Abnormal Sperm Morphology and Recurrent Pregnancy Loss?
Sunday, February 03, 2008
Kenneth F. Trofatter, Jr., MD, PhD
Posted by Concerned_in_Canada to Fruit of the Womb at Thu Jan 31, 11:59:00 AM 2008 "Early Pregnancy Loss - 2":
This is a great thread! Anyway, I have a question regarding recurrent miscarriage and sperm quality. I'm currently facing my third miscarriage in 8 months.(I'm having an ultrasound tomorrow to confirm things...HCG wasn't doubling, now it is but still not looking too good) Anyway, I'm 33 and had my first loss in June 2007 at 6 1/2 weeks, the cause unknown as they don't test first pregnancies. The second was in September at 7 weeks and turned up as a trisomy. Now I'm pregnant again, the levels have been rising but slowly, they've picked up the last few days to double correctly but considering my history I'm not holding my breath for a good result. So, considering we keep getting told by doctors that they are 'sporadic' and 'bad luck' I'm concerned there is more to these chromosomal problems than just chance. We have both had the karyotype testing and all is fine, however my husband has terrible quality sperm with extremely low morphology. His DNA fragmentation is fair. Why with such deformed sperm are our doctors not taking the chromosomal abnormalities more seriously? Can poor morphology increase the risk of miscarriage?
Sorry for the long post...but it’s been a frustrating few months and I'm really starting to lose hope for a healthy pregnancy.
To Concerned in Canada: I thought this was an excellent question and quite frankly I did not have a ready answer. I am not a specialist in Reproductive Endocrinology and even less of one in evaluation of infertility from the male factor (andrology) side of things. The obvious situation in which the male can contribute to recurrent early pregnancy loss is when he is the carrier of a balanced chromosomal rearrangement, such as a Robertsonian translocation, in which he has the correct total amount of genetic material but has a high risk of making sperm that have an incorrect amount and we have discussed this situation in previous posts. Too much or too little genetic material usually results in early miscarriage. We also know that males, who have low sperm counts or very high percentages of abnormal-appearing sperm, have lower chances for achieving conception with their partners. However, our reader asks the question, does the male who is chromosomally normal, but has a high percentage of abnormal-appearing sperm, also contribute to a higher rate of miscarriage in his partner once conception has occurred?
Although the medical literature has supported mixed opinions on this subject over the years, a recent review by Puscheck and Jeyendran (Curr Opin Obstet Gynecol 2007;19:222-28) suggests that “the male contributes to recurrent pregnancy loss due to genetic factors, semen factors, or due to other factors such as age” and sperm morphology may reflect these underlying deleterious conditions. In 1991, Kobayashi and colleagues (Hum Reprod 1991;6:983-6) demonstrated in in vitro fertilization cycles that low percentages of normal sperm morphology were associated not only with lower successful fertilization rates and pregnancy rates per cycle, but also with a greater risk for miscarriages even if embryo transfer was successful.
Egozcue and colleagues (Hum Reprod Update 2000;6:93-105) reported that among infertile couples in which the males were chromosomally normal and there was no identifiable source of infertility in the females, there were greater frequencies of chromosomally abnormal sperm produced by the males as the result of ‘meiotic disorders’ – meiosis being the final stage of sperm production in which the normal chromosomal complement of 46 (23 pairs) is supposed to be halved to just 23 different chromosomes. Among these males they found a greater percentage of sperm with two copies (or none) of single chromosomes, such as chromosome 21 or other autosomes (non-sex chromosomes), two copies (or none) of sex chromosomes (rather than just one X or Y), and sperm that were still diploid, containing 46 chromosomes rather than 23. Obviously, under any of these circumstances, if these abnormal sperm got together with an egg that had a normal number of 23 chromosomes, the resulting baby would end up with too many or too few and the likelihood of miscarriage in early pregnancy would be high.
The results and conclusions of this study were supported by Carrell and colleagues (Obstet Gynecol 2003;101:1229-35) who found the sperm aneuploidy (chromosomal abnormalities) rate in couples with recurrent pregnancy loss to be about twice that of the general population and this was accompanied by diminished percentages of sperm with normal morphology. Similarly, Bernadini and colleagues (Reprod Biomed Online 2004;9:312-20) reported that among men with recurrent pregnancy loss and poor semen quality, elevated frequencies of sperm aneuploidy were found in about 10% of these men who had, individually, sperm aneuploidy rates between 30-34%. In some instances, the high aneuploidy rate may be related to mosaicism (separate populations of cells, one chromosomally normal and the other chromosomally abnormal) that is confined to the germ lines (sperm-producing cells) in the testes (Somprasit, et al., Reprod Biomed Online 2004;9:225-30). Such individuals would appear to be ‘chromosomally normal’ except where it counts!
