Bad eggs as a cause of unexplained infertility

For about 10% of infertile couples we cannot determine what the reason for their infertility is. The diagnostic label we use for them is unexplained infertility, which just means that we cannot provide an explanation as to why they are infertile. For many of these couples , we have now found that the reason for their infertility is poor quality eggs. This can often be a difficult diagnosis to make; and it is one which is often overlooked by many gynecologists , especially when the woman is young and has regular cycles.

Some women with poor quality eggs have poor eggs because they have impaired ovarian reserve. Every woman is born with all the eggs she is ever going to have in her life; and as she gets older, she keeps on depleting her ovarian reserve until she becomes menopausal. However , for at least 10 years before reaching the menopause , her egg quality declines, so that she has enough eggs to produce enough hormones to get regular menstrual cycles, but not enough to make a baby. This is called the oopause. Since her cycles are regular , this lulls her - and her gynecologist - into a false sense of security. The good news is that we now have accurate tests to check ovarian reserve. These include a high-resolution vaginal ultrasound scan to check the antral follicle count; and a blood test to check the levels of AMH , or anti-Mullerian hormone. A low antral follicle count and a low AMH level both suggest poor ovarian reserve. In these cases the problem is that we have to technology to make the diagnosis but the diagnosis is not made properly because of a lack of awareness.

There is an other group of women , who have apparently normal ovarian reserve, but poor quality eggs. The group is much more frustrating to deal with. It is only when we do IVF or ICSI for these women , that we find out that they have an egg problem. Let me explain.

Some of these women will grow eggs poorly in response to superovulation. Such a poor ovarian response is a marker for poor ovarian reserve. Unfortunately, they have a normal antral follicle count and normal AMH levels, which means this diagnosis is made only after the IVF superovulation has started.

The third group is perhaps the most difficult. These are women who grow a sufficient quantity of follicles in response to superovulation ; and have high estradiol levels as well. Egg collection is usually uneventful ; and the doctor often retrieves 8 to 16 eggs for them. If IVF is done, when the fertilization check is performed the following day, much to the embryologist’s surprise and the patient’s dismay , it is found that the fertilization is very poor even though the sperm are fine and actively motile. If ICSI is being done, the embryologist often finds that the eggs are morphologically normal ; or are very fragile. For example, these eggs have granular cytoplasm ; or vacuoles in their cytoplasm ; or dark areas within the cytoplasm. Since normal eggs are simple spherical formless blobs, these subtle cytoplasmic abnormalities are often missed or overlooked. The embryologist may also noticed that the eggs are fragile, and the cell membrane offers little resistance to the injection pipette. Many of these eggs may die during the ICSI process.
Unfortunately , because egg morphology has not been adequately studied , we still do not have good descriptive terms , when talking about these abnormalities. Since the eye only sees what the mind knows, often these abnormalities are not picked up. The patient is often subjected to repeated IVF or ICSI cycles , with the same poor results each time.

Why is abnormal egg cytoplasm such a difficult problem ? In order to understand this, let's first review the important role the egg cytoplasm plays in embryo development. The most dramatic events during fertilisation occur in the nucleus, when the male and the female pronuclei fuse. However, the energy to drive this fusion comes from the mitochondria in the egg - the energy powerhouses of the cell, which power cleavage and cell division. One major problem is that there is no way of testing egg cytoplasmic quality - either clinically, or in the research lab at present. While electron microscopy studies have confirmed these eggs have cytoplasmic abnormalities, this is still an area which has not been adequately studied.

Of course, part of the problem in some labs is that the failed fertilisation is not because of an intrinsic egg problem,but because of poor lab conditions. How can you as a patient find out if the problem is a lab problem ; or a biological problem with your eggs ? This is why, if there are fertilisation problems, it's very important to ask the lab to document egg morphology with photographs and videos, which can then be reviewed later. It's also a good idea to repeat the treatment cycle in a better clinic, to eliminate the possibility that the poor results maybe an artifact created as a result of suboptimal lab conditions ( such as infection; poor quality culture medium; or an unskilled or inexperienced embryologist).

I also think it's time doctors coined new medical terms to describe these egg problems. We could borrow some of the terms we use at present to describe sperm problems ! Thus, if a patient has few eggs ( impaired ovarian reserve), this could be called oligo-ooctyosis ( = few eggs). If the eggs are abnormal, this would be terato-oocytosis ( = abnormal eggs) ; and if the eggs do not fertilise because of cytoplasmic problems, this would be astheno-oocytosis ( = weak eggs).

