Fina Eltes

Reduced semen quality caused by chronic abacterial prostatitis: an enigma or reality? *

OBJECTIVE To investigate whether there is an inter-relationship between chronic abacterial prostatitis and potential infertility. DESIGN As part of the eligibility studies for hyperthermia treatment for chronic abacterial prostatitis patients, a large number of chronic prostatitis patients were referred to us from peripheral outpatient clinics. Sperm analysis was a routine portion of the eligibility studies. To exclude bacterial prostatitis, urine cultures, expressed prostatic secretion, and semen cultures were performed. The patient population was not differentiated on the basis of those suffering from either nonbacterial prostatitis or prostatodynia according to the commonly accepted classification. The control group was the laboratory normal standard group. SETTING Normal human volunteers in an academic and clinical research environment. PATIENTS The first group includes 86 patients suffering from long-standing (1 to 20 years) chronic abacterial prostatitis, according to the commonly accepted classification, with a mean age of 39.9 +/- 9.5 years. The second group includes 101 normal fertile men with a mean age of 31.4 +/- 5.5 years. INTERVENTIONS The routine semen analysis performed included biochemical tests of seminal plasma, bacteriology, and light microscopy. MAIN OUTCOME MEASURE The original hypothesis was based on a reduction in semen quality in these patients caused by chronic abacterial prostatitis. Measurements for sperm motility parameters, morphology characteristics, prostate markers, and white blood cells (WBC) were designed accordingly. RESULTS Statistical comparisons of the two groups showed that several sperm motility parameters, morphology characteristics, prostate markers, and WBC are outside of the normal value ranges in the chronic abacterial prostatitis group. In addition, there is a correlation between the duration of the disease and two important sperm analysis variables: increased prostatic markers and appearance of sperm morphological defects. CONCLUSION From the results obtained, the high incidence of secondary infertility in these patients may be explained.

EFFECT OF ACUPUNCTURE ON SPERM PARAMETERS OF MALES SUFFERING FROM SUBFERTILITY RELATED TO LOW SPERM QUALITY

The aim of this prospective controlled study was to assess the effect of acupuncture on the sperm quality of males suffering from subfertility related to sperm impairment. Semen samples of 16 acupuncture-treated subfertile patients were analyzed before and 1 month after treatment (twice a week for 5 weeks). In parallel, semen samples of 16 control untreated subfertile males were examined. Two specimens were taken from the control group at an interval of 2-8 months. The expanded semen analysis included routine and ultramorphological observations. The fertility index increased significantly (p < or = .05) following improvement in total functional sperm fraction, percentage of viability, total motile spermatozoa per ejaculate, and integrity of the axonema (p < or = .05), which occurred upon treatment. The intactness of axonema and sperm motility were highly correlated (corr. = .50, p < or = .05). Thus, patients exhibiting a low fertility potential due to reduced sperm activity may benefit from acupuncture treatment.

ART success and in vivo sperm cell selection depend on the ultramorphological status of spermatozoa

Summary. Management of male infertility has recently shifted from treatment of the subfertile man towards techniques of assisted reproduction (ART). This study aimed to evaluate the possible role of the ultramorphological status of the spermatozoon with respect to sperm selection in vivo and prediction of ART success. Ultramorphological sperm parameters were assessed retrospectively for 92 males with sufficient sperm density (107 spermatozoa ejaculate−1) whose wives conceived following a stepwise discarding of the female genital tract barriers, using intra‐uterine insemination (IUI) (n= 26), in vitro fertilization (IVF) (n= 45) or intracytoplasmic sperm injection (ICSI) (n= 21). In parallel, sperm samples of 71 fertile males were examined. Normal ultramorphology of all head and tail subcellular organelles was found to be essential for the ability of spermatozoa to pass the lower female genital tract. The ultramorphological migration threshold for this barrier is apparently higher than that essential for oocyte fertilization. No specific indication associated with passage through the upper genital tract was found. A high prevalence of axonema defects was found to impair the ability of sperm cells to penetrate the oocyte investment. The natural fertility index, based on routine sperm parameters and the ultrastructural status of the spermatozoons subcellular organelles was confirmed to be beneficial for directing patients to ART. A discriminative score based on axonema integrity was found to contribute additional information for the first choice decision between conventional ART and ICSI (75% prediction ability). Thus it may be helpful in finding the simplest and least expensive procedure with the greatest long‐term chance for pregnancy.

