By Michael A. Thomas, MD
Professor,
Reproductive Endocrinology and Infertility,
Director,
Division of Reproductive Endocrinology and Infertility,
University of Cincinnati College of Medicine

Dr. Thomas reports no financial relationships relevant to this field of study.

SYNOPSIS: Pregnancy rates following intrauterine insemination are not affected by abnormalities of sperm morphology.

SOURCE: Deveneau NE, et al. Impact of sperm morphology on the likelihood of pregnancy after intrauterine insemination. Fertil Steril 2014;102:1584-1590.

Semen analysis (SA) is the primary method of evaluating the fertility potential of the male partner. Parameters include sperm concentration (count x 106/mL), motility (percent that are moving), and morphology (percent demonstrating normal appearing head, midpiece, and tail). This retrospective chart review evaluated whether isolated abnormal sperm morphology (SSM) in men with otherwise normal concentration and motility affected pregnancy rates when utilizing intrauterine insemination (IUI). A total of 408 couples undergoing 856 IUI cycles were observed. Use of a sperm donor was an exclusion for entry into the study. Couples with isolated abnormal SSM ( 4%, n = 352) were compared to those with normal SSM (> 4%, n = 504). Between the two groups, men with abnormal SSM (mean 2.4% ± 1.2) were of lower age, more likely to have undergone a urologic evaluation, more often diagnosed with male factor infertility (oligospermia, varicocele), and had fewer concurrent female infertility problems. Those with normal SSM had a higher incidence of prior pregnancies, lower rates of unexplained infertility, and lower rates of female factor infertility diagnoses (endometriosis, tubal disorders, and uterine factors). No differences were noted between the two groups with respect to a diagnosis of diminished ovarian reserve, anovulation, female obesity, male hypogonadism, or previous azoospermia. Pregnancy rates (defined as an ongoing pregnancy with fetal heart tones) were not different between couples with abnormal (17.3%) or normal (16.7%) SSM (odds ratio, 0.954; 95% confidence interval, 0.66-1.37). There was no significant difference in pregnancy rates when stratified by morphology: 0-2% (16.7%, 126 cycles), 3-4% (17.2%, 180 cycles), 5-6% (16.4%, 126 cycles), and 7-10% (14.2%, 183 cycles). However, compared to men with normal SSM, male partners with low SSM had lower pregnancy rates if they had a palpable varicocele, but higher rates if they had ejaculatory dysfunction. Concurrent female factors did not have an effect on men in either observation group.

COMMENTARY

Infertility affects one out of six couples, with male factor present in 30-50% of these individuals and the sole cause in 20%. In the 1950s, the World Health Organization (WHO) adopted the parameters for normal SA based on data from 1000 fertile and 1000 subfertile men. These parameters are: sperm concentration of > 20 mil/mL, motility > 50%, and morphology > 50%.1,2 Then, in the 1970s, the WHO published a manual that provided a step-by-step plan on how to perform a SA. This became the accepted standard for analyzing sperm by national and international societies of andrology, reproductive medicine, human reproduction, and pathology.3 In 1986, Kruger and associates developed a stricter criteria of what was normal morphology. Instead of using a microscope under high power and giving a guesstimate of the normal “look” of the sperm, these investigators incorporated a histomorphometric measurement of the sperm head and devised a scheme of pattern recognition for the various defects of the head, neck, body, and tail.4,5 This is done by staining a slide and painstakingly making observations on up to 100 or more sperm. Under these more stringent criteria, a morphology of > 14% is considered normal range and is associated with a good fertility prognosis. Currently, this more rigorous criteria by Kruger set the standard for methodology and was incorporated into the latest WHO sperm laboratory manual,6 which states that normal sperm morphology > 4% of the sperm cells is considered within the 95% fertile reference range. It also reclassifies the lower limit of normal sperm concentration at 15 mil/mL and motility at 40%.

