Recurrent Early Pregnancy Loss - 3 - Chromosomal Causes
Sunday, March 25, 2007
Kenneth F. Trofatter, Jr., MD, PhD
In nondisjunction events, a pair of chromosomes (autosomes or sex chromosomes) may stick together, resulting in one gamete (egg or sperm) with one too many (24) and one with too few (22) chromosomes. Doing the simple math, if either such gamete combines with a normal gamete containing 23 chromosomes from the other parent, the resulting embryo will have either 45 (a monosomy) or 47 (a trisomy) chromosomes. These events can occur with any of the autosomes or sex chromosomes and most result in lethal combinations of genetic material and pregnancies that are lost early in gestation. However, there are situations in which the pregnancy might survive, the best known being Down syndrome (extra number 21 chromosome), Turner’s syndrome (single X chromosome), other sex chromosomal abnormalities such as 47XXY or 47XYY, and trisomies 18 or 13. In reality, even most of these combinations are lost in first trimester, many are lost in mid or late pregnancy, and almost all trisomy 18 or 13 babies are lost shortly after birth if they manage to survive to delivery.
Chromosomal abnormalities that lead to recurrent pregnancy losses, on the other hand, are usually not monosomies or trisomies resulting from nondisjunction. Instead, they result from gametes that have either too much or too little chromosomal material as a consequence of a parent having a chromosomal ‘rearrangement.’ Under these circumstances a parent has the correct total amount of genetic material, but may have two whole chromosomes (either the same or different chromosomes) stuck together, may have a portion of one chromosome exchanged with a portion of another chromosome (balanced translocations), or have rearrangements of a portion of one chromosome within the chromosome in which that genetic material was originally located (usually these are ‘inversions’). The problem with parents who have ‘chromosomal rearrangements’ is that they have a harder time producing gametes with the correct amount of genetic material. Fortunately, most parents with balanced translocations or inversions will eventually ‘get it right’ but it may be only after many pregnancy losses. Even then, because of ‘crossing over’ events that occur during chromosomal replication, they could end up with a baby that has the ‘right number’ of chromosomes but a very small amount missing (microdeletions) or extra that can still lead to serious problems. Parents who have whole chromosomes stuck together on the other hand cannot produce normal gametes.
Diagnostic testing for parental chromosomal rearrangements is fairly simple, but expensive. It is often one of the first diagnostic tests offered to a couple with recurrent early pregnancy loss, although the yield is low because these account for such a small percentage of the problems. Ideally, both parents should be tested, but if resources are limited, it is often best to start with the mother’s chromosome studies (karyotype) since for reasons beyond the scope of this discussion, if a parental chromosomal rearrangement is the culprit, she is the more likely contributor to the problem under many circumstances. If the products of conception from an early loss have chromosome studies performed and reveal that a parental chromosome rearrangement is likely, parental karyotype testing really should be advanced in the diagnostic studies. Although nothing can be done to correct the problem, genetic counseling is warranted so that parents can be appraised of their risks and their options for a successful pregnancy.
60 Comments:
At Fri Aug 24, 02:11:00 PM 2007,
Anonymous said…
Hi-I am 30 years old and have suffered 3 miscarriages. After my third, my Dr. did a karotype and found that I have a Robertsonian translocation between 13 & 14. From what I've learned reasearching this topic, is that I have a 50-50 shot of producing and egg with the correct number of chromosomes or with the same translocation as I have. Is that assumption correct?
Also, is IVF w/PGD our best bet in having a healthy baby?
Is it also true that if I have this translocation that chances are one of my parent's have it and/or my sibling's?
Thanks so much!! My anxiety has been sky-high ever since I found this out and I can't see a genetic counselor until November 1st.
Gina
At Wed Aug 29, 03:44:00 PM 2007,
Kenneth F. Trofatter, Jr., MD, PhD said…
To Gina: These were such great questions, I decided to devote today's entire post, August 29, 2007, to my response. There aare many other readers who may be interested in this.
Check yourself out! Thanks for reading and hope this addresses some of your concerns! Dr T
At Thu Aug 30, 04:51:00 AM 2007,
Anonymous said…
Dear Dr. Trofatter:
My sincere gratitude for not only replying to me but dedicating an entire post in response to my questions. I can't express my gratitude enough. You explained that condition so well, I feel I have a much better understanding of it, and therefore it tremendously helped ease my anxiety.
I have forwarded that link to my family & friends so that it will help them better understand it as well.
Thank you from the bottom of my heart.
Sincerely,
Gina (& her husband too!)
At Thu Aug 30, 03:08:00 PM 2007,
Kenneth F. Trofatter, Jr., MD, PhD said…
Gina: It was my pleasure and thank you for the kind feedback. Sometimes I never know where things go when they are sent into cyberspace!!! Good luck to both of you again.
