Elevated FSH and Aneuploidy?
Tuesday, July 01, 2008
Kenneth F. Trofatter, Jr., MD, PhD
• At Sat Jun 14, 11:29:00 PM 2008, Polly Gamwich said…(and my responses follow her questions in italics):
Hi Doctor,
I am 31 years old. At age 29 I had two miscarriages, the first at 10 weeks due to Turner’s syndrome (45XO) and the second at 8 weeks due to XXYY. When I was 30 I had two chemical pregnancies. I have yet to have a live birth.
I have elevated FSH (12.3), am a compound heterozygote carrier for MTHFR polymorphisms and am currently being treated (with folic acid), and have Hashimoto's thyroiditis, currently being treated for hypothyroidism. I have four questions for you:
1. Am I more at risk of having a chromosomally abnormal baby, as a woman in her 40's might be because of my elevated FSH?
Increased FSH (follicle stimulating hormone) is associated with decreased ovarian reserve and that is associated with aging, as is the risk for producing an egg with an unbalanced chromosomal complement (aneuploidy), BUT the two do NOT appear to be related. Indeed two recent publications clearly show no direct relationship between the FSH level and aneuploidy risk (Massie, et al., Fertil Steril 2007;87;S7 and Thum, et al., Fertil Steril 2007;Oct 20 – epub ahead of print) (Note: FSH is made by the pituitary gland. Its production is regulated by a negative feedback loop secondary to estrogen produced by the ovaries. When estrogen levels are high, FSH levels decrease (are suppressed) and when estrogen levels are low, as occurs during the luteal phase (after ovulation) of the menstrual cycle, menopause, or premature ovarian failure, then FSH levels are elevated).
2. Why does your body allow you to even GET pregnant with chromsomally abnormal babies ... why doesn't it just pass the baby without implantation??
Most chromosomally abnormal babies do NOT make it successfully through the implantation process and of those that do, very few will survive the first trimester.
3. I've had all the testing there is (and more) and we're treating all the problems ... why would my risk of miscarriage go up after the 2nd miscarriage? (I've heard that if you've had two losses you have a better chance of having a healthy pregnancy, however if you have more than 2 miscarriagess you have a worse chance of having a healthy pregnancy ... I would assume this is assuming an untreated issue??)
That is only true if there is NO IDENTIFIABLE CAUSE for the losses. You DO have an identifiable cause - babies that had chromosomal abnormalities. So, that may just be a string of bad luck or there is a very small possibility you are at risk for recurrent aneuploidy for reasons we do not yet understand. I guess I would have several other concerns and these are related to your Hashimoto’s thyroiditis. Hashimoto’s disease is an autoimmune condition characterized by the presence of antibodies against your thyroid gland. Recent studies have confirmed that autoimmune thyroid disease is associated with unexplained infertility and recurrent implantation failure (Belver, et al., Hum Reprod. 2008 23:278-84).
Furthermore, sometimes the presence of one autoimmune condition can be an indicator of others since these result from imbalances in your immune response that cause you to attack your own tissues as if they are ‘foreign’ to your body. Some individuals will develop polyglandular autoimmune syndromes characterized not only by Hashimoto’s disease, but also by premature ovarian failure, type 1 diabetes, and autoimmune adrenal deficiency (Addison’s disease – 90% of which is the result of autoimmune adrenalitis). Other conditions thought to have an autoimmune basis, such as pernicious anemia and myasthenia gravis, may also be found under these circumstances. My question to you, in view of your Hashimoto’s disease and elevated FSH) is have you been screened for any other autoimmune conditions that could have a deleterious affect on your fertility?
4. I get pregnant on every cycle I attempt (4 months we've tried - we've had 4 pregnancies and 4 miscarriages) ... will I have more miscarriages than the average women because my babies seem to implant whether they are healthy or not?
No. I do not think you are unique in that regard. You have just had a rough time with the conception side of things at least as reflected in those babies that were shown to be chromosomally abnormal. In that regard, if it has not been done already, your husband should have a careful semenanalysis performed because there is a possibility he is contributing to the situation as well. I wrote a post on the contribution of the male partners to pregnancy loss and infertility earlier in the year. Also, you might be a good candidate for either IVF and/or prenatal genetic diagnosis (PGD) to help improve your chances of having an implantation of a chromosomally NORMAL embryo!
Thank you,
Polly
Great questions and thanks for writing. Best of luck to you.
Dr T
• At Tue Jun 17, 10:33:00 AM 2008, Polly Gamwich said…
Dr. Trofatter,
Thank you so much for your response. Your articles are excellent and your compassion and respect for women is overwhelming - thank you.
And in my case, of the things that you suggested, I wanted you to know that you're right on. I wanted to follow up to your June 14th response with this:
We are actually testing my eggs (not our embryos - unfortunately, we can't/won't do PGD on embryos for moral/religious reasons) because we were so worried about chromosomal abnormalities being caused by the eggs. We have done one IVF retrieval and we retrieved 6 eggs, 5 were mature: Based on CGH polar body testing of the eggs: 3 were abnormal, 1 was normal and 1 was inconclusive - the good news is - I DO HAVE NORMAL EGGS IN THERE SOMEWHERE! (and note: we did do oocyte vitrification ... I'm curious if you have any articles on that - we know it's not proven, but without being able to do PGD on embryos, it was the best option for us.)
