Recurrent Early Pregnancy Loss - 3 - Chromosomal Causes

Sunday, March 25, 2007

Kenneth F. Trofatter, Jr., MD, PhD

Although 50% or more of sporadic pregnancy losses in first trimester are the result of CHROMOSOMAL ABNORMALITIES, these probably account for less than 5% of recurrent early pregnancy losses. There is also usually a difference in the type of chromosomal abnormalities found under these situations. In sporadic losses, the most common causes are ‘nondisjunction events’ in the final cell division that is supposed to equally divide the chromosomal pairs and create eggs or sperm (gametes) that contain only half (23 chromosomes = 22 different ‘autosomes plus 1 ‘sex chromosome’) the normal chromosomal complement (46 chromosomes = 22 pairs of different ‘autosomes’ plus 2 ‘sex chromosomes’, one from each parent).

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.

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113 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
At Thu Jul 24, 07:52:00 AM 2008, Anonymous said…

Hi, Doctor.
I am 36, and have been pregnant 4 times:
age 34, 2006--Healthy Baby Girl
age 35, Aug-Sept, 2007--natural m/c 8.5weeks
age 36, Dec, '07 - Feb, '08--D&C @ 8.5weeks, later diagnosed as Trisomy 16
age 36, Mar-July '08--D&E @ 17.5weeks, diagnosed via scan & amnio as Trisomy 13

After our second loss, our ob ran blood work to check for chromosomal translocation, and tests on my husband & I came back normal.

Since our latest loss, we have been to see an RE. When my cycle returns, they will begin testing my FSH and give me a saline sonogram to try to determine what course of action might be best.

The genetic counselor & perinatologist have told us these are all "flukes" and we should try again. Three flukes in a row seems like a lot of lousy luck to us.

The RE has mentioned IVF with PGD as a possibility, and he has noted that my ability to get pregnant fairly easily is a point in our favor. Obviously, we'll know more when the first round of tests come back.

Given my situation, what would you recommend? We may be able to afford IVF with PGD.

I know there are no guarantees, but each loss is heartbreaking, and the last one in particular since things seemed to be going so well. Our NT Scan & blood work at 12 weeks gave us a 1 in 750 chance of Trisomy 13 & 18, which is 99.9% sure all was well. It was only at the amnio scan they began to see a problem, and of course, our results confirmed it.

Should we just try again and hope for the best with a CVS at 11 weeks? Or should we try something different and really go for IVF?

I just can't seem to figure out which gives us a better chance of a healthy baby. I don't want any more losses if they can be avoided, and I want to complete my family quickly (just one more baby!) while I'm still ovulating every month and before things get even worse with my eggs.

Please help.
Thanks.
At Thu Jul 24, 08:22:00 AM 2008, Anonymous said…

Hi, Doctor.
I just sent you a question regarding my 3 pregnancy losses in the last 11 months, 2 documented as Trisomies (T16 & T13).

One last question...
If we do decide to just try again on our own, what is the chance of another Trisomy or miscarriage, and what are the chances that all will be well?

And how does this compare to our odds with IVF with PGD?

Thanks.
At Fri Jul 25, 01:16:00 PM 2008, Anonymous said…

Thank you Dr Troffatter for your comments regarding the implications of my husbands brother dying at Age 2. We met with the genetic counsellor and the Doctor today. Their view was it could mean that this particular inversion could survive unbalanced until term, so thought it increased our risk of an abnormal birth for believed it was unlikely.

I tried to ask all my questions when we were at the appointment, but realized I had two more. I would be interested in your view as well!

1) Assuming my husbands brother did die of an unbalanced chromosome complement, Does that fact that my husbands mothers carried him to term mean that my body would as well? Is it just as possible I would miscarry in the first trimester if I carried the same unbalanced baby?

2) Given our situation (we performed IVF with ICSI, started with 10 eggs, only 2 remained at Day 5, the others had all arrested. We performed PGD and found 1 egg was unbalanced, the other was "inconclusive" as they had a technical problem in lab. We transferred the inconclusive egg. We are now 11 weeks pregnant. My last ultrasound showed perfect dating and a strong heartbeat)
Are you able to give a best guess at the odds of our baby carrying an unbalanced complement? OR is it simply impossible to guess given the potential linkage to my husbands brother who died.

We will of course know for sure when we get the CVS results, but the 2 - 3 week wait is killing us! So, we're looking for any directional opinions to help give us a sense of what could happen.

With thanks for your help. I think this is blog is a really amazing thing that you do.

Kelly
At Fri Jul 25, 03:28:00 PM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

To anonymous July 24: I am still not sure what to make of folks like you that have recurrent aneuploidy. The standard answers are what you have been told, "It's a fluke" and that you are at no higher risk than your 'age alone' risk of about 1 in 80-90 for having a chromosommally abnormal baby in first trimester - tha actual risk is probably somewhat higher than that due to very early losses due to aneuploidy. But, my gut tells me that some women may just be at greater risk for nondisjunction (leading to trisomies) than others. The things you have going for you are your ability to conceive and the knowledge that neither you or your husband have a chromosomal rearrangement. With all that said and done, your options remain (none of which guarantee that you will not lose another pregnancy): 1) just go out and get pregnant again on your own; 2) ovarian stimulation and either IUI or IVF alone; or 3) IVF with PGD. The cost is incremental. The adbatages of the assisted reproductive technologies (ARTs) is that they increase the number of possible eggs for conception with each cycle, IVF allows some preliminary screening of the 'quality' of the embryos, and PGD increases the likelihood that a chromosomally normal embryo(s) will be transferred. You would have excellent prospects for the ARTs because of your fertility. You will have to make the final decision yourself based on cost, benefits, and risks. Remember, NONE guarantees a good outcome.
Dr T
At Fri Jul 25, 03:31:00 PM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

