The effect of short term exposure to outdoor air pollution on fertility.

BACKGROUND: There is evidence to suggest that long term exposure to air pollution could be associated with decreased levels of fertility, although there is controversy as to how short term exposure may compromise fertility in IVF patients and what windows of exposure during the IVF process patients could be most vulnerable. METHODS: This prospective cohort study aimed to evaluate the impact of acute exposure that air pollution have on reproductive outcomes in different moments of the IVF process. Women undergoing IVF living in Barcelona were recruited. Individual air pollution exposures were modelled at their home address 15 and 3 days before embryo transfer (15D and 3D, respectively), the same day of transfer (D0), and 7 days after (D7). The pollutants modelled were: PM2.5 [particulate matter (PM) ≤2.5 µm], PMcoarse (PM between 2.5 and 10µm), PM10 (PM≤10 µm), PM2.5 abs, and NO2 and NOx. Outcomes were analyzed using multi-level regression models, with adjustment for co-pollutants and confouding factors. Two sensitivity analyses were performed. First, the model was adjusted for subacute exposure (received 15 days before ET). The second analysis was based on the first transfer performed on each patient aiming to exclude patients who failed previous transfers. RESULTS: One hundred ninety-four women were recruited, contributing with data for 486 embryo transfers. Acute and subacute exposure to PMs showed a tendency in increasing miscarriage rate and reducing clinical pregnancy rate, although results were not statistically significant. The first sensitivity analysis, showed a significant risk of miscarriage for PM2.5 exposure on 3D after adjusting for subacute exposure, and an increased risk of achieving no pregnancy for PM2.5, PMcoarse and PM10 on 3D. The second sensitivity analysis showed a significant risk of miscarriage for PM2.5 exposure on 3D, and a significant risk of achieving no pregnancy for PM2.5, PMcoarse and PM10 particularly on 3D. No association was observed for nitrogen dioxides on reproductive outcomes. CONCLUSIONS: Exposure to particulate matter has a negative impact on reproductive outcomes in IVF patients. Subacute exposure seems to increase the harmful effect of the acute exposure on miscarriage and pregnancy rates. Nitrogen dioxides do not modify significantly the reproductive success.

Low-dose growth hormone supplementation increases clinical pregnancy rate in poor responders undergoing in vitro fertilisation.

Poor ovarian response (POR) often means low success rates after in vitro fertilisation (IVF). We aim to study the impact of a low-dose growth hormone (GH) supplementation in pregnancy rates in poor responders in a prospective, self-controlled study of 64 poor responders to previous IVF cycles, who failed to achieve pregnancy and were supplemented with low-doses of GH in a subsequent cycle using the same gonadotropin dose and protocol. Our primary endpoint was the clinical pregnancy rate (CPR), considering secondary endpoints, the number of retrieved oocytes, embryos, embryo quality and the proportion of cycles with embryo transfer. CPR in the GH group was 34.4%. Significant differences were observed for the GH group both in the number of top quality embryos (0.64 ± 0.88 versus 1.03 ± 1.17, p < 0.05) and cryopreserved embryos (0.3 ± 0.81 versus 0.85 ± 1.49, p < 0.05). This is, to our knowledge, the first clinical trial to use a low dose of GH as a supplement for IVF in POR patients. Despite this low dose, we achieved excellent success rates in patients with a very poor prognosis, at a reasonable cost and without side effects, which makes this a safe and cost-effective alternative.

Random-start GnRH antagonist for emergency fertility preservation: a self-controlled trial.

