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Thursday, 27 March 2014

Demystifying ovarian stimulation

While undergoing treatment of infertility, you are 'bombarded' with a lot of complicated information. It is of course difficult to understand and assimilate the information that is relevant so that informed decisions can be taken. I will therefore attempt to present before you the different aspects in a simplified manner. Let me begin with ovarian stimulation drugs.

The two hormones which 'drive' the growth of the follicles in ovary are Follicle Stimulating Hormone (or FSH) and Luteinising Hormone (or LH). Both these hormones work in tandem leading to the follicle growth that culminates in the release of egg (ovulation) from the ovary. 

In order to induce ovulation artificially, there are two ways: tablets and injections. The tablets (commonest being Clomiphene) do not directly stimulate the ovary, these cause the brain to release FSH and LH at exaggerated levels. The injections on the other hand directly stimulate the ovaries. In the vast majority of women, FSH injections suffice for stimulation. 

Injections that are given for ovarian stimulation are of two types:

  • human Menopausal Gonadotrophins (hMG)purified from natural sources (urine of menopausal women
  • Recombinant FSH (r-FSH): synthesized using technology (Recombinant DNA technology)

rFSH can be given subcutaneously (like insulin injections) and are very expensive. hMG is much cheaper but as effective as r-FSH. However hMG injections can only be given into muscle. Highly purified versions of hMG are also available that are a little more expensive (but not as much as r-FSH) and can be given subcutaneously.

Sunday, 23 March 2014

Ovulation Induction in PCOD

Women with PCOD are a diverse group and therefore the management has to be done by a fertility specialist.  In case you do not have regular periods, the doctor will need to give you medications to bring on a period. In women with PCOD, there are many antral follicles in the ovaries that are in a suspended state and these can respond to hormones. The biggest challenge therefore is that any hormonal treatment intended to cause ovulation causes many or all of these to start growing leading to multiple ovulations and multiple pregnancy. A complication known as ovarian hyperstimulation syndrome (OHSS) can also result.

The process of ovulation induction is most often done with the help of tablets called Clomiphene citrate. These are typically taken in the dose of either 50mg or 100mg (occasionally higher) for five days from the second or third day of a spontaneous or induced period. This is ideally followed by serial ultrasound scans to track the follicle/s that start to grow and eventually ovulate from one or both ovaries. When ovulation is confirmed, the couple are advised to have relations.

Many women with PCOD do not respond to the tablets in which case, they are advised to start daily hormone injections to induce ovulation. The aim is to give the smallest effective dose that would allow ideally a single follicle (but no more than 6 follicles) to grow and release an egg. This is extremely challenging in PCOD and therefore requires a lot of skill and patience. The doctor may have to cancel the treatment and start again at a lower dose of injections in case too many follicles start growing to prevent OHSS and high order multiple pregnancy. It is however not always possible to prevent multiple ovulations as the ovarian response in women with polycystic ovaries can be either too much or too less!

Friday, 21 March 2014

Polycystic ovarian disease: What next?

The most common condition which causes a disturbance in ovulation is Polycystic ovary disease. If your periods are absent or occur more than 35 days apart please consult a fertility specialist rather than wasting time trying to conceive naturally in the absence of ovulation.

When you go to see a fertility specialist, you and your husband/partner will be advised to undergo some basic tests to ensure that there are no other contributory causes to delay in conception. The tests would include hormone tests to confirm that the cause of irregular cycles is PCOD, tests for checking thyroid hormones and prolactin and may include patency test for tubes. You will also be advised to have tests to confirm that you are otherwise healthy and free of infections that can be transmitted to the baby. Once this is done, the doctor will start the process of ovulation induction. 

Weight loss in women who are overweight/obese is highly recommended. When age permits, it is well worth taking the effort to normalize the BMI as the response to treatment is better after weight loss along with a lower risk of miscarriage. Some women who have high levels of insulin will also benefit from taking Metformin tablets. I have had many patients who have conceived at this initial stage of treatment

Ovulation induction in PCOD in the next post....

Monday, 17 March 2014

Ovulation Induction: when?

When ovulation occurs regularly, the menstrual cycles are regular. As a corollary, if the periods are irregular or absent, it can be inferred that ovulation is irregular. There can be three situations where this can happen:
  1. Where the ovary is normal but the stimulating hormones from the brain are absent. This is usually an inborn problem with hypothalamus, a part of the brain that makes pituitary release FSH and LH hormones to stimulate ovary. (Please refer to my earlier post Role of ovary in conception). This condition is often but not always associated with decreased sense of smell.
  2. Where ovulation does not occur despite a normal egg reserve and a normal function of pituitary (Polycystic ovary disease)
  3. Where the egg reserve is so low that ovulation has become irregular. This usually precedes menopause.

Whereas the ideal treatment for situation 3 is to use donated eggs, for the situations 1 and 2 the appropriate treatment would be ovulation induction. Ovulation induction is the process of stimulating the ovary to release one or more eggs. 

PCOD and ovulation induction in my next post....