In addition to sperm aneuploidy, other parameters of sperm evaluation, DNA fragmentation and high DNA stainability, have also been correlated with both abnormal sperm morphology and recurrent pregnancy loss. Carrell and colleagues (Arch Androl 2003;49:49-55) found higher rates of sperm DNA fragmentation in couples with recurrent early pregnancy loss following spontaneous conception. Similarly, Borini and colleagues (Hum Reprod 2006;21:2876-81) found higher early pregnancy loss rates in couples undergoing assisted reproductive technologies, both by in vitro fertilization (IVF) and by conception with intracytoplasmic sperm injection (ICSI) when high sperm DNA fragmentation and abnormal morphology were present. In a very recent (as yet unpublished) study by Lin and colleagues (Fertil Steril abstract online September 2007), abnormalities of sperm DNA structure, high DNA fragmentation and high DNA stainability (HDS), were not correlated with IVF or ICSI fertilization rates, ‘good embryo’ rates or pregnancy rates, but did appear to be correlated higher postimplantation spontaneous abortion rates.
So, in conclusion and in response to our reader’s question, there is evidence to support the premise that in couples with recurrent early pregnancy loss, abnormalities of sperm morphology can reflect underlying abnormalities of chromosome number and DNA structure that may subsequently increase the risk of early miscarriage even after successful conception, spontaneous and assisted. What to do about that is truly outside my realm of expertise, but can probably be addressed by an REI or Andrology specialist! Thanks again for a great question and best of luck to you…
Dr T
Labels: aneuploidy, recurrent pregnancy loss, sperm morphology
16 Comments:
At Mon Feb 04, 08:21:00 AM 2008,
Anonymous said…
Out of curiosity... is it typical to be able to diagnose a trisomy at 7 weeks as this reader indicates was done with her? When I had early losses, I was told that genetic testing would be difficult and likely inconclusive. Is this done via a D&C? Thanks.
At Tue Feb 05, 04:50:00 AM 2008,
Concerned_in_Canada said…
kThank you for the great answer Dr T, this website truly is a life saver!
At Tue Feb 05, 09:53:00 PM 2008,
Aziza said…
Hello Doctor, Well I am currently recovering from my 4th misscarriage. I believe one was a blighted ovum, one was very early immediately after preg test, the next 7 or 8 weeks and the last 9weeks. after the the third I had a work up and I was told it was some kind of vitamin defiency. I cant remember but I think I took a vitamin B supplement.I have taken clomid to conceive. one the misscariages was after taking clomid by they way I have had two very healthy twin pregnancy that went to 34 and 36weeks all 4 children are healthy. Whats going on we want to try one more w/o clomid. Do have an idea of what defientcy I may have had? Thanks
Aziza
At Wed Feb 06, 05:10:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To anonymous Feb 4: Yes, that would have required chromosome studies on products of conception obtained at the time of D&C. Dr T
At Wed Feb 06, 05:12:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To concerned in canada: You're welcome! It's readers like you who ask great questions that make this site worth reading and fun to write for! Dr T
At Wed Feb 06, 05:13:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To Aziza: Sorry, without more information I cannot tell you. BUT, whatever they did (including the clomid) worked, so stick with these doctors and their treatment plans for you! Dr T
At Thu Feb 14, 03:58:00 PM 2008,
Just a girl in the south said…
Hi Dr. T, I am currently 10w pregnant (4th pregnancy) and have suffered three first trimester losses. The third was the only one on which we had testing done, and a diagnosis of trisomy 16 was determined after the d&c. There is a slight assumption that the other two losses were also chromosomally related, but obvsiouly, no testing was done. My question is regarding this fourth pregnancy. What are the chances that there is another chromosomal abnormality with this one as well? We are worried that with the meds I'm on (progesterone, lovenox, extra folic acid) the miscarriage wouldn't just happen spontaneously early on and we could potentially end up with a chromosomal abnormality later on (in 2nd or 3rd tri) that is also not compatible with life. In addition, what is the prognosis for any future pregnancies? Just as an aside, I did take clomid to get pregnant (three times). Thank you. I have found this site to be VERY helpful!