The aim of this study is to evaluate the feasibility and safety of random-start controlled ovarian hyperstimulation (COH) for emergency fertility preservation, regardless of the phase of the menstrual cycle. A self-controlled pilot clinical trial (NCT01385332) was performed in an acute-care teaching hospital and in two private reproductive centers in Barcelona, Spain. Eleven egg donors participated in the study. Two random-start gonadotropin-releasing hormone (GnRH) antagonist protocols were assessed in which ganirelix was initiated on either day 10 (protocol B) or on day 20 (protocol C) of the menstrual cycle and was continued until estradiol levels were below 60 pg/dL. These protocols were compared with a standard protocol (protocol A). The main outcome of interest was the number of metaphase 2 oocytes retrieved. Results from this study show that the number of mature oocytes retrieved was comparable across the different protocols (14.3±4.6 in the standard protocol versus 13.0±9.1 and 13.2±5.2 in protocols B and C, respectively; values expressed as mean ± standard deviation). The mean number of days needed for a GnRH antagonist to lower estradiol levels, as well as the ongoing pregnancy rates, were also similar when protocols B (stimulation in follicular phase) and C (stimulation on luteal phase) were compared with protocol A (standard stimulation). GnRH antagonists can be effectively used for random-start controlled ovarian hyperstimulation with an ovarian response similar to that of standard protocols, and the antagonists appear suitable for emergency fertility preservation in cancer patients.

The impact of donor insemination on the risk of preeclampsia: a systematic review and meta-analysis.

A systematic review and meta-analysis were performed to evaluate whether women who conceive with donor sperm have an increased risk of preeclampsia compared with those who use their partner's sperm. Studies that compared women who were impregnated by donor and partner sperm were included. The main outcomes assessed were preeclampsia and gestational hypertension rates. Altogether, 10,898 women (2342 pregnancies by donor sperm versus 8556 by the partner's sperm) were included from seven observational studies. Conception using donor sperm was associated with an increased risk of preeclampsia (odds ratio [OR] 1.63, 95% CI 1.36-1.95) compared with using a partner's sperm. No difference was observed in the risk of gestational hypertension (OR 0.94, 95% CI 0.43-2.03). In conclusion, pregnancies achieved by donor sperm significantly increase the risk of preeclampsia, although the underlying mechanisms remain unclear. Additional studies are required to confirm these findings.

Diagnostic value of sperm DNA fragmentation and sperm high-magnification for predicting outcome of assisted reproduction treatment.

Over the last years, major improvements in the field of male infertility diagnosis have been achieved. The aim of this study was to determine the diagnostic usefulness of sperm DNA integrity and sperm vacuolisation for predicting outcome in infertile couples undergoing in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI) treatments. A cohort study from 152 infertile couples undergoing sperm DNA fragmentation and high-magnification tests prior to an assisted reproduction treatment was designed. We found that the most predictive cutoff for pregnancy was 25.5% of DNA fragmentation with a negative predictive value of 72.7% (P=0.02). For the degree of vacuolisation, the best predictor of pregnancy was 73.5% of vacuolated sperm grades III+IV with a negative predictive value of 39.4% (P=0.09), which was not statistically significant. In conclusion, sperm DNA fragmentation greater than 25.5% could be associated with higher probability of failure IVF treatment. Regarding the results of the sperm analysis at high magnification, they do not allow us to predict whether or not patients will become pregnant.

Coenzyme Q10 and male infertility: a meta-analysis.

OBJECTIVE: To evaluate the effect of coenzyme Q10 treatments in male infertility, specifically in these parameters: live birth and pregnancy rates, CoQ10 seminal concentration, sperm concentration, and sperm motility. MATERIALS AND METHODS: Systematic review and meta-analysis in male infertility patients with CoQ10 oral treatments. Three trials were included: 149 males in CoQ10 group and 147 males in placebo group. RESULTS: None of the included trials provided any data regarding live births. The results of this meta-analysis show that supplementing infertile men with CoQ10 does not increase pregnancy rates. The analysis showed, among patients receiving CoQ10 treatment, a statistically significant increase in: CoQ10 seminal concentration (RR 49.55, 95 % CI 46.44 to 52.66, I(2) = 17 %), sperm concentration (RR 5.33, 95 % CI 4.18 to 6.47, I(2) = 58 %), and sperm motility (RR 4.50, 95 % CI 3.92 to 5.08, I(2) = 0 %) CONCLUSION: There is no evidence in the literature that CoQ10 increases either live birth or pregnancy rates, but there is a global improvement in sperm parameters. Adequately powered, robust trials of individual and combination antioxidant therapies are required to guide clinical practice.

The effects of letrozole on ovarian stimulation for fertility preservation in cancer-affected women.

