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. Higher levels of abnormal sperm shapes have been noted in men with infertility [Guzick DS. NEJM 2001] but the prognostic value of morphology reading in clinical practice have been questioned by recent research. However, sperm morphology should not be completely ignored, and efforts to improve the percent of normal shapes as much as possible are 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. Using modern guidelines, 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 6th 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 6th 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. [Kruger TF. FertSteril 1986]. The criteria were based on the appearance of sperm which had successfully migrated to the upper endocervical canal after natural intercourse with the assumption that these sperm had superior functional capacity.

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 labs 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 and 6th Editions (2010 and 2021) 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/6th 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 they have almost no data to back-up any clinical relevance to their use.

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 results.

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. [Gatimel N. Andrology 2017]

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 2017 review article 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 quite modest for sperm density (19.2%) and sperm motility (15.1%). [Gatimel N. Andrology 2017] However, for sperm morphology, the CV was considerably higher at 80%. Extra intensive training in reading slides was found to be able to bring this variation down, but not below 50%. In addition, the effects of this 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 legitimate questions regarding whether the sample size evaluated for morphology represents a statistically meaningful evaluation of the entire specimen. [Kohn P. EurUrolFoc 2018] 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 fall into 2 primary areas of concern:

#1) The impact on the ability to conceive and maintain a healthy pregnancy

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

[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.]

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 question 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] 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.  Another meta-analysis of studies found no association between sperm morphology and the rates of sperm chromosomal abnormalities. [Sun F. ReprodBiolEndocrinol 2006] In addition to these findings, 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 globozoospermia (see below), double heads, and multiple tails- some of these will be reviewed in more detail below. [Sun F. ReprodBiolEndocrinol 2006]. Higher rates of sperm aneuploidy have been found in these relatively rare sperm with highly abnormal shapes and these should not be used with IVF/ICSI.

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 100% 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 pinhead sperm formation is 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.

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, including impaired sperm passage through the cervical mucus as well as 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

The use of strict criteria was originally evaluated in its relationship with IVF outcomes. [Kruger TF. Urology 1987]. Most studies on strict morphology outcomes relate to its use with predicting IUI and IVF success rates. However, a 2015 study of 1,177 couples trying to conceive naturally showed no relationship between sperm morphology and the chances of establishing a pregnancy. [Hamilton JAM. HumReprod 2015]. A review of the literature in 2016 “suggests that patients with abnormal sperm morphology alone should not be precluded from attempting natural conception before undergoing assisted reproduction. [Shabtaie SA. CurrUrolRep 2016] Sperm counts and motility are generally considered to have a much larger impact on natural intercourse success rates, and the establishing of healthy pregnancies are not necessarily negatively impacted even with very low (0% normal) strict morphologies. [Kovac JR. AsJAndrol 2017]  This fits with what I personally see in my clinical practice where we routinely have couples establish natural pregnancies successfully with strict morphologies of 0% and 1%.

Intrauterine Insemination (IUI)

Similar to natural intercourse, sperm counts and motility are generally considered much more important parameters for success than sperm morphology. In the past, many fertility specialists felt that if sperm morphologies were decreased, then IUI success rates were low and couples should consider just move on to IVF. This viewpoint seemed to be supported by early research on the topic such as the 2001 meta-analysis looking at 9 studies on the topic. [Van Waart J. HumReprodUpdate 2001]. In this review, 6 of the 9 studies showed a negative impact of low sperm morphology on IUI outcomes. However, most of these studies did not look at the morphology as a factor by itself, but rather found that it was correlated only when other factors were present, such as a low total motile sperm count as well. [Lockwood GM. Andrology 2015]. More recent studies on the topic, however, have shown that morphology does not appear to impact IUI outcomes as long as sperm counts and motility are good. An example is a 2015 study looking at 856 IUI cycles in 408 couples, where pregnancy rates per cycle were 15.7% for men with a strict morphology of 4% or less as opposed to 13.9% when the morphology was 5% or higher. [Devereau NE. FertSteril 2014]. Even for patients with a very low morphology of 0-1%, pregnancy rates per cycle were 21.4%. Similar findings were seen in a 2019 study of 984 IUI cycles in 501 couples, which found a clinical pregnancy rate/cycle of 12.3% in men with a morphology of less than 4% in comparison to 13.0% for men with morphology of 4% or above. [Patel P. JUrol 2019]. In this study, there was also noted to be no change in live birth and miscarriage rates in men with lower morphology. A meta-analysis of 20 studies on the topic in 2018 evaluated 41,108 IUI cycles and noted no significant difference in pregnancy rates when the strict morphology was <4% (12.1%) vs. 4% or above (14.2%). [Kohn TP. JUrol 2018]. This same review also noted no difference in IUI pregnancy rates with very low strict morphology readings of 0% (13.9%) when compared to men with a strict morphology of 1% or higher (14.3%).