Dr T
At Tue Nov 06, 03:09:00 PM 2007,
Anonymous said…
Dear Dr. Trofatter,
First of all, thank you so much for your informative explanations about recurrent pregnancy loss...they have helped me more than I can tell you! I have had four early miscarriages. I've been through testing, was on empirical treatment for my last pregnancy, which did not work. At any rate, my husband just had his karyotype testing done and we learned that he has "pericentric inversion of chromosome 2." We are going to meet with a genetic counselor and I already have lots of questions! I would like to go into our meeting with some understanding as this chromosome "stuff" is so confusing to us! I was told by my RE that if we had a choice between me or him having this inversion, we would rather it be him. Can you explain this anymore?
Thank you so much for your time, Lindsey
At Tue Nov 13, 05:31:00 PM 2007,
Kenneth F. Trofatter, Jr., MD, PhD said…
To Lindsey Nov 6: The genetic counselor will explain in more detail, but women with chromosomal rearrangements are more likely to produce an egg with an unbalanced chromosomal complement than males are to make a sperm. The issue of pericentric inversions, though, is am interesting one. Such abnormalities of chromosome 2 have been associated not only with recurrent pregnancy loss, but also unbalanced fetal chromosomal complements - sometimes very subtle deletions or additions. Sometime in the future I will devote an entire post to this subject. Thanks for reading and for a good question. Best of luck to you and your husband! Dr T
At Fri Dec 14, 05:27:00 PM 2007,
Allison said…
Dr. Trofatter- I am 35 years old and have had 1 live birth and then 2 miscarriages both trisomy (10 & 16). I've been reading that these numerical chromosomal abnormalities are not related to a translocation with the parents but most likely related to either my age or bad luck. I'm trying to decide if we should continue to try (I have no problem getting pregnant) and play the odds of getting a good egg or if 2 back to back miscarriages means I should have myself fully evaluated including ovarian reserve. The tests all seem to lead up to IVF w/PGD which may or may not be worse than miscarrying again. Or am I too old to keep trying?
Thank You! Allison
At Mon Dec 17, 12:21:00 PM 2007,
Kenneth F. Trofatter, Jr., MD, PhD said…
To Allison Dec 14: I agree, it is very unlikely these losses are related to a chromosmal abnormality of either you or your partner. I am leaning toward "bad luck". If you have not had any difficulty getting pregnant, then rather than pursuing IVF, you should probably just try again! The odds are in your favor that things will eventually turn out okay. Since you have had two documented chromsoomally abnormal conceptuses, your risk for having another is gretaer than your age alone risk, so I would highly recommend combined first trimester screening for aneuploidy at 11-13 weeks, even if things go well through early first trimester. good luck and thanks for reading! Dr T
At Tue Jan 01, 08:20:00 PM 2008,
cats2323 said…
Dr. Trofatter - I am a 34 year old female and am currently going through my 3rd miscarriage with my husband. During my 2nd miscarriage my reproductive endocrinologist discovered I have a balanced translocation 46,XX,t(2;15)(p21;q21.2). My husband is normal.
We saw a genetic counselor and she told us our chances of having a live born is 33%, miscarriage 40-50%, and live born with severe mental/physical disabilities 10-15%. She did tell us that 10-15% was on the high end, but that really scared us.
Other sources have told us a 1% chance of having a live born with severe mental/physical disabilities.
My husband and I want to try injections to stimulate egg production and try to conceive more than one embryo knowing that only one would probably survive or not. We are not looking to do IVF, IVF with PGD, or IUI. We are trying natural with the aid of drugs. Do you think this is a good idea?
We are hoping to speak to another genetic counselor that has Ph.D./M.D. rather than years of experience as a counselor. I have yet to find another female with the same translocation as me. If I did and she had carried a healthy baby to term, then that could give me hope. I have even thought about donor egg as a last resort.
At Fri Jan 04, 06:53:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To cats 2323 Jan 1: In my experience, that 10-15% is on the high side. The only real comfort you can take from this situation is that if carry a baby past first trimester, there is a very high likelihood the baby will be normal or be a translocation carrier like you. In all honesty, I have not had a patient with your translocation myself, so it is probbaly orth seeking out the genetic counselor and finding out if there are any special concerns with this chromosomal complement that will increase your risk even further for an aneuploid baby. At least you know what the problem is, so its just a matter of 'keep trying'. Before you consider ovulation induction, you might want to discuss the risks and benefits of that. You could end up in a situation with a normal baby and one or more abnormal babies that do not miscarry because of the normal baby's help in maintaining the pregnancy! Good luck to you and thank for reading.
Dr T
At Thu Jan 10, 09:01:00 PM 2008,
Anonymous said…
Dr. Trofatter,
At age 30, I had a successful pregnancy resulting in a normal and healthy baby. My second pregnancy, at 33 years old, resulted in an early miscarriage. Analysis of the fetal tissue determined the cause of the miscarriage to be trisomy 16.
