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All infertile couples know that the sperm plays a vitally important role in fertility. However, there's still a lot of confusion ! If we need only one sperm to fertilise an egg during ICSI, does the sperm count and motility really matter ? And if it does, how and why ?

The fact that the WHO has kept on changing the definition of what a normal sperm count just testifies to the fact that experts are as confused as patients are. This is especially true when we consider 3 contentious areas. While it's true that the sperm provides 50% of the child's DNA, can it be responsible for:
failed fertilisation after ICSI ?
poor qualty embryos ?
miscarriages ?

In order to drill down further into when the sperm can be responsible for reproductive problems, researchers have developed sophisticated tests to analyse whether the sperm are "normal " or not. In the past, the only tests we had available were the sperm count, motility and morphology. These are admittedly crude tests, and the hope was that newer tests which could directly check the functional status of the sperm's DNA would give us more useful information. Logically, since the man's DNA contributes half of the offspring’s genetic material , it is reasonable to assume that abnormal DNA in the form of fragmented DNA ( when excessive strand breaks are present ) may lead to derangements in the reproductive process.

Let's look at some of these tests.

The tests used for the assessment of sperm DNA integrity can be distinguished into direct and indirect. Direct assays try to detect the actual DNA breaks, while indirect assays quantify the susceptibility of sperm DNA to break after an external insult, such as acid treatment. The most commonly used direct assays are; Terminal Deoxynucleotidyl Transferase-mediated Nick End Labeling (TUNEL), Single Cell Gel Electrophoresis (COMET) and In-Situ Nick Translation (NT) assay. The most common indirect assays are; Flow flow cytometric acridine orange assay, Acridine Orange test (AO), DNA Break Detection-Fluorescence In Situ Hybridization (DBD-FISH) and Sperm Chromatin Dispertion test (SCD).

The very fact that it's such a long list is a testimony to the fact that we really do not understand what the results signify in real life. For example, breaks affecting genes in “silent” areas of the genome are unlikely to have any clinical importance, but no assay can evaluate this factor yet.

The truth is that for the present, there is no differentiation between clinically significant and insignificant fragmentation. While it's true that many studies using a variety of assays have shown statistically significant differences in sperm DNA fragmentation between fertile and infertile men, remember that these refer only to the mean or median . In reality, there is extensive overlap between the values found in fertile and infertile men.

Because these tests are so new, they've not been standardised. Clear reference values have still not been established, just adding to the confusion. Just like conventional semen parameters have been proven to be disappointing at predicting the outcome of IVF, sperm DNA fragmentation has been equally disappointing in predicting pregnancy rates after standard IVF and ICSI.

If you have poor quality embryos and your test shows you have increased sperm DNA fragmentation , it's very tempting to conclude that it's the sperm DNA fragmentation which is responsible for the fragmented embryos. However, this has never been proven ; and please remember this is not necessarily cause and effect. Men with higher sperm DNA fragmentation have had completely healthy and normal babies in their bedroom !

DNA fragmentation is a new parameter for the evaluation of male factor infertility . However, just because it is new does not automatically mean it is better ! In fact, at present it just seems to add to the confusion, rather than clarify it !

I just saw a patient who was 40 years old; she had had 2 miscarriages; and she wanted me to do surrogacy for her. I spent a long time explaining to her why I did not think this was her best choice. Surrogacy is an expensive and complex treatment option, which is best reserved for
women without a uterus. Research shows that the reason for failed implantation is much more likely to be genetically abnormal embryos ( because of poor quality eggs), rather than a uterine problem.

Her reasoning was completely different. The fact I got pregnant means my eggs are OK ! The fact I miscarried means my uterus is defective because it could not hold the baby. This means that if use a surrogate uterus, I will have a baby !

The reality is completely different. The fact that she conceived means her uterus is fine because it allowed the embryo to implant ! However, because the embryo was genetically abnormal, it could not grow any further ! We know that the commonest reason for a miscarriage is a genetic abnormality in the fetus, and this is Nature's defense mechanism, to prevent the birth of an abnormal baby. While these defects are often random, they are commoner in older women. This is because the eggs of older women have more genetically abnormalities, because they have "aged" and have genetic defects, which cannot be screened for. From a purely medical perspective, using donor eggs would be a much better option as it would give her a much better chance of having a baby ! This was my recommendation to her, which she found quite hard to accept.

Logically, it makes no sense for me to clear her misconceptions. After all, I should be quite happy to do surrogacy for her - this is what she wants and I can charge her much more for it ! However, I refused to treat her, and suggested she find another doctor.

I have observed that there are 2 kinds of patients. One group treats me as a professional. They are looking for medical advise and guidance; and want my professional inputs. They have an open mind, and are seeking to form a partnership with me. They want to tap into my professional knowledgebase, so they can make the right decision.

The other group treats me as a technician. They already know what they want - they just want me to do this for them. While this may not be great for my ego ( after all, doctors expect patients to do everything they tell them to !), I am mature enough not to get offended, and am happy to listen to my patients and weight their inputs.

Does this mean I am wishy-washy and will do everything my patients ask me to ? No !

I use a combination of rigidity and flexibility. I am happy to accept patient inputs and preferences and modify my protocols, as as long as they do not affect the outcome ! For example, if patients want us to use the long protocol rather than the short ( which we prefer because it needs fewer injections !)

