Chat Transcipt: Geoffrey Sher, MD: Repeated IVF Failures

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Auditorium with Geoffrey Sher, M.D.
Repeated IVF Failure
 June 1 2005

 

Welcome to an INCIID Chat Auditorium with Geoffrey Sher, M.D., the executive medical director of Sher Institutes for Medicine.

Martha : What a coincidence.... I just received the  news today, my 5th IVF attempt has failed. I am a "poor responder",  and seem to have premature "ovarian failure". Problem in the past has been high FSH level in cycle day 3 resulting in early cancellations of my cycle. Last stimulation protocol  I used micro dose Lupron but was only able to grow 4 follicles. I had 2 positive test results on RIP (reproductive immunophynotype from Millenova.
Geoffrey Sher MD : It's all about the protocol of stimulation. I am very much against micro dose flare protocols for poor responders. It causes LH levels that are too high and increased ovarian testosterone. This has a bad effect on the egg quality and thus embryos. It’s my opinion an  agonist/antagonist conversion protocol would be better. 
Sally : At what point do I switch doctors? I am already with a specialist and just not happy.

Geoffrey Sher MD : If you are asking yourself this question, it is probably the right time to switch. Remember it is about you not about the doctor.

Abigail:  Dr. Sher, I am 28, my husband is 36. He has CBAVD and had a MESA last summer. I seem to have poor response and am on a very high dose of stimulation drugs. My last cycle resulted in 17 eggs and we put back 2 perfect top quality blasts which resulted in a negative pregnancy test result. This was my 2nd complete IVF cycle. My first cycle was cancelled due to poor response. I am getting ready for a FET (Frozen Embryo Transfer) with the remaining blasts. Is there anything I should do differently to prepare to increase implantation? If this FET doesn't work, would a hysteroscopy be helpful to rule out anything else "wrong" with my body? Thanks so much!

Geoffrey Sher MD : It would seem going to FET would be the right thing to do. If you’ll email me I’ll send you an article called,  "Factors Affecting IVF Outcome" which may be of interest to you.
Halley : I had a successful first IVF. The 2nd IVF started off successful up to 6 weeks--growth was good. However, we never saw a heartbeat and a miscarriage was declared at 9 weeks. I'm about to do another IVF cycle and they tested me for antibodies. I tested positive for two thyroid antibodies so now they want me to get more extensive tests that are expensive. Do you think I need to do this since I had one success?
Geoffrey Sher MD : Fifty percent of women who have thyroid antibodies have an immunologic implantation problem that can manifest as failure to conceive or early miscarriage. The way to recognize whether this is the case with you is by doing NK cell activity test (not measurement of the NK cell concentration) as well as T cell activation testing. If either are positive you are probably best advised to consider IVIG therapy administered 7-10 days before expected embryo transfer.

Lori : I'm interested in understanding how many IVF tries are logical (my RE suggests 3) . I have one failed IVF. Should we try again?

Geoffrey Sher MD : Provided your uterine lining is normal (9mm at peak estradiol) and you don't have an abnormal uterus or an immunologic implantation problem, you might simply try again. Make sure you are first tested for the above.

MaryJoJo: I just found out I'm a pregnant with my 2nd child. I am taking heparin because of immune issues. There's a chance of multiples as my beta at 10pt was 409, Do I need to increase my heparin dosage of 5000 units twice daily for multiples?

Geoffrey Sher MD : With our patients we do not usually increase Heparin dosage and we at SIRM usually recommend stopping Heparin completely at the 10th week of pregnancy.

MaryAlice : Good Evening Dr. Sher. Glad you could chat with us. On an  FET cycle, what is the optimal treatment in the 2 week wait for an FET if I can't take Baby aspirin? 
Geoffrey Sher MD : I do not prescribe baby aspirin to my patients. Heparin is only indicated if you have APA or a Thrombophilia of specific variety.