At Fri Feb 15, 10:23:00 AM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To Just a Girl...: I am sure your doctors will follow the viability of the baby very carefully, so the meds should not be an issue. Have either you or your spouse had chromosme studies done to see if one of you is a 'balanced translocation' carrier? If that was the case, then the chance of another conception of a chromosomally abnormal baby is much higher. You already have gotten to a major 'milestone' in this pregnancy, so the risk of aneuploidy goes way down. Some genetic counselors will tell any woman who has had an aneuploid pregnancy documented that the risk of another is a high as 1% but the reasons for that are not entirely clear to me. Anyway, good luck this time and please let us know how things turn out. Dr T
At Sun Feb 17, 08:23:00 PM 2008,
seri said…
I read your answers to du positive blood type..I was 18 and gave blood and was informed I was O pos du positive. I was not sexually active and of course never pregnant and I am white. My Dad was O pos. and Mom was A pos. How can that be... I have never had a blood transfussion, but my husband and daughter has HHT and has required blood.. Should I or we be concerned about transfussions...
At Fri Feb 29, 06:49:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To Seri Feb 17: Given your parents blood types, there is no reason you couldn't have the blood type you were born with. One (at least) of your Rh-positive parents is Du-positive and you simply inherited that. As far as the HHT (hereditary hemorrhagic telangiectasia) in your daughter and husband is concerned, that does not put you at any risk for needing blood transfusions. Your daughter got that only from your husnabd and not from you. It is inherited in an autosomal dominat pattern, i.e., requires only one dose of a bad gene to be expressed. Your daughter needs to be concrened if she gets pregnant, but maybe we can cross that bridge when she comes to it! Thanks for writing. Dr T
At Thu Apr 10, 08:31:00 AM 2008,
Anonymous said…
ANOTHER MORPHOLOGY QUESTION
Hello Doctor !
I have had a number of sperm analyses done over the past year.
The numbers ( volume / count / motility ) are fine apart from morphology which is terrible.
At first it came back at 10% on the Kruger scale which I was assured was not much to worry about (given that 15% good is ok) esp as my count was quite high (over 100million per ml).
A month later it was 8%; then a month later down to 5%.
All of the analyses since then have remained at 5% - apart from one disastrous one which came in at 1% - followed by a sample 3 days later which again came back at 5%.
To me it seems that there is an enormous difference between 10 and 5 %: it is not just a 5% difference it is a 50% drop in good morphology numbers over a period of 3 months.
Ultrasound has detected no varicocele; blood /thyroid tests are normal.
I am doing all the recommended things. Cut down on caffeine and cut alcohol out altogether.
One odd thing is that the best count - 10% - was before I started the no drinking regime.
But I am really puzzled by the variation: a] between 10% and 5% over a short time; and b] between 1% and 5% over a three day period between the last two tests - when we are told the sperm take 3 months to develop - how could there be such a large difference over 3 days ?
So I would appreciate if you could comment on what seems to me a mystery; and also what you think are the chances for IUI or ICSI ?
At Tue Apr 15, 05:05:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To anonymous Apr 10: I appreciate your reading and the questions, but I have never been shy to admit when I am 'outside my realm of expertise' and I certainly am in your case! These are all issues that need to be addressed with a urologist, reproductive endocrinologist, or andrologist who specializes in this area. I do believe that IUI, IVF, or ICSI will be your best bet under these circumstances, but why the variation?, I haven't a clue! Good luck to you! Dr T
At Wed May 07, 07:28:00 AM 2008,
Anonymous said…
My husband has a high morphology. I've been reading that Vitamin C might help in sperm production, however my husband also is a super kidney stone producer and was told to go easy on the Vitamin C. Could his kidney stone production be a reason for his abnormal morphology?
At Fri May 09, 07:15:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To anonymous May 7: I am not aware of any association between kidney stones and abnormal sperm morphology. Perhaps a better question to ask (and for which I do not have an answer because I do not know why he has his kidney problems) is could there be an association between the cause of his kidney stones and the abnormal morphology? Dr T
At Wed May 14, 04:26:00 PM 2008,
Anonymous said…
[Sorry I had posted the wrong email address - this is the corrected post]
I would love to get in touch with the Anonymous poster from April 10 above. I am struggling with similar issues - high sperm count w/lower % of normal sperm, and partner has miscarried 3 times.
My count was well over 150M, with only 5% being normal, so about 8M normal sperm. A second test 2 months later revealed a count of 110M with 3% normal, so only about 3M normal.
Internet research shows that normal sperm count should be 20M w/60% normal or 40M w/30% normal..each number yields about 12M normal sperm.
Although I have more sperm than the average, I have less normal sperm, and this may be causing my partner's miscarriages.
You can email me at fertilityquestion@yahoo.com if you want to discuss further off list. Thanks.
At Fri May 16, 02:56:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To anonymous May 14: Sorry, but I have no way to put you intouch with someone else who left a comment. Privacy issues. All you can hope for is that they return to the site and see your comment!
Dr T
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