How to improve a poor uterine lining

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.

Sometimes, it's the endometrial tissue itself which has been damaged. This is often seen in patients who have had endomterial TB ( tuberculosis) in the past. Similarly, uterine surgery can also disrupt the uterine lining. We find this in women who have had a D&C ( dilatation and curettage) done after having had an anembryonic pregnancy ( missed abortion). Over-enthusiastic curettage can result in the removal of the basal layer of the uterine lining, called the basalis . Once this has been denuded, new endometrial tissue cannot grow and the lining remains persistently thin, resulting in a variant of Asherman syndrome which is very difficult to treat. ( This is why we tell patients who have had a missed abortion to terminate their pregnancy medically with mifegest and misoprostol, and to not do a D&C.)

The other common iatrogenic reason for a poor uterine lining is a hysteroscopic metroplasty which many aggressive doctors do for infertile women to "treat" a narrow uterine cavity ( which is a normal anatomic variant , and should be left well alone !)

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.