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