It is becoming increasing apparent that sperm morphology does not seem to correlate with IUI outcomes, and the data suggests that low morphology should not significantly decrease the chances of success in couples with otherwise good total motile sperm counts.

Standard IVF vs. IVF/ICSI

The original studies on the Kruger strict morphology were performed looking at the impact on outcomes with standard IVF. At that time, a normal strict morphology was defined as ≥ 14%. Couples undergoing standard IVF showed higher fertilization rates with a morphology of 14% or above (88.3%) vs. men with a morphology of less than 14% (49.4%). [Kruger TF. Urology 1987]. Pregnancy rates per embryo were also higher in men with a morphology of 14% or higher (51.5%) as opposed to a morphology less than 14% (18.5%)

Since that time, however, conflicting data has emerged on the impact of strict morphology outcomes on the outcomes of standard IVF. A review of 10 studies in 1998 found that pregnancy rates/cycle were higher in men with a strict morphology of >4% (26.0%) as opposed to <4% (15.2%) with standard IVF. [Coetzee K. HumReprodUpdate 1998]. Several other studies soon after confirmed these findings that decreased strict morphology seemed to have a negative impact on standard IVF outcomes. [Marnet B. IntJAndrol 2000][Gunalp S. HumReprod 2001][Menkveld R. HumReprod 2001]. However, a meta-analysis in 2011 looked at 4 studies that they felt fit the adequate criteria for evaluation, with findings suggesting that standard IVF outcomes were not impacted by low sperm morphologies. [Hotaling JM. FertSteril 2011]

In terms of IVF/ICSI, the data seems appears fairly clear that sperm morphology does not negatively impact outcomes. A study of 3,676 IVF/ICSI cycles in 2015 found that success rates were not decreased when sperm morphology rates were low. [van den Hoven L. Andrology 2015]. A 2011 meta-analysis study mentioned in the last paragraph also found that IVF/ICSI success rates were unchanged by sperm morphology. [Hotaling JM. FertSteril 2011]

Conclusion: A review of available literature in 2017 concluded that sperm morphology does not appear to impact the outcomes of IVF/ICSI. [Gatimel N. Andrology 2017]. In regard to standard IVF, this paper found that the majority of the published studies support the findings that decreased strict morphology may have a negative impact on outcomes. Based on these findings it can be recommended that at this time, men with an abnormal strict morphology (<4%) may benefit from the use of ICSI during an IVF cycle.

Summary of Sperm Morphology

The clinical relevance of the strict morphology on non-IVF treatments seems to continue to diminish as further research on the topic accumulates. A low strict morphology (<4%) can still serve as a screening tool for deciding which men may benefit from an evaluation by a male fertility specialist, and efforts should be made to try and improve the morphology as much as possible by optimizing the environment for sperm production. However, in terms of natural intercourse and “low-tech” treatments from the female side (such as IUI), the predictive value of sperm morphology appears to be minimal, and the current data seems to indicate fairly clearly that a low morphology does not mean that a couple would necessarily benefit by moving directly on to IVF.