How do we tackle this problem in our clinic ? We trouble shoot, by checking if the problem is localised to just single patient; or if it's affect more than one ( which would suggest a lab problem rather than a patient problem). If we think the patient has abnormal eggs after egg retrieval, we take photographs of all these eggs , so the patient has adequate documentation. We prefer doing ICSI as compared to IVF for these patients. However it requires a skilled embryologist , because these eggs need to be handled with care and respect . If ICSI is done in the routine fashion , many of these eggs will die during the cytoplasmic aspiration.

If at the end of the ICSI cycle , we feel the patient has a problem with fragile eggs ; poor quality eggs; all eggs with cytoplasmic abnormalities, we explain this to the patient; and discuss their treatment options.

One possibility is that this was a one off phenomenon for unexplained reasons; and may not recur , if we try again. However , because we feel that the risk of recurrence is high , we change the superovulation protocol, with the hope that a change in medication may help to improve egg quality .

If this also fails , then the only realistic options are to consider either donor eggs or donor embryos. These can be very hard choices to make , especially for a young woman who felt she had normal eggs prior to starting the IVF treatment, because she had regular menstrual cycles , and a normal FSH and AMH level.
This is why we emphasize to patients that while the primary purpose of an IVF cycle is therapeutic , IVF cycles often reveal valuable diagnostic information , which can help us to pinpoint possible problems and create effective treatment solutions. These problems could never have been diagnosed unless IVF had been done !

Traditional adoption versus embryo adoption - which is better ?

One option for infertile couples has always been that of traditional adoption. Many infertile couples will pursue this if repeated IVF cycles fail; while others prefer this to IVF , because it allows them to provide loving care to a child who would otherwise be unwanted. In fact, many infertile couple believe that adoption is an easy solution to their infertility , if everything else fails. However , the sad tragedy is that there are just not enough babies available for adoption. Not only is the demand for adopting babies increasing day by day as infertility becomes more prevalent , the supply of unwanted babies being put up for adoption by the mother has become drastically reduced. This is because unmarried mothers have become a rare phenomenon. Girls are much better informed about their bodies. If they don't want a baby , they use contraception . If they do have unprotected sex, they use emergency post cortical contraception; and even if they do get inadvertently pregnant , they resort to abortions , all of which are easily available on demand. Since contraception and abortions have become so safe and effective, there are very few unwanted babies in most orphanages these days.

So what is the poor infertile couple to do ? After spending years and a small fortune on IVF treatments, they are now forced to wait once again for as long as 3 to 4 years on waiting lists. For non-resident Indians , the wait can be much longer. The influential ones use shortcuts to bypass the waiting list; while others consider adopting a child from less- developed countries.

It is ironic that while the technology of contraception and abortion has reduced the availability of adoptable children, assisted reproductive technology now offers a new option to infertile couples. This is the option of embryo adoption.

Biologically , embryo adoption is exactly the same as a traditional adoption , in that the child and the parents have no genetic linkage. However , here the resemblance ends. Whereas with traditional adoption it is a child who is adopted after birth, in embryo adoption the infertile couple adopts an embryo before pregnancy.

There are many advantages to embryo adoption. There is no waiting list; and the infertile woman gets to experience the pleasure of pregnancy and birth. This obviously enhances bonding between the infertile couple and the child. Another major advantage is that there is no social stigmata involved ; and the couple does not need to get permission from family members or disapproving in-laws. Also , since these embryos are usually of high quality, the success rates are better than 50% per cycle. The only disadvantage is that the treatment can be quite expensive.

You can read more about this option for family building at
www.drmalpani.com/embryoadoption.htm.

Baby Chase - Chap 3 - the quest continues

Open publication - Free publishing - More infertility

Making babies - animated film on everything you wanted to know but didn't know whom to ask !

Most people have no clue what infertile couples go through.

The hunger and longing for a baby – and the frustration and pain of having to deal with failed IVF cycles is something which most infertile couples learn to deal with in the privacy of their bedrooms.

This is why many people end up saying stuff to infertile couples which is inaccurate and unhelpful – and they often add insult to injury by saying hurtful things, even when they don’t intend to cause pain ( for example, “ Just relax and you’ll get pregnant ! “ )

In order to bridge this gap between the fertile world and infertile couples, we have produced an animated cartoon film called, Making Babies – Everything you wanted to know but didn’t know whom to ask ! You can watch it free at
http://ivfindia.com/movie/babymaking.html

How much should doctors charge ?

