Dr Braverman's response on the lack of stem cells in the womb being the cause of RPL

Dr Braverman responsed on his blog to the lack of stem cells in the womb being the cause of RPL. As he points out,a direct cause for RPL was not demonstrated in the Warwick study.  So he explained it clearly on his blog:

http://www.preventmiscarriage.com/Literature-Review-Blog/2016/March/Defect-in-endometrial-stem-cells-key-player-in-r.aspx

Lack of stem cells to blame for recurrent miscarriages

Date:

March 7, 2016

Source:

University of Warwick

Scientists at the University of Warwick have discovered that a lack of stem cells in the womb lining is causing thousands of women to suffer from recurrent miscarriages.

The academics behind the breakthrough are now to start research into a treatment which they believe could bring hope to those who have suffered failed pregnancies.

Professor of Obstetrics & Gynaecology, Jan Brosens led the team who unearthed the link between stem cells and miscarriage. He said: "We have discovered that the lining of the womb in the recurrent miscarriage patients we studied is already defective before pregnancy.

"I can envisage that we will be able to correct these defects before the patient tries to achieve another pregnancy. In fact, this may be the only way to really prevent miscarriages in these cases."

The team found a shortfall of stem cells is the likely cause of accelerated ageing of the lining of the womb which results in the failure of some pregnancies.

Miscarriage is the most common cause of loss; between 15-25% of pregnancies end in miscarriage and one in 100 women trying to conceive suffer recurrent miscarriages, defined as the loss of three or more consecutive pregnancies.

The study, which is a collaboration between the University's Warwick Medical School and Warwick Systems Biology Centre, has been published in the journal Stem Cells.

Miscarriage is the most common cause of loss; between 15-25% of pregnancies end in miscarriage and one in 100 women trying to conceive suffer recurrent miscarriages, defined as the loss of three or more consecutive pregnancies.

The researchers examined tissue samples from the womb lining, donated by 183 women who were being treated at the Implantation Research Clinic, University Hospitals Coventry and Warwickshire NHS Trust.

The team found that an epigenetic signature -- which is typical of stem cells -- was absent in cultures established from womb biopsies taken from women suffering recurrent miscarriages. Indeed, fewer stem cells could be isolated from the lining of the womb from recurrent miscarriage patients when compared to women in the study's control group.

The researchers further found that a stem cell shortage accelerates cellular ageing in the womb. The lining has to renew itself each cycle, each miscarriage and successful birth. This renewal capacity is dependent on resident stem cell population. A shortage of these stem cells in patients suffering recurrent loss is associated with accelerated ageing of the tissue. Ageing cells mount an inflammatory response, which may facilitate implantation of an embryo but is detrimental for its further development.

Professor Brosens added: "After an embryo has implanted, the lining of the uterus develops into a specialised structure called the decidua, and this process can be replicated when cells from the uterus are cultured in the lab.

"Cultured cells from women who had had three or more consecutive miscarriages showed that ageing cells in the lining of the womb don't have the ability to prepare adequately for pregnancy."

Co-author of the study is University of Warwick Professor of Obstetrics and Honorary Consultant at University Hospital Coventry and Warwickshire NHS trust Siobhan Quenby. She said: "The real challenge now is to develop strategies to increase the function of stem cells in the womb lining.

"We will start piloting new interventions to improve the lining of the womb in the spring of 2016. Our focus will be two-fold. First, we wish to improve the screening of women at risk of recurrent miscarriage by developing new endometrial tests. Second, there are a number of drugs and other interventions, such as endometrial 'scratch', a procedure used to help embryos implant more successfully, that have the potential to increase the stem cell populations in the womb lining."

