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Tuesday, February 26, 2013

Does going through IVF cause premature menopause ?

Many women worry that going through IVF will deplete their ovarian reserve , as a result of which they will run out of eggs , reduce their long-term fertility, and reach the menopause earlier. Logically, this makes sense  ! We all know that women are born with a certain number of eggs ; and that their ovaries do not produce any new eggs after birth. If the doctor stimulates the ovaries to grow lots of eggs during the IVF treatment by giving hormonal injections, won’t this mean that there’ll be fewer eggs left in the ovaries after the IVF treatment – especially if they are doing many IVF cycles ? When going through IVF , the doctor harvests several eggs at the time of egg retrieval by stimulating the ovaries with hormones (FSH or a combination of FSH and LH). A woman with a menstrual cycle length of 28 days ovulates only 12 eggs per year. But women going through IVF produce 15 or more eggs at a time. Doesn’t  this mean that IVF depletes the egg reserve faster than usual and can lead to earlier menopause ?

Let’s look at the facts.

The ovaries are a pair of organs situated in the pelvic region of women, one on each side. They act as the reservoir for our eggs. Eggs are the cells which carry half of the information (genetic blue print) necessary for creating a baby. Such precious egg cells are stored, nourished and protected within specialized structures in ovaries called follicles.  A female foetus at around 18-22 weeks of gestation contains about 2,000, 000 follicles in its ovaries and each follicle contains one egg. At the time of birth, a girl has only about 3,00,000 egg left in her ovaries – she’s lost over 80% of her eggs even before being born ! The remaining follicles continue to get depleted during her life time ; and when there are only about 1000 follicles left, she reaches menopause . A woman normally ovulates only about  400 eggs during her lifetime , releasing one mature egg each month , from the time of attaining puberty until reaching menopause. An ovary contains several immature follicles (and hence several eggs!) but not all these follicles will become mature enough to release a functional egg. More than 99.99 % of the follicles (and hence the eggs) are simply lost , without serving their biological purpose.  Human reproduction is remarkably inefficient !

During each menstrual cycle , several ovarian follicles start growing in response to the FSH secreted by the pituitary gland. Of these recruited follicles , only one follicle grows to maturity , and this is called the dominant follicle.  It carries the mature egg which will be released during ovulation. The other follicles which fail to reach maturity are lost . They die, and this natural process is called atresia. During IVF treatment our body is supplied with high amounts of FSH (several folds higher than our body naturally produces), in the form of injections. This high amount of FSH helps to rescue more of the follicles which are recruited during that particular menstrual cycle. This is the reason why IVF specialists are able to harvest several eggs during an IVF treatment. This is also the reason why IVF treatment will not deplete your ovarian ( egg) reserve ! The follicles (  and the eggs inside them) which would normally have died during that particular menstrual cycle are being rescued during an IVF cycle. This is why an IVF treatment will not cause you to go through menopause earlier. This is true even if you do many IVF cycles !

However, do remember that many infertile women are at increased risk for having poor ovarian reserve and reaching menopause early , whether they do IVF or not ! This maybe because they have endometriosis, or because they have undergone laparoscopic surgery.  If they reach menopause earlier than expected after having taken IVF treatment , they are quite naturally going to blame the IVF treatment for this – whereas the reality is that they would have reached the menopause early anyway,  even if they had not done IVF !

Tuesday, February 19, 2013

Adopt, don't shop !

This is a guest post from one of my blog reader. We infertile couples, often come across people, who look at us as if we are sinners when we say we are undergoing IVF treatment to have our baby. Their arguement is "why don't you just adopt, there are so many children without home?". They think adoption is a nicer thing to do instead of spending so much money to have a baby. Some even think doing IVF is against God's wish. This is a comment I received on my article " So, why don't you just adopt a baby ? " I thought this comment by the reader is very honest and explains the problem which is inherent in an adoption proocess. I wish everyone finds this useful too ! Remember, we are not shopping for a baby, we are fighting  for our right to have a baby !

