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The frustrating problem of a thin uterine lining
As an IVF specialist , I often see infertile patients with complex and unusual problems. One of the most challenging problems to deal with is that of the patient with a poor endometrium or a thin uterine lining. Embryos need to implant in the endometrium , and an optimal endometrium is thick and trilaminar.
One of the most frustrating problems in IVF today is the patient with a persistently poor ( thin) uterine lining.
Normally, the endometrium should grow and become thick ( more than 8 mm) and trilaminar as the follicles grow, so that it is receptive and ready to accept the embryos when they are transferred into the uterine cavity.
However, sometimes this does not happen.
We do know that the growth of the endometrium depends upon:
the estrogen level in the blood
blood flow to the uterus and
the health of the endometrial tissue itself
A problem with any of these will cause the uterine lining to remain poor.
Thus, poor estrogen levels will cause the lining to remain thin. This is commonly seen in patients who have a poor ovarian response . It's easy to check this by testing the estradiol level in the blood. If this is low, this is easy to treat by giving estradiol valerate.
As with any other tissue, the uterine lining needs an adequate blood supply to develop optimally. Uterine blood flow can be measured by doing a colour Doppler. While it was originally hoped that this would provide useful information, sadly we still do not know what to do with this data. Doctors have tried improving uterine perfusion by treating these patients with vasodilators
( such as vaginal viagra and nitroglycerine patches), but the results have been mixed.
A normal endometrium requires adequate blood flow ; and high estrogen levels. Thus , if the lining is thin there are 3 possibilities: the estrogen levels may be low; the blood flow is poor; or the endometrium is damaged. We need to systematically examine all these 3 possibilities , so that we can pinpoint what the problem is in the individual patient , and then try to correct it.
If the doctor finds the endometrium is poor during the IVF cycle , often the best option is not to transfer the embryos but to freeze all of them. The patient can then be treated with high doses of exogenous estrogens, to see if this causes the endometrium to become thick. If the endometrium grows well , it's then possible to transfer the frozen embryos after thawing them into an estrogen primed endometrium.
However if the lining remains thin in spite of high doses of estrogen, this means the problem is either one of poor blood supply ; or a damaged endometrium. Some doctors have used color Doppler ultrasound to measure uterine blood flow, but the results with this have been mixed. Others have tried using vaginal viagra to try to improve endometrial blood flow. Since there is no reliable method to assess uterine blood flow , the next step is to determine whether the endometrium has been damaged or not. There are two possible causes of end-organ damage when the endometrium is nonresponsive. One is that the endometrium has been anatomically distorted because of intrauterine adhesions ( a common cause for this in India is uterine tuberculosis. This condition is called Ashermann syndrome; and this can be diagnosed either with a hysterosalpingogram , which shows filling defects within the uterine cavity ; or with hysteroscopy , during which procedure the scars can be surgically removed. However in some patients , even though the uterine cavity is anatomically completely normal ; the uterine blood flow is normal; and the estrogen levels are high, the endometrium remains persistently and frustratingly thin. We then hypothesize that the endometrium has suffered end-organ damage as a result of which it does not respond to estrogens. This condition has never been adequately studied; and it does not even have a name ! Most doctors just call it - " Thin endometrium" . The Latin equivalent for this would be leptometrium ( lepto = thin) . Maybe we should coin a name to describe this condition , so that we can study it properly. Today, this can be an unsatisfying diagnosis to make, because we cannot prove this diagnosis ; and neither can we correct this problem.
If a patient has an unexpectedly poor lining during an IVF cycle, it's often best to freeze all the embryos rather than transfer them in the fresh cycle. We can then work on improving the uterine lining before transferring the frozen embryos back into the uterus.
If patients have a history of a poor lining, we use the following protocol to see if their lining responds to an increased dose of estrogen.
This is the protocol we use.
Tab Lynoral ( ethinyl estradiol) , 0.05 mg , 1 tab daily with dinner, from Day 1 - Day 25.
We do a vaginal ultrasound scan on Day 12 to check the endometrial thickness and texture.
If this is fine, we then include a period by giving Tab Deviry ( medroxyprogesterone acetate) , 10 mg, twice a day from Day 16-25.
We can then transfer the embryos in the next cycle.
However, if the uterine lining remains persistently thin, we try doubling the dose of Lynoral and repeating the scan .
If it still does not improve, this confirms this is an end-organ defect in the endometrial tissue.
This can be very difficult to treat.
For these patients, we do a hysteroscopy, to confirm there is no correctable anatomic problem ( for example, adhesions) which we can remove.
We can also do an endometrial biopsy on Day 2 or 3 of the IVF cycle. This deliberate endometrial injury is supposed to provoke increased uterine blood flow, and sometimes causes the lining to improve.
We have also tried alternative medicine, such as using bromelain , 200 mg daily , to try to improve the uterine lining, but results are mixed.
A recent interesting paper ( Successful treatment of unresponsive thin endometrium, Fertility Sterility, 2011) has described the use of an intrauterine perfusion of Granulocye Colony Stimulating Factor ( G-CSF) . It is believed that the local delivery of cytokines and growth factors can improve the uterine lining. We are currently evaluating this experimental technique in our clinic and the initial results have been very promising !
For patients whose lining remains refractory to all therapeutic intervention, surrogacy is the final treatment option which has a very high success rate.
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