Category Archives: Human Reproduction

BACKGROUND

We previously found that a normal karyotype in a previous miscarriage is a predictor of subsequent miscarriage. However, the prevalence of recurrent miscarriage caused by an abnormal embryonic karyotype has not yet been reported, since embryonic karyotype is not typically analyzed during conventional examinations.

METHODS

A total of 482 patients who underwent both embryonic karyotype determination and conventional examinations for recurrent miscarriage were enrolled in this study. The distribution of the causes and the live birth rate for each cause were examined.

RESULTS

The total percentage of subjects in whom conventional causes of recurrent miscarriage could be detected was 29.5%. The prevalence of the abnormal embryonic karyotype was 41.1% in the subjects in whom no conventional causes of miscarriage could be identified. The prevalence of recurrent miscarriage of truly unexplained cause, that is, of subjects without conventional causes in whom the embryonic karyotype was ascertained to be normal, was 24.5%. Among the patients in whom the first determination revealed an abnormal embryonic karyotype, 76.2% (32/42) showed an abnormal embryonic karyotype in the repeat determination as well. The cumulative live birth rate (71.9%) in women with recurrent miscarriages caused by the abnormal embryonic karyotype was significantly higher than that (44.7%) in women with recurrent miscarriages associated with the embryonal euploidy.

CONCLUSION

An abnormal embryonic karyotype was found to represent the commonest cause of recurrent miscarriage, and the percentage of cases with recurrent miscarriage of truly unexplained cause was limited to 24.5%.The two groups should be distinguished for both clinical and research purposes.

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BACKGROUND

Gap junctions (GJs) allow for direct communication between adjacent cells. They are composed of connexons consisting of transmembrane proteins, connexins (Cxs). The objectives of this study were to determine if GJ proteins GJA1 (Cx43), GJB1 (Cx32) and GJB2 (Cx26) are present in the epididymis of men with a normal epididymis, to assess whether or not Cx expression and localization are altered in azoospermic patients, and to determine if epidermal growth factor (EGF) regulates GJA1 expression.

METHODS

Epididymides were obtained from men with localized testis cancer with active spermatogenesis and histologically normal epididymal tubule (group 1), men with non-obstructive azoospermia secondary to Sertoli-cell only syndrome (group 2) and from azoospermic men with normal spermatogenesis and epididymal obstruction (group 3). Epididymides were subdivided into three segments: caput, corpus and cauda. Quantitative real-time RT–PCR was performed to assess GJA1, GJB1, GJB2 and EGF receptor (EGFR) mRNA levels in epididymides from patients from each group (all n= 3, except n= 1 for caput blockage). A human caput epididymal cell line was then used to determine the role of EGFR signaling on the regulation of human epididymal GJA1.

RESULTS

Real-time RT–PCR analysis revealed that GJA1, GJB1, GJB2 and EGFR were expressed along the human epididymis. In the cauda epididymidis of group 2 and 3 men, we observed a significant decrease in GJA1 (P= 0.0456 and P= 0.0465, respectively) and GJB1 (P= 0.0450 and P= 0.0497, respectively) mRNA levels when compared with group 1 men. We also observed a decrease in EGFR mRNA levels (P= 0.0358) in the cauda epididymidis of group 3 men when compared with group 1. Immunocytochemistry revealed that in the epididymis, GJA1 and EGFR were localized between basal and principal cells and between adjacent principal cells. In group 2 and 3 patients, however, we noted a dramatic increase in cytosolic immunostaining for both GJA1 and EGFR in both principal and basal cells. Using a human caput epididymal cell line derived from fertile men, we demonstrated that changes in GJA1 phosphorylation could be regulated by EGF (P= 0.015) and the extracellular regulated kinase 1/2 signaling pathway (P= 0.03). Furthermore, while the phosphoinositide-3-kinase (PI3K)/AKT signaling pathway did not alter GJA1 phosphorylation, treatment with PI3K/AKT inhibitor LY294002 significantly (P= 0.024) inhibited the EGF-stimulated increase in GJA1 total protein levels at 24 h. Immunolocalization indicated that loss of PI3K/AKT signaling was associated with increased cytosolic localization of Cx43 in this cell line.