One of the great mysteries of medicine for patients is why doctors charge what they do. Some are amazed at the fact that bright young doctors are willing to slave for hours for patients whom they do not know, for an income which is not bad , but which is much less than others ( bankers , for example) command. They admire the fact that doctors are willing to work for 24 hours at a stretch ; and to get up at two o'clock in the morning for emergencies. It can be an arduous lifestyle which disrupts both personal and family life - something which it's not possible to compensate for simply by money.

On the other hand, most patients feel that doctors charge too much. They envy the Mercedes many doctors drive ; and the fact that they take Wednesday off for playing golf. Many resent the fact that they have to pay hundreds of dollars for medical procedures which may just take a few minutes.

Also, it’s a well-known fact that the fees charged can vary considerably – not only from doctor to doctor – but from patient to patient as well ! Patients would be much happier if the medical costs were transparent.

The truth is that the amount which doctors charge is often a mystery for doctors themselves. Most doctors are not very good businessman; and fees are usually set for reasons which are beyond their control.

Since they are used to working for free during their the medical training and residency , young doctors often quite uncomfortable collecting fees for their professional services when they first start weighing hundreds of thousands of dollars in debt. Most use market criteria to set their fees – and charge what other doctors are charging. While this is a useful rule of thumb, in many cases it can be too much- while in others it’s too little.

Many, who are idealistic when they are young, charge enough to make a comfortable living , so that they can cover their expenses , and still have enough to keep the family happy. This is easier to do in smaller towns in India for example , but extremely hard to do in the US , where doctors will start their practice often owing hundreds of thousands of dollars in debt to cover their loans to pay for their educational tuition fees.

Other doctors , who are hard-nosed businessman ,take a much more pragmatic viewpoint . They do an informal market survey to study how much patients in their community are willing to pay for their services – and price these accordingly.
Some doctor will deliberately charge a higher fee than the competition. This is especially true for senior doctors , who feel they have earned the additional income because of their experience and expertise. Others do so because they want to create an air of exclusivity about them , because they know that patients often misinterpret high fees as being equal to a better quality of service. After all , if a doctor charges more, it must be because he is better !

This is especially true for fields such as cosmetic surgery, where patients pay directly for their services, and there is intense competition for patients. Some doctors deliberately charge a premium, not just in order to maximize their income , but to convey that they are better than the rest. However, remember that higher is not always better. On the other hand, lower fees are not always a bargain either !

What I doctors who charge less ? Some doctors are financially quite comfortable , and because they have low overheads , they are willing to charge just enough to cover their costs. They charge enough to cover their staff salaries and electricity costs for example , but they often end up underpaying themselves. Ironically, though the doctors charges less because he doesn't need much money to be contented, the disadvantage of charging low fees is it often conveys to patients that the quality of services may not be as good !

This is why it's quite common to see an escalation of prices. Once one doctors increases his fees , the others often have to do so , in order to toe the line. Fortunately , this is true in the other direction as well, and of one doctor drops his prices , many others will do so as well , in order to stay competitive.
In places like the US where third party payers dominate the market, the ability of the doctor to set his own fees is practically zero. He pretty much has to charge what the third party is willing to pay. As medical insurance becomes prevalent in India, this is going to be true here as well , where the insurance companies are soon likely to call the financially shots.

In countries like the UK, which have a nationalized health service, doctors do not have to worry about how much to charge , because this is a decision which is taken out of their hands . For many doctors, this can be a blessing !

While many doctors pride themselves on their professional skills , and take pride in the fact that they couldn't be bothered about money, the fact of the matter remains that medical private practice is also a business , and unless doctor learns how to charge the right amount for his services, he will often end up underpaying himself. In the long run , this may mean that he may not be able to invest in either updating his professional skills or buying state-of-the-art equipment , both of which can lead to poor quality medical care. He will then end up losing his patients to corporate hospitals, which are extremely good at maximizing their profits. Doctors need to find the right balance, so that they can both enjoy their financial income, as well as their emotional income. Earning money is not a sin just because you are a doctor; and if this money is utilized to improve patient care, this is good for everyone involved.

Converting people into patients !

I recently received this email from an infertile couple. Her gynecologist had recommended a routine vaginal ultrasound scan, which was reported as follows.

Both ovaries are normal in size and shape. There is a well defined hypoechoic cystic lesion in both ovary measuring RT - 11x12.5x10.3 mms with volume 0.7ccs and LT - 12.8x14.3x15.4mms with volume 1.5ccs. It shows marked low level internal echoes and small focal calcification. No evidence of free fluid in pelvic cul-de-sac.Hence bilateral small ovarian lesion -endometrioma.

Their gynecologist had advised them medication to resolve the cyst; and a repeat scan after 6 weeks to confirm the cyst had disappeared.

