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Thrombophilia is a group of inherited or acquired coagulation disorders that have been associated with reproductive failure. However, there are still no clear recommendations on whether its inclusion in the initial study of the infertile couple or patients with recurrent implantation failure is necessary. In this discussion paper, based on a SWOT (strengths, weaknesses, opportunities, threats) analysis, the different aspects of the repercussions of thrombophilia screening and treatment in reproduction are evaluated. To avoid possible subjectivity in the analysis and results of this study, researchers followed Oxford criteria for the evaluation of evidence. The results from the evaluation of the reviewed bibliography seem to indicate that, pending new evidence, it would be advisable not to include thrombophilia screening in the initial baseline study of the infertile couple. There is no evidence to support a clear association between thrombophilia and implantation failure or infertility. Thrombophilia testing in this setting may increase cost, with minimal potential benefit and lead to inappropriate use of anticoagulants with possible deleterious adverse effects. Future well-designed studies are needed to assess the possible benefit of anticoagulant therapy in infertile thrombophilic patients with implantation failure.

SummaryThe transmission of DNA through extracellular vesicles (EVs) represents a novel genetic material transfer mechanism that may impact genome evolution and tumorigenesis. We aimed to investigate the potential for vertical mitochondrial (mt)DNA transmission within maternal endometrial EVs to the pre-implantation embryo and describe any effect on embryo bioenergetics.We discovered that the human endometrium secretes all three general subtypes of EV - apoptotic bodies (ABs), microvesicles (MVs), and exosomes (EXOs) - into the human endometrial fluid (EF) within the uterine cavity. EVs become uniformly secreted into the EF during the menstrual cycle, with the proportion of different EV populations remaining constant; however, MVs contain significantly higher levels of DNA than ABs or EXOs. During the window of implantation, MVs contain an eleven-fold higher level of mtDNA when compared to cells-of-origin within the receptive endometrium, which possesses a lower mtDNA content and displays the upregulated expression of mitophagy-related genes. Furthermore, we demonstrate the internalization of EV-derived mtDNA by trophoblast cells of murine embryos, which associated with a reduction in mitochondrial respiration and ATP production.These findings suggest that the maternal endometrium suffers a reduction in mtDNA content during the preconceptional period, that mtDNA becomes packaged into secreted EVs that the embryo uptakes, and that the transfer of mtDNA to the embryo within EVs occurs alongside the modulation of bioenergetics during implantation.

Chronic endometritis is a pathology often associated with reproductive failure, but there are still no clear recommendations on whether its inclusion in the initial study of infertile couples is necessary. In this discussion paper, based on a SWOT (Strengths, Weaknesses, Opportunities, Threats) analysis, the different aspects of the repercussions of chronic endometritis in fertility are evaluated. To avoid possible subjectivity in the analysis and results of this study, the researchers followed the Oxford criteria for the evaluation of evidence. The results from the evaluation of the reviewed literature seem to indicate that, pending new evidence, it would be advisable not to include chronic endometritis in the initial baseline study before assisted reproduction in order not to delay other assisted reproduction treatments. However, it would be advisable in cases of repetitive implantation failure and pregnancy loss after having undergone IVF with viable embryos and before continuing with costly reproductive processes, since results could be improved. The development of randomized studies assessing the impact of antibiotic treatment as a possible therapeutic option in infertile women with chronic endometritis, as well as the possible impact on endometrial microbiota and receptivity/implantation, would allow for the establishment of more precise clinical guidelines in this regard.