Does acupuncture treatment affect sperm density in males with very low sperm count? A pilot study

Summary. Classic therapies are usually ineffective in the treatment of patients with very poor sperm density. The aim of this study was to determine the effect of acupuncture on these males. Semen samples of 20 patients with a history of azoospermia were examined by light microscope (LM) and scanning electron microscope (SEM), with which a microsearch for spermatozoa was carried out. These examinations were performed before and 1 month after acupuncture treatment and revealed that the study group originally contained three severely oligoteratoastheno‐zoospermic (OTA), two pseudoazoospermic and 15 azoospermic patients. The control group was comprised of 20 untreated males who underwent two semen examinations within a period of 2–4 months and had initial andrological profiles similar to those of the experimental group. No changes in any of the parameters examined were observed in the control group. There was a marked but not significant improvement in the sperm counts of severely OTA males following acupuncture treatment (average = 0.7 ± 1.1 times 106 spermatozoa per ejaculate before treatment vs. 4.3 ± 3.2 times 106 spermatozoa per ejaculate after treatment). A definite increase in sperm count was detected in the ejaculates of 10 (67%) of the 15 azoospermic patients. Seven of these males exhibited post‐treatment spermatozoa that were detected even by LM. The sperm production of these seven males increased significantly, from 0 to an average of 1.5 ± 2.4 times 106 spermatozoa per ejaculate (Z = ‐2.8, P≤0.01). Males with genital tract inflammation exhibited the most remarkable improvement in sperm density (on average from 0.3 ± 0.6 times 106 spermatozoa per ejaculate to 3.3 ± 3.2 times 106 spermatozoa per ejaculate; Z = ‐2.4, P≤0.02). Two pregnancies were achieved by the IVF‐ICSI procedure. It is concluded that acupuncture may be a useful, nontraumatic treatment for males with very poor sperm density, especially those with a history of genital tract inflammation.

Relationship between human sperm lipid peroxidation, comprehensive quality parameters and IVF outcome

Summary. The membranes of human spermatozoa contain an extremely high concentration of polyunsaturated fatty acids and are therefore susceptible to lipid peroxidation damage. The aim of this study was to retrospectively determine the association between the lipid peroxidation levels of washed spermatozoa, as indicated by thiobarbituric‐acid‐reactive substance concentration, and: (a) semen quality evaluated by basic routine, biochemical, cytological and quantitative ultra‐morphological analyses; (b) IVF fertilization rate. Semen samples from 45 male partners of couples who had been referred for IVF treatment due to a female infertility factor were evaluated for quality as well as for thiobarbituric‐acid‐reactive substance concentrations. The latter were found to have a negative correlation with total sperm count, semen volume, zinc/fructose ratio, and the integrity of sperm acrosome and axonema. It was suggested that lipid peroxidation has a deleterious effect on the ultramorphological status of the sperm cells and, thereby, on the male fertilization potential. The content of the seminal fluid, about 30% of which is produced by the prostate, may protect spermatozoa from this destructive process. A negative correlation was also found between thiobarbituric‐acid‐reactive substance concentrations and IVF fertilization rate. When the patients were subdivided into fertilizing (fertilization rate >0%) and nonfertilizing (fertilization rate = 0%) subgroups (n= 33 and n= 12, respectively), the former exhibited significantly lower thiobarbituric‐acid‐reactive substance concentrations than the latter. A new IVF fertilization index based on the lipid peroxidation level was established. This index had a predictive power of 93% (94% sensitivity and 92% specificity). The clinical value of this index should be further verified.