 A good post and certainly pertinent to anyone experiencing infertility. I've actually been "looked down upon" by quite a few people for wanting to pursue IVF. And of course, the critics are either completely uninterested in ever having children or have a litter of babies themselves. What bugs me the most is that they seem to think that it's the job of the infertile to save the troubled children of the world. Granted, that is a noble endeavor, but why is it any more MY duty than those who are fertile?

Most people don't know how immensely complicated (and expensive!) adoption is. In some cases, it's even cheaper to succeed at IVF than adoption. And even after you've shelled out tens of thousands of dollars, there still is no guarantee that everything will go smoothly. Some of my acquaintences tried to adopt abroad and their child got stuck in limbo in a state nursing facility for 2 years after birth. Believe me, if adopting were as simple as taking a stroll to the local catholic monestary to pick up a child, I'd be a father many times already!

But if its one thing that troubles me least about adoption it's the genetic difference. I always saw something romantic about choosing to love a child, rather than being coerced into the relationship by Darwinian destiny. What DOES bother me is that, when you adopt, everyone seems to want to get their talons in your child one way or another. In the United States, domestic adoption is a seller's market, which means adoptions are "open." In other words, the "birth parents" stay in regular contact with THEIR children and sap away the joys of parenthood while the adopting parents shoulder all of the burden. If it's one thing I simply couldn't handle, it would be some stranger visiting at Christmas, telling my child how much he/she takes after THEM.

Even if you adopt from abroad, there is this accepted truth in society that somehow your child is not entirely your child. That some essential part of them remains in the place that they were born. That you must pay some kind of homage to the "culture" from which their soul has apparently sprung forth. And its this social perception of adoption that strikes me most painfully: that even though you put in 100 percent of the love that any other parent would, the adopted child can only really be half yours, in the end.

In the United States, our television channels are littered with shows about adopted children going off to reunite with their "birth" parents. That they simply felt lacking until they were able to become one with with their "birth family" again. All the while the adoptive parents are expected to stand back and smile. The adoptive parent is expected to share the thing that parents of biological children are NEVER expected to share. It may sound selfish, but I could never share my children in this way. It would break my heart.

And so I think that's what pushes me toward IVF most.

Friday, February 15, 2013

Do IVF drugs increase the risk of cancer ?

Infertile women go through lot of emotional turmoil, and to add insult to injury, there are lots of misconception regarding the use of fertility drugs. Some link fertility drugs with gynaecological cancers; while others even believe that children born out of fertility treatment carry an increased risk for developing certain kind of cancers. What is the truth ? 

It’s easy to understand why women would have this belief – it sounds quite logical ! We know that breast cancer is a hormonally dependent tumour; and that estrogen levels are high during IVF treatment. Also, a lot of hormonal injections are given during an IVF cycle , in order to help the women grow lots of eggs. If the hormonal stimulation helps them produce a lot of eggs, it’s quite reasonable to conclude that this ovarian overactivity may increase the risk of developing ovarian cancer later on as well ! Husbands are understandably scared about the impact of these drugs on their wives, and don’t want to risk her heath in their quest for a baby.  

Please remember that being infertile is itself a significant risk factor for developing certain kind of gynaecological cancers. For example, women who were never pregnant have a higher risk of developing breast cancer. This is because both pregnancy and breast feeding reduces a woman’s exposure to the estrogen hormone produced by her ovaries, which stimulates the growth of the cells lining the mammary glands in the breast. Pregnancy and breast feeding also mature these breast cells into milk-producing cells , and these mature cells are refractory to the transforming effect of hormones. Women who had a full-term pregnancy also have a lower risk of ovarian and endometrial cancers – the higher the number of full-term pregnancies , the lesser is their risk of developing these kinds of gynaecological cancers. You can read more about this at 