Similarly, some patients want to use rec FSH for superovulation, instead of the urinary HMG we prefer ( because it's as good and much less expensive !) and I am happy to comply.

However, I will not allow them to do anything which I feel is not right ! I am a professional , and
the buck still stops with me. I will not let them make a wrong decision, no matter what. Thus, if a patient asks me to transfer 5 embryos , I will request them to find another doctor.

Many patients come to me with preconceived notions, especially if they have done IVF treatment elsewhere. Websites and Bulletin Boards are also powerful sources of information - both good and bad ! These patients can be quite a challenge for doctors . If they are well-informed, we can learn a lot from them - but if they are not, it can be quite frustrating to get them to separate facts from reality !

The failure of an IVF cycle always causes major heartburn. The next question is - Why did the IVF cycle fail ? What should I do next ? Did I get good quality medical care ? Or should I change my doctor ?

This is always a hard question to answer, because even if the quality of medical care provided is excellent, the IVF cycle can still fail. How is the patient to judge the quality of technical competence of the IVF clinic ? Did the cycle fail because the clinic was bad ? Or was it just bad luck ? You cannot rely on a doctor's bed side manner to judge his clinical skills - you need more tangible evidence - but what should you be looking for ?

Fortunately, the answer is very easy - you should ask for photos of your embryos ! The core competence of a good IVF clinic is to produce high quality embryos. Of course, whether these embryos will implant and become babies after they are transferred is not something which any doctor can control - but the quality of the embryos is a tangible end point which can easily be measured and compared.

I feel every patient should ask their IVF clinic for photos of their embryos - and most good IVF clinics will routinely provide these to their patients, even without being asked. Good clinics are proud of their skills - and are happy to show off the embryos they make in the IVF lab to their patients !

If your doctor refuses to give you a photo of your embryos, you should worry a lot ! What does he have to hide ? And why ?

And if you need help in making sense of your embryo quality, please email your embryo photos to me, and I'll be happy to help !

I seem to be seeing an epidemic of tuberculosis ( TB ) these days ! Practically all Indian patients who come to me have been treated with anti TB drugs ! Most gynecologists now routinely test the
endometrium ( uterine lining) for TB using a new generation of fancy ( and very expensive !) tests such as PCR ( polymerase chain reaction) . In the past, the only test available for making a diagnosis of TB was by growing the TB bacillus in the laboratory; or by finding tubercles on histological examination. However, both these methods are quite insensitive.

This is why PCR was introduced with great hope. This test amplifies a specific segment of DNA and labs believed that finding DNA sequences unique to the tubercle bacillus in the endometrial tissue would help to make a unequivocal diagnosis of TB infection. Unfortunately, this test has proven to be unreliable because it is too sensitive and can pick up even minute quantities of DNA, leading to many false positives. Because it is very expensive, it has not been validated in the fertile population, and in some labs, over 50% of the samples sent to them test positive for PCR for TB ! This obviously means the test is unreliable, but doctors continue doing it, without understanding its limitations and pitfalls – and patients are unnecessarily subjected to the trauma of 9 months of useless treatment !

Here's one simple reason why I feel the test is unreliable. When the tubercle bacillus reaches the genital tract ( from the lungs) , it first attacks the fallopian tubes and then later damages the endometrium . This means that whenever the endometrium is TB PCR positive, tissue from the fallopian tube should also be PCR positive. However, for many patients whose endometrium is positive, the fallopian tube is negative !

The other group of tests which is very popularly misused to make the diagnosis of TB are the blood tests which test for the presence of antiTB antibodies – both IgG and IgM. Firstly, remember that these tests are not picking up the presence of the TB bacillus – they are only testing for the presence of antibodies ( produced by the immune system to protect the body !) against the TB bacillus. As most Indians have been exposed to the TB bacillus, it is hardly surprising that many have the presence of antiTB antibodies, and often test positive. Doctors often believe that this is proof of TB infection, and promptly start treatment ! Similarly, the Mantoux skin test also tests merely for the presence of immunity against TB – and can be similarly misinterpreted.

In summary, the diagnosis of TB of the genital tract remains notoriously difficult to make. Most patients are misdiagnosed as having TB when in fact they don’t, and many are treated for no good rhyme or reason !

If your gynecologist diagnoses you as having genital TB based on these unreliable tests, then please do NOT start anti-TB medicines. Please insist on getting a second opinion from a physician, preferably once who is a TB specialist !

The truth is that no one really knows how to interpret these results - but no doctor will admit to this fact. What does a positive test mean ? Nothing ! I am sure if a controlled study is done , a lot of fertile women will also turn out to have positive tests for TB ! ( Actually, this would be an easy study to do ! Fertile women who are scheduled for a laparoscopic tubal ligation could have their endometrial biopsy done at the same time and this could be sent for testing for TB. It is my prediction that over 50% of these samples will turn out to be positive ! I'd love to be proven wrong !)

What's the result of all this testing ? A lot of unnecessary expense; and even worse , this leads to 9 months of unnecessary treatment with toxic drugs with unpleasant side effects. As a result of this waste of time, patients get fed up and frustrated. Sadly, most gynecologists are pretty clueless about what these results means - and it's much easier to "do something" ( prescribe antiTB medicines) rather than explain to the patients that nothing needs to be done !