Success of acupuncture treatment in patients with initially low sperm output is associated with a decrease in scrotal skin temperature

Poor spermatogenesis in patients with inflammation of the genital tract is associated with scrotal hyperthermia. These patients can benefit from acupuncture treatment. We conducted a study to verify whether the influence of acupuncture treatment on sperm output in patients with low sperm density is associated with a decrease in scrotal temperature. The experimental group included 39 men who were referred for acupuncture owing to low sperm output. The control group, which comprised 18 normal fertile men, was used to define a threshold (30.5 degrees C) above which scrotal skin temperature was considered to be high. Accordingly, 34 of the 39 participants in the experimental group initially had high scrotal skin temperature; the other five had normal values. Scrotal skin temperature and sperm concentration were measured before and after acupuncture treatment. The five patients with initially normal scrotal temperatures were not affected by the acupuncture treatment. Following treatment, 17 of the 34 patients with hyperthermia, all of whom had genital tract inflammation, had normal scrotal skin temperature; in 15 of these 17 patients, sperm count was increased. In the remaining 17 men with scrotal hyperthermia, neither scrotal skin temperature nor sperm concentration was affected by the treatment. About 90% of the latter patients suffered from high gonadotropins or mixed etiological factors. Low sperm count in patients with inflammation of the genital tract seems to be associated with scrotal hyperthermia, and, consequently, acupuncture treatment is recommended for these men.

Sperm ultramorphology as a pathophysiological indicator of spermatogenesis in males suffering from varicocele.

Varicocele of spermatic veins is considered to be one of the major causes of male infertility associated with reduction of sperm quality. The pathophysiology of this condition is not yet completely understood. The aim of this study was to shed light on the pathophysiology of varicocele by identifying semen parameters, especially sperm ultramorphology, which improve following high ligation of the spermatic vein. Seventy‐five males with diagnosed varicocele were included in this study. Semen parameters were assessed prospectively using light microscopy, semen biochemistry and sperm quantitative ultramorphological analysis, before high ligation and 3–9 months after high ligation. The control group consisted of twenty‐five untreated varicocele patients who underwent two semen examinations within 3–9 months. No statistical difference in any of the examined variables was found between the two examinations in the control group. The treated patients exhibited a significant improvement in sperm density, progressive motility, percentage of normally formed spermatozoa, agenesis of sperm acrosome, chromatin condensation and incidence of amorphous heads compared with the pretreatment condition (P≤0.01). In contradiction, no significant improvement was observed following treatment in any of the sperm tail subcellular organelles. It is concluded that varicocele may cause deleterious alterations in early spermatid head differentiation during spermiogenesis and that varicocele patients with a high incidence of sperm acrosome and nucleus malformations are appropriate candidates for varicocele correction.

Quantitative ultramorphological analysis of human sperm: fifteen years of experience in the diagnosis and management of male factor infertility.

The advantages of quantitative ultramorphological (QUM) sperm analysis in the diagnosis and treatment of male infertility are presented. The QUM methodology is based on three elements: complementary scanning electron microscopy and transmission electron microscopy observations of 7 sperm cell subcellular organelles (acrosome, postacrosomal lamina, nucleus, neck, axoneme, mitochondrial sheath, and outer dense fibers); systematic classification of the specific ultramorphological malformations into 4 pathological and the normal categories, indicating the morphological state of each subcellular organelle; and comparison between well-defined reference groups with opposite fertility status or treatment conditions. QUM has established 2 indices for the in vivo and in vitro male fertility potential: (1) Natural Fertility Index (NFI), with accurate prediction (97% sensitivity and 90% specificity) of 80% of the male patients; and (2) IVF score, with prediction of 76% of the nonfertilizing and 90% of fertilizing IVF groups. QUM has enabled assessment of ultramorphological indications for varicocele and radiation exposure. Varicocele causes defects in sperm head organelles related to early spermatid development, whereas ionizing radiation causes amorphous head shape. QUM established criteria for specific non-in-vitro therapeutic interventions, including varicocelectomy, follicle-stimulating hormone (FSH) administration, and acupuncture. The varicocele index enabled correct classification of 79 and 89% of patients with and without varicocele. Males with idiopathic impairment of sperm acrosome and nucleus are potential responders to FSH treatment, whereas patients exhibiting low sperm activity are candidates for acupuncture treatment. Patients with a low Natural Fertility Index are recommended for an assisted reproduction technique (ART). based on the ultramorphology of the tail axoneme. Patients who achieved pregnancy following intrauterine insemination or in vitro fertilization and those whose wives conceived only following intracytoplasmic sperm injection were classified with accuracy of 78 and 74%, respectively. QUM sperm analysis is clinically informative, nontraumatic, and cost-effective, and is recommended when the male infertility factor cannot be clearly diagnosed by routine tests prior to first ART trial.