What do the data show ? To assess whether the risk of cancer after doing IVF increases or not is an extremely complex task , because there are so many other variables which have to be taken into account . Simple examples include: an individual’s life style, family history of cancer and their exposure to carcinogens, all of which are likely to confound the results . This is why these studies are very hard to conduct. One such recent study involving 9175 Finnish women showed that the general risk of cancer or the risk of hormone-related cancer was not increased by IVF (PMID:22343550). Another study in Lancet examined the incidence of breast and ovarian cancer in 10,358 women referred for IVF between 1978 and 1992. They concluded that ovarian stimulation during IVF does not increase a woman’s risk of breast cancer. They also found that there was no significant increase in ovarian cancer after ovarian stimulation for IVF. On the other hand, they concluded that women with unexplained infertility had an increased risk of ovarian cancer ! (PMID:7475593).
This is good news. Remember that IVF hormonal injections are natural hormones, which get excreted promptly from your body, and do not linger on to cause mischief later on. Over 2 million IVF babies have been born worldwide over the last 30 years, and we have not seen an increased prevalence of breast or ovarian cancer, so this is very reassuring. Going through IVF will not increase your chance of having cancer at a later age. Infertile women should try to ensure they have a healthy lifestyle , because infertility by itself is a significant risk factor for certain forms of gynaecological cancers – but this is simple common sense advise , and you don’t need a doctor to tell you this !

Thursday, February 7, 2013

Will embryo(s) fall out after embryo transfer ?

A fear which is wide-spread among IVF patients is – will my embryo fall out if I stand up or walk around after the embryo transfer ? This is quite a reasonable worry – after all, if the embryos are transferred through the uterus through the cervix, then why can’t they come out through the same route?  However, if you understand the anatomy of the uterus , these doubts will vanish and you will fell much more confident and comfortable during your 2ww.

Women imagine that when the doctor puts the embryos inside the uterus, they are deposited inside a space within the uterus in which the microscopic embryos can roll freely!  They believe that if they rest, the embryos will settle down and stick to the wall of the cavity. After all, when you stick two pages together with glue, don’t you leave them undisturbed for some time to allow the glue to set ? They are worried that if they walk about, the embryos will be disturbed from their resting place , and may fall out of the cavity.

In reality, the uterus is a muscular organ , about the size of your fist. When people hear the word ‘uterine cavity’, they imagine that there is a real cavity within the uterus ( like a cave, perhaps) , but this is not true. The cavity we talk about is not a true cavity , but just a potential cavity . The walls of the uterus are in contact with each other – after all, there cannot be any empty areas inside the
body ! For example, press your palms together. There is no real space between them , since your palms are touching each other. What happens when you insert a small ball in between your palms ? The ball has created a space for itself ! In the same way , a uterus which doesn’t have an embryo inside it carries only a potential space. Only when the embryo grows in size will this space enlarge. Do you know that at 5 weeks of gestation your embryo is just the size of a sesame seed ? Imagine what will happen if you keep a seed between your pressed palms and move your hands in whatever way you might wish to ? There is no way the seed will be dislodged  - it is safe , snug and secure in its resting place. This is exactly what happens to your embryos inside your uterus !  Nothing you do can dislodge an embryo – NOTHING (even jumping or running) ! If the embryo is healthy and if your endometrial layer is receptive , the embryo will stick to the wall and bury itself inside the lining (just like a seed does , when planted in fertile soil). External physical activity cannot influence this natural biological process which occurs in utero.

A lot women refuse to go to the bathroom for a few hours after the embryo transfer, because they are scared that if they pee, their embryo will fall out of the uterus. They just end up making themselves completely miserable – and I worry that an overdistended bladder can actually cause uterine contractions needlessly ! Others are scared that if they cough or sneeze after the transfer, they will ruin their chances of success. Please do not obsess – remember that nature has designed the body with enough intelligence, that you don’t need to worry at all !

After the transfer, the uterus can contract (for example , during an orgasm, which often occurs while sleeping during  the 2ww ), but the progesterone produced during the luteal phase will prevent these uterine contractions from dislodging the embryo. Intercourse and orgasm cannot cause any harm after the transfer – after all, fertile couples do have sexual intercourse during the 2ww, and they get pregnant all the time.

