Christopher L. R. Barratt

A double-blind randomized placebo cross-over controlled trial using the antioxidant vitamin E to treat reactive oxygen species associated male infertility

OBJECTIVE To determine the effectiveness of the in vivo administration of vitamin E as treatment for reactive oxygen species-associated male infertility. SETTING University-based center for reproductive medicine. DESIGN Double-blind randomized placebo cross-over controlled trial. PATIENTS, PARTICIPANTS Thirty healthy men with high levels of reactive oxygen species generation in semen and a normal female partner. INTERVENTIONS Patients were allocated to two groups according to the blinded randomization. Each patient received either 600 mg/d of vitamin E (Ephynal, 300 mg tablets; F. Hoffman-La Roche Ltd., Basle, Switzerland) (order A) or identical placebo tablets (order B) for 3 months. Then after a 1-month wash-out period the patients were crossed-over to the other treatment. MAIN OUTCOME MEASURES Improvement in the in vitro function of the spermatozoa measured by conventional semen analysis, computerized motility assessment, determination of reactive oxygen species generation, binding to the zona pellucida of the unfertilized human oocyte in a competitive zona binding assay, development of hyperactivated motility (both spontaneous and in the presence of 20% of the natural agonist, human follicular fluid) and pregnancy. RESULTS Rise in the blood serum vitamin E levels after treatment accompanied by improvement in one of the sperm function tests: the zona binding assay. The zona binding ratio for order A improved from 0.2 (range 0 to 0.5) before treatment to 0.5 (range 0.1 to 1.0) after treatment, the corresponding values for order B were 0.2 (range 0 to 1.0) before treatment and 0.3 (range 0.1 to 0.7) after treatment. CONCLUSION Oral administration of vitamin E significantly improves the in vitro function of human spermatozoa as assessed by the zona binding test.

The contribution of a hidden male factor to unexplained infertility

OBJECTIVE To assess sperm function in patients with unexplained infertility in comparison with normal fertile men. DESIGN Prospective study. SETTING Infertility outpatient clinic and donor insemination program, University Department of Obstetrics and Gynecology at the Jessop Hospital for Women, Sheffield, United Kingdom. PATIENTS Nineteen patients with unexplained infertility and nineteen normal fertile men from a donor insemination program. MAIN OUTCOME MEASURES Monitoring of reactive oxygen species generation; computerized assessment of the hyperactivated motility pattern of the spermatozoa under capacitating conditions, with and without the addition of follicular fluid (FF); evaluation of sperm-zona pellucida (ZP) binding. RESULTS Reactive oxygen species generation was not significantly different between the study and control group. Follicular fluid-induced hyperactivation (HA) was significantly lower in patients with unexplained infertility than in the donors, but no difference was found comparing spontaneous HA (without FF) between the two groups. Follicular fluid-induced HA was completely absent in 39% of infertile men and only one fertile man. A low sperm-ZP binding ratio (< or = 0.3) was observed in 28% (5/18) of patients with unexplained infertility. In all, nine infertile men (47%) had 0% FF-induced HA and/or low sperm-ZP binding ratio. CONCLUSIONS Assessing FF-induced HA and sperm-ZP binding may have clinical significance in distinguishing a subgroup of men with unexplained infertility with sperm function abnormalities in which the fertilizing capacity of the spermatozoa might be reduced. These patients cannot be identified by the conventional semen analysis. Both tests may also be useful in planning the appropriate treatment for couples with unexplained infertility.

Semen Characteristics of 49 Fertile Males

We examined the semen characteristics of 49 men whose partners had conceived within the last 16 weeks.

Ultrastructural Morphometric Data of Human Spermatozoa/Morphometrische Daten für den Nachweis von abnormalen oder unfruchtbaren menschlichen Spermatozoen

Summary: A morphometric study of the volumetric parameters of human spermatozoa has been carried out, volume densities being obtained by point counting and converted to absolute volumes by employing the point‐sampled intercept method. Data for the Spermatozoa from the semen of 15 recently fertile men are presented. The significance of the results is discussed in relation to results obtained by other methods and in relation to the building of a diagnostic reference database.

Peritoneal sperm recovery can be consistently demonstrated in women with unexplained infertility.

Diligent analysis of PF 10 to 20 hours after midcycle intracervical insemination with husbands semen in couples with unexplained infertility showed that sperm are consistently able to transverse the reproductive tract in this group of patients. However, this finding does not necessarily imply that the sperm were retained at the site of fertilization or that they were competent to achieve oocyte fertilization. Therefore, further experiments obtaining sperm from the tubal isthmus to assess the effects of their sequestration there on their ability to fertilize human oocytes are needed.

The importance of employing stringent methods to recruit fertile male controls

Summary. Two methods of recruiting fertile male controls were evaluated and compared. The first group was recruited from the partners of women attending an antenatal clinic without obtaining details of their reproductive history. The second group was recruited after obtaining a detailed reproductive history from the couple and employing stringent entry criteria. Entry criteria for the second group included a length of exposure to the risk of pregnancy of not more than 12 months and no previous episode of involuntary infertility for either partner. There were significant differences between the distributions of semen parameters obtained from the two groups, indicating that the selection criteria for “fertile” men significantly influence results obtained and therefore that it is important to employ stringent criteria for the recruitment of fertile male controls. The group which was recruited by stringent criteria (mean length of exposure to the risk of pregnancy of 3 months) was characterised by a significantly higher median concentration of spermatozoa which exhibited slow linear or nonlinear motility. This confirms the findings of a previous study which suggested that slow linear or nonlinear motility are superior forms of spermatozoal motion.

Physiological and Proteomic Approaches to Understanding Human Sperm Function

Sperm dysfunction is the single most common defined cause of infertility. Approximately 1 in 15 men are subfertile and the condition is increasing in frequency. However, the diagnosis is poor and, excluding assisted conception, there is no treatment because of our limited understanding of the cellular, biochemical, and molecular functioning of the spermatozoon. The underlying premise of our research program is to establish a rudimentary understanding of the processes necessary for successful fertilization. We detail advances in our understanding of calcium signaling in the cell and outline genetic and proteomic technologies that are being used to improve the diagnosis of the condition.

Postcoital test: which form of spermatozoal motility is associated with a good fertility outcome?

Summary The objectives of this study were to examine the predictive value of the PCT in relation to treatment‐independent conception rates, to determine which cutoff point best predicted fertility outcome, and which form of spermatozoal motility on PCT is most significantly related to fertility outcome. A prospective study was undertaken of couples referred for the investigation of “unexplained” infertility. One hundred and twenty six couples were recruited between July 1984 and April 1986. On further investigation female infertility factors were identified in 32 (25%) of couples, who were therefore excluded from the study. All conceptions were treatment independent. The relationship between the result of the postcoital test and the chance of conception was studied using a modification of Coxs regression model of life table analysis. The mean length of involuntary infertility prior to referral was 75 months (range = 18–192, SD 39.2). The mean length of follow‐up was 18 months (range = 1–34, SD 8.4). A 98% follow‐up rate was achieved. Eighteen women conceived, giving a 32‐month treatment‐independent conception rate of 22%. A cutoff point of one spermatozoon exhibiting sluggish motility per HPF was the most effective method of classifying the results of the postcoital test (X2 4.28, P = 0.037, RR = 4.7. This would suggest that the most efficient form of spermatozoal motion in cervical mucus is slow or sluggish motility.