Mutations at the mitochondrial DNA polymerase (POLG) locus associated with male infertility.

Human mitochondrial DNA polymerase, encoded by POLG, contains a polyglutamine tract encoded by a CAG microsatellite repeat. Analysis of POLG genotypes in different populations identified an association between absence of the common, ten-repeat allele and male infertility typified by a range of sperm quality defects but excluding azoospermia.

Differentially expressed DNA sequences following recovery from unilateral testicular torsion in rat.

The molecular response during recovery from torsion-induced stress in the testis is diverse with a variety of mechanisms. In this study, using unilateral testicular torsion in rat as a model, we used subtractive hybridisation to identify differentially expressed DNA sequences in the torsioned and control testes. Three genes were identified as being down regulated in the torsioned testis compared with controls: Control Testis genes 1, 2 and 3 (CT1, CT2 and CT3). Two genes were up regulated in the torsioned testes: Torsioned Testes genes 1 and 2 (TT1 and TT2). Differential expression was confirmed by Reverse Northern blot analysis. An homology search revealed that CT1 had 88% homology with rat metallothionein cDNA; CT2 had 81% homology with rat cell surface antigen in MHC class I, but no homology could be found for CT3. TT1 had 92% identity with rat Rieske iron-sulphur protein mRNA whereas TT2 had 73% identity with a human clone of unknown function (RP 11-252D22). These results indicate that changes in gene expression occur following torsion induced stress, and that identification of differentially expressed genes may provide insights into the mechanisms of cellular tissue damage in this model.

Single-step method for the determination of the amount of the common deletion in mitochondrial DNA.

A fluorescent-based quantitative PCR assay to measure the percentage of the common deletion in rat mitochondria is reported. The amount of the common deletion is measured relative to the amount of total mitochondrial (mt)DNA. The use of a heterologous competitor construct allows the reaction to be monitored to ensure that exponential accumulation of products occurs. The use of fluorescence-labeled primers provides a safe and sensitive means to quantify products without any adjustment for size. This assay will allow the quantitative determination of the common deletion with one dilution range.

Relationships between prolactin and follicle-stimulating hormone during early pregnancy and the puerperium.

This investigation studies the relationship between the concentrationss of prolactin and FSH in the serum during pregnancy and the puerperium. A single dose of 5 mg bromocriptine during early pregnancy induced a profound fall in the serum level of prolactin with a substantial rise 20 h later. During the initial reduction in the concentration of prolactin, no alteration was noted in the level of FSH but during the subsequent increase in the prolactin concentration, there was a significant (P less than 0.05) decrease in the concentration of FSH. During week 1 of the puerperium, the concentrations of FSH and prolactin were significantly lower in lactating women than in women who were not breast feeding, but there was no significant difference between the concentration of FSH in women who had suppressed lactation with bromocriptine and in those whose lactation was suppressed by non-hormonal methods. when the concentration of FSH was measured every 10 min during a 30 min breast feed, there was a marked but short-lived rise in the serum concentration of prolactin but no change in the level of FSH. These results suggest that an increase in the serum level of prolactin in pregnancy can have a suppressive effect on the production of FSH. Although acute suckling-induced hyperprolactinaemia in the puerperium has no such effect, the maintenance of lactation in the long term does suppress the concentration of FSH in the serum.

Infertility in men with retrograde ejaculation: the action of urine on sperm motility, and a simple method for achieving antegrade ejaculation.

The profound effect of urine on sperm motility is demonstrated. Two patients with retrograde ejaculation and infertility who achieved antegrade passage of semen by ejaculation on a full bladder are described. The use of this method of management in patients with infertility due to retrograde ejaculation is discussed.

Clinical findings and testicular histology in three hyperprolactinemic infertile men.

Three azoospermic infertile men with marked hyperprolactinemia are described. All three men had clinical evidence of distal genital tract obstruction, and one man had evidence of severe spermatogenic arrest. The histology of testicular biopsies taken from each of these men is described and the role of hyperprolactinemia in male infertility is discussed.

Congenital absence of the vasa deferentia presenting with infertility.

Congenital absence of both vasa deferentia is not an infrequent cause of sterility. Between April 1975 and December 1981, 11 men out of a total of 749 presenting with infertility were diagnosed as having congenital absence of both vasa deferentia. Subsequent clinical investigations showed that FSH levels were within the normal range (2-10 mIU/ml), blood karyotype (XY) was normal, and testicular histology demonstrated normal spermatogenesis. Seminal volume was markedly reduced in nine patients (range 0.25-1.0 ml). In three out of four patients tested, seminal fructose was found to be completely absent. Of the 11 patients, eight subsequently had exploratory surgery. In four men, the whole epididymis was present on both sides, while the other four had varying parts of one or both epididymides absent. In six of the eight patients explored surgically, no trace of the vasa deferentia could be found, while one other patient had thin fibrous cords in the anatomical site of the vasa deferentia. A possible cause for the abnormality and the importance of seminal fructose estimation are discussed.

A test of the human sperm acrosome reaction following ionophore challenge. Relationship to fertility and other seminal parameters.