QUANTITATIVE ULTRAMORPHOLOGICAL (QUM) ANALYSIS OF HUMAN SPERM: DIAGNOSIS AND MANAGEMENT OF MALE INFERTILITY

The advantages of quantitative ultramorphological (QUM) sperm analysis in the diagnosis and treatment of male infertility are presented. QUM methodology is based on three elements: (1) complementary SEM and TEM observations of 7 sperm cell subcellular organelles: acrosome, postacrosomal lamina, nucleus, neck, axoneme, mitochondrial sheath, and outer dense fibers; (2) systematic classification of the specific ultramorphological malformations into 4 pathological and the normal categories, which indicate the morphological state of each subcellular organelle; and (3) comparison between well-defined reference groups with opposite fertility status or treatment conditions. QUM analysis has enabled the establishment of two indices that optimally express the in vivo and in vitro male fertility potential: The Natural Fertility Index (NFI), which allowed an accurate prediction (97% sensitivity and 90% specificity) of 80% of the naturally fertile and suspected infertile male patients, and the in vitro fertilization (IVF) score, which enabled prediction of 76% of the nonfertilizing and 90% of the fertilizing IVF groups. Validation tests confirmed these data. QUM also enabled assessment of ultramorphological indications for varicocele and radiation exposure: Both male factor etiologies indicated a persistent effect on the natural fertility potential, as expressed by structural changes in the nucleus. Varicocele was found to cause defects in the sperm head organelles related to early spermatid development, whereas ionizing radiation resulted in amorphous head shape. Criteria for specific non-in vitro therapeutic interventions such as varicocelectomy, follicle-stimulating hormone (FSH) administration, and acupuncture treatment were established. A varicocele index, which enabled the correct classification of 79 and 89% of the patients pre- and post-high ligation, respectively, was suggested to be a good indicator for varicocele which affects the fertility potential. Males exhibiting idiopathic impairment of sperm acrosome and nucleus were found to be potential responders to FSH treatment, whereas patients exhibiting low sperm activity proved to be good candidates for acupuncture treatment. Indications for selecting the optimal appropriate assisted reproduction technique (ART) procedure were found: Patients with a low Natural Fertility Index should be recommended for ART. A first choice ART selection should be performed according to an ART index based on the ultramorphological examination of the tail axoneme. The above index enabled correct prediction of 78% of the patients who achieved pregnancy following conventional ART (intrauterine insemination or IVF) and 74% of those whose wives conceived only following intracytoplasmic sperm injection. QUM sperm analysis is clinically informative, nontraumatic, and in the long run also cost-effective. This analysis should be performed when the male infertility factor cannot be clearly diagnosed by routine tests and prior to the first ART trial.

Relation of human sperm acrosin activity and fertilization in vitro

The aim of the study described here was to determine the possible contribution of the acrosin activity test to routine semen analysis in enhancing the precision of the prognosis of IVF success in a group of patients in which the contribution of the egg factor to infertility was ruled out (20 cases) compared to a control IVF group (39 cases). Semen analysis, acrosin activity and acrosome ultrastructure were determined for all semen samples. The group with high fertilization rates was comprised of normozoospermic patients while the group with low fertilization rates was comprised of astheno‐teratozoospermic patients. The mean acrosin level of the positive IVF group was significantly higher than that of the negative group (51.7 ± 33.2 and 28.6 ±13.7, respectively). Two parameters: per cent motile spermatozoa and acrosin level, were found to have a significant positive correlation with subsequent successful IVF (r = 0.36, P < 0.006; r = 0.37, P < 0.004, respectively); and agenesis of the acrosome was found to have a significant negative correlation (r = ‐0.33, P < 0.01). The ability of these parameters to correctly predict fertilization success was 59%, with 5% false positive, among which 15.4% was predicted solely by the acrosin level (above 54 μIU 106 cells−1) and 23% solely by per cent motile spermatozoa (above 50%). Abnormalities of the acrosome ultrastructure did not contribute further to the correct classification. The apparent clinical benefit of the acrosin level test is discussed.