Iwan Lewis-Jones

Sperm chromosomal abnormalities are linked to sperm morphologic deformities

OBJECTIVE To describe the association between specific sperm morphologic abnormalities and sperm chromosomal abnormalities on multicolor interphase fluorescence in situ hybridization (FISH). DESIGN Case report. Reproductive medicine unit in a tertiary referral center. PATIENT(S) Three infertile men with severe oligoasthenospermia and total teratozoospermia who were referred for IVF treatment. MAIN OUTCOME MEASURE(S) Incidence of spermatozoal chromosomal aneuploidy for chromosome 18 and the sex chromosomes by using FISH. RESULT(S) Morphologic assessment of sperm revealed a high incidence of double heads, multinucleated sperm heads, and multiple tails. Hormone profiles and karyotyping of peripheral lymphocytes were normal in the three men. The proportion of sperm with disomy, trisomy and tetrasomy for chromosome 18, and the sex chromosomes in each patient was 100%, 76%, and 82.5%, respectively. CONCLUSION(S) Specific morphologic abnormalities of sperm may be associated with higher incidence of chromosomal abnormalities. Resolving infertility by offering patients in vitro fertilization/intracytoplasmic sperm injection must be approached with caution because of the significant risk for embryonic aneuploidy and chromosomal abnormalities in any subsequent offspring.

The sperm deformity index: a reliable predictor of the outcome of oocyte fertilization in vitro *

OBJECTIVE To evaluate a novel expression of sperm morphological parameters, the sperm deformity index, as a predictor of fertilization in vitro. DESIGN Prospective blind clinical trial. SETTING Academic tertiary referral center. INTERVENTION(S) Detailed sperm morphological assessment applying strict morphological criteria and a multiple entry technique for an unselected male population undergoing IVF. The sperm deformity index, defined as the average number of deformities per sperm assessed, was calculated. PATIENT(S) One hundred fifty-eight patients undergoing IVF treatment. Females with conditions negatively influencing fertilization were excluded. MAIN OUTCOME MEASURE(S) Fertilization rates and pregnancy. RESULT(S) Seventy-three percent of patients achieved fertilization. Patients achieving fertilization had a significantly higher median proportion of normal forms and a significantly lower median sperm deformity index than the nonfertilizers. The receiver operator characteristic (ROC) curves identified cutoff points that maximized the sum of sensitivity and specificity at sperm deformity index 1.6 and normal forms 4%. The sperm deformity index had a greater sensitivity (96%), specificity (72%), positive predictive value (90%), and negative predictive value (86%) than the proportion of normal sperm morphology (87%, 69%, 89%, 66%, respectively) at the optimal cutoff points. The area under the ROC curve was greater for the sperm deformity index (0.875) than for the proportion of normal sperm morphology (0.622). Achieving pregnancy did not correlated with sperm morphology. CONCLUSION(S) The sperm deformity index is a more reliable predictor of the outcome of fertilization in vitro than the proportion of normal sperm morphology and can assist to identify patients who require techniques such as intracytoplasmic sperm injection.

Endometrial integrin expression in women undergoing in vitro fertilization and the association with subsequent treatment outcome

OBJECTIVE To study the endometrial expression of three integrins (alpha v beta 3, alpha 4 beta 1, and alpha 1 beta 1) in women undergoing IVF-intracytoplasmic sperm injection (ICSI) treatment and assess whether they could be used to predict subsequent treatment success.Prospective observational study. Healthy volunteers in a large teaching hospital. PATIENT(S) Sixty-six patients attending for IVF-ICSI treatment. INTERVENTION(S) Timed endometrial biopsies were taken, during the implantation window at LH + 7-9 days, from women before IVF-ICSI treatment. MAIN OUTCOME MEASURE(S) Histological dating of endometrium and immunohistochemical staining intensity of alpha 4 beta 1, alpha v beta 3, and alpha 1 beta 1 integrins. The integrin levels were correlated with subsequent success rates. RESULT(S) There was a statistically significantly greater expression of alpha v beta 3 in the luminal epithelium of those patients who had successful treatment. However, treatment was successful in some patients with negative expression. CONCLUSION(S) Integrins are important markers of endometrial receptivity. There is an association between an in-phase endometrial biopsy, with positive luminal alpha v beta 3 integrin expression, and subsequent treatment success. However, the clinical value of assessing the endometrium before treatment has drawbacks, and further work needs to be done before this can be considered a clinically useful test.

Reproductive potential of fresh and cryopreserved epididymal and testicular spermatozoa in consecutive intracytoplasmic sperm injection cycles in the same patients

OBJECTIVE To determine if the cryopreservation of epididymal and testicular spermatozoa alters their reproductive potential by examination of patients who underwent consecutive cycles of ICSI using fresh and then cryopreserved spermatozoa. DESIGN Retrospective review. SETTING Tertiary care university hospital. PATIENT(S) One hundred sixty-two consecutive cycles of ICSI were analyzed. Thirteen patients were identified as having undergone treatment with freshly retrieved epididymal spermatozoa; these patients subsequently underwent treatment with spermatozoa cryopreserved from that cycle. Eighteen patients underwent ICSI with freshly retrieved testicular spermatozoa; these patients subsequently underwent treatment with spermatozoa cryopreserved from that cycle. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Fertilization rates and pregnancy rates. RESULT(S) The fertilizing capacity of epididymal spermatozoa remained unchanged after cryopreservation and subsequent thawing, with fertilization rates of 58% and 57% for fresh and cryopreserved spermatozoa, respectively. Testicular spermatozoa, however, showed a significant decrease in fertilizing capacity after cryopreservation when compared with freshly retrieved spermatozoa (52% and 71%, respectively). Pregnancy rates appeared unaffected by the cryopreservation of epididymal spermatozoa (fresh, 3/13; frozen, 2/13) or testicular spermatozoa (fresh, 2/18; frozen, 5/18). CONCLUSION(S) This study offers further evidence that motile epididymal spermatozoa retain their fertilizing capacity after cryopreservation. The data presented on testicular spermatozoa suggest that although cryopreservation may reduce the fertilizing capacity of testicular spermatozoa, there is no decrease in pregnancy rates.