Sarah : I have a history of apparent implantation failure. (Pregnancies never lasted long enough for a positive home pregnancy test.) When implantation or early pregnancy is repeatedly unsuccessful with apparently good embryos from IVF, what, if anything, can be done?
Geoffrey Sher MD : It is important to have a hysteroscopy or a saline ultrasound to evaluate the uterine cavity and a full immunologic evaluation including APA, NKa, ATA, RIP and ANA. Email me at gsher@sherinstitute.com and I will send you details as well as a copy of my article "Factors Affecting IVF Outcome". Ready
Tandy : My first IVF was unsuccessful, just got the beta last week, negative. I have stage IV endometriosis and I have been reading about endo causing possible implantation failure. My RE isn't very big on immune testing (they only test after 2 miscarriages) but if I have endo and that could mean I might have immune issues. What would your suggestions be?
Geoffrey Sher MD : Endometriosis is associated with immunologic implantation problems in about 1/3 of cases regardless of severity of the endometriosis. Treatment with selective immune therapy may be helpful here. If you have more questions, please feel free to email me. [Editors note: You may also want to visit the IMMUNE ISSUES Forum with its medical reproductive immunologist RE moderator]
Tammy : The thing I'm confused about is the lab website says there is a 50% miscarriage risk with the two positive thyroid antibodies, so did that mean I just got lucky the first time? I will be 40 in a couple months, so I don't have a lot of time to get this right.
Geoffrey Sher MD : If you had a baby in spite of thyroid antibodies, it is my opinion you probably do not have an immunologic implantation problem. 
Sharon : On my first IVF I was told my eggs had vacuoles and weew abnormally shaped. I had 25 ER, 20 mature, 14 fertilized. Transferred 3 grade 1 blast 8 celled which was a chemical. FET of 2 blast was BFN. Are my eggs just bad like my RE says?
Geoffrey Sher MD : Age is the major determinant of egg quality. The protocol of ovarian stimulation can also play a role. Simply because the eggs were mature does not mean they were chromosomally normal. The protocol of stimulation must be individualized especially in high responders, poor responders, and women over 35. 
TobbyJean : Dr. Sher, what is you opinion on IVIG? I just received the news of another failed IVF. I did not use IVIg.
Geoffrey Sher MD : IVIG is helpful in certain cases of repeat IVF failure due to immunologic factors. Usually if the NK cell activity is increased IVIG may be beneficial but some women with increased NK cell activity still get pregnant without IVIG. We simply don't know enough on how to differentiate between those who need IVIG and those who do not. Thus the clinical circumstances play a big role in deciding. [Editor’s Note: Please see the fact sheet: Immunology May be Key to Pregnancy Loss]

Ellin : Can you tell me about the blood tests for RPL and what steps or medicines you use if the results come back positive?: My doctor ordered Protein C and S, MTHFR, Factor V and APA/LAC because I had a chemical pregnancy on my 1st IVF.
Geoffrey Sher MD : MTHFR, factor V Leiden are thrombophilias and they do not cause early pregnancy loss. If you email me at gsher@sherinstitute.com I will send you a list of the tests you need. 
Eleanor : After 1st IVF w/ SIRM-CI  my betas went from 5 to 3.  I was diagnosed with elevated APA. With my 2nd IVF (same SIRM clinic) we added Heparin and this IVF resulted in an ectopic pregnancy. My tube ruptured, so I had emergency surgery with the right tube removed. I'm gearing up for IVF #3, but am wondering how much my chances are increased for having another ectopic pregnancy? We have been trying to conceive for 5 1/2 yrs. My husband and I are both 32. Thanks.
Geoffrey Sher MD : The ectopic pregnancy was an accident and the risk is 1 in 30 with IVF the same with your next try. Good luck. 
Louise:  What is you opinion on IVIG? I just had a failed cycle. My doctor is not a proponent of IVIg since he thinks this is not my problem.  Instead he  thinks my problems are increased levels of FSH on CD3. However, I tested positive twice on the Reproductive Immunophenotype test (for natural killer cell activity done through Millenova). I am leaning towards egg donation now since in addition I am a poor responder to the stimulation meds. Should I consider IVIg if I went this route?
Geoffrey Sher MD : IVIG is helpful in certain cases of repeat IVF failure due to immunologic factors. Usually if the NK cell activity is increased IVIG may be beneficial but some women with increased NK cell activity still get pregnant without IVIG. We simply don't know enough on how to differentiate between those who need IVIG and those who do not. Thus the clinical circumstances play a big role in deciding. [Editor’s Note: Please see the fact sheet: Immunology May be Key to Pregnancy Loss
I would need to know much more to answer your question. However, it is a critical question because if you do have an immunological implantation problem you won't get pregnant with OD (Ovum/Egg Donation) either. You need to be fully evaluated

