Medical treatment of male infertility

The opinions of specialists on the medical treatment of male infertility has been altered by two events: the advent of epidemiology, which demands studies with control cases, and the advances achieved in in vitro fertilization. Apart from cases of hypogonadotropic hypogonadism, no type of male hypofertility has found an unquestionably effective treatment. Yet it is probable that varicocelectomy, treatment of genital infection and, in rare cases of hormonal deficiency, hormonal treatments that stimulate Leydig and Sertoli cells may have positive effects. In idiopathic oligo-astheno-teratospermia, which is the most frequently encountered type of infertility, several treatments are currently being tested but have not been fully evaluated. Quite recently, attempts at treating patients immediately before in vitro fertilization have started, but the results are not yet available.     

Endocrinologic features of male infertility

We measured FSH, LH, PRL and Testosterone levels in serum and seminal fluid of 100 patients, 30 fertile and 70 infertile. Plasma Testosterone was similar in different groups of patients, while seminal fluid concentrations were higher in plasma as compared to the seminal fluid. Plasma Prolactin did not show any significant variation among the different groups, whereas seminal Prolactin was always found to be higher than that in plasma. The values of plasma FSH were significantly increased in the patients with testicular hypoplasia. Seminal and plasma LH values did not show any significant variation among the different groups.     

Y-chromosome microdeletions and male infertility

OBJECTIVE: To develop a simple assay using the silica wool filtration (SIFT) procedure to estimate percentage of acrosome-reacted (AR) sperm. SETTING: Private andrology laboratory. MATERIALS AND METHODS: Capacitated sperm processed by the SIFT procedure to remove nonviable sperm and those with broken membrane were acrosome reacted by induction with a calcium ionophore. Following the acrosome reaction, the sample was processed by the SIFT procedure. Sperm concentration and acrosomal status were also determined before and after the SIFT procedure. RESULTS: The SIFT procedure prevented AR sperm from filtering (mean +/- SD, 22.2 +/- 1.9 vs. 9.8 +/- 4.9%). The mean percent of sperm retained in the filter (SIFT assay: 61.8 +/- 21.5%) was significantly higher than the percent of AR sperm estimated by a staining technique (26.4 +/- 7.3%), but they were significantly correlated (r = .34) with each other. The filtration of capacitated sperm prior to induction of the acrosome reaction eliminated, or at least minimized, the possibility of falsely increasing the percent of AR sperm estimated by the SIFT assay. The higher estimate obtained by SIFT assay, therefore, suggests that it may be estimating sperm at various stages that are undergoing the acrosome reaction. CONCLUSION: The findings suggest that the SIFT assay could be used to estimate the percentage of AR spermatozoa.     

The varicocele and male infertility

Varicocele is accepted as a common cause of male subfertility, even though many men with varicocele appear to have normal fertility. The pathophysiology of the varicocele effect on fertility remains unclear, but the association of varicocele with decreased testicular size, abnormal testicular histology, and abnormal semen parameters is clearly established. Because a small varicocele may impair fertility, it must be diligently sought, and the Doppler stethoscope may be helpful in establishing the diagnosis when a venous thrill is equivocal during the Valsalva maneuver in a standing patient. Abnormal semen parameters should be demonstrated in subfertile males with varicocele prior to advising varicocelectomy. Decreased sperm motility or a "stress pattern" in the semen should be documented; however a decreased sperm count may or may not be present. Various surgical approaches are available. When suprainguinal approaches have been used, failures have been shown to be attributable to secondarily incompetent cremasteric system veins. When high inguinal approaches are used, unsuccessful operations are probably secondary to a failure to identify one of the several venous tributaries that may be present at this level. The surgeon's approach should be based on available data, and his patients should be informed that failures are possible with any method of varicocelectomy until experience indicates otherwise. In most series, improvement in semen quality and pregnancy rates have been reported in a significant percentage of patients undergoing varicocelectomy for infertility. However, prior to subjection of the patient to varicocelectomy, the wife of the varicocele patient should be thoroughly studied (and treated when indicated).     

Y chromosome microdeletions in male infertility

A new protocol for computed tomography (CT) imaging of the midfoot is described. This imaging technique places the CT cuts parallel to and perpendicular to the talus-first metatarsal axis, as viewed on the lateral CT scout image. For imaging the midfoot, this technique is an improvement over previously described hindfoot or midfoot protocols.     

Spinal cord injuries: male infertility aspects

The diagnostic yields and complication rates of closed lung biopsies were determined by responses to a questionnaire. Of 5,255 procedures reported, 30% were aspiration biopsies (AB), 7% tissue core biopsies (CB), 2% trephine biopsies (TR), 37% bronchial brush biopsies (BB), and 23% transbronchial biopsies (TB). Of these biopsies, 70% were done for suspected neoplasms. The diagnostic accuracy rates were: AB=82%, CB=84%, TR=86%, BB=61%, and TB=56%. Mortality rates were: AB=0.1%, CB=0.3%, TR=2.9%, BB=0.0%, and TB=0.3%. Transthoracic needle biopsies (AB, CB) had the highest overall diagnostic accuracy, with an associated low mortality and moderate morbidity.     