To Kelly: Since we do not really have any idea what happened to your husband's brother, I cannot even begin to speculate. Most unbalanced chromosomal abnormalities will miscarry. However, since things are going so well, I believe you have > 95% chance that this baby is chromosomally normal. Just let us know for sure when you find out! Dr T
At Fri Jul 25, 05:12:00 PM 2008, Anonymous said…

Thank you Dr Toffater for your response. I really appreciate it. So, in our ongoing saga, we just got some additional information. Since my husband wasn't even born when his brother died, he didn't know very much about it. I just had his Mom and Dad over for coffee to tell me a bit more about the situation. Turns out - he didn't have seizures at all! This was just something my husband had thought he heard. His parents explained to me that his brother was totally fine at birth, developed normally, was walking and talking normally for his age. He was prone to high fevers when he was ill. One night the fever was so bad they took him to the hospital and he died that night. The Dr's were never sure exactly what he died from, but officially it was complications from some type of infection.

With everything we've read about this type of inversion, I assumed a live born baby with an abnormal complement would have suffered considerable more severe problems?

So, I'm thinking perhaps this is less of a linkage than we believed. I just left a message for our genetic counsellor to let them know.

At this stage, I think all we can do is wait for the CVS results, but this news does make me feel a bit better and I thought I would share with you. Don't you?

I promise to post when we have the news in a couple weeks.

Thanks again
Kelly
At Mon Jul 28, 05:00:00 PM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

To Kelly: Thanks for the update. The odds are in your favor. I look forward to hearing about the final results. Dr T
At Tue Jul 29, 05:43:00 PM 2008, Anonymous said…

Dr. T.
Thank you for your response to my question about my recurrent Trisomy losses this year. It seems there is no easy answer.

One other thing I've read about is that what day a woman ovulates can impact the viability of a pregnancy. Even as a teen and into my 20's, my cycles have always been 5-6 weeks long. Then I was on birth control pills for many years, but when I stopped taking them, my cycles returned to their usual length.

Is it true that ovulating late in a cycle can mean that an egg is less likely to have the energy or ability to divide properly?

Our daughter was conceived on day 26. Miscarriage #1 conceived on day 29. Miscarriage #2 (T16) was conceived on day 27. Loss #3 (T13) was conceived on day 14. This is the only time that I can recall, and certainly since I began charting in Jan. '06, that I have EVER ovulated so early, and of course, I thought it would be a good thing.

Anyway, is there any merit to this theory at all? If so, and if there is no way to bring my ovulation up earlier, it may point us further in the direction of IVF with PGD.

Your thoughts, as always, are appreciated.

Thanks.
Shana
At Wed Jul 30, 04:37:00 PM 2008, Anonymous said…

Hello, I'm not sure if this is the right place to post this question, but am interested in your view. I am a 32 year old woman who has Kallmann's syndrome. This was diagnosed when I didn't go through puberty and had a absent sense of smell. After going through fertility treatment I am now 5 months pregnant with my first child - a boy. My Doctor was never able to find a genetic mutation confirming Kallman's and we have no family history that I'm aware of. He told me I likely have a sporadic version and that the liklihood of passing it on to my child given this is low, but could happen.

Are you familiar at all with this syndrome? I'm curious in your thoughts on the liklihood of me passing this on to my baby boy.

Thank you
Noelle
At Fri Aug 01, 06:24:00 PM 2008, raye said…

Dear Dr. Trofatter
This is a very helpful blog to women who are suffering Trisomy issues.

My first pregnancy loss (age 36) was April 28/07 confirmed T13 at 12 weeks. D&E necessary.
My second loss at 37 was expelled naturally at 8-9 weeks without enough material for karotyping.
My third loss this past month July 12/08 at 37 was my son at 19 weeks confirmed T21 with SUA but physically perfect (so far). Labour and Delivery 27 hours. Stillborn. We are reeling with grief.

I concieve easily and quickly. With another birthday next week we are devastated. My husband and I tested genetically fine after the first loss. We are also being told this is bad luck as I am 120lbs, lean, fit and health conscious.I am not overweight and do not smoke, drink etc..

We are considering IVF. I wonder if I should get my eggs checked? Trying again naturally is possible at 38 but I feel like my ovaries are a refrigerator of rotting fruit. IVF seemed like a great answer. Now that I am looking at IVF I see there are genetic risks for imprint disorders, a higher rate of cancers, autism and cerebral palsy. Why is no one discussing these issues?

I only want one healthy baby. Kudos to all the women here who already have one. They don't know how lucky they are!

I am now afraid of another genetic failure naturally and terrified of a genetically abnormal baby through IVF.

I'd appreciate your opinion.
Raye
At Fri Aug 01, 06:27:00 PM 2008, raye said…

Dear Dr. Trofatter
This is a very helpful blog to women who are suffering Trisomy issues.

My first pregnancy loss (age 36) was April 28/07 confirmed T13 at 12 weeks. D&E necessary.
My second loss at 37 was expelled naturally at 8-9 weeks without enough material for karotyping.
My third loss this past month July 12/08 at 37 was my son at 19 weeks confirmed T21 with SUA but physically perfect (so far). Labour and Delivery 27 hours. Stillborn. We are reeling with grief.

I concieve easily and quickly. With another birthday next week we are devastated. My husband and I tested genetically fine after the first loss. We are also being told this is bad luck as I am 120lbs, lean, fit and health conscious.I am not overweight and do not smoke, drink etc..

