Is it time to reconsider how sperm morphology is reported?

Consider This

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Authors:

Kristin Van Heertum, M.D., Anupama Kotha, M.D., Mabel Lee, B.A., Sara Maskal, B.S., Gretchen Collins, M.D., Kiranpreet Khurana, M.D., Rachel Weinerman, M.D., Brooke Rossi, M.D., James Liu, M.D., James Goldfarb, M.D.,

Division of Reproductive Endocrinology & Infertility, University Hospitals Cleveland Medical Center Department of Ob/Gyn, MetroHealth Case Western Reserve University School of Medicine Department of Urology, University Hospitals Cleveland Medical Center

Consider This:

Most, if not all, fertility specialists can say that they have had patients referred to them because of an isolated abnormal morphology on semen analysis. We, as likely with other programs, have found men referred for isolated low morphology to be greatly stressed needlessly. As one of many examples, we recently saw a couple who had been trying to achieve pregnancy for over 6 months.  Their generalist OB/GYN appropriately obtained a semen analysis that was normal except for a morphology of 3%.  The generalist told him he needed to see an infertility specialist because 97% of his sperm are abnormal. The husband had been having some sexual dysfunction especially with timing intercourse.   After hearing that 97% of his sperm were abnormally shaped, he was not able to have intercourse at all.  We have also seen similar reactions even when men’s morphology was “normal”.  It is often hard to convince men that having 95% of their sperm being abnormally shaped is acceptable.  How would any of us feel if we were told that 95% of any part of us is not normal?

  Not only can this can be incredibly anxiety provoking for patients but it may generate further healthcare cost for a likely unindicated referral to a male reproductive specialist. Isolated low sperm morphology does not appear to provide significant information in the clinical evaluation of infertility. However, we have found that despite trying to address this issue with non-fertility specialists, they continue to be overly concerned by such results and convey this concern to their patients.  With the adoption of the strict Kruger criteria into the 2010 WHO semen analysis reference values (1), more men are considered to fall into the category of having “abnormal” morphology. However, one has to wonder what is the clinical value of having a cutoff as low as 4%?  Assuming other parameters are normal, is there clinical value in knowing the normal morphology is 5% rather than 3% particularly when this assessment is often subjective and inconsistent?  A recent study examining morphology assessment techniques in France found a wide variety of assessment tools being used, often with no quality control measures and many clinicians readily admitting they do not trust or rely on the results (2) It has been purported that a major advantage of the strict Kruger criteria for sperm morphology may be to guide determining  the mode of insemination to use in IVF (3). However, there is insufficient data to show that it predicts efficacy in patients not undergoing IVF (4-7). Furthermore, with the increasing use of PGS and the prevalence of the diagnoses of unexplained and male factor infertility, many fertility programs are preferentially, if not exclusively, using ICSI in their IVF cycles. To further explore this issue, we looked at the last 252 couples going through IVF at our institution. Of 76 cycles with male factor infertility, 8% had normal morphology by the strict Kruger criteria.  Nineteen per cent of those with presumed non-male factor infertility or those undergoing PGD/PGS had normal morphology.   Thus while the group with male factor had a significantly lower chance of normal morphology ( p<0.05), a significant majority of men presumably without male factor had abnormal morphology.  Similarly median percentage of normal morphology was significantly less in the male factor group 1%, vs. 2.15% in the presumed non-male factor group (p < 0.01). However, the median motility in the presumed non male factor group was below the normal value. These findings underline the fact that many men (in this case a large majority) without apparent male factor infertility have “abnormal” morphology.  In 2014, Kashanian and Brannigan proposed that sperm morphology may be a “surrogate marker” for sperm function (8). This may indeed be the case, though no further evidence has arisen which points to an additional clinical use for sperm morphology. In fact, there have been several  studies over the years that show morphology to not be predictive of IUI outcomes (4-7). Given all the factors discussed above, many fertility specialists tend to dismiss the morphologic assessments reported on semen analyses or at least feel it is of limited clinical value. The American Urological Association has issued a statement that sperm morphology by the strict criteria has not been shown to be consistently predictive of fecundity and should not be used in isolation to make prognostic or therapeutic decisions. (9)  Based on the limited usefulness of the current reporting of morphology  and the significant stress the current reporting system causes patients, it seems it is time to reconsider how sperm morphology is reported.

References:

1. Cooper TG, Noonan E, von Eckardstein S, Auger J, Baker HWG, Behre HM, et al. World Health Organization reference values for human semen characteristics. Hum Reprod Update 2009;16(3):231–45.  2. Gatimel N, Mansoux L, Moreau J, Parinaud J, L??andri RD. Continued existence of significant disparities in the technical practices of sperm morphology assessment and the clinical implications: results of a French questionnaire. Fertil Steril 2017;107(2):365–372.e3.  3. Lundin K, Söderlund B, Hamberger L. The relationship between sperm morphology and rates of fertilization, pregnancy and spontaneous abortion in an in-vitro fertilization/intracytoplasmic sperm injection programme. Hum Reprod 1997;12(12):2676–81.  4.  Karabinus DS, Gelety TJ. The impact of sperm morphology evaluated by strict criteria on intrauterine insemination success. Fertil Steril 1997 67 536-41. 5. Sun y, Li B, Zhu WB, Feng GH, Yang CL, Zhang YH. Does sperm morphology affect the outcome of intrauterine insemination in patients with normal sperm concentration and motility? Andrologia 2012, 44 299-304. 6. Deveneau NE, Sinno O, Krauseb M, Eastwood D, Sandlow JL, Robb P, et al. The impact of sperm morphology on he likelihood of pregnancy following intra uterine insemination.  Fertil Steril 2014, 102: 1584-90 7. Lemmens L, Kos S, Beijer C, Brinkman JW, van der Horst FAL, van den Hoven L, et al. Predictive value of sperm morphology and progressively motile sperm count for pregnancy outcomes in intrauterine insemination. Fertil Steril 2016;105(6):1462–8.  8.        Kashanian JA, Brannigan RE. Sperm morphology and reproductive outcomes: A perplexing relationship. Fertil Steril 2014;102(6):1561–2.  9. The Optimal Evaluation of the Infertile Male: AUA Best Practice Statement. United States: American Urological Association; 2010. 

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Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders. The journal publishes juried original scientific articles in clinical and laboratory research relevant to reproductive endocrinology, urology, andrology, physiology, immunology, genetics, contraception, and menopause. Fertility and Sterility® encourages and supports meaningful basic and clinical research, and facilitates and promotes excellence in professional education, in the field of reproductive medicine.

2 Comments

Go to the profile of Ranjith Ramasamy
Ranjith Ramasamy about 1 year ago

I love the argument the authors present on sperm morphology. I think rather than try to change the way the morphology is reported, we need to learn how to interpret it. To tell a couple they "cannot conceive naturally" because they have 0% strict morphology is incorrect. We published a recent meta analysis showing that IUI pregnancy outcomes are similar even in men with abnormal sperm morphology (PMID: 29129781).

Go to the profile of Craig Niederberger
Craig Niederberger about 1 year ago

This is a really important argument. With the exception of azoospermia, the bulk semen analysis has never proven to be particularly predictive of male reproductive potential. It's time that we find new ways to interrogate sperm.