would worry about is bleeding that is red and heavy like a period. This is not good, and should not occur if the hormones progesterone and/or estrogen have not been discontinued. Some patients will experience slight spotting 3-5 days after embryo transfer and refer to this as "implantation bleeding." Whether or not this is caused by implantation is not known. Implantation should not cause bleeding. However, again, if it is not bright red blood that is heavy like a period, it should not cause worry.

The body is a fluid and dynamic structure and there will be many sensations that patients report during this period. Some will report many types of “pains”, some will have “cramping” and some will have “bleeding”. Most of these symptoms are not of any consequence but cause patients to needlessly worry. Some doctors have referred to these “pains or cramping” as implantation related. That may be the case but no one knows for sure. Certainly with implantation, the uterus is undergoing changes and cramping tends to be one way that uteri react. So, if the timing is appropriate, namely at the point where implantation would be expected as described above, then these sensations could certainly be related to it. Of course, onset of one’s period can also be signed by cramping but this is usually accompanied by bleeding. If adequate hormone replacement is given in the luteal phase of the process, then the period should not start until the medications are stopped. That is the cause of the onset of the bleeding and cramping associated with a period; it is the withdrawal or abrupt drop in hormone levels. Some will claim that this is the uterus “stretching or growing” but this could not be the case at this point in the pregnancy. 

The embryo is like a mere fleck of dust within the cavity and not big enough for the uterus to begin “growing.”Some patients will experience sharp or stabbing pains, on the other hand, that may not be from implantation but more from the ovaries. About three days after the retrieval, the ovaries will refill with fluid and this stretching of the follicles and ovaries certainly can cause pain in one side or both sides. This is the pain sensation that most patients have during this period of time. Post IVF complications causing severe pain include Ovarian Hyper stimulation Syndrome (OHSS), ovarian torsion (twisting), ovarian flow of blood, Ectopic pregnancy and Pelvic infection. 

If the pain is mild, then intervention is probably not required but if severe, it could be one of these serious medical problems that will require medical treatment because they could be life threatening. You should know, however, that these complications are very rare. On the other hand, if you have had a positive pregnancy test and these symptoms occur impending miscarriage could be another source of cramping or pain.Bleeding within this period of time is also a very common complaint. In most cases this bleeding is inconsequential but it could also indicate problems such as inadequate hormone support for the Luteal phase, thereby causing the endometrial lining to start to slough. 

It could also indicate that the period is starting or that an abnormal pregnancy exists or is being miscarried. When the bleeding is light, I usually will reassure my patients that no intervention is required. For one, there is no intervention that can be done, other than checking hormone levels and increasing the progesterone if the level is inadequate. Secondly, this could be normal, if in fact it is implantation bleeding. Thirdly, if vaginal progesterone is used, the progesterone may be causing the cervix to be more delicate or friable and therefore cause cervical bleeding. If implantation bleeding is accompanied by pain or heavy bleeding, you should consult with your obstetrician.