Friday, August 05, 2011

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.






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13 comments:

  1. The G-CSF seems like a clever idea, kudos to the group that came up with that one and I hope your trial works!

    ReplyDelete
  2. Thanks for the discussion...there are any woman who have queries and feel awkward to go ahead and ask...this could be a wonderful forum for such discussion.

    ReplyDelete
  3. where can i have G-CSF wash done in Asia?

    ReplyDelete
  4. We now do this routinely for patients with a thin lining

    Dr Aniruddha Malpani, MD
    Malpani Infertility Clinic, Jamuna Sagar, SBS Road, Colaba
    Bombay 400 005. India
    Tel: 91-22-22151065, 22151066, 2218 3270, 65527073

    Helping you to build your family !

    My Facebook page is at www.facebook.com/Dr.Malpani

    You can follow me on twitter at http://twitter.com/#!/drmalpani

    Watch our infertility cartoon film at http://www.ivfindia.com

    Read our book, How to Have a Baby - A Guide for the Infertile Couple,
    online at www.DrMalpani.com !

    Read my blog about improving the doctor-patient
    relationship at http://blog.drmalpani.com

    ReplyDelete
  5. Hi Dr, great post and blog. I am from China. My wife had TB when she was 14, and was completely cured then. We are now 29 and TTC for. 1 year with no luck. Dr suggest to check the tubes and then was found both are blocked. Followed is a hysteroscopy performed last month. Dr. said not possible to clear the tubes and remove the adhesion. One good thing is that no TB is found in endomterial lining. Then my wife took progynova for 21 days as the 1st session to build up lining but unfortunately find out that her lining was only 3mm. One Dr says wait the period and see how it goes, and the other Dr says the lining may never thicken! What is your opinion? Before the surgery, her lining was up to 5mm though. We pray the lining would grow at any cost. Pls advise!

    GAO.S

    ReplyDelete
  6. Anonymous9:11 PM

    Hi doctor, pls what would be your protocol for a pof patient using donor eggs. I dint have much problem growing the lining in my first failed cycle. But I just want ur advice/help to make sure my clinic does everytin right in my next cycle starting soon. Tank u.

    ReplyDelete
  7. Most POF patients have a normal uterus and will grow a good lining after taking estradiol valerate ( Progynova)

    ReplyDelete
  8. Anonymous11:47 AM

    Tanks for ur prompt reply. Am the POF poster above. I ve started my procedure and my clinic placed me on buserelin injection for 2wks after which I would take progynova. Do I realy need the buserelin cos they were not able to convince me. I have a feeLing they don't realy know the procedure for a POF patient.
    I got to 3weeks the laSt time b4 I started bleeding. I live 5hrs drive away from my clinic. Do you think I should travel back after my procedure?

    ReplyDelete
    Replies
    1. No, patients with POF do NOT need buserelin since you are naturally downregulated

      Delete
  9. Anonymous10:18 AM

    With reference to article "Vaginal sildenafil (Viagra): a preliminary report of a novel method to improve uterine artery blood flow and endometrial development in patients undergoing IVF." published in Human Society of Human Reproduction and Embryology, Human Reproduction vol. 15 no. 4 pp.806-809, 2000; what is your opinoin on success of treatment by using Sildenafil Citrate with Estradiol Valerate as new combination therapy. Also what precaution you will suggest in this therapy and possible side effects from which patients can suffer.

    ReplyDelete
    Replies
    1. Most doctors have stopped using vaginal viagra - unfortunately, it does not work well

      Delete
  10. Anonymous7:46 PM

    Hello sir,
    Is thickness of 6.5 to 7.5 mm enough for IVF success?
    I have had a few rounds of IVF failures and my lining hardly reaches 8 mm now.
    I had TB 7 years ago due to which my tubes got blocked.
    Is thin lining in my case due to TB?
    I do not have adhesions or any other problem in uterine cavity as mentioned in laparoscopy. But my lining has also reached 9 mm few years ago as seen in scan but recently it hardly surpasses 7 mm. What could be the reason?

    ReplyDelete
    Replies
    1. It's hard to provide a reason for a thin lining in most patients.

      Have you tried intrauterine perfusion of Granulocye Colony Stimulating Factor ( G-CSF) ?

      Delete

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