Mandy : I've had 2 DE failures in 2004 I also had 2 blighted ovums and 1 m/c all natural! I will be cycling this month with Dr Batzofin. I will be doing IVIG and Heparin. Anything else I should be doing?
Geoffrey Sher MD : You will be in very good hands and knowing the screening process that Dr. Batzofin implements I am sure that he has addressed the variable that can affect outcome appropriately. Good luck.
Donna : I too have had repeated implantation failure with positive betas; one from IVF, one from FET both with very good embryos. I have had the immunologic testing and all came back fine. What will the hysteroscopy be able to detect?
Geoffrey Sher MD : It will detect small surface lesions that could create a foreign body response in the uterine lining. Such lesions would be missed by HSG in 40% of cases. Ready
Hope : If pregnancy is a lowered immune state, why is it necessary to take IVIg?
Geoffrey Sher MD : The attachment of the embryo to the uterine lining defies the normal tissue response to a foreign transplant. Our very existence is attributable to very magnificent immunologic adaptations in the uterine lining that allows the foreign graft to take. Is it so surprising that such sophisticated mechanisms could go wrong? They can and they indeed do.

 

Pru:  What is a good protocol for poor responders (over 35)?
Geoffrey Sher MD : Email me at gsher@sherinstitute.com and I will send you details of the agonist/antagonist conversion protocol (A/ACP) which we have found to be optimal in such cases as yours. Ready

Tracy : Hello Dr. Sher, prior to using DE, we conceived 2x and m/c'd once at 10 wks; once at 8.5 wks - no heartbeat at ultasound. We've done 5 DE (donor egg) cycles with 3 different donors. We had terrible fertility rates. I've had some immune testing done, but my doctor does not really believe in it. ACA, MTHFR, APA, lupus, protein, etc. all negative/normal. One MTHFR mutation came back +; other one. I am on mega doses of Rx of folic acid and heparin during cycle. Do you think this could be undiagnosed male factor infertility?
Geoffrey Sher MD : First of all, MTHFR and factor V Leiden are not likely to prevent implantation or early pregnancy loss. ACA and Lupus anticoagulant measurements are totally inadequate to evaluate for immunologic implantation problems. Email me and I will send you information. Ready
Leslie : I have pretty close to normal semen numbers - low on morphology and high dna fragmanton. Do you know how I can fix this?
Geoffrey Sher MD : Go to http://www.proceptin.com  and order proceptin which provides an excellent blend of antioxidants and vitamins that can improve the DNA fragmentation index in more than 60% of cases. 
Annie : Dr. Ahlering repaired my septate uterus in March 05. We have 3 frozen expanded day 6 blasts for this FET, would you recommend to transfer 3 if all 3 survive the thaw? I have had 2 mc's of twins from IVF #2 and 3 at 8 and 10 weeks each time, due to subchorionic bleeds where septum was removed a few years ago. What would you recommend for # of embies to transfer if all 3 make the thaw?

Geoffrey Sher MD : I would thaw all 3 because frozen embryos have a slightly reduce implantation potential over fresh. Ready
Cindy : What are your thoughts about PGD? We had signed consents and paid to do it with that cycle that I had a miscarriage, but the lab forgot to do it. Do you think it would help pick the most normal embryos?
Geoffrey Sher MD : PGD with FISH to decide on which embryos to choose which tor transfer is of no value because FISH can only evaluate 8 or 9 of a possible 23 chromosome pairs. It has been shown therefore that even if PGD with FISH is normal there is still a 40% chance of undetected chromosome abnormalities so why do it?

Carol : I have factor v leiden. What kind of complications or problems can this cause?

Geoffrey Sher MD : Mid pregnancy loss, placental insufficiency and intrauterine growth retardation, possibly hypertension in later pregnancy and blood clotting problems during and after pregnancy. But not failed implantation or early pregnancy loss. Treatment involves folic acid supplementation and sometimes Heparin throughout pregnancy. Ready

Linda : If a person had a normal pregnancy and delivery, does that rule out a future immunological implantation problem?

