Category Archives: Human Reproduction

BACKGROUND

Low-dose aspirin therapy could improve remodelling of maternal spiral arteries during early placentation and prevent subsequent pregnancy-related hypertensive disorders. We investigated whether low-dose aspirin therapy reduces the incidence of hypertensive pregnancy complications in unselected IVF and ICSI patients when medication was started prior to pregnancy.

METHODS

A total of 487 patients who underwent IVF/ICSI were randomized to receive 100 mg aspirin (n = 242) or placebo (n = 245) daily, starting on the first day of gonadotrophin stimulation. Pregnant women continued the medication until delivery. A total of 107 patients (52 with aspirin and 55 with placebo) experienced live birth and were included in this follow-up study. The main outcome measure was the incidence of hypertensive pregnancy complications.

RESULTS

Embryo transfer took place in 227 (94%) women in the aspirin group and in 229 (93%) women in the placebo group. The live birth rate between the aspirin (22.9%) and placebo (24.0%) groups did not differ significantly (P = 0.78). The overall incidence of hypertensive pregnancy complications was 15.4% (8/52) in the aspirin group and 18.2% (10/55) in the placebo group (P = 0.70, 95% confidence interval for the difference of proportions –17 to 11%). There were two cases of severe pre-eclampsia in the aspirin group and three cases in the placebo group.

CONCLUSIONS

In the present study, the incidence of hypertensive pregnancy complications did not differ statistically significantly between low-dose aspirin and placebo groups in unselected IVF/ICSI patients, when medication was started concomitantly with gonadotrophin stimulation and continued until delivery.

The study was registered at clinicaltrials.gov. NCT00683202.

BACKGROUND

Transforming growth factor-β cytokines have various biological effects in female reproductive tissue, including modulation of inflammatory response and induction of immune tolerance to seminal antigens in the reproductive tract. However, no studies have analyzed the presence of growth/differentiation factor-15 (GDF-15/macrophage inhibitory cytokine-1) in seminal fluid or demonstrated the quantity and form of GDF-15, its possible role or the relationship between its concentration and semen quality.

METHODS

The form and the concentration of GDF-15 were determined in 53 seminal plasma samples of both fertile and infertile men by ELISA and western blot. The sperm cells of three volunteers were treated with recombinant GDF-15, and cell viability and apoptosis were assessed by flow cytometry. The effect of GDF-15 on vaginal epithelial cells and peripheral blood mononuclear cells (PBMCs) was analyzed by quantitative RT-PCR.

RESULTS

The GDF-15 concentration in seminal plasma ranged from 0.2 to 6.6 µg/ml as determined by ELISA. Western blot analysis revealed that GDF-15 is present in the active form. In vitro cultivation of sperm cells with GDF-15 did not affect their viability or rates of apoptosis; however, it did inhibit proliferation of PBMCs and induce expression of FOXP3 in CD4+CD25+ cells.

CONCLUSIONS

To the best of our knowledge, this is the first demonstration that GDF-15 is an abundant cytokine in seminal plasma, although its concentration is not associated with semen quality or the fertility/infertility status of the donors. Moreover, our data show that GDF-15 displays immunosuppressive characteristics.

BACKGROUND

The Piwi subfamily of genes is involved in spermatogenesis for the maintenance and meiosis of germline stem cells. Mice bearing targeted mutations in Piwi genes (Miwi, Mili and Miwi2) are sterile with distinct defects in spermatogenesis. We hypothesized that Piwi gene polymorphisms could be a risk factor for spermatogenic failure.

METHODS

For this study, 490 patients with idiopathic azoospermia or oligozoospermia and 468 fertile controls were recruited from an infertility clinic. Nine single nucleotide polymorphisms (SNPs) of four Piwi genes (PIWIL1/HIWI, PIWIL2/HILI, PIWIL3/HIWI3 and PIWIL4/HIWI2) were genotyped using the SNPstream^® 12-plex platform and the Taqman method.

RESULTS

An SNP in the 3'untranslated region of HIWI2 and a non-synonymous SNP in HIWI3 were significantly associated with an altered risk of oligozoospermia. The variant-containing genotypes of HIWI2 rs508485 exhibited a significantly increased risk, with an odds ratios (OR) of 1.49 [95% confidence interval (CI), 1.02–2.18], and individuals with HIWI3 non-synonymous rs11703684 variant genotypes exhibited a significantly reduced oligozoospermia risk (OR = 0.70; 95% CI, 0.49–1.00). The haplotype analysis showed that a common haplotype of HIWI2 was associated with a significant reduction in the risk of oligozoospermia (OR = 0.73, 95% CI, 0.56–0.97). In addition, to assess the cumulative effects, we performed a combined unfavourable genotype analysis. A significant trend towards increased risk of oligozoospermia with an increasing number of unfavourable genotypes was observed (P for trend < 0.001).