Unexplained infertility is a relevant indication for controlled ovarian stimulation associated to intrauterine insemination. The "step-up" and "step-down" gonadotropin-based protocols were designed to reduce multiple pregnancy and ovarian hyperstimulation syndrome in polycystic ovary syndrome patients, but there is no related evidence in normoovulatory women undergoing intrauterine insemination. Our aim was to compare the efficacy and safety of both protocols with intrauterine insemination in unexplained infertility patients.Randomized clinical trial including 145 women with unexplained infertility randomly following the step-up (n=73) or step-down (n=72) protocol. In the step-up group, patients started on day 3 of a spontaneous cycle administrating recombinant FSH 75IU sc/day, increasing it to 150IU if no response after 7 days. In the step-down, patients started administrating 150IU sc/day, constantly decreasing it to 75IU after 5 days. Recombinant hCG was administered when a follicle reached ≥18mm diameter.Clinical pregnancy rate was higher in the step-up group than in the step-down (20.5% vs . 8.3%; p =0.037). Significant differences between step-up and step-down protocols were found regarding days of rFSH administration (8.83±4.01% vs . 7.42±2.18%; p =0.001) and cancellation rate due to hyper response (8.21% vs . 25%; p =0.05). No differences were detected in miscarriage rates, multiple pregnancy rates/cycle and hyper stimulation syndrome incidence.The step-up protocol is longer-lasting but more effective obtaining pregnancies than the step-down in patients with unexplained infertility undergoing intrauterine insemination. This effect could be explained by lower cancellation rates due to ovarian hyper response than the step-down protocol, with no differences in ovarian hyper stimulation syndrome incidence.

Resumen Introduccion Existe evidencia actual de que los resultados perinatales de los recien nacidos de pacientes sometidas a fecundacion in vitro (FIV) con transferencia de embriones en fresco (TEF) son peores en comparacion con la transferencia de embriones congelados (TEC). Existen dudas sobre si la causa estaria relacionada con la tecnica de vitrificacion o con la estimulacion ovarica realizada previo a la FIV. El objetivo de este estudio es comparar el riesgo de parto prematuro en pacientes sometidas a FIV segun si realizaron TEF o TEC. Material y metodos Estudio de cohorte retrospectivo con datos del Registro Nacional de Actividad de Tecnicas de Reproduccion Asistida-Registro de la Sociedad Espanola de Fertilidad entre 2010 y 2015, incluyendo a las mujeres con un embarazo unico obtenido por FIV autologa (FIV-AO) y FIV con donacion de ovocitos (FIV-DO). Resultados Se registraron 371.308 ciclos de FIV: 263.306 FIV-AO (172.626 TEF y 90.680 TEC) y 108.002 FIV-DO (57.944 TEF y 50.048 TEC). La prevalencia de parto prematuro fue del 12% en FIV-AO y del 18,6% en FIV-DO. Se observo una disminucion del riesgo de parto prematuro temprano despues de la TEC solo en FIV-AO (OR: 0,87; IC 95%: 0,75-0,99), mientras que un aumento del riesgo de presentar parto prematuro tardio y moderado despues de la TEC, tanto en FIV-AO (OR: 1,12; IC 95%: 1,04-1,20) como FIV-DO (OR: 1,17; IC 95%: 1,08-1,26). Conclusiones Tanto FIV-AO como FIV-DO presentan una elevada prevalencia de parto prematuro. La criopreservacion se asocia con un menor riesgo de parto prematuro temprano en comparacion con la TEF en pacientes sometidas a FIV-AO; no obstante, se observo un aumento del riesgo de parto prematuro tardio y moderado tanto en FIV-AO como en FIV-DO. Estos hallazgos deben ser analizados con precaucion debido a las limitaciones metodologicas.

Controversial results exist on mid-term effects of Roux-en-Y gastric bypass and sleeve gastrectomy on hypertension remission. The aim of the present systematic review was to study 5-year hypertension remission after both procedures. One-year hypertension remission and SBP and DBP pressure change at 1 and 5 years after both surgical techniques were also evaluated. We searched MEDLINE, EMBASE and The Cochrane Central Register of Controlled Trials (CENTRAL). Thirty-two articles were included (six randomized controlled trials, 18 cohort and eight case-control studies). The proportion of patients with hypertension remission was greater for those treated with gastric bypass compared with sleeve gastrectomy at 5 years (RR = 1.26, 95% CI = 1.07-1.48) and 1 year (RR = 1.14, 95% CI = 1.06-1.21). Gastric bypass and sleeve gastrectomy did not differ in terms of SBP or DBP change. Patients treated with gastric bypass present a higher hypertension remission rate at 1 and 5 years.