Thursday, 13 March 2014

Preconception check-up

It is a good idea for a couple who have started trying to conceive to see a doctor to ensure that the pre-existing diseases are controlled as well as possible with medicines that affect the growing baby as little as possible. This will also enable as yet undiagnosed medical conditions to be identified and treated. 

There are a lot of women with undiagnosed Diabetes who conceive. Women with PCOD, family history of Diabetes or with an increased body mass index should ideally get themselves checked. High blood sugars can cause structural abnormalities in the unborn child, miscarriage, growth problems etc. "Glycosylated Haemoglobin" or HbA1c will indicate the average blood sugars in the three months preceding the test. Dietary changes and/or medicines can then enable normalisation of blood sugars. If blood sugars are normal (HbA1c < 5.6%) at the time of conception and during pregnancy, there is little impact of diabetes on pregnancy.

Last but not the least, all women who are trying to conceive must take Folic acid tablets in the dose of 5mg daily as soon as they decide to start trying. This will prevent  some of the congenital abnormalities related to brain and spinal cord (such as anencephaly and spina bifida). In case you prefer taking prenatal multivitamins, take folic acid tablet in addition. 

Sunday, 9 March 2014

Unexplained Infertility

I have at long last come to the very last in the series of my posts on causes of infertility. Fertility specialists have a set of tests that includes checking at least the semen analysis, tests to confirm ovulation and tests to confirm tubal patency. In 15-30% of infertile couples no cause can be found on investigations.  In these couples the delay in conception may either be a chance delay or there may be a subtle or as yet undetected cause. It is a little disconcerting to get this diagnosis of course. But there is a silver lining here. The couples in this category have the best chances of conceiving!

On an average only about 20% of women get pregnant in a monthly cycle. At the end of one year of regular relations, approximately 85% of couples achieve pregnancy. The 15% that remain are advised to seek advice. These are not necessarily infertile though they may have some degree of subfertility or it may be a chance event. In the latter case trying for a little while longer will enable the couple to conceive. Of note is the fact that 60% of couples will achieve a pregnancy in the second year of trying, but if you have been trying for three years or more, the chances of a conception are very low at 1-2%.

The message that I am trying to convey is that the course of action that you take is up to you. If you are anxious you can seek help at the end of a year of trying. It may be better if you at least get investigated to ensure that there is no obvious cause for the delay and then continue to try on your own for the next year. However, if you have already been trying for several years, it would be highly recommended to seek help with a fertility specialist immediately. Many infertility units would recommend IVF if you have failed to achieve pregnancy after cohabiting for more than 3 years! 

Do not despair, there is hope!

Thursday, 6 March 2014


When a man goes for a semen test, the one thing that he dreads the most either consciously or subconsciously is an abnormal result. It is impossible to fathom the blow to a man whose sperm test shows no sperms. The immediate reaction is that of despair and disbelief, of denial and anger.

The process starts in the millions of sperm producing tubules in the testes where special cells called Spermatogonia multiply and after a maturation process (that takes nearly 72 days) form sperms. The newly formed sperms are stored in a structure called Epididymis. During ejaculation the sperms are brought up and mixed with fluids secreted by the prostate and the seminal vesicles. This final fluid is semen. 

The condition where there is a total absence of sperms in the semen sample (checked on two occasions) is called Azoospermia. This condition is present in approximately 1% of all men and 10-15% of infertile men. This condition can either happen because there has been a damage or insult to the sperm production mechanism or because the sperms are being produced but unable to come out through the ducts and into the ejaculate (due to an obstruction or an anomaly in the ducts). 

Sperm production is under hormonal control and some endocrine conditions may impair sperm production. These are potentially correctable with medicines. In case of an obstruction, technology is available that involves retrieval of sperms from the testes and the couple can undergo IVF using these sperms. Where the sperm production machinery has started failing due to a disease or an insult (such as chemotherapy or radiation therapy), it may still be possible to use the few sperms that are present in the testes. In those men where there is no sperm production whatsoever, using donated sperms is the only option. This can be decided by an andrologist after appropriate hormone tests and a testicular biopsy to assess the situation.

Monday, 3 March 2014

Smoking and Fertility

The effect of smoking on health is common knowledge. However most people do not know the degree of damage smoking can do to the fertility in both men and women. 

In the men, many studies have documented the effects of smoking on the number, motility and the shape of sperms. Many men who smoke can have normal sperm parameters on testing. Do not think that no harm has been done in these. The genetic material (DNA) in the sperm cells is packaged and stabilized by proteins (called protamines). In smokers, the ratio of the two types of protamines is altered and this leads to the sperm DNA being vulnerable to damage. Studies have also shown that the fertilizing capacity of sperms can be affected and the embryos can stop growing after a few days. The chances of pregnancy are therefore lower.  

In women, the effects of smoking are stark. The quality as well as the quantity of eggs is affected. This leads to a delay in conception and increase in miscarriages. ICSI, a technique in which sperm is injected to achieve fertilisation, cannot overcome the damage caused and the chances of pregnancy after IVF/ICSI are almost half as that of non-smokers. Women who smoke also have an earlier menopause because of the effect of smoking on the ovaries.

Smoking is therefore discouraged in men and women who are yet to complete their family.