22 Responses to “Age, Aneuploidy and Ovarian Reserve: Why Customized Stimulation Protocols are Essential”

1. zorana says:

   December 10, 2009 at 6:01 am

   I am 42 years old, I have just finished a protocol with 56 menopure, I had 2 folicules, doctor said they very "empty", my AMH is very low, what would your recomend me for the next time? No stimulation at all?
   Thank you

   Reply
2. Geoffrey Sher, MD says:

   December 10, 2009 at 3:05 pm

   No stimulation at all would be a mistake in your case, You probably need an agonist/antagonist conversion protocol (A/ACP) with estrogen priming. Read elsewhere on this blog about this protocol.

   Feel free to set up a consultation by phone if you want to discuss further.

   Geoff Sher

   Reply
3. Trudy says:

   December 11, 2009 at 5:34 am

   Thanks for writing this.
   I did five IVF cycles, age 33-34. The first two I don't think I stimmed long enough (RE was worried about hyperstim) and had a lower number of mature eggs, but decent fert rates but then not a great number of on target embryos (but a few). Third one was antagonist and we added Menopur and had AWFUL fert rates. Fourth one went to a 'famous' clinic and was put on MDL which made no sense to me. My E2 was way too high right away (2600 on day 4 of stims with FSH) and I think the LH ruined my eggs. Only 2 out of 12 fertilized and they looked dark and grainy with fragmented polar bodies (which previous embryologist had never detected). Fifth cycle I begged for no LH to be added and the clinic relented initially, but ended up pushing for Menopur added in on day 3 of stims because my E2 was low (of course it ended up hitting near 7,000, which I knew would happen–I'm always slow). We had better maturity rates and better fert rates and more on target embryos and actually had a chemical–the further we'd ever come and the only happiness we'd ever had from IVF (getting a positive HPT was incredible.) We also did two uterine biopsies prior and an FET (of day 3 embryos) and I do think those two things significantly helped my uterine receptivity, as I have a history of borderline uterine hyperplasia. We've always done day 3 transfers.

   If I had unlimited funds I'd try one more time and do NO LH until later in the stim phase because I do think we have a few good eggs in there, it's just a matter of finding them and being delicate with their stimulation. I'd repeat the biopsies too, which I think helped. But we're out of funds and it it just breaks my heart that we're at the end of our A.R.T. road and still have empty arms (and wallets!).

   Now if only there were a study studying patients crazy enough to do a sixth IVF

   Reply
4. Geoffrey Sher, MD says:

   December 11, 2009 at 9:16 am

   I understand fully and would advise you to contact INCIID and apply for their INCIID the Heart program thatoffers free IVF to qualifying couples.

   Frankly I think their could be something else afoot too…namely an implantation issue…but I agree with your opinion.

   Geoff Sher

   Reply
5. Shrinepass says:

   December 14, 2009 at 10:21 am

   Hi, I would absolutely love your feedback as I think your article speaks to my situation… I started at 36 and am now 38. I had 6 failed IUIs, 3 failed IVFs, plus 2 frozen IVF cycles. I froze the last 2 cycles as we discovered I had immune issues. After being treated for that (LIT, NK, TNF, plus anti-ovarian antibodies which are supposedly untreatable) we actually have opted to go the route of a surrogate focusing on egg quality for now! Also as an fyi, I have produced 2 perfect and high quality embryos, 2 decent quality embryos, and 1 genetic swing – average quality embryo – out of 2 IVFs (first IVF got nothing, and #4 and 5 are frozen and untested).

   My first IVF was a Lupron, Bravelle, Repronex cycle in which we only got 1 fertilized and genetically tested very poor. 2nd and 3rd IVF which were the best, I did natural antigon with Bravelle and Menapur (adding ganirelix at the end). 4th IVF (frozen) I did a microdose flare Lupron again with Bravelle and Menapur. 5th IVF (frozen) I did precycle ganirelix and estrace then did the regular Bravelle and Menapur which was my worst cycle along with IVF #1.

   So it seems to me I do good on a natural antigon where we use Bravelle and Menapur with no ganirelix up front (it is used at the end to keep me from ovulating for 2 to 3 days).