CONCLUSIONS

Together, these data suggest that in azoospermic men decreased expression of EGFR may be responsible for decreasing GJA1 levels and increasing its cytosolic localization via the PI3K/AKT signaling pathway.

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BACKGROUND

Intracytoplasmic sperm injection (ICSI) is the primary treatment for male infertility. However for this procedure, with the exception of visual morphological selection, there is no standardization for sperm selection. Recently, the hypo-osmotic swelling test (HOST) has been proposed to potentially select sperm with intact membranes. The aim of this study is to evaluate the ability of this technique to select functional sperm in terms of apoptosis and morphology, as well as nuclear integrity.

METHODS

A total of 20 semen samples were randomly collected from men who attended the Andrology Unit of the Isfahan Fertility and Infertility Center. Semen samples were washed and exposed to hypotonic conditions, before being fixed and simultaneously assessed for membrane integrity as well as abnormal morphology, DNA fragmentation and protamine deficiency by using Papanicolaou, TUNEL and CMA3 staining techniques, respectively. The remaining semen samples were washed with calcium buffer and stained by Annexin V, then exposed to hypotonic conditions before being assessed for early apoptosis along with membrane integrity.

RESULTS

HOST grade ‘d’, followed by grade ‘c’, showed the highest percentages of healthy sperm, whereas sperm of HOST grade ‘g’ in which anomalies in terms of apoptosis, abnormal head morphology or nuclear immaturity or membrane damage, were most frequently observed in the samples assessed.

CONCLUSIONS

Integration of HOST into the sperm selection procedure may provide a valuable tool for selection of functional sperm required for ICSI. According to this study, insemination of HOST grade ‘g’ sperm should be avoided during ICSI.

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STUDY QUESTION

Does follicular flushing during assisted reproductive technologies (ART) improve the number of oocytes retrieved?  

SUMMARY ANSWER

Follicular flushing during ART does not result in a greater number of oocytes in normal responders.

WHAT IS KNOWN ALREADY

Despite limited evidence supporting the use of follicular flushing, it continues to be a common procedure in many ART clinics. Prior studies have provided conflicting results regarding the routine use of flushing during oocyte retrieval.

STUDY DESIGN, SIZE, DURATION

Systematic review and meta-analysis of 518 patients who participated in 6 randomized trials over 20 years.

PARTICIPANTS/MATERIALS, SETTING, METHODS

Literature searches were conducted to retrieve randomized controlled trials on follicle or ovarian flushing in ART. Databases searched included PubMed, EMBASE, Web of Science and the Cochrane Database of Clinical Trials (CENTRAL). Six trials that included 518 subjects matched the inclusion criteria. Studies included were limited to trials that were published, randomized trials comparing oocyte retrieval with a single-lumen pick-up needle versus follicle flushing after direct aspiration with a multi-channel oocyte pick-up needle in ART patients.

MAIN RESULTS AND THE ROLE OF CHANCE

In each of the trials, measures of the oocyte yield (oocytes retrieved divided by follicles aspirated), total oocytes retrieved, fertilization or pregnancy were not different when comparing direct aspiration with follicle flushing. Four trials reported a higher operative time with follicle flushing. Results of the meta-analysis indicated no significant differences in the oocytes retrieved [weighted mean difference: 0.07, 95% confidence interval (CI): –0.13 to 0.29] or the oocyte yield (odds ratio: 1.06, 95% CI: 0.95–1.18) between the non-flushing and flushing groups.

LIMITATIONS, REASONS FOR CAUTION

All trials featured an open label design and the majority of patients in this meta-analysis were normal responders. The applications of these results to poor responders, patients undergoing natural cycle ART or minimal stimulation ART should be made with caution.