After an embryo transfer , bed rest is absolutely unnecessary. I have heard from women who have been forced to spend 2 weeks in bed after the embryo transfer – and many of them have done so because of their doctor’s orders ! ( I think the reason some doctors continue to give this outdated advise is a clever way of subtly blaming the patient if the cycle fails ! “ You didn’t get pregnant even though I did such a good job with your IVF treatment , because you did not rest properly “ is their subliminal message) . Even a couple of days in bed can do you harm , physically and emotionally. Bed rest may increase body aches and back pain , and makes your physically uncomfortable.  Resting may actually reduce uterine blood flow by reducing pelvic circulation. Bed rest creates havoc  with your mental well-being as well ! When you lie down in bed all the time and have nothing to do, your mind will start to play all sorts of games with you. The end result is an unhealthy obsession with your body’s symptoms and signs – and this often causes panic , which does not help after a stressful IVF cycle.  The bed rest, rather than resting your mind, often causes more stress !

Please do not restrict your normal day-to-day activities after an embryo transfer.  Use your common sense, and do not do any strenuous activity which might cause you to blame yourself if your cycle fails ! And what happens if your mother in law enforces house arrest ? Remember that she has been brainwashed , and is following well-meaning but misguided advise, based on centuries of myths and misconceptions about bed rest and pregnancy. She is not trying to harass you – she is just trying to help you to have a baby , based on her personal ( but flawed) world view ! Please don’t rock the boat by flatly refusing to listen to her – just give her this article to read , so she understands why bed rest does not help!  And if she is still unconvinced, please share this with her - Bed rest has not been scientifically proven to improve pregnancy rate after embryo transfer(PMID: 19590224)

Friday, February 1, 2013

Embryo Transfer

The process of embryo transfer

The day when our in-vitro embryos return back to us (to their mama !) is one of the most exciting moments of an IVF cycle. We forget the struggles we went through when we are admiring our microscopic babies under the microscope. Embryo transfer is one of the rate-limiting steps in an IVF cycle and plays a pivotal role in determining IVF success. 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. Embryo transfer done badly by an inexperienced doctor can change the fate of an IVF cycle –there is a vital intangible “physician factor” involved in determining the outcome of an IVF cycle! 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. 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 ? As usual there are many questions: come let us find the answers together.

What is an Embryo Transfer ?

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 !

How is an embryo transfer performed ?

During ET, the doctor puts you in the undignified lithotomy position in the operation room, 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 ( a long thin hollow soft sterile plastic tube) 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 ( which consist of the embryos floating in a microscopic drop of culture medium)  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  (through the cervix) 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 ET procedure , in order to hold your hand and provide you with emotional support , so that you remain stress-free and relaxed. 

Are there any variations in the transcervical embryo transfer method ?

Transcervical embryo transfer is performed in two ways – without ultrasound guidance (traditional ‘clinical touch’ method) and with ultrasound guidance. 

In the traditional ‘clinical touch’ method , the catheter is positioned blindly in the “desired position” ( about 1 to 2 cm away from the uterine fundus), 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 ?

As usual , this is a hotly 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 (uteri and cervixes come in many different shapes and sizes !) 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 (remember that the cervical canal and uterus are at an angle to each other) 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 maybe 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. 

1.      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.

2.      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.

3.      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.

4.      Catheter choice

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

5.      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.

6.      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 (there might be bleeding , and the patient many experience pain) ; or the embryo transfer cannot be performed at all. The presence of an acute curvature between uterus and cervical canal (utero-cervical angulation) 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 beforehand , 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 ?

1.      Transmyometrial embryo transfer

2.      ZIFT

 Transmyometrial embryo transfer

In this method , using a special Towako 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.


ZIFT stands for zygote intrafallopian 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 gestation. 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 !

Some FAQs about embryo transfer :

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