   At most I have about 7 antrofollicles. So I am a low ovarian reserve and I have a terribly low AMH number while my FSH has tested at a high of 14.5 and a low of 7.5.

   I have been off for 4 months (last IVF 9/09) trying to line up a surrogate and we should be ready to go mid January. Though I am nervous because my periods / cycles have been weird. I am ovulating early and then my cycle starts around day 30ish. While this last month I ovulated early (day 9ish) and then my cycle started on day 25. This inconsistency makes me worry that my body is changing while I had hoped that the 4 months off would do good???

   If you have any comments on the protocols, I would be amazingly greatful as I embark on my last effort to get good eggs. Seems that my sticking with Bravelle and Menpur goes against what you think my group would do well with? What should I consider looking at as a protocol???

   Reply
6. Geoffrey Sher, MD says:

   December 14, 2009 at 11:11 am

   I frankly need much more information about the exact immunologic issue being dealt with. I recognize from your post that you have been found to have autoimmune issues but did you have a natural killer cell activity (NKa) test done (i.e. the K-562 target cell test)? AND did you and your husband get an alloimmune panel done for DQa/HLA matching? THEN, how did this get treated. Did you receive IL or IVIG and if so when was the 1st dosage given.

   These are important issues because if you do and your husband does not have an alloimmune "clash" with DQa/HLA matching + NKa, then you do NOT need a gestational surrogate at all.

   My suspicion is that you have produced poor quality eggs and using a gestational surrogate won’t address this issue at all. It sounds as if you do have diminished ovarian reserve, in which case a "microflare protocol" is not optimal and taking high dosages of LH/hCG containing gonadotropins such as Repronex and/or Menopur won't help either.

   I think you need an agonist/antagonist conversion (long) protocol wit estrogen priming (A/ACP+E2V.

   Might I suggest that you read up on all these issues in this blog and that you consider talking to me about your problem? Simply call 800-780-7437 and set this up.

   Geoff Sher

   Reply
7. Shrinepass says:

   December 14, 2009 at 3:41 pm

   Thank you very much for your response. I will try to answer. I do have immune issues. I have had high TNF, high NK, and I have had the DQa/HLA issue. I have done 2 doses of IVIG and 2 intralipids (over a period of time) which very successfully brought my TNF and my NK numbers to normal after an adverse flare from doing Humira. With regards to the DQa/HLA my husband and I have done LIT twice. As of November, all of these immune factors are line with being cleared for cycle. The one that I seemingly can't change is the anti-ovarian antibodies which is the highest the immune doctor had ever seen. I am on 1mg dexamethasone for that for 2 months now and continuing until mid January with surrogate.

   So we think we are dealing with potential egg quality issues along with knowing about immune issues. We have taken a different approach than many intended parents would do. We have jumped to a surrogate immediately even though it seems my immune issues are in check. At our age, we feel we don't have time to continue to try and potentally fail. If the issue is egg quality and not immune, than we will KNOW for sure and move to an egg donor on try 3. If it is not, then we will have a child. There is logic in there just different!

   So my last protocol I was on estrace and ganirelix before the cycle started, then went to the bravelle and menapur after my cycle started. I will look into this and see if this is what you are talking about. The last cycle did not go well. I will also have to check on what "high doses" means. I know I have taken 3 Bravelle and 1 Menapur vials morning and night (= 6+2 total for day) but I don't have any more to look at actual dosage.

   Again, thanks so much!!! I will look more into this and read more of your blog.

   Reply
8. Geoffrey Sher, MD says:

   December 14, 2009 at 5:20 pm

   I think you have made a wise decision with regard to using a gestational surrogate, given the combined autoimmune +alloimmune components operative here.

   However, I respectfully submit that you would be far better off without a microflare protocol and/or a heavy dosage of LH-containing medications (see my article .."An Individualized aproach to ovarian stimulation …" elsewhere on this blog. I further think that you would do best on an agonist/antagonist conversion (long) protocol with estrogen priming (see the relevant article on this protocol, esewhere on this blog).

   Good luck!

