How to treat unexplained infertility?

A couple walks into an Infertility clinic, their 4th so far, to collect the results of the investigations they underwent last week. Their consulting doctor sits with them and they come to know that all their investigations have come out to be normal, again, for the 4th time, in as many clinics. They are frustrated, which is understood , as they have been married for 6 years now and running from one clinic to the other. They have been told by their previous consultants that their case comes under the category of unexplained infertility. This is an educated couple, but it is difficult for them to comprehend that they are not able to conceive naturally without any identifiable cause.

Unexplained infertility is the term used for such an infertile couple in whom all the investigations conducted have yielded normal results and yet they are unable to conceive spontaneously. In other words, these couples suffer from infertility due to such causes that cannot be diagnosed with the present resources and investigations available. Around 15-20% of all infertile couples fall under this category of infertility.

To label a couple under this category, all the investigations related to fertility should have been performed and should come out to be normal. The scope of such investigations include ovulation studies or in simple words the status of eggs in a women, its reserve, timely development and ovulation of follicle, hormonal status of women including AMH, thyroid and prolactin levels , status of her fallopian tubes, whether patent or not or presence of some abnormality in tubes, investigations to rule out other underlying disease such as diabetes, liver disease, anemia and such as these can affect female fertility in multiple ways. For male partner, a detailed semen analysis from an expert andrologist can go a long way in finding a manageable cause of infertility.

Age of the female partner is a very important factor as many couples in the category has a female partner over the age of 35 years.

In such cases, the quality of the eggs and its reserve itself is challenged in . Other reasons which can possibly lead to unexplained infertility are – failure of egg to enter fallopian tube, failure of fertilization to occur, defect in transporting fertilized ovum from fallopian tube to the uterine cavity for implantation, and failure of implantation of embryo itself.

Unfortunately, all these reasons are beyond the scope of present available investigations and also beyond the scope of proven available treatments. One more factor which can be a cause of unexplained infertility is patient’s immunology.

Immunity is the capability of the body to fight against infections and protect us. In some women, her immunity ends up working against the sperms and the fertilized embryo and can also lead to failure of implantation. There is a limited proven data available to justify routine testing for immunological factors in cases of unexplained infertility from the very outset.

Laparoscopy and hysteroscopy as a routine first line investigation in all cases of unexplained infertility is not justified and need not be done right away in all such cases but it can yield some information and pathology that can be treated.

Now let us come to the most important part , the treatment available for such couples. We will try and outline a stepwise and individual approach. The first step in such cases is ovulation monitoring. Spontaneous ovulation and its timing during the menstrual cycle is the starting point and can serve as guide to “timed intercourse” which might turn out to be beneficial in a small minority of cases.

Further, first line of treatment for all such couples is Intrauterine Insemination -IUI , along with ovulation induction. Ovulation induction is the process whereby the ovary is minimally stimulated with the help of oral drugs started after menstruation starts, followed by monitoring of growing follicle and then timing the IUI with ovulation,which can be spontaneous or triggered .

IUI has a slightly better chance of success in cases of unexplained infertility as compared to other infertile couples. IUI is to be used as the first line treatment in couples where the duration of marriage is less and the age of female is below 35 years with good reserve of eggs. Another line of treatment is In Vitro Fertilization / Intracytoplasmic sperm injection, IVF/ICSI .

This is the next line of management in patients where IUI has not yielded any results , or it can be used as first line of treatment in cases where the age of wife is 35 years or more, duration of married life is more or in cases where reserve of eggs now stands challenged.

In IVF/ICSI , eggs from female partner are retrieved through a process that includes stimulation of ovaries and retrieval of eggs under anesthesia, then the eggs are fertilized with husband’s sperms. The fertilized embryo’s are then cultured in laboratory settings by expert embryologists and they are then finally transferred into the uterine cavity of wife.

This is a technique which, if done with expertise , yields a high pregnancy rates of around 70% and above and the chances are even better in patients of unexplained infertility. The widespread availability of infertility clinics, use of newer technologies and better medicines has brought down the cost of this treatment in present scenario and it is now within the reach of common man.

The crux of the discussion is that the couples who have been labeled as cases of unexplained infertility and are avoiding any active treatment because all their investigations have turned out to be normal need to consult a dedicated infertility center for early initiation of correct line of treatment.

Earlier the treatment is started , more are the chances of achieving a healthy pregnancy and option of more treatment avenues is open.