Am I now at an increased risk of this happening again? Should my husband and I seek genetic counseling and/or undergo testing to determine if there are any chromosomal abnormalities in either of us? As much as I want another child, I'm terrified of going through this again and I don't know if the odds are in my favor or not. Thanks so much for your time.
Sincerely,
Kristen.
At Sat Jan 12, 05:00:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To Kristen Jan 10: Somewhere between 10-25% of all pregnancies miscarry and the vast majority are the result of chance chromosomal abnormalities, most resulting from nondisjunction (the same event that leads to most Down syndrome). Trisomy 16 rarely gets very far into a pregnancy before the baby is lost. Since you are so concerned about the possibility of another baby with aneuploidy, I strongly recommend you go to a good genetic counselor to put things in perspective. Some genetics folks will quote you a rate of another baby with a chromosomal abnormality as high as 1% once you have had one. That rate is about 4-5 times your age alone risk at age 33. It is unlikely you will have another baby with trisomy 16. The genetic counselor will be in a position to review your options, and the risks and benefits, for early fetal evaluation and diagnosis if you prefer. I am sorry for your loss, but the odds are heavily in your favor that things will work out better the next time. Thank you for reading and best wishes. Dr T
At Sat Jan 12, 10:55:00 PM 2008,
Anonymous said…
Dr. Trofatter,
Thanks for both your time and reply. Your site is very thorough & informative and has provided me with much insight. Thank you for sharing your expertise.
With gratitude,
Kristen.
At Wed Jan 16, 07:50:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
Your welcome Kristen. Thanks for the kind words! Dr T
At Mon Jan 21, 06:28:00 AM 2008,
Anonymous said…
Dr. Trofatter,
I am finding myself turning to you for your knowledge again! Thank you for sharing your expertise and compassion. I have to say that I am exhausted of all of this and don’t know what to do next. The genetic counselor that we met with a couple of months ago explained some of the odds and told us that we basically have a 50% chance each time we conceive of having a miscarriage. Because my husband’s inversion of Chromosome 2 is a “bigger” chunk rearranged, then the chance that we have an abnormal live birth is about 1%. We’ve already had 4 miscarriages and no live births. We are trying again to conceive naturally, but already have it in the back of our minds that we are going to try IVF with PGD if we have another miscarriage. What are the odds of that working out in our favor? Also, I became pregnant within the first “try” with my first two pregnancies. However, my last two took a lot longer –a few months (relative speaking!) and was only achieved with a progesterone /pregnancy booster shot on the day of my ovulation. So, I now correlate those shots with miscarriages. My thoughts are that I wouldn’t have gotten pregnant to begin with if not for the boost. Do you have thoughts on the pregnancy booster at ovulation?
Thank you for your time, Lindsey
At Fri Jan 25, 08:19:00 AM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To Lindsey Jan 21: The primary advantage of either ovulation induction or IVF is that you increase the odds of having multiple eggs (particularly with the IVF cycles) at one time. That would increase the odds that one of those would be chromosomally normal and survive. The IVF/PGD route will be VERY expensive, so clarify with the genetic counselor the prospects for an accurate disgnosis in your case and remember, even if a 'normal' embryo is transferred there still might not be a successful implantation although many IVF programs now have success rates of > 50% even when only a single embryo is transferred. Best of luck to you and stay in touch, okay? Dr T
At Wed Feb 27, 11:11:00 AM 2008,
Anonymous said…
Hi, Your conversation with other people intrigues me. I had a healthy, normal baby at age 27. I am now age 29, and recently delivered a stillborn at 24 weeks gestation with Trisomy 13, 13;14 translocation. We have never had any problems with pregnancy but I am scared that we will not be able to have another healthy baby like our son. We have been advised to do parental testing, which we are doing to see if this is familial. My husband has a brother with Downs - which we were told is a "fluke." I am driving myself crazy with the wait. Can you tell us if we should consider PGD with our situation, since pregnancy is not a problem and how the impact of being a carrier would affect it? Thank you Dr.
Rachel
At Sun Mar 09, 12:35:00 PM 2008,
Anonymous said…
Hi - I am 39 years old. I had a miscarriage at 11 weeks due to a blighted ovum. We terminated our 2nd pregnancy at 18 weeks because the baby had T21 with many problems and my placenta was abrupting. No one has ever told me there is a link between the blighted ovum and Down's Syndrome. I was told the chance of T21 recurring was 1% plus whatever my age risk would be. Is it crazy for us to try again? or do we still have a good chance of having a healthy baby? I also don't understand why my placenta abrupted and worry about this happening again. My doctor feels that I was probably getting ready to miscarry on my own. I don't drink, smoke or do drugs and am healthy otherwise. What are the chances I would have another abrupted placenta?