   Geoff Sher

   Reply
9. D says:

   March 22, 2010 at 10:02 am

   Hi. I am 32 and I have recently been told that I have low ovarian reserve and that I have "eggs of a 46 year old" I realize this is an issue with the quantity of the eggs I have left. Does this also affect the quality? How much does this increase my chances of having a child with a chromosonal disorder/special needs?

   Reply
10. Geoffrey Sher, MD says:

    March 25, 2010 at 6:57 am

    It affects accessibility to eggs but with optimal stimulation it should not affect egg quality. See the article on this blod on an individualized aproach to ovarian stimulation for IVF. The one caviat is that it is much more difficult to achieve optimal ovarian stimulation in women with diminished ovarian reserve.

    Give me a call at 702-892-9696 and we can discuss your situation indepth.

    Geoff Sher

    Reply
11. Trying says:

    September 24, 2012 at 7:12 pm

    Dear Dr. Sher,

    I am 43 years old (approaching 44) with an AMH level of .63 ng/L. I realize there are a lot of factors against me. I have never had children (I am single, and only turned to ART in the last year or so.
    So far I have had two medicated IUIs with frozen (donor) sperm. For the first, my levels were:
    FSH(11.2), LH,(7.01) Estradiol (30.6) hCH <1.00 TSH (1.72)+ Prolactin (16.8) taken on 2nd day of menstrual cycle@ July 1st 2012

    For the first attempt, I was on 100 mg of clomid for 5 days (days #3-7) and 2 days of bravelle (150 UI) (on day 7 & 9) plus a trigger shot, and estradiol (2 mg vag) and progesterone suppositories (to compensate for a thinned lining). I had 10 antral follicles on day 3 with 5 good follicles on day 11 (21.7mm, 18.4 mm, 17.4 mm, 15.9 mm, 19.9 mm) plus a small one at 10.7 mm). My uterine lining was 4.7 on day 3 of the cycle and 6 on day 11. On day 11 myEstrogen was 970 and my LH was 6.63

    2st IUI: (August 2012)
    For the second attempt, my clomid was reduced to 5 days at only 50 mg on days 3-7 (to protect my lining) plus 3 days of bravelle (days 5,7 &9). This time I had 9 antral follicles on day 3 and 2 good eggs on day 11 (19.4 mm and 17.9 mm) plus 2 small ones (13.6 and 10.7).
    My uterine lining this time was 4 on day 3 of the cycle and 9.1 on day 11. On day 11 my Estrogen was 495 and my LH was 5.08

    I realize I have a lot of things against me. Age being the most significant, but how much hope do I have? I am looking into IVF with aCGH testing but realize that the stimulation protocol will be critical. What would you use in my case?

    Thank you so much.

    Reply
    • Geoffrey Sher says:

      September 25, 2012 at 11:38 am

      Please understand that IUI (a procedure that I first introduced into the medical field in 1984) is not for women over 40., not for women with diminished ovarian reserve (DOR), regardless of their age, and certainly not using clomiphene . Your chances of success doing what you have been doing are less than a 3% per month of trying. In my opinion, you need IVF with embryo banking and CGH embryo selection and you need it stat because time is running out..

      See below on how to access the information on all these issues.\

      Might I recommend that you go to the home page on this very site, find a “search bar” and type in the following subjects into the bar and it will take you to all the relevant articles I posted there.
       “An Individualized Approach to Ovarian stimulation” (posted on November 22nd, 2010)
       “Ovarian Stimulation in IVF: Why is it important to down-regulate LH?”
       “Agonist/Antagonist Conversion Protocol”
       “Age and IVF outcome”
       “Embryo Implantation………” (Part-1 and Part- 2—-Posted August 2012)
       “Traveling for IVF from Out of State/Country– The Process at SIRM-Las Vegas” (posted on March, 21st 2012)
       “A personalized, stepwise approach to IVF at SIRM”; Parts 1 & 2 (posted March, 2012)
       “IVF success: Factors that influence outcome”
       “Staggered IVF”
       “Embryo Banking”
       “Clomiphene citrate usage”
       “IUI”

      YPlease consider calling 800-780-7437 or 702-699-7437 to arrange a video conference (or Skype) consultation (free of charge to those who reside in the United States or Canada). If need be, someone from SIRM-Patient Relations can contact you in advance of the consultation and assist you in setting this up through your computer. Such audiovisual interaction it is much more personable than a discussion by telephone. However, if you prefer the latter, this too can be arranged.