Acrosome reaction capacity was tested on semen samples from 53 fertile and 26 subfertile men. Preparations were divided into two aliquots after 3 or 24 hours of culture. One aliquot received 10 mumol/L calcium ionophore A23187 in dimethyl sulfoxide (DMSO) and the other received DMSO alone. Acrosome reactions were scored on ethanol-permeabilized smears using fluorescein isothiocyanate (FITC)-conjugated Pisum sativum lectin. The following factors were analyzed: the spontaneous reaction rates (control); induced reaction rates (ionophore-challenged); and the difference between the two, being the proportion of spermatozoa in the population capable of reacting in response to calcium influx (acrosome reaction to ionophore challenge [ARIC]). While spontaneous reactions bore no relation to fertility, induced reactions and ARICs were significantly reduced or absent in subfertile men, indicating acrosomal dysfunction as a likely cause of fertilization failure. The test was shown to have a predictive value for fertility comparable to that of the hamster ovum sperm penetration assay and to be a simple and cost-effective addition to existing semenology.

Postmolar contraception.

Recent studies on the etiology and the cytogenetics of trophoblastic tumors suggest that hydatidiform mole and choriocarcinoma may be conditions with no causal relationship. With the advent of newer diagnostic methods which aid in the early diagnosis of pregnancy and help to differentiate it from abnormal pregnancy together with the increasing concern over the safety of use of the contraceptive measures following a hydatidiform mole, it is suggested that a period of postmolar contraception may no longer be necessary. The follow-up of these patients should include serial sonography in association with other currently available methods. Pregnancy should also be allowed to occur naturally if the patient so desires.

PIP: The practice of advising a women with hydatidiform mole to use contraception for 1-2 years before planning pregnancy is re-examined in the light of new information on etiology and cytogenetics of mole, risk of developing choriocarcinoma, as well as new technologies for following early pregnancy. The risk of choriocarcinoma after molar pregnancy has been reported at 1-15%, while the risk after all other types of pregnancy varies widely in the literature. Incidence of trophoblastic tumors varies much less in population-based estimates. It is unknown whether the risk of choriocarcinoma is the same for all 3 cytogenetic types of moles, homozygous complete XX, heterozygous complete XY or partial mole. It is likely that a defective ovum is the pathologic basis for mole and choriocarcinoma. The risk of subsequent malignancy is unrelated to the histologic appearance of the mole. The risk of habitual mole ranges from 1:50 to 1:150. As habitual moles recur, the risk of chorionic malignancy falls to extinction. Contraception does not affect the risk of choriocarcinoma: the reason why contraception was advised is that HCG levels due to normal pregnancy could not be distinguished from those due to mole before the advent of quantitative radioimmunoassay and ultrasound. Now normal pregnancy can be documented as early as 1 week after conception by radio receptor assay for HCG, combined with serial ultrasound.

Relationship between testicular morphology and sperm production following ischaemia in the ram.

Arteriosclerosis was induced in the internal spermatic artery of rams to determine if this condition is implicated in the aetiology of testicular pathology which causes male infertility. Data were collected on sperm concentration and motility for 56 days following surgery to provide an index of testicular function. Testes were then weighed and a testicular biopsy score count was performed on histological sections to assess spermatogenic potential of seminiferous tubules. Vascular disturbance caused focal damage of the seminiferous epithelium, similar to that seen among infertile men, and a reduction in ejaculate volume, sperm concentration and sperm motility. Sperm concentration decreased following ischaemia yet was maintained to some degree by a germ-cell depleted spermatogenic epithelium. Normal testicular morphology was maintained above a testis weight of about 120 g (for an individual testis), but below this threshold spermatogenesis was severely impaired. In conclusion, these data have provided information on the relationship between testicular morphology and function following ischaemia in the ram. Furthermore, the morphological changes induced in the testis were similar to those seen among infertile men and, by their focal nature, could explain the distinction between oligozoospermia and azoospermia in men exhibiting spermatogenic arrest.

Practitioner reporting of birth defects in children born following assisted reproductive technology: Does it still have a role in surveillance of birth defects?

BACKGROUND: National assisted reproductive technology (ART) data collections that rely on practitioners' reports of birth defects have consistently reported lower proportions of children with birth defects than record linkage studies that link ART infants to birth and malformation registers. METHODS: We compared the birth defect data reported to the national Australian Assisted Conception Data Collection (ACDC) by practitioners at three Western Australian ART clinics with the birth defect data identified on the Western Australian Birth Defects Registry (WABDR) through record linkage of all the pregnancies conceived at these clinics to the WABDR. Cases are reported to the WABDR by multiple statutory and voluntary sources. RESULTS: We found that the national ACDC significantly underestimated the prevalence of birth defects in WA-born ART infants. Less than one-third of ART children identified with a major birth defect on the WABDR were reported to the ACDC. CONCLUSIONS: Although national ART data collections provide valuable information on pregnancy rates and short-term pregnancy outcomes such as multiple birth and birth weight, we strongly recommend that birth defect information used for patient counselling is preferentially drawn from large studies that have used record linkage to high-quality birth defect registers.

Urinary Symptoms and total hysterectomy.

A prospective study of urinary symptoms before and after total hysterectomy for a variety of gynaecological disorders has been made in 104 women. 62% were symptomatic preoperatively. Of this group 11% of the preoperatively symptomatic and 25% of the preoperatively asymptomatic either had their symptoms worsened or had symptoms appear 6 months after the operation. However, the total number of symptomatic women was reduced to 50% 6 months postoperatively. The case against total hysterectomy in the production of urinary symptoms remains to be proven.

Clinical assessment of male infertility in the era of intracytoplasmic sperm injection.

This communication outlines the major causes of infertility in the male and, where indicated, the application of in vitro fertilization and intracytoplasmic sperm injection in their treatment. It also points out that there are many types of infertility in the male where other methods of treatment are also successful and where reproductive technology is unnecessary.