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What causes recurrent implantation failure?

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Posted on Thu, 28 Jul 2016
Question: I have had 4 failed IVFs. Age 33yrs. My main problem is Endometriosis. Had chocolate cyst in my ovary. All hormones normal - AMH 3.23 in 2014 Now AMH 2.89. No BP Sugar. But BMI 26. Husband sperm test Excellent.

FAILED - 1st IVF was long protocol with lupron and bravelle (2 units). 10000IU HCG trigger. Got 11 follicles, 9 eggs, 8 matured, 5 fertilised, 2 transferred (1 grade A & 1 grade B) , 1 frozen, 2 discarded due to arrest.

Had Hysertoscopy to remove polyp.

FAILED - 2nd IVF was agonist protocol with gonal F (300) and cetrotide (from day 7). Ovidrel trigger. Got 11 follicles, 8 eggs, 6 matured, 6 fertilised, 3 transferred (2 grade C & 1 grade CD) , 0 frozen, 3 discarded due to arrest.

Diagnoised Endometriosis and Hydosalpinx. So had a Lap and tubes were clipped (Uterus side) and ovary that was attached to uterus was released. Had a cyst in left ovary. It was aspirated. Adhesions were cleared from Ovary, Bladder and Rectum.

I was on Lupron Depot. Dint have periods for 3 months after the earlier laparascopy.

FAILED - 3rd IVF - Short / agonist Protocol - Recagon 450IU and Cetrotide (from day 6). 5000IU HCG trigger. WORST CYCLE. Scan was showing close to 20 follicles, but got 9 eggs, 8 matured, 5 fertilised. All frozen due to High progestrone. Had an FET 2 months later. Out of 5 frozen 3 made it after thaw. Transferred 3 embryos (all grade C to D).

FAILED - 4th IVF - Long & Short Protocol (13days Stimulation) - Buserlin 20 units from day 21 of previous cycle. Got periods and Started Stimulating from Day 3 - Gonal F 225IU and Buserlin 8units, Eutropin 2 Units alternate days. Had 13 Follicles - Retrieved 12 Eggs, 9 Mature, 9 Fertilised, 4 Arrested on Day3. Transferred 2 8cell and 1 7 cell (10-15% Fragmentation) with Assisted Hatching. 2 Frozen (1 5 & 1 6 Cell (less than 10% fragmentation). Had Intralipid IV 6 days before embryo transfer.

Before the 4th IVF, I took Supplements Coq10 200mg, DHEA 75MG, Fertisure F & Follinal Plus took for about 7 weeks before Stimulation. Started Eutropin (1 unit alternate days), Ecospirin 75mg, Cystop M(Metformin 500 & Myoinistol 600), Ovasafe (n acetylcysteine 600mg) 5 weeks before stimulation.
After Embryo Transfer, I was Only on Folic acid 10mg, Fertisure F, Ecospirin 75, Prognova 2mg 3 times a day, 100mg gestone Injection, Cystop M & Ovasafe.

In my IVF 1 to 3, after Egg retrieval & Embryo, I used to have minimal pain just for about a day or 2. N very mild spotting 1 day after embryo transfer. I would be completely normal after that. The 4th IVF was done after 1 year and 8 months after my lap.