      Geoff Sher

      Reply
12. Ria says:

    January 3, 2013 at 5:47 am

    Hi doc,
    I am 31 now and have had 5 failed IVFs due to implantation prob and one natural pregnancy which got miscarried at 2nd month.
    I have now tested for TNF alpha and Immunophenotype.

    TNF alpha – 725.728 pg/ml reference range
    Normal: 600 pg/ml

    NK Cell Activity
    CD3(Pan T cells) 81.3%
    CD19(B cells) 12.6*
    CD56+CD16+cell 10.2
    CD56 Cells 17.8*

    I also have ATA >1300.
    Now my doctor has suggested LIT to bring down TNF alpha.
    Doctor is it worth doing the treatment as we dont want to invest anymore in ineffective treatments.
    I have had 2 round of IVf with IVIG also, but I guess I need a higher dose of IVIG/IL.
    I will be on LIT for 5 months prior to any attempt at IVF.

    Please suggest.

    Reply
    • Geoffrey Sher says:

      January 3, 2013 at 10:54 am

      While TH-1 cytokine analysis (TNFa and IFN gamma() is helpful in assessing uterine NK cell activation (NKa), the gold standard remains the K-562 target cell test. However, elevated cytokines often correlate with NKa. 50% of women with thyroid antibodies have NKa (see below). If this is not adequately treated with down-regulation, you will not achieve a viable pregnancy in the vast majority of cases. While LIT might reduce the NKa, the one we know works is Intralipid with steroids (dexamethasone). That is highly effective, far less expensive and legal in the United States.

      Please go to the home page of this blog (www.IVFauthority.com ). When you get to the look for a “search bar” in the upper right hand corner. Type in the following subjects into the bar and it will take you to all the relevant articles I posted there.

       “Thyroid Autoimmune Disease and IVF”
       “Immunologic Implantation Dysfunction” (posted on May, 10th and on May 16th respectively.
       “Embryo Implantation………” (Part-1 and Part- 2—-Posted August 2012)
       “Traveling for IVF from Out of State/Country– The Process at SIRM-Las Vegas” (posted on March, 21st 2012)
       “A personalized, stepwise approach to IVF at SIRM”; Parts 1 & 2 (posted March, 2012)
       “IVF success: Factors that influence outcome”

      Consider calling 800-780-7437 or 702-699-7437 to arrange a telephone or Skype consultation (free of charge to those who reside in the United States or Canada) so we can discuss your case in detail.. While an audiovisual (Skype) interaction is much more personable and preferable than a discussion by telephone, either will suffice.

      Geoff Sher

      Reply
13. Ria says:

    January 3, 2013 at 5:50 am

    reference range for TNF alpha as per clinic is
    Normal: 600 pg/ml

    thnx

    Reply
14. Ria says:

    January 3, 2013 at 5:53 am

    reference range for TNF alpha as per clinic is

    Normal : less than 200 pg/ml
    Moderately high: 200 to 400
    high : 400 to 600
    very high : greater than 600 pg/ml

    Reply
15. Lia says:

    February 25, 2013 at 1:48 pm

    Hello Dr. Sher,

    I am 39 yrs old (40 in July), husband is 33. We have been trying to conceive for 3 ½ yrs now. Have had 3 natural pregnancies and all 3 miscarried at 8-10 weeks with explanations of the last two having chromosomal defects. We decided to work with a fertility doctor and started the IVF process last year September. I had autoimmune testing done and all normal; RE said I basically have a very low ovarian reserve and husband has a low strict morphology score. RE started us both on vitamins and supplements in Sept 2012 (which we are still taking). Me – 75mg DHEA, 600mg CoQ10, and prenatal, Husband — 400mg CoQ10, Fertility Blend for Men and Multi-Vitamin. In Oct 2012, I was put on Estrace, Progesterone and Testoterone. Nov 2012 started my stims, 150 Menopur, 450 Gonal F and Ganilrelix added in 5 days later. RE cancelled that IVF cycle saying my body wasn’t responding to the stims and only 1 follicle was present. We took a break for 2 ½ months and just started our 2nd round of IVF this past Friday. RE started me on 10 units of Lupron (1 in am and 1 in pm) and 2 days later (last night) I added in 150 Menopur, 600 Gonal-F, 0.3cc Saizen and Dexamethasone (orally). My question to you is does this protocol make sense, what is your opinion? I go in for my first U/S and BW on Wed. Thank you.