We are considering IVF. I wonder if I should get my eggs checked? Trying again naturally is possible at 38 but I feel like my ovaries are a refrigerator of rotting fruit. IVF seemed like a great answer. Now that I am looking at IVF I see there are genetic risks for imprint disorders, a higher rate of cancers, autism and cerebral palsy. Why is no one discussing these issues?

I only want one healthy baby. Kudos to all the women here who already have one. They don't know how lucky they are!

I am now afraid of another genetic failure naturally and terrified of a genetically abnormal baby through IVF.

I'd appreciate your opinion.
Raye
At Thu Aug 07, 12:23:00 PM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

To anonymous July 29: I don't think ovulating late decreases the division rate of cells in the embryo, but it does decrease the likelihood of implantation. This is something we have known for years and it is probably related to 'receptors' in the endometrium that are not in synchrony with the embryo generated by delayed ovulation. One of the things I have always done with women who have ovulatory irregularity and recurrent pregnancy loss is to offer ovulation induction to move the time of ovulation closer to days 13-14 and improve the opportunity for synchrony with the endometrium. That would be a good starting place in your case. Best of luck! Dr T
At Thu Aug 07, 12:30:00 PM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

To Noelle: It is my understanding that many cases of Kallmann's syndrome are sporadic as the result of new mutations and you are very unlikely to pass that on to a child. You still might want to have the child screened for sense of smell at an early age! Congratulations on your pregnancy and best of luck for the rest of it! Let us know how you do! Dr T
At Thu Aug 07, 12:34:00 PM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

Raye: I know you have been through a lot and are scared and sad, but the odds are still in your favor. I think you should discuss your assisted reproductive technology options with a reproductive endocrinologist. Ovulation induction with IUI or IVF (with or without preimplantation genetic diagnosis) might significantly improve your chances for a chromosomally normal baby. Best of luck and let us know what you decide to do! Dr T
At Tue Aug 12, 05:06:00 PM 2008, heather said…

VERY FRUSTRATED, HOPE you can help!

Dr. T
I have Robertsonian Balanced Translocation of 13 & 14. Our first pregnancy we had a Healthy Girl who is now 3. Since then we have been TRYING to complete our family with another child. WE HAVE HAD BAD LUCK!!!! In a year we have had 3 miscarriages at week 19, 13, & 8. We found out I had RBT after the 2nd loss when they did genetic testing on my husband & I.
They have done testing on ALL the losses & found NONE of them had ANY abnormalities, & they were ALL BOYS.
I know with RBT miscarriage rate is 50% plus the normal 10-15%. BUT 3 losses with NO reason is difficult to understand.
We just saw a fertility specialist who said are ONLY chance is IVF. Otherwise we can keep trying & either miscarry or GET LUCKY. IVF is really not an option due to expense. They also want to do an HSG ultrasound with Saline.
My questions are: 1. Since my problem is staying pregnant & NOT getting pregnant, what will the HSG show. I have had MANY ultrasounds, I would think a uterine abnormality would have been picked up OR I would not carry a pregnancy as far as I do?
2. Is there a test/testing I should be asking for or looking into?
3. Could our 80+ year old house or 2001 Van be the cause in ANY WAY. These are the ONLY 2 factors that have been constant with all 3 losses?
4. Is there ANY chance it could be hormone inbalance with me?
5. What are YOUR suggestions?

We REALLY want more children, but if it is going to be a ROLL of the dice each time, I don't know how much our family can go through.

HOPING you have SOME ideas!!!

Thanks A BUNCH for your time answering questions in our quest to have what we have dreamed of our whole life.

Heather
At Fri Aug 15, 05:39:00 PM 2008, Anonymous said…

Hi Dr Troffatter,

We corresponded a few times regarding my husbands pericentric inversion of chromosome 2. I just wanted to let you know that we received our CVS results and our baby boy has a 100% normal chromosome karyotype!!

We could not be more thrilled. We are now almost 4 months along and everything is going well. I wanted to say thank you so much for your guidance and direction. Kelly
At Fri Aug 15, 05:45:00 PM 2008, Anonymous said…

Thank you Dr for your comments on the liklihood of me passing Kallmann's on to my child. I actually have a quick follow up question that we meant to ask the genetic counsellor and forgot. When you pass on a disorder like Kallman's to your child, what are the chances that your child has a different manifestation of the disorder than you do?

The thing we are most worried about is cleft lip/cleft palate. I've read that these things are sometimes associated with Kallmann's. I personally did not have either of these things. I just couldn't smell and didn't have a normal puberty until I supplemented with hormones at age 14.

Do you happen to have any sense of the liklihood of significant variances in the symptoms of Kallmann's when it's inherited?

By the way, we do know that the Kallman's isn't x-linked in my situation as we performed CVS and they were not able to find this on the baby's sample or my own sample.

Any thoughts would be greatly appreciated.

Noelle
At Sat Aug 16, 07:00:00 PM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

To Heather: Part of the evaluation in your case should be to perform a sonohysterogram or hysteroscopy (to look for correctible intrauterine abnormalities you might have acquired over time), screen for hormonal abnormalities such as thyroid disease and perhaps look for evidence of a thrombophilia, especially if all the losses were chromosomally normal. There is a possibility that you carry an "X-linked" genetic abnormality tha is lethal to boys, but that is less likely. You have had one healkthy child, so there is a good chance you will be successful again - but as you stated, it depends on how much heartache you are willing to take to get there. Bst wishes and let us know what you find out!
Dr T
At Fri Aug 22, 06:23:00 PM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

To Noelle: Kallmann's has "variable penetrance" which means that there can be a vriety of different abnormalities as well as in the severity of those abnormalities. In the case of cleft lip/palate, that may seem like a terrible problem, but with the skillful surgeons available today, they can achieve remarkable results in fixing those abnormalities. Take care and it was good to hear from you again. dr T
At Sat Aug 23, 11:23:00 AM 2008, Anonymous said…