Survival rates for fertile women with cancer have increased significantly, lending importance to considering the possibility of motherhood after cancer. This study was a retrospective analysis of a prospective database comparing two groups of patients who underwent fertility preservation after being diagnosed with either breast cancer or a non-hormone-dependent cancer between 2009 and 2011. Nineteen oncology patients were included in the study. The objective was to assess the efficacy of ovarian stimulation with aromatase inhibitors versus a standard antagonist protocol. This study sought to quantify oestradiol concentrations in patients receiving letrozole and to determine the length of time between diagnosis of malignancy and onset of fertility preservation. Number of mature oocytes retrieved in the non-hormone-dependent cancer group was comparable to that in the breast cancer group (15.4±8.19 versus 16.3±7.31). Oestradiol concentrations were higher for patients with non-hormone-dependent cancer (1666.4±739.42 pg/ml versus 829±551.11 pg/ml, P=0.006). There were no differences between the groups in the length of time between diagnosis and fertility preservation (17.4±4.93 versus 16.4±1.74 days). Oestradiol concentrations of breast cancer patients on the letrozole protocol remained much lower than those of patients on the antagonist protocol.

Use of high-magnification microscopy for the assessment of sperm recovered after two different sperm processing methods.

OBJECTIVE: To compare the quality of sperm samples obtained after density-gradient centrifugation and swim-up by performing a nuclear structural analysis with high magnification microscopy at ×8,000. DESIGN: Prospective and randomized split-sample study. SETTING: Reproductive Medicine Center. PATIENT(S): Sperm samples from 53 male-partners of couples undergoing infertility treatment. INTERVENTION(S): Samples were analyzed by high magnification microscopy before and after preparation and classified according the level of nuclear vacuolization. MAIN OUTCOME MEASURE(S): Recovery rate, motility rate and percentage of sperm scoring each of 4 grades of vacuolization in fresh and processed sample. RESULT(S): Both sperm processing methods, swim-up and density gradient centrifugation, allow the selection of sperm with lower nuclear vacuolization and presumably lower DNA fragmentation than the whole ejaculate. CONCLUSION(S): Swim-up produces samples with less vacuolization, but the recovery rate is also lower. The choice of processing technique would then depend on whether intrauterine insemination, IVF or ICSI/IMSI is to be performed. A prospective randomized study scoring fertility rates would be necessary to directly access the influence of these methods on the fertility outcome.

Paraoxonase-1 is only present in traceable amounts in seminal fluid and does not show any relationship with male subfertility.

UNLABELLED: Study Type - Aetiology (case series). LEVEL OF EVIDENCE: 4. What's known on the subject? and What does the study add? Oxidative stress seems to be one of the biochemical causes of defective sperm function. Paraoxonases are antioxidant enzymes that degrade lipid peroxides. There is a paucity of data on the possible role played by these enzymes in the pathophysiology of male sub-fertility. The present study shows that testicular tissue of sub-fertile patients clearly expresses paraoxonases-1, 2, and 3. These findings suggest a role for these enzymes in the protection against lipid peroxidation inside the cell. However, the concentration and activity of paraoxonase-1 in semen are negligible and are probably the result of cellular catabolism, with no significant biological function. OBJECTIVE: To characterise the immunohistochemical sites of paraoxonase (PON) 1, PON2 and PON3 in human testicular tissue, and to analyse PON1 levels in semen, aiming to investigate the role played by these enzymes in the pathophysiology of male subfertility. PATIENTS AND METHODS: The present study was performed in 41 semen samples from normal donors and in 52 semen samples and ten testicle biopsies from patients who were being evaluated for causes of subfertility. RESULTS: Immunohistochemical analyses showed high levels of PON1 and PON3 expression in testicular tissue. PON2 expression was also detected, albeit at weaker levels. Oxidative stress indicators in biopsies were low and localized in some specific areas of the seminiferous tubules. PON1 was detected in seminal fluid at very low levels but with no significant differences between patients and controls. Receiver-operating characteristic analysis showed a low diagnostic power of semen PON1 levels. CONCLUSIONS: The present study shows high protein expression levels of PON1, PON2 and PON3 in testicular cells. The concentrations and activities of PON1 in semen are negligible and are probably the result of cellular catabolism, with no significant biological function in the testes.