Sperm Morphology

Sperm Morphology

Morphology refers to the number of sperm that have perfectly normal shapes. In my experience, the morphology reading is the one semen analysis parameter that generates the most confusion among clinicians and anxiety among couples. Most of the time this concern is not warranted, as among the three most significant parameters (density, motility, and morphology), morphology is arguably the least important in terms of determining a man’s overall fertility potential.  However, sperm morphology should not be completely ignored, and efforts to improve the percent of normal shapes as much as possible is recommended.

 

HOW IS THE MORPHOLOGY READING DETERMINED?

Morphology evaluations take into consideration multiple aspects of a sperm’s shape, including its head, midpiece, tail, and the presence of cytoplasmic droplets. Abnormal sperm morphology is called teratospermia. Typically, a lab will evaluate 200 sperm in a specimen and determine what percentage of these sperm have perfectly normal shapes. Some labs just report the percentage of sperm with normal shapes, while others will then break down the reasons why the other sperm were abnormal. An example could look like this:

 

            Normal sperm                        5%

            Head defects                           90%

            Midpiece defects                    2%

            Tail defects                             2%

            Cytoplasmic droplets             1%

 

Morphology readings are highly subjective and rely upon the training and experience of the person performing the evaluation. I therefore typically only take into consideration the morphology findings from fertility-specific laboratories (not hospital-based labs).

 

MORPHOLOGY CRITERIA

There are several types of guidelines that you may see used for sperm morphology on a semen analysis report, and the report will generally state which of these criteria they are using. The two most commonly used are the World Health Organization guidelines (third edition) and the Kruger strict criteria.  You may also see a reference to the fifth edition of the WHO guidelines, which are essentially the same as the Kruger strict criteria.

 

Kruger Strict Criteria

The most clinically useful morphology criteria is the Kruger “Strict” morphology (which as mentioned above, is the same as the WHO 5th edition criteria).  The Kruger criteria were developed in 1986 by a physician named Thinus Kruger and were based upon the evaluation of sperm that had successfully migrated to the cervix following natural intercourse. The original 1986 guidelines used a figure of 14 percent or greater normal forms as the cutoff for “normal” morphology. However, the strictness of the guidelines has changed over the years. 

Most fertility-specific labs now use 4 percent or more as their definition of “normal” (as do the latest WHO guidelines), but you will still find some that report the old Strict criteria cut-off  (14%) or some other normal level (e.g. 8%).  I personally use the 4 percent figure as the lower limit of “normal,” although some of the labs in my area still print the higher 14 percent guideline on their official semen analysis reports (a source of endless confusion and anxiety for my patients).  I also rarely see Strict morphology readings higher than 10%, so as long as I can get a man’s Strict morphology to 4% or above, then I am satisfied with this.

Note: If the Strict morphology is "0%", this does not usually mean that there are absolutely no sperm with a normal morphology.  Rather this means that less than 1% of the sperm have completely normal shapes.

 

World Health Organization Guidelines

Since 1980, the World Health Organization (WHO) has issued guidelines for what it considered “normal” semen morphologies.  Over the decades, the criteria for what the WHO considers normal has gotten progressively more rigorous.

 

             WHO Edition                           Normal Morphology Range

         1st Edition (1980)                                       80.5%

         2nd Edition (1987)                                      50%

         3rd Edition (1992)                                       30%

         4th Edition (1999)                                       14%

         5th Edition (2010)                                        4%

 

Starting with the 4th edition, the WHO criteria mimicked the Kruger Strict morphology definition of normal being ≤ 14%.  In 2010, the 5th edition again changed in step with the Kruger criteria by defining normal as ≤ 4%.  In terms of clinical utility, I feel that the WHO 5th edition has the most relevance to fertility outcomes.  Many labs still use the WHO 3rd edition (normal ≤ 30%) but I do not find their use particularly meaningful in helping determine a man’s fertility potential.

 

Other Morphology Criteria

There are some other morphology criteria that you may occasionally see used by hospital labs, such as the ASCP (American Society of Clinical Pathology) guidelines. I have not found these to be useful and recommend that these men get repeat testing at a fertility-specific lab that can provide a more accurate strict morphology evaluation.