Hi Dr. T,
My husand and I have had 3 miscarriages in the past 11 months. I am 25 years old and otherwise very healthy (except that I have MS but it is under control). The first one was a "chemical pregnancy" in Dec '07, the second was a "normal" pregnancy (heartbeat shown at 6 weeks), and then we lost the baby at 8 weeks (Feb '08) and the last was a "blighted ovum" and I had my second D&C in June of '08. The fact that all three were different, does that make things more difficult to diagnose the problem? Could all of these cases be related to chromosomal abnormalities?
Thank you,
Lindsay
At Tue Aug 26, 06:17:00 PM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

To Lindsay: They all COULD be chromosmaly abnormal, but I really think you need a more thorough evaluation, especially because of your MS. There are many different reasons you could be miscarrying and even though you are young, I would suggest proceeding with that evaluation sooner than later. The last couple of posts in this series provide some idea what that workup would involve and possible options for therapy. Best wishes. Dr T
At Tue Aug 26, 07:02:00 PM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

To Kelly: Congratulations and thanks for letting us know. Hope the rest of the pregnancy is wonderful! Tell us when the baby's born. Dr T
At Fri Aug 29, 12:32:00 PM 2008, Polly Gamwich said…

Hi Dr. Troffater,

You and I conversed in your comment section of this post back on Jun 16th, 17th, and 21st.

I wanted to ask you a follow up question:

If you re-read my earlier posts you will see that we have had 4 pg's on 4 attempts, all ending in miscarriage due to chromosomal abnormalities. Clearly we are ovulating eggs that can get fertilized. We have just completed our second round of freeze-all IVF. For both cycles I seemed to stimulate like a champ - getting 15-18 follicles each cycle, but we only retrieved 5-6 each time and we only got 1 & 4 mature eggs. Please remember that I am young, have elevated FSH, have AMH of 1.0, and am positive for AOA - though I stimulated better than I should have for my FSH values.

Can you explain how I can get pg naturally on every attempt, but when we go through IVF I have empty follicles? This does not make sense to me.

Thank you,
Polly
At Tue Sep 02, 06:43:00 PM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

Polly: I don't know. You are truly a mystery to me. Do you know if you were exposed to some toxic materials, chemicals, or radiation early in your life that may have affected your "eggs"? I am grasping at straws. Please keep me updated. I will learn by your experiences as well! Dr T
At Sat Sep 06, 12:49:00 PM 2008, Anonymous said…

Dr T.
Thank you for all your time in answering so many complicated questions.
I have had 4 pregnancies and 1 chemical pregnancy. My first pregnancy was our first "try", was uncomplicated, the picture of ease and innocence, and our healthy son is now 3.
The others have occurred over the last year and half. The second pregnancy was a missed miscarriage around 9 weeks, we had previously seen a heartbeat around 7 weeks. I did have a D&C procedure but did not request pathology.
The next, just two months later, was the chemical pregnancy. I received faint positive HPTs for several days before menstruation began.
I then got pregnant the very next month and carried again until about 9 weeks. This turned out to be a partial molar pregnancy. I was monitored for several months according to protocol and needed no follow up treatments.
I just had the most recent D&C a few days ago. We never saw a heartbeat with this one, but it was measuring correctly at 6w2d. A follow-up 5 days later showed no new growth.
We are still awaiting pathology on the most recent, as well as chromosomal analysis results on myself and my husband.
I should also mention that with both the partial molar and the most recent miscarriage there was a second undeveloped gestational sack in the uterus.
I know that the results we are awaiting will give us much more information, but our doctor seems to be almost expecting something to turn up in our chromosomes.
I have also had blood work for recurrent loss, including clotting disorders, and all has come back negative. I am very, very borderline hypothyroid, but without symptoms we have not chosen to treat it at this point.

Is it possible my eggs are just bad? With this many miscarriages, plus the fact that there was an additional sack with the last two...that's an awful lot of eggs to not make it, is it not?
Any insight from you is greatly appreciated.
Thank you
At Sat Sep 06, 12:50:00 PM 2008, Anonymous said…

Follow up information to my question just posted regarding 4 pregnancies and 1 chemical. I am 34 and my husband is 37.
Thank you.
At Wed Sep 10, 03:47:00 PM 2008, Polly Gamwich said…

Hi Dr. Troffater,

I'm so glad it's not just me that's crazy!! I told my first RE that I'm a reproductive anomaly - she smiled nicely and asked me to try to stay positive ... I thought I was being funny!

The only thing I can think of is that my mom went through sudden onset menopause at age 36, so I'm already predisposed to it. We do not have Fragile X or abnormal genetics. However, she did smoke (like a chimney I might add!) during my time in utero and both parents smoked around me until I moved out of the house at 18 ... I've seen one study that links bad ovaries to the offspring of women who smoked while gestating. That's my theory.

Well, I'm glad you're also mystified. I will definitely keep you updated.

I work at Stanford University and have cycled with a former Stanford Professor ... I stump them too.