Geoffrey Sher MD : Not always.
Ellen : What can be done about surface lesions that show up with hysteroscopy but not HSG? My HSG was fine so I have not had hysteroscopy

Geoffrey Sher MD : They can be removed by D&C or hysteroscopic resection. 
Barbara : Is getting a low positive on an HCG test (ending in a chemical pregnancy) a better sign than a pure negative? What does getting a chemical pregnancy add to a diagnosis?
Geoffrey Sher MD : Getting a chemical pregnancy tells you that you are able to produce embryos that go to blastocyst otherwise there would not have been a positive Beta. In a sense it represents a "dark cloud with a silver lining" and suggest that you are more likely to be successful in the future. 
Suzy : Does weight play a big role in the sucess of ivf?
Geoffrey Sher MD : Not unless there are extremes (anerexic or severe obesity). Ready

Betty : We've conceived twice on our own, both of which ended in m/c at 10 wks & 8.5 wks. Am a poor responder with hi FSH - moved to DE. Have 5 failed DE cycles using 3 diff donors. (1 chem pg; 1 twin pg ending in m/c at 7 wks). Horrible fert. rates altho nothing shows up in DH's testing. RE does not go for the immun testing, but ordered some. All norm/neg...We're using donated embryos for a FET in 2+ weeks. Am on baby asa, Rx folic acid and will be taking heparin - empiracally. Any other ideas?
Geoffrey Sher MD : This sounds very much as if you might have had an implantion problem that has gone unrecognized, all along. It is time to have a proper evaluation for implantation failure (immunologic, anatomical, etc) before proceeding any further. 
Heidi : I am a poor responder as well and my doctor followed the microdose lupron protocol. I never heard about the A/ACP protocol. W/o going too much into detail, what's the main difference, or where can I read up on it?

Geoffrey Sher MD : I have strong reasons to feel that micro dose flare is less than ideal in poor responder. Email me at gsher@sherinstitute.com and I will send you the information. 
Zelda : Have you seen women with poor eggs and NKA+ be successful on a donor cycle without IVIG?

Geoffrey Sher MD : Yes I have and not everybody who has NKa+ has an immunological implantation problem but they are more likely to have one if they are NKa+ that is why I keep emphasizing that each case must be judged on its own merits. A woman who keeps failing IVF or has repeated unexplained miscarriages in spite of good embryos would be one who I would be more emphatic on giving IVIG to than someone who de novo came up with a positive NKa without having failed IVF before. 
Kip : We've had awful fertilization rates on all three fresh DE cycles especially on the IVF embryos (as opposed to ICSI) - even though S.A. and SCSA testing all came back good. If we have un undiagnosed male factor, can this impact implantation of the embryos?

Geoffrey Sher MD : If the SCSA was normal I doubt that this is a sperm problem. More than likely it has to do with the protocol of stimulation, your age or both. You need an individualized approach if you are to address this issue. Not knowing your case history it is not possible to comment further constructively. 
Kim : What is your opinion of taking dhea when over 40 for ivf cycle?

Geoffrey Sher MD : I don't know of any evidence of its efficacy. 
Silvia:  At what point after repeated failures (3 IVF's and 1 FET) given that there was adequate number of eggs produced, do you recommend moving on to donor eggs?

Geoffrey Sher MD : It is not as simple as that. I mentioned earlier that before going to OD it is important to rule out factors that would prevent pregnancy in this setting as well. For example if there is an implantation problem preventing pregnancy ovum donation will likely fail as well. 
Hope : I was seen in your Sacramento clinic this past march after our 3rd first trimester miscarriage (all natural cycles). All my tests were normal. We were told my husband's low morphology might be causing the losses. If we go the IVF route, wouldn't we have the same chance of miscarriage if the morphology remains low? Would we have a better chance with IVF?

Geoffrey Sher MD : I suggest that you have SDIA (virtually the same as SCSA) done on your husband's sperm. If this is normal I doubt it is a sperm issue. 
Lemmie: I am two months away from being 40, so I am concerned about Down's syndrome. I think that PGD screens for that. Also, do you think PGD damages the embryos or leads to miscarriage?