MY PROBLEMS ARE
1. This time right from egg retreival, I had severe pain. It subsided two days later.
2. At the time of day 3 embryo transfer, I was given Ugesic (tablet) & anxit .25mg 1 hour before. I had minimal pain on the day of transfer.
3. The next day after embryo transfer, I wokeup with severe pains in my lower abdomen. I couldnt even move.
4. Whn I called the clinic I was given HYOCIMAX 10MG. After that, the pain subsided a little. But still i was in a lot of pain. Every day around the time I was given, Gestone Injection, The pain would aggravate.
5. I also started taking Duphalac 5ml and banana to avoid constipation. But the lower abdomen pain was always there despite regular bowel. From the date of embryo transfer till the next 3 days, I had very minute tiny bits of brown tissue like spotting most of the times. It stopped 3 days later. But I was very much bloated. Was drinking 3lts of water per day.
6. My progesterone, E2 and Beta HCG values 7 days after the transfer was 146, 1900 & 9.4.
7. My progesterone, E2 and Beta HCG values 9 days after the transfer was 48, 195 & 3.7. Bloating and pain started to reduce.
8. My progesterone, E2 and Beta HCG values 14 days after the transfer was 30, 58 & 0.4.
9. A scan showed that Both my ovaries were attached to my uterus and there were 2 tiny cysts on my right ovary. But these were there even at the time of stimulation.

QUERY
I have always had a regular 26day cycle. With pain in first or second day of period and only a 3day flow with 4th day spotting. I have never had problems with my uterus. It was always more than 9mm at the time of transfer. Also had a beautiful 3 layered lining. This time even my transferred embryo quality was satisfactory. No matter what the protocol was, I have ultimately landed with 4-5 embryos only. And this time, the embryos were good. But I was in immense pain through out. And the cycle failed... it has given me more grief.
I want to know why my embryos are getting arrested on Day 3. Despite an improvement in egg quality? Why is the implantation failing? Is my only option donor eggs? I belong to a very sensitive and conservative family and hence, the very feeling of using a donor egg gives me nightmares about all the tauntings that I have to face lifelong. Feel like my life is over. Please help. Its a do or die situation for me.
doctor
Answered by Dr. B. Radhakrishnan. Nair (50 minutes later)
Brief Answer:
Implantation failure

Detailed Answer:
Hi
greetings.
I can understand your concern. Nice that you have given complete details.
From the history as you correctly said ,you are getting eggs and more than 5 embryos in each cycle. Endometriosis can cause severe pain and though the hydrosalpinx was disconnected adhesions may cause problems during oocyte retrieval.
All the possible protocols and suppliments were tried on you.
Certain implantation failures are unexplained.
You should be discussing with your infertility specialist 2 options.
1.Another cycle,and half the embryos can be transferred in to your uterus and another in to a surrogate.
2.donor egg.
The reason need not be of ovum or embryo ,it could be even implantation failure.I am sure they would have done hystroscopy and the cavity is normal.
What ever decision you take should be early.Delaying will not improve any of the parameters , instead worsen it.
Hope my answer helps you.
Regards
Above answer was peer-reviewed by : Dr. Veerisetty Shyamkumar
doctor
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Follow up: Dr. B. Radhakrishnan. Nair (20 minutes later)
Thank you. My uterine cavity is normal as confirmed via hysteroscopy.

My pain subsided after 8 days of embryo transfer. Iam completely pain free now and am expecting my periods. So if the embryo transfer was deferred would it have given me success?

On the other hand, If I have another laparascopy and remove all the adhesions and hydrosalpinx, and have an FET 2 months later, will it help in implantation? As i told u, I would rather leave this world than to have a surrogate for my child. Iam not adamant. But I know my consequences which I have to face lifelong.
doctor
Answered by Dr. B. Radhakrishnan. Nair (1 hour later)
Brief Answer:
Implantation failure