Until my next update ...
Polly
At Tue Sep 16, 04:08:00 PM 2008, Anonymous said…

We have just found out that my partner has chromosome abnormalities which probably resulted in the 3 miscarriages we have had. I believe he has translocation between chromosomes 3and 6. I just wondered if you could tell me what sort of chance we have of having a succesful pregnancy. Thanks
At Mon Sep 22, 07:33:00 PM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

Toanonymous Sept 6: Sorry for the delay in my response, but I did not receive your comment in my mailbox until this weekend with about 180 others! It is unlikely that your "eggs are just bad". However, the one thing you did not tell me is your age. If you and your husn=band are chromosomally normal, the babies could have still been abnormal. However, under those circumstances, I would recommend a sonohysterogram and possibly hysteroscopy to evaluate the uterine cavity for evidence of scar tissue or other abnormalities. If your thrombophilia workup was negative then perhaps your borderline thyroid condition is contributing. Women with hypothyroidism and antithyroid antibodies are at greater risk for early pregnancy loss as well. Let me know the results of your studies and I will give you some more of my thoughts. Best wishes. Dr T
At Mon Sep 22, 07:34:00 PM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

To Polly: Thanks for the update and I look forward to hearing from you again! Dr T
At Mon Sep 22, 07:39:00 PM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

To anonymous Sept 16: I wrote a post on Robertsonian translocations on August 29, 2007 (http://www.healthline.com/blogs/pregnancy_childbirth/2007/08/robertsonian-translocations.html). That should answer many of your questions. Your odds for eventually having a normal baby are good, but it may take having to put up with the anguish of repeated miscarriages as well. Another option is in vitro fertilization (IVF) with preimplantation genetic diagnosis (PGD). Best wishes to you. Dr T
At Sun Sep 28, 09:00:00 AM 2008, Anonymous said…

Dr T. We corresponded earlier this month. Thank you for your response.
Here is my earlier post for reference:

I have had 4 pregnancies and 1 chemical pregnancy. My first pregnancy was our first "try", was uncomplicated, the picture of ease and innocence, and our healthy son is now 3.
The others have occurred over the last year and half. The second pregnancy was a missed miscarriage around 9 weeks, we had previously seen a heartbeat around 7 weeks. I did have a D&C procedure but did not request pathology.
The next, just two months later, was the chemical pregnancy. I received faint positive HPTs for several days before menstruation began.
I then got pregnant the very next month and carried again until about 9 weeks. This turned out to be a partial molar pregnancy. I was monitored for several months according to protocol and needed no follow up treatments.
I just had the most recent D&C a few days ago. We never saw a heartbeat with this one, but it was measuring correctly at 6w2d. A follow-up 5 days later showed no new growth.
We are still awaiting pathology on the most recent, as well as chromosomal analysis results on myself and my husband.
I should also mention that with both the partial molar and the most recent miscarriage there was a second undeveloped gestational sack in the uterus.
I know that the results we are awaiting will give us much more information, but our doctor seems to be almost expecting something to turn up in our chromosomes.
I have also had blood work for recurrent loss, including clotting disorders, and all has come back negative. I am very, very borderline hypothyroid, but without symptoms we have not chosen to treat it at this point.

Is it possible my eggs are just bad? With this many miscarriages, plus the fact that there was an additional sack with the last two...that's an awful lot of eggs to not make it, is it not?
Any insight from you is greatly appreciated.
Thank you

To answer your question, I am 33 and my husband is 36.
We have since received results on pathology - it was concluded to not have been another molar pregnancy, but was inconclusive otherwise. My dr is still trying to get more information from the lab, but apparently the tissue did not grow for chromosomal analysis. So we now have another miscarriage with no information. Is the fact that the tissue did not grow representative of anything?

Mine and my husband's chromosomal analysis came back normal.

Also, is the timing of a miscarriage representative of the cause? My first was around 9 weeks - does that make it more or less likely to be an abnormality or hematological/immunological cause?
And since I carried the partial molar to 9 weeks, would that rule out hematological or immunological causes?
The most recent was lost at 6w2d. Does that indicate that the cause may differ from the first?

I'm just at a loss. We are seeing a RE tomorrow and a hematologist in the coming weeks, but I worry that we don't have enough information for a diagnosis and treatment options.
Thanks again for all your efforts with this blog!
T
At Sun Sep 28, 09:11:00 AM 2008, Anonymous said…

In addition to my other post regarding the two miscarriages and partial molar...as I mentioned, the ultrasound from both the partial molar and the most recent miscarriage showed a second gestational sac (empty). Are these two additional sacs considered blighted ovum? You mentioned somewhere that there are numerous causes for blighted ovum, but I can't seem to find any research. Can you please enlighten me?
Thanks you
T
At Thu Oct 02, 07:44:00 AM 2008, Anonymous said…

Hello Dr. Trofatter,

Last April a D&E had to be carried out due to the detection of a 'blighted ovum' around 8 weeks. I got pregnant after three months and upon some routine blood tests found to have htpothyroidism. The doctor started a medication of thyroxine supplements immediately. A TVS carried around 8 weeks showed three gestational sacs. Two showed embryonic echoes without any heartbeat. One was a blighted ovum. The conception of the triplet was normal, i.e without any medication.The doctor repeated a TVS after two weeks and a D&C was carried out yesterday. However, he did not send the prodcuts of conception for any chromosomal analysis. The doctor suggested that we visit him after a month with a chromosomal test of both me and my husband.

What are the chances of a successful pregnancy the next time ? What are the logical steps we need to follow to increase the chance of a successful pregnancy the next time. I'm 32 years old and my husband is 39. For your information , the last TVS also reported a 'polycystic ovary'.
At Fri Oct 03, 10:04:00 PM 2008, Anonymous said…

Hello Dr. T,
I am a 36 year old woman and have had a total of 6 pregnancies. My first 2 pgs ended at 7.5 weeks. My 2nd loss was tested and chromosomes were normal. After seeing an RE and having an hysterogram done, he found scarring in my uterus. The issue was corrected through lap surgery. I went on to have a healthy baby girl who is almost 3yrs old. In Nov of 2007, I got pg again but m/c at 5wks. OB considered it a "fluke". My next pg in Feb this year turned out to be a blighted ovum and wasn't discovered until 11wks (1st u/s). I had a D & C performed and pathology testing on the conception products. Testing was back normal.
I received the recurrent loss work up again-
another hysterogram-all clear.
all the bloodwork was normal
We were told to simply keep trying and RE would monitor me from the start. I got pg again in early Sept and had an u/s as early as 3wks. My HCG levels were good and RE noted that my uterine lining was very thick and healthy. He even said he was 'betting on this pg' only for me to start bleeding 5.5 weeks later. RE is baffled and is unsure why this is happening.
Do you think PGD and IVF would help us? Do you think we have a strong chance of another healthy baby? Is it possible that perhaps I may have a genetic issue with carrying boys since I have a girl and my 2nd loss showed female chromosomes?