 

Considerations to Keep in Mind When Looking at Sperm Morphology

I recommend checking sperm morphology during semen analysis testing in couples having fertility problems, but I always like to keep in mind that there are some inherent problems with the testing and interpretation of sperm morphology.

1) Differences in Preparation and Criteria of Evaluation

For many years, wide variations existed in how slides were prepared and stained in the lab for evaluating sperm morphology.  As described above, the criteria for what is considered “normal” have also changed considerably over the years.  Most fertility-specific labs have recently tried to take a more uniform and standardized approach to sperm morphology evaluations, but significant variations still exist.  I always like to keep this in mind as I see morphology results from different labs, as well as when I read scientific research articles from around the world which try to evaluate the clinical implications of sperm morphology abnormalities.

2) Subjective Nature of the Evaluation

Counting sperm numbers and calculating what percentage of them are swimming is a fairly straightforward endeavor for trained lab personnel.  However, accurately evaluating sperm shapes on a wide range of very stringent morphological criteria is a much more difficult task.  Different lab technicians often read the same morphology slides very differently.  Wide ranges of inter-lab and intra-lab variations have consistently been found by studies looking at the ability of lab technicians to accurately and consistently evaluate sperm morphology slides.  A nice 2017 review article by N. Gatimel et al. in the journal Andrology found that when lab technicians were shown standardized slides for reading, the degree of variation of their findings (called CV, or coefficient of variation) was 19.2% for sperm counts, and 15.1% for sperm motility.  However, for sperm morphology, the CV was a considerably higher 80%.  Extra intensive training could bring this variation down, but not below 50%.  Also, the effects of training appeared to dissipate over time.  In one study, if regular follow-up training was not consistently maintained, most lab technicians showed declines in competency after only 6 to 9 months, and only 26% were able to maintain their competency after 40 months.

3) Basic Statistics

There are questions about whether the sample size evaluated for morphology represents a statistically meaningful evaluation of the entire specimen.  Keep in mind that a semen specimen can have more than 100 million sperm in the sample, but typically only 200 of these sperm are evaluated in order to calculate a Kruger strict Morphology. From a basic statistics standpoint, if only 0.0002 percent of the sperm are being evaluated, it’s hard for me to see a significant clinical difference between a sample that shows 5 percent normal forms and one that shows 3 percent normal forms when samples sizes are so small.


CLINICAL IMPACT OF MORPHOLOGY

 

The role of sperm morphology and its impact on male fertility has 2 primary areas of concern:

#1) The concern regarding an increased risk of genetic abnormalities or health problems for subsequent offspring

#2) Its impact on the ability to conceive and maintain a healthy pregnancy

 

[Note: The recommendations made in this section (and whole website) represent the best overall conclusions taking from evaluating the scientific literature as a whole. Studies can be found on most any topic in male infertility that contradict the conclusions/recommendations of this website.  This is especially true regarding controversial topics such as sperm morphology, due to the wide range of different criteria that have been used over the years, as well as the large inter-lab variability in the consistency of the reading of slides.  The following recommendations are made on the best available data derived from meta-analyses of these studies as a whole.]

 

Concern of Genetic and/or Health Risks in Future Children

Many couples look at the results of their semen analysis test and see “98% head defects” and panic.  If the sperm DNA is stored in the sperm head, and the vast majority of these sperm heads are abnormal, does using these sperm have a higher chance of passing on potential genetic problems to future children?  Fortunately, the answer to this questions appears to be “No”.