Geoffrey Sher MD : Yes, PGD will screen for Down's Syndrome and if your sole objective is to prevent this condition or miscarriage due to it then PGD is indicated. However, PGD in general does not help in the selection of embryos for transfer because in so doing you cannot rule out some of the most common chromosomal causes for failed implantation. 
Agatha : I was wondering if you have all your patients go through immune testing to rule out things first before starting IVF, etc. I just feel like a lot of REs aren't into doing the immune testing. What is your protocol?

Geoffrey Sher MD : No, absolutely not. Immune testing is done very selectively because in the absence of predisposing factors it is very unlikely to play a role. 
Tracy : I have not had any IVF treatments yet – but I have a question if I may? At my age, 39, what tests should I take? I’ve taken my blood tests and everything is healthy – but haven’t taken a hormone test (next week). Should I have any tests done for the problems discussed here or is it too early to worry about such things? My reason for IVF is one blocked tube and ectopic pregnancy (7 years ago) in the other tube. HSG showed right tube open but laproscope shows a lot of scaring. Thank you.

Geoffrey Sher MD : Email me and I will send you the information that is too copious to post here.

Alice : Are there any new numbers to show the sucess rates for women under 35 undergoing IVF for the first time when all lab tests have fallen into the 'normal' range?

Geoffrey Sher MD : There are figures that you can find on various web sites. Our statistics are posted on the SIRM web site, www.haveababy.com. Ready
Julie : What is the definition of early pregnancy loss? How many weeks?

Geoffrey Sher MD : Pregnancy lost in the first trimester (first 13 weeks). Ready
Gerry : what is the optimal lining measurement you would recommend on a cycle? FET this time around and I have had to use Viagra for lining building, but we are doing the lupron and E2V shots this time for the FET.

Geoffrey Sher MD : 9mm on the day that progesterone is started. 8-9mm is the intermediate value and under 8 poor results can be expected. Ready
Tanya : I am undergoing ivf for the first time, all labs have come back to be normal.. I am cycling right now, and we are uncertain how many embies to have put back after fert. we are hoping for one baby, would be great with twins, but the higher the number the higher multiple odds.. any Geoffrey Sher MD : This is where our embryo marker expression test (EMET) is great. It measures HLAg produced by the early embryo and if the level is high that embryo has a much better chance of implanting. This is how we are able to select embryos at SIRM. There were two articles published on this last month by us. One was in the May "Human Reproduction" and another in the May "Fertility and Sterility" take a look. I would suggest that if you were under 35 to have 2 embryos put back. 35 to 40, 3 and over 40 it really doesn't matter because triplets are almost unheard of in women over 40. Ready
Freda : Any special foods we should eat to be more succesful?
Geoffrey Sher MD : Just eat healthy foods and in reasonable amounts. Complex vitamin supplementation may help and try to avoid caffeine and nicotine and alcohol.

 

Mary : My brother has Evan's syndrome - which is a combination of autoimmune hemolytic anemia and another thing I can't remember. He now has t-cell angioimmunioblastic lymphoma. My grandmother had lupus. Does that increase my chances of having immune problems?
Geoffrey Sher MD : Yes, unfortunately it does. 

Melly : Other than implantation problems what can NKA+ cells cause?
Geoffrey Sher MD : If there are no NK cells then the placenta can grow through the wall of the uterus such that after delivery it won't dislodge (placenta accreta) this sometimes necessitates hysterectomy. 
Molly : can lining be too thick? Mine was at 11.
Geoffrey Sher MD : 11 is great and I am not aware of a thickness that is too great unless there is uterine pathology. 
Dolores : I was lucky enough to conceive my daughter on the first try at IVF but we have been trying for another sibling and have gone through 2 fresh cycles 4 frozen. All were perfect cycles good embryos good lining not sure what could be wrong. Can this possibly be an immune issue? Or what else should we try?
Geoffrey Sher MD : Then have your husband checked for a varicocele by a urologist because if this is present it can cause the problem. Treatment usually causes reversion.

Geoffrey Sher MD : I am afraid we have to go now. Thank you for inviting me and thank you Sharon for typing on my behalf. Anybody with questions unanswered is free to email me and I will respond promptly. Also may invite any of you to call Sharon Benzel at 800-780-7437 and set up a free telephone consultation with me. Good Night and thank you all for attending. Geoff Sher 

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