I am really at a loss...and scared of not being able to carry another to term.

Thank you, Julesie
At Mon Oct 06, 05:51:00 PM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

To T: Even if you and your husband have normal chromosomes, all of the miscarriages may still have had chromosomal abnormalities. However, you need a throrough workup at this point from the hormonal, medical, uterine anatomical, immunologic, and hematologic standpoint. This could be an acquired thrombophilia or a uterine cavity defect or even the "hypothyroidism" coming into play. I am glad you have selected an REI to begin this process. Please let us know what gets done and any results that point to a cause of your problems. Thank you for writing and I wish you the best. Dr T
At Mon Oct 06, 05:57:00 PM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

To anonymous Oct 2: Chromosomal studies may be reasonable but they are expensive and only a small part of the work up for recurrent early pregnancy loss. If your ovaries are really "polycystic" yopu will need a more thorough hormonal evaluation and perhaps a workup for genetic and acquired thrombophilias. The treatment and your chances of carrying a pregnancy depend on the reasons for the losses (if any are found). At your age, the prospects are usually very good for success, but I would recommend a low threshold for asking for a consultation with a reprodcutive endocrinologist if you are not successful within the next year. Regards, Dr T
At Tue Oct 07, 06:51:00 PM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

To Julesie: Before going the IVF route, you might simply consider empiric ovulation induction, progesterone support and starting heparin or lovenox in mid-luteal phase. You don't seem to have much trouble getting pregnant (unless there is something you haven't told me) but there may be a problem with implantation. You also may be someone who has subclinical endometriosis. This appears to impair implantation. Our REI group will try 3 months of lupron followed by ovulation induction in women they suspect of having this as a source of their losses. Best wishes and thanks for reading. Dr T
At Thu Oct 09, 12:27:00 PM 2008, Anonymous said…

Hello Dr. Trofatter,
I am 27.5 and my husband is 34. I have been off birth control for 2 years this Nov. We started timing intercourse via an OPK and charting my BBT and we were able to conceive on our 4th month of trying (Sept. 17) and it ended as a chemical pregnancy...I have never been tested for anything because there has never been any reason to test me. No woman I am related to has had any reproductive difficulties. My husband had a SA because he has been through several treatments for Melanoma (he is currently NED for 3 yrs!!). 10 years ago when he was dx he was on high dose Interferon for a year. Then he did a few doses of an experimental Melanoma vaccine. Could the Interferon have caused DNA fragmentation in his sperm? His SA showed normal on everything except he has 1% morphology. We never even thought we'd be able to conceive on our own, but we did...is that good news or is it bittersweet meaning we may just continue to miscarry because of possible DNA fragmentation? Also, does DNA fragmentation mean the chromosomes are "messed up" or does it mean something entirely different? He also had a horrible staph infection almost 10 years ago stemming from a surgery he had and it almost killed him. Could that have had an effect? We are meeting with our RE on Monday, but I am wondering if you think a DNA fragmentation analysis is necessary? Thanks! You seem very supportive and understanding of women :)
At Thu Oct 09, 07:05:00 PM 2008, Anonymous said…

Thank you, Doctor. I appreciate your time and your efforts in helping women such as myself. Best, Julesie
At Tue Oct 28, 01:26:00 PM 2008, Lori said…

Hi - I am 29 years old and have suffered 6 miscarriages, all have been before 6 weeks. I have been going to a fertility specialist for about 6 months now. I have had all the blood work up completed, the endometrial biopsy and a sonohystogram. My fertility specialist sent me to a hematologist for additiona blood work. I just went a couple weeks ago and I was told that he will perscribe Lovenox when I get a positive pregnancy confirmation. I tested positive for the double mutation C667T MTHFR and my homocystein levels are normal. I also have elevated levels of IgM. Do you believe I should be on Lovenox?? My fertility specialist recommended IVF/PGD becasue of the 6 early miscarriages, shouldn't this be the last resort becuase it's so expensive??! I also did test positive for low progesterone on day 21 one month but my doctor says the endometrial biopsy was in phase but he said we could try a couple months of clomid with IUI, would this help?? Any information would be appreciated!! Thanks,
At Fri Oct 31, 06:32:00 PM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

To Julesie: Thank you for reading and writing to us! Good luck! Dr T
At Fri Oct 31, 06:37:00 PM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

To anonymous Oct 9: I doubt any of the things you mentioned contributed to your husband's SA problems, but perhaps some of the chemotherapy (not the interferon) he might have received for his melanoma therapy did. I would ask that your REI send you to an expert andrologist to ask those very same questions. I claim no expertise in that area myself! Best wishes! Dr T
At Wed Nov 12, 06:05:00 AM 2008, Anonymous said…

Hello Dr Trofatter I am 42 years old and just have had a still born baby due to Edwards syndrome. He was my second boy after 12 years;we are totaly devastated our consultant told us w're just extremly unlucky. We would love to try again but due to our ages my husband is 40;W're very frightened something will happen again can you offer some advice?
At Thu Nov 27, 04:05:00 PM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