Kate
At Tue Mar 11, 06:06:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To Dr Rachel: Before you can be counseled regarding your risks, the first thing you need to find out is if either you or your partner is a balanced chromosome 13:14 translocation carrier. If not, your risks are very low (but still a little higher than your age alone risk) and if one of you is a carrier, you will have to make a decision as to whether you just 'keep trying' and wait for the dice to roll your way or go through PGD following IVF (VERY EXPENSIVE). At your age, most women will choose to simply 'keep trying'. Let us know what you find out and good luck to you!
Dr T
At Tue Mar 11, 06:12:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To Kate Mar 9: The 'blighted ovum' and the baby with Down syndrome may or may not have been related unless one of you has a Robertsonian translocation involving chromosome 21. There are reasons other than chromosomal abnormalities for blighted ova. At your age, even though the risk of having a chromosomal abnormality are increased, the odds are still in your favor with each pregnancy that the baby will be normal. The placental abruption was most related to an abnormal placentation BECAUSE the baby had trisomy 21. Remember, most chromosomally abnormal babies will miscarry in the first or second trimester. Good luck to you in the future. Dr T
At Thu Mar 13, 07:33:00 PM 2008,
Kate said…
Dr. Trotter,
Thank you for your response. I don't have the Robersonian Translocation for 21. I was wondering if you buy in to any of the research indicating a link between a women's ability to metabolize folic acid and T21. I have read several studies all suggesting we need at least 3-4 mg of folic acid along with B12 and B6 and that it should significantly reduce the risk. My OB doesn't beleive it, but gave me an extra mg of folic acid just because of the other benefits - spina bifida etc. Should I have my homocysteine levels checked? All of the studies talk about these levels being high in women who have had children with T21. Any thoughts? Thank you.
At Wed Mar 19, 06:16:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To Kate Mar 13: If you concerned, a fasting homocysteine level would be a reasonable thing to request. I cannot think of anything safer than folic acid, so I also thing it is reasonable to ask for a higher dose of the folic acid. Cannot say it will help, but it might, and it certainly won't hurt! Dr T
At Sat Apr 12, 08:39:00 AM 2008,
Anonymous said…
Dear Dr. Trofatter,
I am 38, at 24 weeks pregnant and just found out at my Level II ultrasound yesterday that my baby girl had passed (maybe a day or two). My 1st & 2nd trimester blood screenings were slightly abnormal showing a PAPP-A ratio of 1 in 277 associated w/Down S. However, the ultrasound measurement for nuchal translucency was normal. At my first Level II U/S visit they expected to see signs of spina bifida, but the baby's spine and organs looked fine, yet she measured 2 weeks smaller for date (at 18 or 20 weeks). They suggested we (husband & I) do amnio, but we declined since termination was not an option for us whether she had anomolies or not...so why put the baby at more risk and mess with the sack? We opted to have on going ultrasound screenings to monitor baby's development and they noticed two weeks ago, she had an echogenic bowel/dilated rectum and poor heart beat tonations (I forget the medical term). But b/c she was still small, we had to go back yesterday for further look into a more developed heart. I noticed her movements had minimized days back and I was experiencing some cramping but there was no blood, so I thought it was Braxton Hicks-prep contractions or round ligament pains. To find out she is dead at 6mos along is just devastating.
We were "briefly" given options to remove her (baby) either by induction or D&E since I never miscarried and I understand it's considered a fetal loss/still birth. We have decided to induce labor so she will be intact and an autopsy w/chromosomal testing can be done....most importantly for closure. The perinatologist told us to just let her know when we decide, so they can make the appropriate hospital arrangements.
Unfortunately, our perinatologists haven't been the greatest communicators/genetic counselors, and much of what we know about the "terms" given, has come through researching the internet.
My questions to you doctor are:
1. How long is it safe for me to have the baby inside before induction to remove her? What can happen otherwise?
2. I have never had a baby and this is my 2nd "miscarriage." Should I do karotype testing for translocations in addition to the findings of the baby's autopsy and chromosomal testing?
3. My husband is 42, and I'll be turning 39 in December (just married a yr and 2 mos now). He has a 12 y/o daughter but we really want a biological child of our own and sibling for her. Would we have more chances at our age of a healthy successful pregnancy going the IVF route?
I appreciate you taking the time to read my long comment. This pregnancy has been emotionally stressful. Plus, I am grieving and am in most need of your expertise at this time. I greatly hope you can respond. Thank you.
~Heidi
At Tue Apr 15, 07:19:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To Heidi: I am so sorry for your loss. From what you describe, it is most likely he baby had either a chromosomal abnormality or a congenital viral infection, the most common being cytomegalovirus. There is still also the possibility of a 'genetic' (or syndromic) condition , but this is less likely. Most women will eventually go on to miscarry on their own. Your risks over time are related to infection (bacterial) or abnormalities of you blood clotting system if the baby stays inside for too long, but even those are rare. The best reason for getting things competed as quickly as possible is that i will be much easier for the doctors to determine a cause. If you wait too long, they may not be able to do chromosomal stucies on either the baby or the placenta. The other erason is that at your age, if you want to try to get pregnant again, it may be better sooner than later.