Sub-zonal insemination for extreme male factor infertility

When in-vitro fertilization (IVF) is used for severe male infertility, the zona pellucida constitutes a major barrier to sperm-oocyte interaction, a barrier that may, in principle, be overcome by micro-injecting one or more spermatozoa into the sub-zonal perivitelline space ('sub-zonal insemination' or SZI). We have defined suitable patients for SZI as having 'extreme' male factor in that they have either shown a failure of fertilization in previous IVF cycles or had < 50 000 motile spermatozoa recoverable after semen preparation. (This is distinct from those with only 'severe' male factor in whom sufficient (> 50 000) motile spermatozoa could be recovered from a semen preparation.) A total of 213 SZI cycles were performed at Sydney IVF in the 4 year period September 1988 to September 1992, for extreme male factor patients with previous IVF failures or extremely low sperm numbers for whom SZI was the first option (about two-thirds and one-third of cases respectively). A total of 138 embryo transfers are reported, producing 20 clinical pregnancies after performing SZI on 1899 oocytes. One patient miscarried at 12 weeks gestation and there have been nine normal deliveries (so far) of 10 healthy infants. The first delivery was in February 1990. One pregnancy was achieved in the only patient in whom spermatozoa were obtained by epididymal aspiration, and transfer of three cryopreserved embryos in another patient resulted in a singleton pregnancy. Of the 492 oocytes fertilized, 282 had two pronuclei (57.3%) and normal embryos were transferred in 138/213 (64.8%) treatment cycles, giving an overall pregnancy rate of 14.5% per embryo transfer or 9.4% per cycle.(ABSTRACT TRUNCATED AT 250 WORDS)     

Molecular approaches to the diagnosis of male infertility

We investigated the effects of aging and/or swimming training on the antioxidant enzyme system in diaphragm of mice. Young (2 months old) and old (26 months old) male mice were swimming-trained for 6 weeks (1 h/day, 5 days/week). Cu,Zn-Superoxide dismutase (Cu,Zn-SOD) activity was significantly upregulated with aging, and swimming training definitely enhanced the activity only in young mice. Neither aging nor swimming training had overt effect on Mn-SOD activity. Glutathione peroxidase activity in young mice was significantly increased after training, but not in old mice. Both of immunoreactive Cu,Zn-SOD and Mn-SOD were significantly increased with aging but were unaffected by swimming training. Consequently, physical training significantly enhanced the specific activity of Cu,Zn-SOD in young mice, but not in old mice. Meanwhile, swimming training significantly increased xanthine oxidase activity in both age groups, the extent of the increase being greater in old mice than in young mice. We concluded that the antioxidant enzyme system in mouse diaphragm trends to be upregulated with aging, but that swimming training improved the system only in young mouse diaphragm.     

Genetic abnormalities and male infertility. A comprehensive review

We have previously observed that ciliary neurotrophic factor (CNTF) can prevent the degeneration of androgen-sensitive perineal motoneurons and their target muscles, the bulbocavernosus and levator ani (BC/LA), in perinatal female rats. Response to CNTF is dependent on the expression of the alpha component of the CNTF receptor (CNTFRalpha). In the present study, we examined the developmental profile and androgen regulation of CNTFRalpha gene expression in BC/LA muscle, thigh muscle, and lumbosacral spinal cord. CNTFRalpha mRNA was abundantly expressed in the BC/LA and thigh around the time of birth; expression declined progressively after birth and remained low into adulthood. In contrast, CNTFRalpha message remained high in the lumbosacral spinal cord throughout development. Androgen regulation of CNTFRalpha expression was examined in prenatal animals by administering the androgen receptor blocker hydroxyflutamide from embryonic days E18 through E21. Four days of androgen deprivation caused a significant up-regulation of CNTFRalpha mRNA in the BC/LA, thigh, and spinal cord of male fetuses. After castration in adulthood, CNTFRalpha expression in the BC/LA transiently increased, then decreased below control levels. Expression of CNTFRalpha in thigh muscles and the lumbosacral spinal cord was not affected by adult castration. Thus, the perineal muscles and motoneurons are potential sites of direct CNTF action, and expression of the CNTFRalpha gene is modulated by androgen, especially in the androgen-sensitive perineal muscles. Transient up-regulation of CNTFRalpha following castration or androgen receptor blockade may represent a protective response designed to counteract the muscle atrophy normally induced by androgen withdrawal.     

Use of immature germ cells for the treatment of male infertility

Both animal experimentation data and preliminary clinical experience converge to suggest that normal progeny can be obtained by fertilizing oocytes with spermatids, the youngest male germ cells to have a set of haploid chromosomes. Spermatids can be obtained from the ejaculate of many patients with non-obstructive azoospermia. The use of ejaculated spermatids in the treatment of non-obstructive azoospermia is thus to be considered as an alternative to that of testicular spermatozoa. Fertilization with ejaculated spermatids makes it possible to avoid the potential adverse consequences of extensive testicular biopsy and may thus become the treatment of first choice. The recourse to testicular spermatids represents a treatment of last chance if no spermatids can be recovered either from the ejaculate and no spermatozoa from the testis.     

Two cases of male infertility with pathological dilatation of ejaculatory duct

Culturing of rabbit pre-implantation embryos was performed in Ham's F10 medium supplemented with polyvinylpyrrolidone. Under these culture conditions, day 6 post coitum blastocysts increased their diameter within 24 h to 80% of that of day 7 blastocysts grown in vivo. Despite this substained growth, the embryonic disc remained undifferentiated with clear signs of degeneration after 24 h of culture. Basic fibroblast growth factor (bFGF) was able to overcome this developmental block. After 12 h of culture, day 6 blastocysts showed pear-shaped embryonic discs, and after 24 h, the primitive streak with Hensen's node was visible. The bFGF had no comparable effects on day 5 and day 7 blastocysts. The embryonic discs of day 5 blastocysts degenerated, even in the presence of bFGF, whereas day 7 blastocysts were able to form their primitive streak, also in the absence of bFGF. TGF beta 1 did not promote embryonic development in vitro. The data indicate that the onset of mesoderm formation in the rabbit is controlled by a growth factor of the FGF-family.