Detailed Answer:
Hi
Don't be disheartened as the life will not end with out a successful IVF treatment.Since we don't know the reasons for the abdominal pain the role of delayed Embryo transfer is inconclusive.
Repeat surgery for adhesiolysis may not improve fertility.Your AMH is decreasing and after each endometriotic cyst removal it will further compromise the ovaries.
If hydrosalpinx was not clipped it could have been removed during the second lap.
Certain things are unexplained and unknown.
The quality of eggs may not improve after the surgery.
Only you and your husband need to know about donor eggs and surrogate.
I still recommend my options.You can go ahead with a second look laparoscopy.If you decide latter it may be late.so plan for your own egg and half embryos in you and surrogate.
That will rule out,whether the problem was with the egg or uterus for implantation.
Hope my answer helps you. Regards
Above answer was peer-reviewed by : Dr. Vaishalee Punj
doctor
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Follow up: Dr. B. Radhakrishnan. Nair (1 hour later)
Ok Dr.
Can I get stimulated - retrieve the eggs via laparascopy and have adhesiolysis in the same Lap? In that case, I can have my endo cleared and also my eggs wouldnt be affected. And two or three months later, can I have a mix FET cycle? also with Donor egg embryos? What about Mitochondria Transfer from donor eggs? will it help? Will embryo glue help with implantation? Please let me know. I know that I seem very anxious and impatient. But a surrogate is completely out of question. That is why. My father in law is a Surgeon and the doctor who is performing my IVF this time is his friend. And there s no possibility of secrecy. Unfortunately... He funds my whole IVF.
doctor
Answered by Dr. B. Radhakrishnan. Nair (14 minutes later)
Brief Answer:
Implantation failure

Detailed Answer:
Hi
I can understand your situation.
It will not be possible to do laparoscopic adhesiolysis and egg retrieval in the same sitting.
In your previous query (2014) you have mentioned about defective ovum.
Chances of improving ovum after 2 years is very remote.
I was suggesting other option worrying about implantation failure rather than quality of embryo or ovum.
I have no idea about any centres doing mitochondrial transfer and embryo glue in XXXXXXX It may be available .Please discuss that with your ivf consultant.
Another reason to suggest the other option was ,your doctor has tried all the possible ways to treat your infertility.
You can always take a second opinion from a different IVF centre in XXXXXXX
Hope you are convinced. Regards
Above answer was peer-reviewed by : Dr. Vaishalee Punj
doctor
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Follow up: Dr. B. Radhakrishnan. Nair (1 hour later)
This time my ovum quality was very good. But they now want my husband's sperm DNA fragmentation test to be done as my embryos did well till day 3 and get arrested only later. If egg retrieval and adhesiolysis cant be in the same sitting, I will first do my IVF. and the following month Can I have a lap?

Please tell me some other solution such that I can improve my chances of embryo implantation. My uterus has been perfect... no polyps, perfect 3 layers and more than minimum 9mm lining always.... :(
doctor
Answered by Dr. B. Radhakrishnan. Nair (11 minutes later)
Brief Answer:
Implantation failure

Detailed Answer:
Hi
semen analysis was normal earlier or had any issues?
DNA fragmentation can be done if abnormal or there is varicocele.
It should be reverse .Get the hystroscopy and laparoscopy done and later IVF.
It may be done from a well experienced gynaec laparoscopic surgeon as there could be severe adhesions.If at all adhesiolysis and removal of the affected tubes to be successful he should be very well experienced as it is a repeat surgery.
I still recommend you to keep all options open at the time of ovum retrieval , as after every chance the quality and success need not improve than before.
Good luck and regards
Above answer was peer-reviewed by : Dr. Prasad
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Dr. B. Radhakrishnan. Nair

OBGYN

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What causes recurrent implantation failure?

Brief Answer: Implantation failure Detailed Answer: Hi greetings. I can understand your concern. Nice that you have given complete details. From the history as you correctly said ,you are getting eggs and more than 5 embryos in each cycle. Endometriosis can cause severe pain and though the hydrosalpinx was disconnected adhesions may cause problems during oocyte retrieval. All the possible protocols and suppliments were tried on you. Certain implantation failures are unexplained. You should be discussing with your infertility specialist 2 options. 1.Another cycle,and half the embryos can be transferred in to your uterus and another in to a surrogate. 2.donor egg. The reason need not be of ovum or embryo ,it could be even implantation failure.I am sure they would have done hystroscopy and the cavity is normal. What ever decision you take should be early.Delaying will not improve any of the parameters , instead worsen it. Hope my answer helps you. Regards