You might consider having chromosomal studies done on yourself to look for evidence of a balanced translocation, but I would not recommend that if the baby turned out to be chromosomally normal.
IVF may increase your chnaces for a successful pregnancy by virtue of the large number of embryos that can be obtained (and stored for subsequent cycles), but that is expensive and you are pushing the 'age limit' that some REI programs will not exceed. I wish you the best of luck. Please let us know what you find out about this baby and, again, I am sorry. Dr T
At Wed Apr 23, 09:34:00 PM 2008,
Dawne h said…
I am 39 & now only 9 weeks pregnant with second child. I've had 2 miscarriages prior to the birth of our little boy who has Down Syndrome. Any idea what the chances of having another baby with a chromosomal disorder are? I'm not really interested in a CVS or Amnio as by that time I would be incapable of aborting. My husband on the other hand feels otherwise (He suffers a great deal of depression over our boy and unfortuantely has a rahter negative outlook). Looking for a bit of ray of sunshine to lessen the stress....
At Thu Apr 24, 06:15:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To Dawne Apr 23: Your chance of having a baby with Down syndrome based on age alone is about 1 in 140. In midpregnancy, the chance of the baby having Down's is about 1 in 100 and it is even higher in first trimester. The chance of the baby having ANY chromosomal abnormality is about twice any of these risks. Since your husband and you have different feelings about this right now, I would sugggest that you consider having "combined first trimester screening for aneuploidy" at about 11-12 weeks as a way of getting a more reliable estimate of risk than that based on your age alone. That will provide you with more information upon which to base discussion and will not hurt the baby in any way. I wish you the best of luck. Please let us know how things turn out. Dr T
At Wed May 07, 09:13:00 AM 2008,
Anonymous said…
I'm so sorry for your recent personal loss and other issues going on in your life and completely understand that you may be slow to respond. Take the time you need to heal as all of us on this post do for our losses.
My question is about recurrent loss with no real reason. I'm 35 years old and have a 3 year old son. This past year I've had 3 early miscarriages all trisomy's. I've gone through all the testing with my RE and only had some minor issues:
- CCT: FSH 5.2/4.8
-Chromosonal for both me and husband: normal
-Follicles: 3 left; 6 right
- + for MTHFR homogenous (normal homocyctine levels and taking cerefolin)
- + anti-thyroid antibody (3 TSH panels all normal)
-All other blood tests normal
Why am I producing abnormal eggs? Is it related to the MTHFR even though it is homogenous? The next steps are IUI or IVF w/PGD. Even if we do IUI and generate 3-4 eggs are my changes of repeat trisomy so great now that we should just move to IVF?
At Thu May 08, 07:48:00 PM 2008,
Anonymous said…
This is an addition to my previous post on Wed May 07, 09:13:00 AM 2008. My OB indicated that I was tested twice for Factor VIII and one was positive and other was not. Could that be causing trisomy's? Also, my husbands sperm is above average in all categories so he's ecstatic of course :)
At Fri May 09, 07:02:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To anonymous May 7/8: For some reasons that are poorly understood, having had pregnancies that are trisomies increases the risk in some women for more pregnancies with trisomies (above their 'age alone' risk). There is a possibility that this is related to the homozygous MTHFR polymorphism and there is also the possibility that you have simply had a string of bad luck. I guess I would like to know if all the trisomies were the same or were they different. The only reason I ask is that if they were all the same, then another possibility is that your ovaries may have some 'mosaicism' - two populations of cells, one of which is abnormal, even though your blood chromosome studies are normal. Perhaps your doctor can better explain that to you. The two things you have going for you are that you have had a normal baby and you seem to be able to get pregnant. So, you can just keep trying, or you can undergo IVF (I don't think IUI is the answer here), get more embryos and simply have your doctors transfer the 'healthiest looking' ones as they always do. That may reduce you chance of aneuploidy. PGD is VERY expensive and unless you have money to burn, I would first try the other approaches. Best of luck and thank you for writing. Dr T
At Mon May 12, 02:39:00 PM 2008,
Anonymous said…
Thanks for your reply. All the Trisomies have been different (10, 16, 22) and the genetic counselor said that the trisomy 10 isn't even considered a pregnancy since nothing usually develops. In terms of PGD I may be able to get my insurance to cover it since I have now had 3. I could keep trying but I've read that at my age over 70% of my eggs could be aneuploid given my history. Is that possible?