Leukocytes in semen from men with spinal cord injuries.

OBJECTIVE To assess the leukocyte populations in semen samples from men with spinal cord injuries (SCIs) and their relation to sperm motility. DESIGN Cross-sectional study. SETTING A joint spinal cord injury and fertility clinic at an academic tertiary referral center for fertility treatment and a university-based department of immunology. PATIENT(S) Nine men with chronic SCIs and seven healthy sperm donors as controls. INTERVENTION(S) Semen samples were obtained by electroejaculation from men with SCIs and by masturbation from donors. MAIN OUTCOME MEASURE(S) Leukocyte populations determined by immunohistochemical techniques, bacteriologic assessment of urine, and sperm density and motility. RESULT(S) The most cellular specimens were antegrade specimens obtained from men with SCIs and coexisting urinary tract infections. The highest proportion of leukocytes occurred in retrograde samples from men with SCIs and urinary tract infections. The most predominant leukocytes in all specimens were granulocytes. Infection increased the number of T cells and the degree of cell activation. There was no significant correlation between leukocyte populations and total motile sperm counts. CONCLUSION(S) Increased numbers of leukocytes in semen samples from men with SCIs are the result of urinary tract infections. The reduced sperm motility seen in men with SCIs does not correlate with the numbers of leukocytes; therefore, other factors also contribute to the semen abnormalities in these patients.

Seasonal variation in assisted conception cycles and the influence of photoperiodism on outcome in in vitro fertilization cycles

The effect of seasonality and daylight length on mammalian reproduction leading to spring births has been well established, and is known as photoperiodism. In assisted reproduction there is much greater uncertainty as to the effect of seasonality. This was a 4-year retrospective analysis of 2709 standardised cycles of IVF/ICSI. Data was analysed with regard to the 1642 cycles occurring during the months of extended daylight (Apr – Sept) and those 1067 cycles during winter months of restricted light length (Oct – Mar). The results showed that there was significant improvement in assisted conception outcomes in cycles performed in summer (lighter) months with more efficient ovarian stimulation 766iu v880iu/per oocyte retrieved (p = 0.006). There was similarly a significantly improved implantation rate per embryo transferred 11.42% vs 9.35% (p = 0.011) and greater clinical pregnancy rate 20% vs 15% (p = 0.0033) during summer cycles. This study appears to demonstrate a significant benefit of increased daylight length on outcomes of IVF/ICSI cycles. Whilst the exact mechanism of this is unclear, it would seem probable that melatonin may have actions at multiple sites and on multiple levels of the reproductive tract, and may exert a more profound effect on outcomes of assisted conception cycles than has been previously considered.

Concentration of Interleukin-12 in the peritoneal fluid is not influenced by the presence of endometriosis, its stage or the phase of the menstrual cycle

Background. IL‐12 is a key immunomodulatory cytokine. Its presence or concentration in peritoneal fluid is not related to the presence of endometriosis or the stage of the disease. A study was carried out to gain insight into the role of IL‐12 in the development and maintenance of endometriosis in relation to menstrual cycle.

The value of routine estradiol monitoring in assisted conception cycles

Background. Traditional monitoring of an in vitro fertilization (IVF) treatment cycle includes regular estradiol levels and ultrasound scans in an attempt to reduce the risk of ovarian hyperstimulation syndrome (OHSS). The need for estradiol monitoring remains controversial.

Placental-type alkaline phosphatase in human seminal plasma from fertile and infertile men.

Solid-phase enzyme immunoassays, based on monoclonal antibodies reactive with different forms of human placental-type alkaline phosphatases, were applied to their detection in human seminal plasma from fertile and infertile men. The placental-like form of alkaline phosphatase (PLAP-like AP), known to occur in testicular tissue, was found in normal seminal plasma. The incidence of detection and levels of this isoenzyme correlated significantly with the designated fertility status of the donor. Seminal plasma (PLAP-like AP) may reflect germ cell function and/or access of testicular products to the ejaculate.

Optimal treatment for poor responders to ovarian stimulation: does in vitro insemination offer any advantages to intrauterine insemination?

A retrospective study was performed of 1832 consecutive in vitro insemination (IVF)/intracytoplasmic sperm injection (ICSI) cycles over 18 months, to analyse the benefits or otherwise to the patient of continuing with in vitro treatment or converting the assisted conception cycle to intrauterine insemination (IUI). Two hundred and seventy cycles were identified in which three follicles or fewer were obtained after controlled ovarian hyperstimulation; in 143 of these cycles, the clinicians or patients elected to abandon all treatment, whereas treatment was continued in 127 patients. In 79 cycles, the patients proceeded with IVF/ICSI and in 48 patients, the cycles were converted to IUI. Data were analysed with regard to the clinical pregnancy rate. In addition, the data for IUI were compared with eight cycles of supraovulation IUI (S/IUI) performed over the same period. There were no significant differences in clinical pregnancy rates among any treatment modality 6/48 (12.5%), 6/79 (7.7%) and 1/8 (12.5%) for IUI, IVF and S/IUI, respectively (P = 0.64). The lowest total number of motile spermatozoa required to achieve pregnancy using IUI was 2.0 × 106. In conclusion, it appears that, if the treatment is suitable, patients who respond poorly to controlled hyperstimulation for IVF would not be disadvantaged in achieving a pregnancy by offering them conversion to the medically and financially less interventional IUI.