Sperm Aneuploidy

Sperm aneuploidy is a term which describes abnormal levels of chromosomal abnormalities in sperm, and can be evaluated with specialized testing, such as FISH (fluorescent in situ hybridization).  The concern is that if genetically abnormal sperm fertilize an egg, then the resulting embryo (and subsequent child) can have genetic abnormalities as well.  A 2017 review article on morphology in the journal Andrology (N. Gatimel. Andrology 2017, 5: 845-62) found that most studies showed a slightly elevated rate of sperm aneuploidy in men with teratospermia, but this rate was not significantly different than men with only low sperm counts and motility.  In other words, poor semen parameters of any kind were associated with mildly increased rates of sperm aneuploidy, but that abnormal morphology did not represent a higher risk factor than other parameters.  Also, these elevated rates of aneuploidy were only seen in ejaculated sperm, but did not appear to persist after egg fertilization.  It is known that the unfertilized egg has very efficient screening mechanisms for weeding out defective sperm and preferentially letting normal sperm through its outer layers to start the fertilization process. Also, nature seems to be very efficient at identifying embryos that do have genetic abnormalities and not allowing them to progress (i.e. resulting in spontaneous early miscarriage). Of course, these mechanisms are not 100 percent efficient, but rates of health problems and birth defects do not seem to be higher in the children of men with lower morphology readings, whether the pregnancy was established by natural intercourse, inseminations, or standard IVF.  There is some concern about whether there is an increased risk of birth defects when using ICSI, since this technique bypasses some of the egg’s natural screening mechanisms. However, nature’s efficiency at removing genetically defective embryos again helps to ensure that the vast majority of ICSI babies are born completely healthy and normal.  Also, when ICSI is used, the lab is usually able to carefully select individual sperm for use that have completely normal shapes. Therefore, it is generally considered that elevated levels of sperm morphology defects are not considered a significant risk factor for having subsequent children with genetic abnormalities, birth defects, or other health problems.  Only a few rare exceptions exist to this general rule, such as in men with Macrocephalic Sperm Syndrome (see the “Rare Sperm Morphologic Abnormalities”section below).

 

Sperm DNA Fragmentation

Elevated levels of sperm DNA fragmentation (DFI) have been associated with decreased fertility as well as increased rates of pregnancy loss.  Elevated levels of DFI are not generally felt to increase the risk of genetic and/or health problems in subsequent offspring.  The majority of studies have shown that abnormal sperm morphology has no significant correlation with elevated levels of sperm DNA fragmentation.

 

Impact of Morphology of Fertility and Fertility Treatment Outcomes

Concerns have been raised as to the extent to which elevated levels of sperm morphologic abnormalities can decrease a couple’s chances of conception.  Various hypotheses have been proposed as to how sperm morphology could potentially impact fertility.  Some studies have raised concerns that morphologic defects could lead to impaired sperm passage through the cervical mucus, while others have suggested decreased binding to the egg zona pellucida during egg fertilization.  However, these findings are controversial, and the exact mechanism of morphologic defects leading to reduced fertility is not known.  More concrete (though still controversial) data is available on the degree to which morphology plays a role in fertility outcomes based on different fertility treatment options utilized by couples.

 

Natural Intercourse

There is no general consensus on the extent to which abnormal sperm morphology can impair fertility with natural intercourse.  However, a review of studies by the University of Miami “suggests that patients with abnormal sperm morphology alone should not be precluded from attempting natural conception before undergoing assisted reproduction.”(Shabtaie SA et al. Curr Urol Rep 2016, 17: 67).  Sperm counts and motility are generally considered to have a much larger impact on natural intercourse success rates, though attempts should be made to optimize sperm morphology as much as possible to optimize the chances of success.

 

Intrauterine Insemination (IUI)

Similar to natural intercourse, sperm counts and motility are generally considered much more important parameters for success than sperm morphology.  Though there is no definitive consensus on this topic, the majority of recent large review studies show that morphology should not preclude the use of IUI so long as the post-wash total motile sperm counts are good (Gatimel N. et al. Andrology 2017, 5: 845-62).  Multiple studies have shown that even with very low sperm morphologies of 0-1%, decent pregnancy rates with IUI can be attained (Lockwood GW et al. Andrology 2015, 5: 1088-93)(Sparks A. et al. ASRM abstract 2003; 80).