At Tue May 13, 05:37:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To anonymous May 12: You are at incrreased risk because of the consecutive trisomies resulting from nondisjunction but 70% seems a little high. PGD is certainly an option and would increase your chances for a succcessful, chromosomally normmal pregnancy. Of course the other option is to just keep trying. It is going to be very important given your history that, even if you succeed and get later into first trimester, you consider either CVS or an amniocentesis to check the baby's karyotype. I will remain curious about what you do and how things turn out, so please stay in touch. Regards, Dr T
At Sun Jun 01, 06:16:00 PM 2008,
Anonymous said…
I am 38 years old and I have had 3 miscarriages, first one at 8.5 weeks testing showed normal chromosomes, then I was diagnosed with PCOS, 2nd miscarriage was a blighted ovum, 3rd pregnancy I have a healthy daughter, 4th pregnancy resulted in another miscarriage -cause was trisomy 16. Although my doctor suggested genetic testing but it seems that 2 previous healthy chromosome results would rule out either my husband or I being a carrier. is that true? Is there anything we can do to improve my egg quality? What are the chances of another healthy pregnancy?
Thanks Sherri
At Tue Jun 03, 06:48:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To Sherri: I doubt chromosomal testing of you and your husband will provide any new information. I have more questions than answers for you right now. Are use seeing an infertility specialist/ With your PCOS, has ovulation induction been tried and what was used? Do you have any other medical problems? Dr T
At Thu Jun 12, 12:21:00 PM 2008,
Anonymous said…
Hi. I'm 35 years old. I had my first son 4 years ago. I had to use ovulation induction medicine. He is healthy. I had a miscarriage about 6 months after his birth. No testing done. I had my second son 2 years ago. We also used ovulation induction for this pregnancy, and he is also healthy. Since then, I have had two miscarriages. The first was after natural conception--tests results showed only one sex chromosome (my doctor called it Turner's Syndrome?). The second was after using Clomid. The testing said the fetus had Trisomy 15. Do you think there is a chormosomal abnormality with my husband or me? Should we have the testing done (I know its expensive)--or do you think there is another underlying problem? Or just some sort of bad luck?
At Sat Jun 14, 11:29:00 PM 2008,
Polly Gamwich said…
Hi Doctor,
I am 31 years old. At age 29 I had two miscarriages the first at 10w due to Turners, the second at 8w 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), treated Compound Hetero MTHFR, and treated Hashimoto's 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 b/c of my elevated FSH?
2. Why does your body allow you to even GET pregnant with chromsomally abnormal babies ... why doesn't it just pass the baby w/o implantation??
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 m/c? (I've heard that if you've had two losses you have a better chance of having a healthy pg, however if you have more than 2 m/c's you have a worse chance of having a healthy pg ... I would assume this is assuming an untreated issue??)
4. I get pregnant on every cycle I attempt (4 months we've tried - we've had 4 pregnancies and 4 m/c's) ... will I have more m/c's than the average women b/c my babies seem to implant? healthy or not.
Thank you,
Polly
At Sun Jun 15, 09:19:00 AM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To anonymous June 12: It just sounds like a string of bad luck. Most sporadic first trimester losses are the result of fetal chromosomal abnormalities. At least you know why you lost those babies and it is unlikely to be the result of any chromosomal abnormality of you or your husband based on those fetal chromosomal studies. Best of luck in the future. Dr T
At Mon Jun 16, 06:09:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To Polly June 14: 1) Increased FSH is associated with decreased ovarian reserve and that is associated with aging, as is the risk for 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.
2) Most chromosomally abnormal babies do NOT make it sucessfully through the implantation process and of those that do, very few will survive the first trimester.
3) 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.
4) No. I do not think you are unique in that regard. You have just had a rough time with the conception side of things. 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 this sometime over the past year. Also, you might be a good candidate for either IVF and/or prenatal gentic diagnosis (PGD) to help improve your chance of having an implantation of a chromosomally NORMAL embryo!
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. Troffater,
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/religous reasons.) b/c 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 w/o 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 RE's still have yet to do a traditional SA. 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 antioxident supplements for three months and we will retest his men soon. If this turns out to be a problem, we'll move to IVF w/ICSI.
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 woman.
Take care,
Polly
At Thu Jun 19, 11:38:00 AM 2008,
Anonymous said…
Hi- I am 28 years old and I have three healthy children. My oldest is 10 (not with husband)then 2 1/2 and last 11 months. I just went through a missed miscarriage and the genetic testing showed the baby had trisomy 16 and Turner Syndrome. My doctor said it was just a fluke but my husband is very worried that it will happen again. I'm also worried. What are the chances of it happening again. We really wanted 4 children but should we just stop sense we have 3 healthy children. Thank you so much for your time.