They wanted a second opinion, as to whether this was good advise.

Please read the report carefully again. Don't worry about the gobbledygook or the medical jargon. My point is that medical scan reports are often deliberately full of this, in order to worry patients and send them scurrying to their doctors. The cyst is about 10 mm in size - this means it's only about 1 cm ! It's extremely small - and the only reason it can be detected is because the ultrasound machines today are high resolution machines, on which the images can be zoomed, till normal anatomical structures can be interpreted as "lesions" which need treatment ! Unfortunately, most people are innumerate ; and not sophisticated in enough to interpret the report. Others trust their doctor blindly - and expect him to do what is needed. This is why George Bernard Shaw said that all professions are a conspiracy against the laity !

The beauty of this scan is that the doctor has done everything by the book ! He has simply reported everything he saw - in excruciating ( and unnecessary ) detail ! So why am I finding fault with him ?

Many reasons ! For one, this report is "pseudo-accurate" ! It's simply impossible to measure structures in terms of 0.1 mm ! While it's possible to position electronic calipers and read off their readout, this simply shows that the doctor is not applying his mind ! This is false accuracy and precision which misleads the patient.

Secondly, the interpretation is highly suspect. The ovary is normally a cystic structure, and this tiny "cyst" could just as well be a normal ovarian follicle, which contains a mature egg , rather than a "lesion".

Thirdly, he has deliberately reported his measurements in mm rather than cm - thus making the "lesion" appear larger. This can mislead poorly informed patients !

So is the radiologist not very bright ? On the contrary - he is very smart - he is a willing accomplice in the game being played by the referring gynecologist !

Doctors often send patients for scans. This is often to rule out problems - and to show patients how careful and thorough they are. Most patients are happy do these scans - after all, what's the risk of doing just a test ?

The trick is that the radiologist then "finds abnormalities" - even though he knows they are of no importance, and may be just normal anatomic variants. The patient reads the report - and then worries because of all the abnormalities which have been picked up. Off he goes back to the gynecologist, for treatment. The doctor is happy to comply , because this means more follow up visits - and additional income !

It's possible to milk this for many months because the new ultrasound machines can pick up tiny fibroids and cysts for practically all women, because these are such common findings ! The woman has now been converted into a patient - and she is now stuck on a game which shuttles her back and forth from radiologist to gynecologist, and it's extremely hard to escape this.

The danger is not just that of the money being wasted on the overdiagnosis and overtreatment - or on the unnecessary anxiety which is created. The bigger risk is that sooner or later some trigger happy gynecologist will decide that the cyst is not responding to medical treatment - and needs to be removed surgically. This unnecessary surgery will actually reduce the woman's fertility - thus making her an infertile patient who will need to come and see me !

I have discussed gynecological scans in this post - but the tragedy is that this charade is played out in practically all fields today !

Why the consultant must take the patient's history himself

It’s very common these days to find that busy consultants often do not take the patient’s history themselves. Because they are so busy and need to maximize their efficiency , usually the history is taken by an assistant or a nurse. This person has a standard preprinted form ; and asks questions mechanically to ensure that the form is completely filled. The patient then goes with this filled in form to see the consultant; who then proceeds to examine the patient and orders tests.

The advantage of this system is that is maximizes throughput for the consultant, who can then see about 10 patients in an hour. It also ensures that all the information in the form is completely and systematically filled out .

While many consultants will swear by this system because it's one they have used for many years, the sad truth is that this is not the best method for the patient. The quality of the patient's history depends to a large extent on the clinical expertise of the doctor asking the questions - and an experienced clinician is far better at this as compared to a junior doctor or a preprinted form. In fact I feel the distinguishing factor between an experienced doctor and a junior is that a good doctor knows how to take a history ; which questions to ask; and how to interpret these questions . Unfortunately , this is not something which can be taught easily ; and is not efficiently done with the check box system.

This is why in real life , when a patient is referred to a senior consultant, the one thing which this doctor will do ( which was often not done properly before ) is sit down and talk to the patient. Many more puzzling clinical problems are solved by a carefully taken history , rather than by ordering more lab tests or scans.

Not only will taking the history personally improve the care the patient gets, this history taking session is a great opportunity for the consultant to establish rapport with the patient and build trust and confidence in the doctor’s skills. It also gives the clinician a chance to connect with the patient and display empathy and compassion. This can be hard to do nowadays, when clinic visits have to be compressed within 10 minutes. Unfortunately , by not giving patients the time and respect that they deserve, we end up doing everyone a disservice.