To anonymous Nov 12: Unfortunately, I cannot turn back the hand of time. At age 43, your chance of delivering a baby with Down syndrome is about 1 in 40 and the risk for all chromosomal abnormalities is about 1 in 31. First trimester risks that the baby has a chromosomal abnormality are almost twice these. That is chance you will have to face when you get pregnant and there is nothing you can do (short of IVF with preimplantation genetic diagnosis) to get around those odds. But despite those high risks, the odds are still higher that you would have a chromosomally normal baby if you do conceive. Best wishes! Dr T
At Wed Dec 17, 07:29:00 PM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

To Lori Oct 28: Hi. I am sorry for my delayed response but I just got your comment in my mailbox this week. I am not sure what to advise in your case. MTHFR polymorphisms alone are usually not the cause of recurrent early miscarriages. Howeevr, we have found in our own practice that women with subclinical endometriosis may be at risk for RPL. At your age,before moving to IVF/PGD (which is extremely expensive and I am not sure justified in your case yet), I would go the 'full court press' empiric therapy route (assuming other major causes of RPL have been ruled out). Start high dose folic acid and a baby aspirin before attempting conception. Begin progesterone support and lovenox in mid luteal phase (I am assuming you are having regular menstrual cycles and have had no trouble actually conceiving). If that did not work, consider taking 3-6 months of Lupron and then undergoing ovulation induction with the same empiric regimen mentioned above. Best wishes and let us know what finally works. The odds are in your favor that something will. Dr T
At Thu Jan 01, 02:30:00 PM 2009, Mary said…

Hi Doc,
I am so happy I found this post! I am 35 years old have a very happy healty 3 year old. My problems started with the next one, My husband and I have been trying for 2 years to get pregant, I cant count the number of chemical pregnancys I have had... I finally got pregnant in Feb of 08 had a bleed at 10 weeks with no cramping but it turned out to be nothing, then had the N/trans test done showing a nacula fold of 2.7 with my age 35 they sugested I have an amnio. So I did at 15 weeks, it went well got my results back 4 weeks later, they were all fine. I still went on to mc at 21.5 weeks baby Violet died in my arms my Husband and I were devastated that happened in May of 08. I took about a month to stop bleeding and heal. I went on to start trying again in Aug had 2 more chemical pregnancys before falling pregnant in October, I felt like all was going to be fine wasnt worried and I knew it was going to be a boy from the start. Well few days ago I started to have a clearish sometimes yellow very strechy discharge, no smell. It lasted for about 3 days and got heavier not enough to soak my undies though. Then I woke up on the Dec 29 with some cramping was very worried so I called my gyne he said to wait and see what happens becasue Im only 10.6 weeks along, so I wait and they schedule my with an ultra sound first thing next morning. Mean while later that night I started to bleed a bit and I thought for sure it was over, thats was the start and It was over.... I went for the ultra sound with out any hopes. I went in and to mine and my husbands amazment he was in there all was fine the cervics look good and heart beat was strong no leaks or clots showed up so I was excited went home and rested bleeding stoped around 12 noon and cramps subsided a bit. I thought all was going to be well if I just rested.. So I did all day. Later in the day the cramps stared again and got bad enough that I needed some relife I also had the most putrid smelling gas to go along with all of this. No runny stools they were solid. I called my Gyne he said I could take a ponado( same as tylonal) and I also took a charcol tablet to absord the gas it worked cramps stoped and so did the gas. Went to sleep woke up to go and check on my daughter around midnite. Looked on my pad to make sure there was still no blood but to my surprise I was bleeding again, cramps started right up and got pretty hectic I took another ponado and tried to sleep hoping that all would be well, it wasnt I wound up in the emergency room with no pain med except pethadine I misscarried at 10 am yesterday morning. They kept me in for the night giving me a D&C later that day..... Sorry this is so long but I want you to to have all the facts.
Before my last m/c I had all of my blood work done to see if anything was wrong. Histologically I am fine except for a melthy folate reductose problem but my homosystine levels are all fine so they said not to worry because its only on one copy..... So then we went on and had my Husbands and my chromosomes checked they also all came back fine. After my first still born at 21.5 weeks I went again and had all my blood work done and all is still fine even went to see a high risk docter for a second oppinion still all was fine. I think the amnio caused the first m/c.10 minutes before she was born her heart was still beating it was 107 which is distressed I know but was still beating in anycase. The woman who did the n/trans fold test also did the amnio, when I calld her to tell her what happened she went back and chaulked it up to some kind of a heart defect and not to the amnio..... But upon doing my reasearch I found thats m/c have been documented up to 18 weeks after an amnio has been done I figure she didnt want me to ruin her stats... So I think it was the amnio but any way the other thing is a few days prior to each m/c I gave in to my husbands desires and we had sex could that also be a possiblilty somthing to do with his sperm and my cervics... I dont know but I am desperate to find some kind of an answer. Is my body rejecting the pergancys because I also know that this one was alive as well I saw it swimming around in bliss the day before...I am now thinking I will go the fertilty rout as something has to be a miss. Or do you think Im just having bad luck? Sorry for my english it is not the best. Please give me your opinion soonest.
Kind regards,
Mary
At Mon Mar 23, 10:44:00 AM 2009, Anonymous said…