 

Standard IVF

Using the original Kruger Strict Criteria (where “normal” was defined as ≥ 14%), studies show that standard IVF had low chances of success when the morphology was 0-4% and normal if the morphology was >14% (with intermediate success for men with morphology readings between 5-14%).  Meta-analysis reviews have shown that most studies show that decreased sperm morphology (<4%) by the Strict criteria have a negative impact on standard IVF outcomes.

 

IVF/ICSI

In theory, ICSI should be able to overcome issues of decreased sperm morphology, since only completely normal sperm can be selected out and used to inject the eggs.  The majority of studies back this view, showing the sperm morphology does not impact either the fertilization or pregnancy rates when ICSI is utilized. 


Rare sperm morphologic abnormalities

 

Globozoospermia

There is a rare type of teratospermia called globozoospermia, in which sperm have small round heads that lack an acrosome cap (which is needed for the sperm to penetrate an egg). A good fertility-specific lab will usually indicate on the semen analysis report if all of the sperm are lacking an acrosome cap.  If all of the sperm are affected, then this is called Total Globozoospermia Syndrome.  The cause of this syndrome is not known but there are felt to be genetic factors involved in some men. Pregnancy rates in patients with globozoospermia are usually quite low, even with the use of IVF/ICSI.  Specialized IVF laboratory techniques, such as assisted oocyte activation (AOA), have been found to potentially improve fertilization rates in some of these cases.

 

Microcephalic Sperm

Microcephalic sperm have head sizes that are <2.5 micrograms in width and <3.5 micrograms in length.  Acrosome abnormalities are common in these sperm.  Microcephalic sperm are associated with elevated levels of sperm DNA fragmentation, and tend to have low fertilization and pregnancy rates, even with the use of ICSI.

 

Pin Head Sperm

Pin head sperm have tails, but no head.  The cause of these are not known.  If used with ICSI, fertilization of the egg can occur, but not embryo progression (i.e. a viable pregnancy cannot be established with the use of these sperm).

 

Macrocephalic Sperm

Macrocephalic sperm have large irregular heads, and often multiple tails (average 3.6 tails per head).  If all of the sperm are affected, this is called Macrocephalic Sperm Syndrome.  Macrocephalic sperm generally have high rates of sperm aneuploidy.  Genetic causes have been identified in some men, as has the use of sulfasalazine for inflammatory bowel disease.  Use of these sperm for ICSI is contraindicated due to the concern of passing on genetic abnormalities to the resulting offspring.


My general overview of the clinical impact of sperm morphology

 

I feel that the Kruger strict morphology (which is the same as the WHO 5th edition criteria) can have an impact on fertility outcomes.  Other forms of morphology (e.g. ASCP and WHO 3rd edition) do not have meaningful clinical correlation and I do not use them in my practice.  In terms of natural intercourse, the strict morphology by itself is a fairly weak predictor of whether a couple will be able to establish a pregnancy.  There is more controversy surrounding the relationship of strict morphology and IUI outcomes, but the general consensus is that the post-wash total motile sperm count is a much more accurate predictor of whether IUI is going to be successful. 

I routinely see couples who have been successful in establishing a pregnancy either naturally or with IUI despite the man having a strict morphology as low as 0 percent normal forms. That being said, I think that for couples having problems conceiving, it is worthwhile to take steps to try to improve the man’s Kruger strict morphology as much as possible.  Some female fertility specialists feel that if their own lab gives a man a very low morphology reading (e.g. ≤2%) then their chances of IUI success is low regardless of sperm counts and motility.  As a general rule, though, if the post wash total motile count is good, then a low morphology should not necessarily preclude a trial of IUI (rather than just jumping straight to IVF/ICSI).  However, in couples undergoing IUI where the man’s morphology is quite low, I recommend that they should consider moving on to IVF after two or three unsuccessful IUI cycles, instead of the usual three to four IUI cycle attempts. 

In terms of IVF, I feel that there is decent data to suggest that if the strict morphology is low (<4%), then the use of ICSI can improve fertility outcomes (though again, this approach is not without controversy).

Just know that these (or really any) opinion on sperm morphology is controversial and you will encounter a wide variety of viewpoints on the significance of sperm morphology among both male and female fertility specialists.