WIDER IMPLICATIONS OF THE FINDINGS

Follicle flushing does not improve ART outcomes in normal-responding patients and should not be performed. This meta-analysis should solidify this recommendation as it includes the largest trial published on the subject and is consistent with a recently published Cochrane review.

STUDY FUNDING/COMPETING INTEREST(S)

This work was supported, in part, by the Program in Reproductive and Adult Endocrinology, NICHD, NIH, Bethesda, MD. The authors have no competing interests to declare.

TRIAL REGISTRATION NUMBER

N/A.

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BACKGROUND

The incidence of overweight and obesity in men of reproductive ages is rising, which may affect fertility. Therefore, this study aims to assess the associations between BMI, central adiposity and sperm parameters in men of subfertile couples.

METHODS

Ejaculate volume (ml), sperm concentration (millions per ml), percentage of progressive motile and immotile spermatozoa and total motile sperm count (millions) were measured in 450 men of subfertile couples visiting a tertiary outpatient clinic for reproductive treatment and preconception counseling.

RESULTS

Overweight was negatively associated with the percentage of progressive motility type A [β –0.32 (SE 0.2), P = 0.036] and positively associated with the percentage of immotility type C [β 0.21 (SE 0.07), P = 0.002]. Obesity was negatively associated with ejaculate volume [β –0.23 (SE 0.1), P = 0.02], sperm concentration [β –0.77 (SE 0.3), P = 0.006] and total motile sperm count [β –0.91 (SE 0.3), P = 0.007]. Waist circumference ≥102 cm, a measure for central adiposity, was inversely associated with sperm concentration [β –0.69 (SE 0.2), P = 0.001] and total motile sperm count [β –0.62 (SE 0.3), P = 0.02]. All associations remained significant after adjustment for age, ethnicity, active and passive smoking, alcohol and medication use and folate status.

CONCLUSIONS

This study shows that in particular, sperm concentration and total motile sperm count in men of subfertile couples are detrimentally affected by a high BMI and central adiposity. The effect of weight loss on sperm quality and fertility needs further investigation.

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BACKGROUND

No questionnaire is currently available for the presurgical diagnosis of adnexal torsion (AT). Our objective was to develop a predictive model for AT, based on the Self Assessment Questionnaire for Gynecologic Emergencies (SAQ-GE) designed for triaging women with acute pelvic pain.

METHODS

We performed a multicenter prospective trial conducted in five hospitals in France. Four hundred and ninety-six (496) women with acute pelvic pain (Numeric Rating Scale >4), including 31 with AT, were recruited from September 2006 through April 2008. An AT score was built using the SAQ-GE.

RESULTS

Five criteria were independently associated with AT confirmed by surgery: unilateral lumbar or abdominal pain [adjusted diagnostic odds ratio (aDOR), 23.3; 95% confidence interval (95% CI), 3.0–178]; absence of leucorrhea and metrorrhagia (aDOR, 7.0; 95% CI, 2.5–20), ovarian pain (aDOR, 5.5; 95% CI, 1.5–21), unbearable pain (aDOR, 5.0; 95% CI, 1.4–18) and vomiting (aDOR, 3.7; 95% CI, 1.6–9.0). The SAQ-GE torsion score was based on these five criteria and its values range from 0 to 10. The low-risk group (SAQ-GE torsion score <7), based on the score values, has a sensitivity (Se) of 96.7% (95% CI, 90.5–100), a negative predictive value of 99.7% (95% CI, 99.1–100) and a negative likelihood ratio (Lr–) of 0.05, ruling out AT with a probability of AT of 0.3% (95% CI, 0.0–0.9). Cross-validation of the model was performed using the jackknife resampling procedure, retrieving an unbiased Se of 87.1 (95% CI, 75.1–99.1) and a specificity of 74.2% (95% CI, 70.2–78.2).

CONCLUSIONS

The SAQ-GE torsion score may prove useful for screening for AT in patients experiencing acute pelvic pain.

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