Hi Dr. Trotter,

I posted back in March 2008 after I lost a baby with Downs Syndrome at 18 weeks. Prior to that I had an early miscarriage and was told it was a blighted Ovum. Last month I lost another baby at 14 weeks and was told she had Turner's Syndrome. I am 40 and know my age is really against me so we are not going to try again. I have been told T21 and Turners are not related in any way, but I can't help but wonder if this is really just my bad luck or if we have an issue. I have a 6 year old daughter and am wondering if we should go through genetic testing to see if my husband and I have something that we could have possibly passed down to her? I don't want her to suffer losses like I have. I guess it would just be easier for me to understand the loss if there was a medical reason and not just bad luck.
At Sat Apr 25, 10:40:00 PM 2009, Anonymous said…

hi dr.t i just found ur blog and am grateful i just have one question. what are the odds of having a blighted ovum more than once? thanks tamara
At Wed May 06, 12:57:00 PM 2009, Rosie said…

My husband and I have been TTC since I was 34.5 yrs of age. I am now 37.5 yrs old. During these past few years, I have had 4 natural pregnancies. First: no Hearbeat at 11.4 weeks, had a D&C, path report and chromosome tests showed normal female karyotype so I still don't know why the first pregnancy failed. Second: miscarried naturally at 5 weeks for blighted ovum. Third: no heartbeat at 10.5 weeks, had a D&C, tests showed Turner Syndrome. Fourth: carried to 18 weeks, opted for 2nd trimester termination with D&E as amnio showed Trisomy 21.

For the first, second and third pregnancies, the team of docs I was seeing seemed to think that I have no trouble getting pregnant naturally, but just couldn't hold on to a pregnancy after the first trimester. That theory is now incorrect since I was able to carry my fourth pregnancy to the second trimester (and maybe to full term if I hadnt decided to terminate).

First and second pregnancy, I was only taking PNV. Third pregnancy, they put me on PNV+Folate+prometrium+Baby ASA. Fourth pregnancy, they put me on PNV+Folate+compounded progesterone suppositories+Baby ASA+Lovenox+Prednisone

We (my husband and I) have had genetic testing (we have no family history of any genetic problems), DQ alpha tests, chromosome analysis, compatability blood tests, semen analysis, hysterosalpingogram, endometrial biopsy, immunology testing for Natural Killer cells, endocrinology testing for hormonal problems (Fsh, Lh, testosterone, PCOS workup, Tsh, etc....), rheumatological tests (ANA, anticardiolipin antibody, antiphospholipid AB, lupus workup, etc....). ALL THE TESTS CAME BACK NORMAL.

I use to live in Virginia and just moved to California. During these years, I have seen 1 genetics doctor, 2 rheumatologists, 2 perinatologists, 5 OB's, 5 RE's! Why? Because I needed to gather all my info and get different opinions to see what's wrong with me. My question is this: should I give up, or could I be a candidate for IVF+PGD? Is their any hope for me?
At Wed May 27, 02:27:00 PM 2009, Rose said…

My husband and I have been TTC since I was 34.5 yrs of age. I am now 37.5 yrs old. During these past few years, I have had 4 natural pregnancies. First: no Hearbeat at 11.4 weeks, had a D&C, path report and chromosome tests showed normal female karyotype so I still don't know why the first pregnancy failed. Second: miscarried naturally at 5 weeks for blighted ovum. Third: no heartbeat at 10.5 weeks, had a D&C, tests showed Turner Syndrome. Fourth: carried to 18 weeks, opted for 2nd trimester termination with D&E as amnio showed Trisomy 21.

For the first, second and third pregnancies, the team of docs I was seeing seemed to think that I have no trouble getting pregnant naturally, but just couldn't hold on to a pregnancy after the first trimester. That theory is now incorrect since I was able to carry my fourth pregnancy to the second trimester (and maybe to full term if I hadnt decided to terminate).

First and second pregnancy, I was only taking PNV. Third pregnancy, they put me on PNV+Folate+prometrium+Baby ASA. Fourth pregnancy, they put me on PNV+Folate+compounded progesterone suppositories+Baby ASA+Lovenox+Prednisone

We (my husband and I) have had genetic testing (we have no family history of any genetic problems), DQ alpha tests, chromosome analysis, compatability blood tests, semen analysis, hysterosalpingogram, endometrial biopsy, immunology testing for Natural Killer cells, endocrinology testing for hormonal problems (Fsh, Lh, testosterone, PCOS workup, Tsh, etc....), rheumatological tests (ANA, anticardiolipin antibody, antiphospholipid AB, lupus workup, etc....). ALL THE TESTS CAME BACK NORMAL.

I use to live in Virginia and just moved to California. During these years, I have seen 1 genetics doctor, 2 rheumatologists, 2 perinatologists, 5 OB's, 5 RE's! Why? Because I needed to gather all my info and get different opinions to see what's wrong with me. My question is this: do you think it's time for me to move on to IVF with PGD, or should I try naturally again?
Thanks,
Rose
At Sat Jun 27, 08:24:00 PM 2009, Anonymous said…

Dear Dr. Trofatter -- I'm so glad that I found your website. Thanks so much for the explanation about recurrent pregnancy loss...I am 41 years old and understand that my age is against me. In addition to my age alone, I had two missed abortions (trisomy 4 & 9) in the past six months. My ob told me that these numerical chromosomal abnormalities indicated that there were nothing genetic wrong with either my husband or me, and we just had bad luck. He doesn't think we need to see a RE. Instead he said we should just keep on trying.
I know time is running out for me. What are our options? Should we keep trying or should we try IVF with PGD?
Sincerely
Grace
At Thu Jul 02, 07:39:00 AM 2009, Kenneth F. Trofatter, Jr., MD, PhD said…

To Grace: Time is certainly NOT on your side. I think you should seek out an REI who can discuss your options and cater a care plan to your budget. The procedures you refer to are extremely expensive but they might be the most efficient way to improve your prospects for a healthy pregnancy. Thanks for writing and best of luck.
Dr T

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Recurrent Early Pregnancy Loss - 3 - Chromosomal Causes

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