Painful Shoes

Life is a mystery to be lived, not a problem to be solved

Until we tried to have a baby, I pretty much believed that if you want something badly enough in life, you can make it happen. If I didn’t get the job I wanted, I’d just shrug off the rejection and apply for another. If I didn't like where I was living, I'd move.  I've always believed that we choose our own destiny.  I dislike the phrase "It just isn't meant to be". With enough determination and perseverence we can make all our dreams come true. Being in control makes us feel safe. Sometimes when we want something so badly, this control can become obsessive. We will try everything to make it happen. Now, 8 miscarriages and several failed IVF cycles later, the reality has hit me, that some things in our lives we just have no control over. Mainly, life and death. My Reproductive endocrinologist finally admitted that he doesn't know the reason why I keep having losses. He said we may never find the answer as to why. A few years ago, he thought he had an answer. Abnormal chromosomes. He told us that this is usually the case with RPL. I'd had 3 miscarriages from spontaneous conceptions (2 confirmed aneuploid ) and I was afraid of having more. So we embarked on a donor egg program. Excellent grade embryos. I miscarried again. No heartbeat at 8 1/2 weeks. So we had our remaining frozen embryos pre-genetically screened (PGS). One was aneuploid. Ah, maybe there was our answer! We now had three normal embryos. While we were waiting 4 months for the results, I had gotten spontaneously pregnant again and miscarried. Let's not try naturally anymore my Dh and I decided. Crazy, as much as we wanted to have a child, we were now preventing pregnancy. 3 FET's in 2015 resulted in Two chemical pregnanices and a BFN. 
We are still left wondering, why did this happen? There is a reason, but even if we knew what that reason was, it wouldn't guarantee success. Because we just aren't in control of life..and we aren't in control of death either.

BFN

RE phoned me himself to tell me that my beta was negative. He said he doesn't believe my thyroid levels are the issue because although my Free T4 is on the high end of normal at 1.8. He said he would be willing to order the allo-immue testing through Dr Braverman, but he cannot sign the form on his website and doesn't understand why Dr B insists on having his name tied to the clinic's. So I am on my own for getting the immune testing done. Dr Hamersley has ordered the immunology testing for a lady I know. However, the extensive immune panel costs $7,500 which includes Dr B's interpretation. It is not a bad price if we were cycling with his clinic but we are not. Re asked if there should be an allo-immune issue how would Dr B treat it. Possibly intralipids or Ivig, depending on what the immune issue is. My clinic is unwilling to prescribe either of these. Since he had no suggestion as to the next step I suggested maybe donated embryos or donor sperm &egg might work. He then told me that they are starting a donor embryo donation program soon due to the high demand. I will have to talk to the financial councellor and see if we can get a partial refund from the Donor egg program to use towards the Embryo donation program. 

When your RE says there is nothing more that can be done and he suggest a gestational carrier and you are financially drained and know that is not an option.  I just can't explain the feeling of total hopelessness. He said he wished he knew the reason why I keep losing PGS normal embryos but is totally at a loss. We could have transfered more than one embryo at a time and we would have been on cycle #3 by now. But we did eSET each time and that is why it took us almost 2 years to use up our embryos. Why is it always my fault? First bad eggs and now my immune system? Doesn't seem fair. In my defense, Dh said it could be his sperm. RE argued that icsi fixes any issues with sperm morphology. Or perhaps our donor's eggs? After she cycled for us, she was taken out of their database and her eggs were sent to a frozen egg bank. This usually means there were no live births from her eggs.  I asked on several occasions if he could find out this info but he just replied that her after eggs were sent to the egg bank there is no way he could find out any info on her. Makes me wary of choosing another Egg donor.  After our phone conversation, RE wrote me an email saying he would still like to do everything within his power to help us and to keep in mind the Embryo donation program. For the first time since we have been on this journey, I feel like Dh and I have come to the end of the road.

10dp5dt- Thwarted by my thyroid again!

It took a whole week to get my thyroid levels back! Endocrinologist said my TSH jumped from 1.6 before  I started estradiol to 3.2. That was a week ago, so it's probably even higher now! She had doubled my synthroid to 50 mcg but it didn't make much difference since last FET my TSH had jumped to 3.8 when I had the chemical pregnancy. My Thyroid levels were perfect before the stupid estrogen. IVF just isn't for me. When I get pregnant naturally I have abnormal chromosomes.  Can't win. Beyond frustrated! Beta is tomorrow but I know it's going to be negative.

6dp5dt

Transfer was at 2:45pm on Friday so it hasn't been quite 6 days since transfer, but I got a squinter on an IC with FMU at 7am. The lack of symptoms is worrying me. I usually have sore veiny breasts and white CM by now. This time nothing. I felt sharp implantation cramps on the morning of 4dpt, so holding on to hope for that and the faint hpt. It was darker last FET at this point. The 2ww is a killer with this being our last embryo.  Praying.