Since SSM was first introduced as an adjunctive method of analyzing sperm cells, it was quickly adopted by fertility and andrology centers worldwide since a number of studies demonstrated that poor morphology using the Kruger criteria was associated with the ability to predict the success or failure of in vitro fertilization (IVF). In 1998, a literature review found that SSM 4% was associated with poor IVF outcomes.7 Since most sperm morphology abnormalities are associated with head defects, the technique of intracytoplasmic sperm injection (ICSI) is often necessary. ICSI allows a single sperm to directly enter a single oocyte, therefore decreasing the risk of nonfertilization secondary to the inability of the sperm head to penetrate the zona pellucida.

A number of studies have also analyzed whether SSM can predict the success of an IUI cycle. Studies noted a decrease in pregnancy rates with low SSM,8-10 but just as many studies showed no difference.11-13 However, these data are suspect since the majority were small in number. This current study under review is important since the larger cohort of couples and analysis of other fertility factors are considered.

The SA is the starting point in all fertility workups to rule out the male component. Now that the SA is standardized across all laboratories, when all the three major portions of the SA (head, midpiece, tail) are in the normal WHO reference ranges, male factor infertility is unlikely (< 5%).6 Therefore, a fertility expert or gynecologist can focus his/her attention on the female partner before making a diagnosis of unexplained infertility.

Some clinicians believe that men diagnosed with an isolated SSM should be relegated to the use of the more costly and invasive IVF procedure without attempting IUI. At the University of Cincinnati, an IUI cycle with ultrasound monitoring and medications cost about $1420. However, an IVF cycle with or without ICSI with monitoring and medications costs approximately $14,000. Because this current study demonstrates that IUI success is the same whether one of the components of the SA is normal or not, couples who do not have the finances to undergo an IVF cycle should be reassured that IUI may give them the same chance of achieving a pregnancy as someone with a normal SA, despite the presence of a secondary female fertility factor. Therefore, the take-home message is that men with a normal sperm concentration and motility but low SSM with or without a concurrent female factor are still considered subfertile and may need more than timed intercourse alone to achieve parenthood. But the rush to IVF as the only treatment option should be reconsidered.

REFERENCES

  1. Macleod J. Semen quality in 1000 men of known fertility and in 800 cases of infertile marriage. Fertil Steril 1951;2:115-139.
  2. Macleod J, Gold RZ. The male factor in fertility and infertility. III. An analysis of motile activity in the spermatozoa of 1000 fertile men and 1000 men in infertile marriage. Fertil Steril 1951;2:187-204.
  3. Wang C, Swerdloff RS. Limitations of semen analysis as a test of male fertility and anticipated needs from newer tests. Fertil Steril 2014;102:1502-1507.
  4. Kruger TF, et al. A quick, reliable staining technique for human sperm morphology. Arch Androl 1987;18:275-277.
  5. Menkveld R, et al. The evaluation of morphological characteristics of human spermatozoa according to stricter criteria. Hum Reprod 1990;5:586-592.
  6. World Health Organization laboratory manual for the examination and processing of human sperm. 5th ed; 2010.
  7. Coetzee K, et al. Predictive value of normal sperm morphology: A structured literature review. Hum Reprod Update 1998;4:73-82.
  8. Van Waart J, et al. Predictive value of normal sperm morphology in intrauterine insemination (IUI): A structured literature review. Hum Reprod Update 2001;7:495-500.
  9. Hauser R , et al. Intrauterine insemination in male factor subfertility: Significance of sperm motility and morphology assessed by strict criteria. Andrologia 2001;33:13-17.
  10. Spiessens C, et al. Isolated teratozoospermia and intrauterine insemination. Fertil Steril 2003;80:1185-1189.
  11. Lee RK, et al. Sperm morphology analysis using strict criteria as a prognostic factor in intrauterine insemination. Int J Andrology 2002;25:277-280.
  12. Check ML, et al. Reevaluation of the clinical importance of evaluating sperm morphology using strict criteria. Arch Androl 2002;48:1-3.
  13. Karabinas DS, Gelety TJ. The impact of sperm morphology evaluated by strict criteria on intrauterine insemination success. Fertil Steril 1997;67:536-541.