Category Archives: Human Reproduction

BACKGROUND

Prognostic models for natural conception help to identify subfertile couples with high chances of natural conception, who do not need fertility treatment yet. The use of such models and subsequent tailored expectant management (TEM) is not always practiced. Previous qualitative research has identified barriers and facilitators of TEM among patients and professionals. The aim of this study was to assess the prevalence of those barriers and facilitators and to evaluate which factors predict patients' appreciation of TEM and professionals' adherence to TEM.

METHODS

We performed a nationwide survey. Based on the previously identified barriers and facilitators two questionnaires were developed and sent to 195 couples and 167 professionals. Multivariate analysis was performed to evaluate which factors predicted patients' appreciation of TEM and professional adherence to TEM.

RESULTS

In total, 118 (61%) couples and 117 (70%) professionals responded and 96 couples and 117 professionals were included in the analysis. Patients' mean appreciation of TEM was 5.7, on a 10-point Likert scale. Patients with a lower appreciation of TEM had a higher need for patient information (P = 0.047). The professionals reported a mean adherence to TEM of 63%. Adherence to TEM was higher when professionals were fertility doctors (P = 0.041). Facilitators in the clinical domain were associated with a higher adherence to TEM (P = 0.091). Barriers in the professional domain had a negative impact on adherence to TEM (P = 0.008).

CONCLUSIONS

The limited implementation of TEM is caused by both patient and professional-related factors. This study provides practical tools to improve the implementation of TEM.

Source:
http://humrep.oxfordjournals.org/rss/current.xml

BACKGROUND

There is currently no consensus about indications for surgery for infertility associated with colorectal endometriosis. The aim of this study was to evaluate cumulative pregnancy rates (CPRs) after ICSI–IVF cycles in patients with colorectal endometriosis and to identify determinant factors of fertility outcome.

METHODS

Prospective longitudinal multicentre study from January 2005 to June 2011. We included 75 patients with colorectal endometriosis and proved infertility without prior surgery for deep infiltrating endometriosis. Univariable analysis was used to identify determinant factors of pregnancy rate. CPR was calculated using cumulative-incidence methods from log-rank test and Kaplan–Meier curves. For multivariable analysis, Cox proportional hazards model was used.

RESULTS

For CPR per patient analysis, the total number of cycles was 113 and the median number of cycles per patient was 1 (range: 1–3). In the whole population the CPR per patient after three ICSI–IVF cycles was 68.6%. The CPR for patients with or without associated adenomyosis was 19 and 82.4%, respectively (P= 0.01). In addition, a patient age over 35 years (P= 0.02) and anti-Mullerian hormone serum level under 2 ng/ml (P= 0.02) were associated with a decreased CPR per patient. At multivariable analysis, adenomyosis [HR = 0.34, 95% CI (0.12–0.99), P= 0.49] was associated with a decreased CPR.

CONCLUSIONS

Our data confirm that ICSI–IVF offers a high CPR per patient. However, determinant factors of CPR should be taken into account when informing couples of their options.

Source:
http://humrep.oxfordjournals.org/rss/current.xml

BACKGROUND

Polychlorinated biphenyls (PCBs) are common environmental contaminants that represent an important risk factor of reproductive disorders in chronically exposed human populations. However, it is not known whether a short accidental exposure of embryos to PCBs before implantation might influence their further development and whether the effect might be reversible.

METHODS AND RESULTS

To this aim, in vitro-matured sheep blastocysts were incubated with 2 or 4 µg/ml Aroclor 1254 (A1254), a mixture of 60 PCB congeners for 48h after which blastocyst proliferation and ability for outgrowth in vitro were assessed. Blastocysts exposed to A1254 showed: (i) reduced proliferation and cell number (particularly in the inner cell mass compartment); (ii) accumulation of vacuoles and lipid droplets, diffused mitochondrial damage and up-regulation of autophagy markers (ATG6 and LC3), all signs indicative of deregulated autophagy, and (iii) massive cell death. Although exposed embryos resumed growth following A1254 removal, their subsequent development remained severely perturbed.

CONCLUSIONS

These findings indicate that short exposure of blastocysts to PCBs leads to its damage characterized by deregulated autophagy and subsequent cell death.

Source:
http://humrep.oxfordjournals.org/rss/current.xml

BACKGROUND

Increased global industrial activity has exposed humans to a wide variety of chemical substances some of which, called ‘endocrine-disrupting chemicals’ (EDCs) or ‘endocrine disruptors’, can disrupt the endocrine system in the body. The ovarian follicle is a very fragile micro-environment where interactions between hormones, growth factors, the oocyte and its surrounding somatic cells are essential to generate a fully competent oocyte. In vitro experiments suggest that EDCs can disturb this finely tuned balance, but very scarse in vivo data are available to confirm this assumption. Therefore, we have investigated if the presence of EDCs in human follicular fluid is a risk factor for the developmental competence of an in vivo exposed oocyte. Furthermore, because of the limited access to human follicular fluid, we verified if follicular fluid contamination can be predicted based on EDC levels in serum.