CONCLUSIONS

We present the first epidemiologic evidence supporting the involvement of genetic polymorphisms in Piwi genes in spermatogenic failure.

Ovarian reserve is determined by the number of primordial follicles in the ovary. Quiescent primordial follicles are activated for growth and pass through stages of development before they reach the antral stage. Then a cohort of antral follicles is recruited for further growth, dominance and ovulation under the cyclic stimulation of gonadotrophins. What triggers the initiation of growth in primordial follicles has remained a mystery for decades. However, recent studies on mutant mouse models have shown that primordial follicles are maintained in a dormant state by the actions of various inhibitory molecules to preserve the follicle pool, such as the transcription factor Foxo3a, PTEN (phosphotase and tensin homolog deleted on chromosome 10) and Tsc-1 (tumour suppressor tuberous schlerosis complex). Mice with deletions of these oocyte-specific genes exhibit premature activation of dormant primordial follicles, and all primordial follicles become depleted in early adulthood, causing premature ovarian failure. Other oocyte and somatic cell-derived growth factors are also involved in the early, gonadotrophin-independent phase of follicle growth via autocrine and paracrine interactions. Interestingly, some of these factors also play critical roles at later stages of follicle growth, such as the process of selecting the dominant follicle, by modifying the response of the follicles to gonadotrophins and inhibiting premature luteinization. Therefore, a thorough understanding of the molecular aspects of folliculogenesis is of paramount importance in the context of translational medicine and future clinical applications in human reproduction.

BACKGROUND

So far, research on the patients’ perspective on fertility care has mainly focused on women. Our primary aim was to explore what is important to men with respect to care related to testicular sperm extraction (TESE) and to identify strengths and weaknesses of that care.

METHODS

This was a mixed-method study including phenomenology on interviews with 17 ‘interview participants’ (a purposive sample with diversification for the TESE result) who received a TESE treatment at a tertiary university clinic. Strengths and weaknesses of our TESE-related quality of care were identified. Additionally, a telephone questionnaire was answered by 15 ‘rating participants’ not willing to be interviewed and the questionnaire was analyzed quantitatively.

RESULTS

Interview participants wanted more than effective treatment and attached importance to the attitude of fertility clinic staff, information, time flow, personalized care, ‘all that is necessary’, coaching, a homely atmosphere, continuity, privacy and separate accommodation. The satisfaction of rating participants (independent of the TESE result) was problematic for ‘overall experience’, ‘physician at the day clinic’ and ‘gynecologist at discussion of the result’. The attitude of fertility clinic staff and information were the most obvious strengths of our TESE-related care. Weaknesses were lack of practical information on post-surgical recovery and waiting times in the waiting room.

CONCLUSIONS

TESE patients focus not only on clinical effectiveness but also on patient-centeredness of care, and this has led to organizational changes and a new patient information brochure in our center. Qualitative research is useful to examine, understand and improve the patient-centeredness of care.

BACKGROUND

Monitoring assisted reproductive technology (ART) is essential to evaluate the performance of fertility treatment and its impact on birth rates. In Europe, there are two kinds of ART registers: voluntary and mandatory. The validity of register data is very important with respect to the quality of register-based observational studies. The aim of this paper is to determine the degree of agreement between voluntary and mandatory ART registers.

METHODS

The two sources for the data compared in this study (referring to 2005 and 2006) were FIVCAT.NET (an official compulsory Assisted Reproduction Registry within the Health Ministry of the Regional Government of Catalonia, to which all authorized clinics, both public and private, performing assisted reproduction in the region are obliged to report) and the register of the Spanish Fertility Society (SEF), to which data are provided on a voluntary basis. The SEF register data were divided into two groups: (i) data from clinics in Catalonia (SEF-CAT); (ii) data from the rest of Spain, excluding Catalonia (SEF-wCAT). The techniques compared were IVF cycle using patients’ own eggs (IVF cycle) versus donor egg cycles.

RESULTS

For IVF cycles, the voluntary ART register reflected 77.2% of those on the official one, but the corresponding figure was only 34.4% with respect to donated eggs. The variables analysed in the IVF cycle (insemination technique used, patients’ age, number of embryos transferred, pregnancy rates, multiple pregnancies and deliveries) were similar in the three groups studied. However, we observed significant differences in donor egg cycles with regard to the insemination technique used, pregnancy rates and multiple pregnancies between the voluntary and the official register.

CONCLUSIONS

Data from the voluntary ART register for IVF cycles are valid, but those for donor egg cycles are not. Further study is necessary to determine the reasons for this difference.