We've been suffering through miscarriages for two years and our Reproductive Endocrinologists still have yet to do a traditional semenanalysis. We're having one done in a few weeks. But we have had the Sperm DNA Defragmentation (SDFA) test done on my husband and it came back 50% abnormal - I guess that means that either the DNA is bad or the ability for the DNA to appropriately work with the egg's DNA is affected - is this what the post you refer to is about? Anyhow, my husband has been taking antioxidant supplements for three months and we will retest his semen soon. If this turns out to be a problem, we'll move to in vitro fertilization with intracytoplasmic sperm injection.
I just thought I'd close the loop on some of your statements/comments/questions.
Again, Doctor, I really appreciate your dedication to your field and the support you provide to so many women.
Take care,
Polly
Note: Oocyte vitrification is a relatively new cryopreservation technique in which the ice formation is totally avoided (Bagchi, et al., Expert Rev Med Devices 2008;5:359-70). Using this technique, mature or immature oocytes are retrieved following ovarian stimulation and then cryopreserved for further attempts at in vitro fertilization. Recent studies have demonstrated that not only is the technique successful in achieving pregnancy, “the results indicate that the mean birth weight and the incidence of congenital anomalies are comparable to that of spontaneous conceptions in fertile women or infertile women undergoing in-vitro fertilization treatment…” (Chian, et al., Reprod Biomed Online. 2008;16:608-10).
Dr T
Labels: autoimmune thyroiditis, FSH, oocyte vitrification, recurrent aneuploidy, recurrent pregnancy loss
4 Comments:
At Wed Jul 02, 10:28:00 PM 2008,
Paul Baker said…
Hi Dr. T, first off, I would like to apologize for this post. Being a male, I am not in need of an OB/Gyn, but it's been a long time since we have spoken. My name is Paul Baker, and you took the time to allow a 22 year old young man to learn how to do a successful venipuncture. Your lab assistant, who's name I won't mention also helped. The reason being, my mom worked for you and Dr. Kleinman. Not sure if the last name rang a bell, it has been 17 years. My mom, Carol, told me about this site. So, now, I've been a nurse for the past 15 years, and currently going back to school, and it's non medical, Cyber Security and Computer Forensic Technology. Your name comes up quite frequently, because you were by far , the best she's ever worked for. Again, I would like to thank you for allowing me to experiment, and be my "guinea pig". If you don't remember, I stuck you 3 times, your assistance once and my mom once, and was successful each attempt, a true testament to your teaching abilities. Things are going well, struggled through the testicular cancer and right orchiectomy May '06, skin cancer surgically removed December '07, and still off work now, until Monday from a umbilical hernia repair in late May. I'm engaged to a woman, who is truly the answer to my prayers. I could not ask for anyone better, and with all I've been through the past 2+ years, I could not have made it without her. I've wasted enough of your valuable time, thank you for your patience and time to read this. And by the way, thanks again for the time you took over 17 years ago as well. As you can see, we still talk about the impact you may not realize you've had on our lives. I wish you all the best, The University of South Carolina is lucky to have you. Paul Baker ( pbaker@sssnet.com )
At Thu Jul 03, 05:27:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To Paul: Thank you so much for writing and of course I remember you and your Mom. My 'lab assistant' became my wife and for many years she stayed in touch with your Mom as well - though I am not sure if she has kept that up since our move to SC. Please tell her I said hello. It sounds like you have had a rough couple of years, so as for so many of my readers here, I will be pulling for you too! Thanks for updating me and for the kind words and best of luck for your marriage! It is all the people we touch in our lives that make us who we are and I truly appreciate your thoughts. Dr T
At Fri Jul 04, 07:55:00 AM 2008,
Anonymous said…
Hi Dr.T,
I am 30 years old and I have suffered two miscarriages in the past 6 months. One at 8 weeks and the other at 5 weeks. My karyotype showed that I have a balanced paracentric inversion on one chromosome 10. The exams also showed a MTHFR C667 mutation and I am taking folic acid. My husband is normal.We went to a genetic counselor and she suggested that we keep on trying naturally. She gave us no statistics, not did she explain how high the possibility is of another miscarrige or of an abnormal offspring. I have thought of PGD and IVF but my husband is really against it because of the possible sideeffects. I have also thought of asking a second genetics counselor. Any advice would be highly appreciated. You can understand our anxiety and frustration. Thank you in advance
At Sat Jul 12, 08:22:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To anonymous July 4: You have a chromosomal rearrangement, but we still do NOT know if that was actually the cause of your miscarriages unless you had chromosomal studies done on the products of conception? I think at your age, I would simply recommend to keep trying. If you have no other reasons identified for your miscarriages, and remain unsuccessful, then you can start thinking about IVF and preimplantation genetic diagnosis as a means of improving the 'efficiency' of the proicess. By the way, the single MTHFR polymorphism is not the likely cause of you losses.
Dr T
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