    Reply
    • Geoffrey Sher says:

      February 25, 2013 at 8:12 pm

      I honestly believe the ovarian protocol choice is pivotal. Clearly you have diminished reserve (DOR). Respectfully, I am not in favor of “flare Lupron protocols” in women with DOR.I also do not believe in Antagonist protocols with DOR.

      Please go to the home page of this blog, (www.IVFauthority.com). When you get there look for a “search bar” in the upper right hand column. Then type in the following subjects into the bar, click and this will take you to all the relevant articles I posted there.

      1. “An Individualized Approach to Ovarian stimulation” (posted on November 22nd, 2010)

      2. “Ovarian Stimulation in IVF: Why is it important to down-regulate LH?”

      3. “Agonist/Antagonist Conversion Protocol”

      4. “Traveling for IVF from Out of State/Country– The Process at SIRM-Las Vegas” (posted on March, 21st 2012)

      5.“A personalized, stepwise approach to IVF at SIRM”; Parts 1 & 2 (posted March, 2012)

      6. “IVF success: Factors that influence outcome”

      Consider calling 800-780-7437 or 702-699-7437 to arrange a telephone or Skype consultation (free of charge to those who reside in the United States or Canada) with me so we can discuss your case in detail.. While an audiovisual (Skype) interaction is much more personable and preferable than a discussion by telephone, either will suffice.

      Geoff Sher

      Reply
16. Angel says:

    February 28, 2013 at 2:54 am

    Hi,

    I love your site and have been learning a GREAT deal about everything you post. I thought you could help me with some advice?
    I am 40, with high AMH of 20 and FSH of 6.5, we had 2x failed iui’s last yr, monitored and medicated. My husband has above average count and morphology.
    Jan was our first ivf ICSI, and we had success, only for it to stop growing around 6wks. The cycle produced 9 eggs, but only 5 were mature, 3 fertilised and 1 hatching blast made it to day 5 transfer.

    I never see anything about high ovarian reserve with fertility issues, yet that is us. The pregnancy also have me mild OHS, which was very painful and stretched tummy, but no difficulty breathing or any other symptoms. My progesterone was near 700 at positive beta! At trigger my E2 was 6700 (Australian measuring system).

    When we go again, we are looking to stim longer, and perhaps freeze them to get more embryos with less risk of ohs.

    What do you think of it all? Why isn’t it working? Just a matter of the draw now that I’m 40?

    Reply
    • Geoffrey Sher says:

      February 28, 2013 at 7:18 am

      I understands! Did the products of conception get tested chromosomally?

      Be sure to be on the lookout for an immunologic or anatomical implantation dysfunction before going again.

      Geoff Sher

      Reply
      • Angel says:

        May 2, 2013 at 7:29 pm

        Hello! I did not realise you responded! Thank you for responding!
        We tested our embryo and it came back with full Trisomy 16. The placenta and all other tissue tested very good. WE were told that T16 is a random and very common fluke and nothing to do with us.
        We have just completed ivf #2 and moved to a freeze all to avoid ohss, so that we could stim longer and get more mature eggs. WE got 16 eggs, 12 mature, 10 fertilised and all doing well on day 3.
        Day 5 left us with only 2 high grade blast to freeze. On day 6, we had 2 x C grade blasts and 1 x B grade morula, so they said they were not good enough to freeze.
        We could not afford CGD testing and hope that the T16 was random. We were also told T16 is very unlikely to occur again.

        Now waiting for a full cycle before FET. Fingers X’d!!

        Reply
        • Geoffrey Sher says:

          May 3, 2013 at 6:28 am

          Good luck!

          Geoff Sher

          Reply