Amanda
At Sat Jun 21, 05:08:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To Polly June 17: Thank you so much for getting back to us. I am sure many other readers will appreciate your response. I wish you the best of luck. We will all be pulling for you! Dr T
At Sat Jun 21, 05:12:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To Amanda: the MOST COMON cause of sporadic miscarriages are chromosomally abnormal babies, even in someone who has never had problems before. Most chromosomally abnormal babies will not survive the first trimester just like what happened to you. There is nothing you or your husband did wrong to cause the loss. Trisomy 16 is actually one of the more common abnormalities found in early miscarriages. So, the chance of this happening again at your age is probably less than 1%. Could it happen again - of course, but there is no reason you shouldn't try unless you have simply made up your mind to have no more children. Best wishes. Dr T
At Thu Jun 26, 09:45:00 PM 2008,
Anonymous said…
Hi Dr. Trofatter.
I 35 years old and have had four pregnancies:
1. ruptured ectopic
2. healthy baby girl
3. blighted ovum
4. trisomy 16
We did not have the testing done on the blighted ovum and I have been diagnosed but successfully treated for hypothyroid since the birth of our daughter.
My questions are:
1. Should we do genetic testing?
2. Could the Blight Ovum have been a trisomy?
3. What are the chances for another healthy baby?
4. Do we need to see an RE?
5. Since we have had a healthy child, what are the chances of a chromo abnormality in one of us?
We have not had a hard time getting pregnant- just a hard time having healthy pregnancies.
We want to have as much info as possible prior to trying again.
Thanks so much,
Hopeful
At Tue Jul 01, 11:12:00 AM 2008,
Anonymous said…
Hello, I really enjoy reading your blog. My husband has a pericentric inversion of chromosome 2. We completed IVF with PGD and on our Day 5 transfer, found there was only 2 fertilized eggs remaining. 1 carried an unbalanced karyotype. The other was 'inconclusive" as there was a problem reading the slide. We elected to transfer the inconclusive egg. I'm now 7 weeks pregnant and we have our first ultrasound tomorrow.
We plan to have CVS during week 10. My question is, what is the liklihood that an unbalanced embryo would have made it this far? We are cautiously optimistic, but still very worried about our chances for a successful pregnancy.
At Tue Jul 01, 11:49:00 AM 2008,
Anonymous said…
Further to my previous post regarding my husbands pericentric inversion of chromosome 2. I forgot to mention our ages. I am 32. My husband is 27. For both of us, this is our first attempt at having a child. We found out about my husbands inversion doing a routine check of his semen which identified a very low sperm count that prompted the karyotype analysis.
Any insight you can provide is very much appreciated
Kelly
At Tue Jul 01, 05:33:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To hopeful: If you have had no trouble getting pregnant, I do not think you need to see an REI doctor at this point. The blighted ovum was very likely to be a chromosomal abnormality as well and trisomy 16 is actuallly one of the more common chromosomal abnormalities that results in early pregnancy losses (those babies rarely get past 8-9 weeks). So, your chances of having another normal baby are VERY good. It is also unlikely (although still possible) that either of you has a chromosomal rearrangement. I would not recommend spending the money on those studies at this point because all I would tell you to do is "try again" anyway even if one was found. I would of course recommend first trimester screening for aneuploidy at 11-12 weeks when you do get pregnant again. Good luck and thanks for reading! Dr T
At Tue Jul 01, 05:35:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To Kelly: The odds are in your favor. There is probably less than a 5% chance the baby has an unbalanced karyotype at this point. Best of luck for the rest of the pregnancy and let us know how things turn out! Dr T
At Wed Jul 02, 11:41:00 AM 2008,
Anonymous said…
Thank you Dr Trofatter. Today we went for our first ultrasound and the fetus measurements were on track and we saw/heard the baby's heartbeat! Still cautiously optimistic, but I'm hopeful this is another good sign the baby does not have an unbalanced karyotype?? Don't think we'll feel really relieved until the CVS results, but am thinking this is a good hurdle.
Kelly
At Thu Jul 03, 06:08:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
Hi Kelly: Yep, just take things one step at a time right now. Bet everything will be fine! Dr T
At Sun Jul 06, 08:20:00 AM 2008,
Anonymous said…
Hi - I'm 34 years old and my husband was just diagnosed with a pericentric inversion of chromosome 2 as well. We met with a genetic counsellor who told us we had approximately a 50/50 chance of my husband producing abnormal sperm, but only a 1% chance of having a live born chromosomally abnormal child. We've been doing some research online and have found several studies that seem to suggest that it's the size of the inversion that will determine if the sperm is abnormal. My husbands inversion is 43% of chromosome 2. My question is - in your experience, is 50/50 just theoretical? We're trying to determine if we should just 'keep trying'. So far we haven't had a pregnancy or a miscarriage, but are wondering if the egg never makes it to implantation. We've been trying for 1 year.
Any thoughts at all?