METHODS

Follicular fluid (n = 40) and serum (n = 20) samples from women undergoing assisted reproductive technology (ART) were analyzed by means of gas chromatography combined with mass spectrometry to examine the presence of different EDCs, such as polychlorinated biphenyls, polybrominated diphenyl ethers and organochlorine pesticides. Statistical models were used to investigate the relation between the characteristics and ART results of the patients and the contamination status of their follicular fluid and to assess the capacity of serum samples to predict follicular fluid contamination.

RESULTS

Chlorinated biphenyl 153 (72 ± 44 and 201 ± 106 pg/ml) and p,p'-DDE (392 ± 348 and 622 ± 406 pg/ml) were the compounds found in the highest concentrations in follicular fluid and serum samples, respectively. A new variable principal component 1, representing the overall contamination status of the follicular fluid samples, is strongly associated with fertilization rate (P < 0.00001) and the proportion of high-quality embryos relative to the amount of retrieved oocytes (P < 0.05), even when the analysis is adjusted for age, estradiol concentration, BMI, fertilization procedure and male subfertility as explanatory variables. The strong correlations between the EDC concentrations in serum and follicular fluid (r ≥ 0.93) allowed us to build regression models, which accurately predict EDC concentrations in the follicular fluid based on serum samples.

CONCLUSIONS

An overall higher EDC contamination in the follicular micro-environment was associated with a decreased fertilization rate and consequently with a lower chance of an oocyte to develop into a high-quality embryo. In addition, EDC concentrations in serum were reliable predictors of the contamination status of the follicular micro-environment.

Source:
http://humrep.oxfordjournals.org/rss/current.xml

BACKGROUND

Sperm chromatin is highly condensed and relatively resistant to chemical and physical treatments. The purpose of this study was to explore the highest temperature that sperm can tolerate and still produce live offspring.

METHODS

Mouse sperm were heated in a water bath at 50, 65, 80 or 95°C for 30 min before they were microinjected into mouse oocytes. Fertilization, embryo development and 1-cell embryo karyotypes were evaluated. Epigenetic reprogramming including DNA methylation and histone H3K4-trimethylation were evaluated by immunofluorescent staining.

RESULTS

The ability of mouse sperm to activate the egg after ICSI was heat sensitive; only 20% of eggs were activated by sperm that had been heated to 50°C and none was activated by sperm heated to 80°C. However, if eggs were activated artificially, mouse sperm subjected to 80°C for 30 min were able to produce live offspring, while 95°C treatment disabled sperm decondensation after ICSI. Once the heat-treated sperm nucleus had developed into a pronucleus, sperm chromatin was able to undergo normal active DNA demethylation and histone methylation. Aberrant chromosome rates increased from 16.3 to 100% when the temperature was raised from 50 to 95°C.

CONCLUSIONS

Heat treatment destroys integrity of sperm chromatin in a temperature-dependent manner. Eighty degree Celsius was the highest temperature that mouse sperm could withstand and still produce live offspring.

Source:
http://humrep.oxfordjournals.org/rss/current.xml

BACKGROUND

The progesterone-regulated glycoprotein glycodelin-A (GdA), secreted by the decidualized endometrium at high concentrations in primates, inhibits the maternal immune response against fetal antigens and thereby contributes to the tolerance of the semi-allogenic fetus during a normal pregnancy. Our earlier studies demonstrated the ability of GdA to induce an intrinsic apoptotic cascade in CD4⁺ T-lymphocytes and suppress the cytolytic effector function of CD8⁺ T-lymphocytes. In this report, we investigated further into the mechanism of action of GdA controlling perforin and granzyme B expression in CD8⁺ T-lymphocytes and the mechanism of action of GdA leading to lymphocyte death.

METHODS

Flow cytometry analysis was performed to check for the surface expression of interleukin-2 receptor α (IL-2Rα) and intracellular eomesodermin (Eomes) in activated T-lymphocytes, whereas quantitative RT–PCR analysis was used to find out their mRNA profile upon GdA treatment. Western analysis was carried out to confirm the protein level of Bax and Bcl-2.

RESULTS

GdA reduces the surface expression of the high-affinity IL-2R complex by down-regulating the synthesis of IL-2Rα (CD25). This disturbs the optimal IL-2 signalling and decreases the Eomes expression, which along with IL-2 directly regulates perforin and granzymes expression. Consequently, the CD8⁺ T-lymphocytes undergo growth arrest and are unable to mature into competent cytotoxic T-lymphocytes. In the CD4⁺ T-lymphocytes, growth factor IL-2 deprivation leads to proliferation inhibition, decreased Bcl-2/enhanced Bax expression, culminating in mitochondrial stress and cell death.

CONCLUSIONS

GdA spurs cell cycle arrest, loss of effector functions and apoptosis in different T-cell subsets by making T-lymphocytes unable to respond to IL-2.

Source:
http://humrep.oxfordjournals.org/rss/current.xml