How do you diagnose unexplained infertility?

First of all we have to really be very scientific and obviously, there is nothing called unexplained. Everything that we don’t understand is put in a box and that box is called unexplained. So, definitely endometriosis and especially sub-clinical endometriosis like I already mentioned that because we can’t do the gold standard diagnosis because it is a surgery, those patients will remain undiagnosed and that is why a large percentage of them might be sub-clinical endometriosis. In one study actually the percentage was up to 7% but that was one study I don’t remember on the top of my head what percentages were attributed in various studies but definitely it can make a significant chunk.
The other significant chunk can be the problems related to immunology. There are various antibodies in the body especially present when other autoimmune factors like diabetes, rheumatoid arthritis or such personal or family histories present. There is another entity called problem with the natural killer cells which is going to make an important part of the implantation process. There is another aspect of whether the body is able to make enough blocking antibodies which is actually basically the blocking antibodies so that the mother’s immune system doesn’t feel that the baby is a virus or a cancer and doesn’t kill it so, it accepts it. It’s very intriguing how nature has designed it that there is a whole another body inside a body and then it is accepted but when this mechanism fails and when the body recognizes a new antigen as something foreign and rejects it so, definitely all those undiagnosed patients can be missed and they are again put in the box called unexplained. I do practice reproductive immunology, there are very few doctors who practice reproductive immunology to the extent that we do but we do it very carefully in a very rightly selected small group of patients in our whole practice. I take at least one hour explaining to the patient why now they qualify for this kind of therapy because this therapy has not gained enough evidence because it is very expensive to do these studies and with time we will have them but it is not there yet.
When we have that history of repeated miscarriages and nothing is explaining it and then we do a few tests and then I believe in not going vertically into one thing that you just keep checking one side of immunology but I go horizontally and I check antibodies, th1, th2 ratio and NK cells, DQ alpha. It makes more sense to go horizontally and do one basic test like endometrial immune profile. There’s a new test called KIRS in which the sample goes to Chicago and we wait for a couple of weeks and all this. So, we check a bit on every side that there is anything wrong and obviously it is guided by the history of the patient, for example, someone has thyroid issues or someone has massive diabetes history in the family or herself. I would think of making sure that there are no antibodies of other nature in her body. Similarly my other decisions are guided by that. That makes us very unique by the way that as a team, we try to not go too deep into one thing but we try to check everything horizontally and find out if some area is the problem area and then we go deep into that depending on how patient has to accept that whole thing actually is not based still on massive evidence but it is still experimental in nature and that is the information the patient needs to know and then she can go ahead and test more and treat more. There are various modalities. Some of them can have side effects like allergies so, it has to be very carefully selected. There are various modalities like use of intralipids or lid therapy – all those things have to be very carefully selected, in a very small set subset of patients only they should be very carefully given, not to everybody who has miscarriages for example. There are other tests like LED in which we check the the partner’s bloods also and see whether there is a problem in the HLA and the other areas why is the women’s body not accepting the baby, especially when it’s an early miscarriage and repeat it and there is no other problem. All these patients, if not tested, will be labeled as unexplained in otherwise a standard fertility practice which is not doing a very advanced practice that includes reproductive immunology but I have to emphasize this that this is only beneficial to a small subset of rightly selected patients and not everyone should be spending thousands and grams of pounds just without any genuine rationale behind that.

Unexplained subfertility in general terms would be considered to be couples who have tried for a reasonable length of time, the label sometimes given at the year mark, certainly by the two year mark, that is a statistical point, where standard assessment of fertility has not shown a significant problem. In other words the couple is having reasonably regular intercourse to give themselves the opportunity of conception, the fallopian tubes are okay, the woman is ovulating on a regular basis and the man has a normal or near normal sperm test and therefore nothing obvious to pick up to say there is something going on here to fundamentally reduce your chances.