Thank you in advance,
Emma & Jay
At Sun Jul 06, 05:52:00 PM 2008,
Anonymous said…
Dear Dr. T,
Just stumbled across your blog. Wish I had found it sooner. Here is a little about my histoy... I have had 5 MC's
#1- Age 31 blighted Ovum
#2- Age 33 Healthy pregnancy resulting in a baby boy
#3- Age 35 loss at 12 weeks Trisomy 21
#4- Age 37 Loss at 8 weeks Trisomy 16
#5 - Age 38 Loss at 10 weeks Trisomy 21
#6 - Age 38 Loss at 10 weeks also Trisomy 16
I am now 39 and currently 5 weeks pregnant. I have absolutely no issues getting pregnant, in fact I am ridicously fertile. I have had genetic evaluation. The counselor found no genetic issues with either my husband or I. She said the mere fact that I have had all losses due to chromosomal issues it is an indication of poor egg quality. I had my FSH tested a year ago and it was excellent at 5.5. I have been told time and time again it is "bad Luck" but jeez how much bad luck can one person have LOL!!! Now that I am pregnant again and praying to everything in sight that this one is healthy (even though my age is against me) is their anything you think I could be missing? i.e. should I be on certain meds? or are my doctors correct in saying it is Bad Luck????
Thank you so much for you time
Denise
At Sat Jul 12, 07:23:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To Emma and Jay: Assuming no other cause of "infertility" has been found, you should just keep trying or consider in vitro fertilization and preimplantation genetic diagnosis. If you have not heard of that, ask your doctors to explain. Dr T
At Sat Jul 12, 07:24:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To Emma and Jay again: If you have not even conceived in the past year, it really might be worth seeing an infertility specialist to look for other causes. Dr T
At Sat Jul 12, 07:29:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To Denise: Trisomies 16 and 21 are VERY common chromosomal causes of first trimester loss. If neither you or your husband have chromosomal rearrangements, then the best things to do are either just keep trying or consider in vitro fertilization with preimplantation genetic diagnosis. The latter is very expensive, but you are also running out of time and have really had a string of "bad luck." But, maybe this pregnancy will do just fine and all that will be unnecessary! Good luck. Dr T
At Sun Jul 13, 04:52:00 AM 2008,
Anonymous said…
Thank you Dr Trofatter. We have seen an infertility specialist. This is how we found out about my husbands inversion. The specialist advised we could either keep trying OR try IVF with PGD. We are worried about the high cost of IVF/PGD. The part we're confused about is how some sperm could be normal and some sperm could be abnormal? The bottom line for us is that if my husband produces even 30% normal sperm - we will take our chances and hope to conceive with one of those sperm. But we are worried he may not make ANY normal sperm (despite what the genetic counseller told us about 50/50) in which case we're just wasting time.
At Sun Jul 13, 07:37:00 AM 2008,
Anonymous said…
Thanks for the response Dr T. I agree, I am running out of time and IVF with PGD is very, very expensive with no guarantees. I am hoping this one is healthy, that's really all I can do. I read on one of your previous posts about possible Mosaicism of the ovaries. Do all the Trisomies have to be the same i.e. All 21 or All 16 for this diagnosis? Best Regards, Denise
At Tue Jul 15, 10:28:00 AM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To anonymous July 13: Theoretically, about half the sperm should be normal and half should carry the chromosome with the pericentric inversion. Remember, the normal chromosomal complement is 46 (23 pairs) and when we make gametes (eggs or sperm), the total number of chromosomes are reduced during meiosis to 23 (from 46) so that when the two of you get together, you end up with a baby that has 46.
Dr T
At Tue Jul 15, 10:30:00 AM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To Denise: Mosaicism usually involves only two populations of cells, one normal and one abnormal. So, yes, if there was a population of cells that had trisomy 16 or 21, then that would increase the risk for repeated aneuploidies of the same type - again, very rare. Dr T
At Wed Jul 16, 03:46:00 PM 2008,
Anonymous said…
Thanks for the response.
At Mon Jul 21, 05:20:00 PM 2008,
Anonymous said…
Hi there, We corresponded a few weeks ago regarding our situation. My husband has a pericentric inversion of chromosome 2. We performed IVF and are now 10 weeks pregnant with out first child. We are completing CVS next week. I have one question we've been considering. My husband had a brother that died at 2 years of age after being ill with seizures since birth. As this was in the 70's, his family didn't do very much research about it, so we're not certain what caused his death. It occured to us however that it is possible that my husbands mother or father had passed on an unbalanced chromosome 2 to his brother and this was the cause of his problems.
We're just speculating of course. But, in your experience, is it possible that he could have had an unbalanced chromosome arrangement and survived until age 2?
We've been operating under the assumption that a live birth is very unlikely, so every week that goes by we're more confident that the baby has a balanced karyotype.
Should we be less confident given this potential linkage in your opinion? Recognize you would just be guessing as well, but that you may have some thoughts.
At Wed Jul 23, 01:23:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To anonymous July 21: The simple answer is, Yes, especially if he had other problems. But they should be able to tell if your baby has an unbalanced chromosomal complement when they do the CVS. Please tell the genetic counselor about your husband's brother. Good luck and keep us posted! Dr T
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