BackgroundThere 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.MethodsThis 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), PM2.5abs, and NO2and 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.ResultsOne 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 PM2.5exposure on 3D after adjusting for subacute exposure, and an increased risk of achieving no pregnancy for PM2.5, PMcoarseand PM10on 3D.The second sensitivity analysis showed a significant risk of miscarriage for PM2.5exposure on 3D, and a significant risk of achieving no pregnancy for PM2.5, PMcoarseand PM10 particularly on 3D. No association was observed for nitrogen dioxides on reproductive outcomes.ConclusionsExposure 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.

This systematic review of literature and meta-analysis of observational studies reports on perinatal outcomes after frozen embryo transfer (FET). The aim was to determine whether natural cycle frozen embryo transfer (NC-FET) in singleton pregnancies conceived after IVF decreased the risk of adverse perinatal outcomes compared with artificial cycle frozen embryo transfer (AC-FET). Thirteen cohort studies, including 93,201 cycles, met the inclusion criteria. NC-FET was associated with a lower risk of hypertensive disorders in pregnancy (HDP) (RR 0.61, 95% CI 0.50 to 0.73), preeclampsia (RR 0.47, 95% CI 0.42 to 0.53), large for gestational age (LGA) (RR 0.93, 95% CI 0.90 to 0.96) and macrosomia (RR 0.82, 95% CI 0.69 to 0.97) compared with AC-FET. No significant difference was found in the risk of gestational hypertension and small for gestational age. Secondary outcomes assessed were the risk of preterm birth (RR 0.83, 95% CI 0.79 to 0.88); post-term birth (RR 0.48, 95% CI 0.29 to 0.80); low birth weight (RR 0.84, 95% CI 0.80 to 0.89); caesarean section (RR 0.84, 95% CI 0.77 to 0.91); postpartum haemorrhage (RR 0.39, 95% CI 0.35 to 0.45); placental abruption (RR 0.61, 95% CI 0.38 to 0.98); and placenta accreta (RR 0.18, 95% CI 0.10 to 0.33). All were significantly lower with NC-FET compared with AC-FET. In assessing safety, NC-FET significantly decreased the risk of HDP, preeclampsia, LGA, macrosomia, preterm birth, post-term birth, low birth weight, caesarean section, postpartum haemorrhage, placental abruption and placenta accreta. Further randomized controlled trials addressing the effect of NC-FET and AC-FET on maternal and perinatal outcomes are warranted. Clinicians should carefully monitor pregnancies achieved by FET in artificial cycles prenatally, during labour and postnatally.

RESEARCH QUESTION: Does a freeze-all strategy improve live birth rates in women of different age groups? DESIGN: Retrospective cohort study of 1882 first embryo transfer cycles, performed between January 2013 and December 2015. Reproductive outcomes between fresh (FRESH) or frozen (FROZEN) embryo transfers were compared in patients stratified by age: 38 years. Student’s t test for independent samples and χ(2) analyses were used as needed. A multivariable logistic regression analysis was performed adjusting for age, triggering drug, number of retrieved oocytes, number of transferred embryos, and percentage of top-quality embryos. MAIN RESULTS AND THE ROLE OF CHANCE: Live birth rates (LBR) were significantly higher for FROZEN in the 38 years groups, LBR for FROZEN vs FRESH were not statistically different (30.9% in the FROZEN group vs 29.3% in the FRESH group, p = 0.70, and 19.8% in the FROZEN group vs 12.7% in the FRESH group, p = 0.07, respectively). The multivariate analysis found a significantly positive effect of performing FROZEN on LBR in the younger group (OR 2.46, 95% CI 1.31–4.62; p = 0.005) but had no impact in women between 35 and 38 years (OR 1.01, 95% CI 0.55–1.83; p = 0.98) or older (OR 0.96, 95% CI 0.43–2.13; p = 0.92). CONCLUSIONS: Performing a freeze-all strategy seems to result in better reproductive outcomes when compared with a fresh ET in women under 35 years, with no significant impact on older women.

RESEARCH QUESTION: In women with singleton pregnancies conceived after assisted reproductive technologies, does the in vitro fertilization with oocyte donation (IVF-OD) affect the perinatal and maternal outcomes compared to autologous in vitro fertilization (IVF-AO)? DESIGN: Systematic review and meta-analysis of studies comparing perinatal and maternal outcomes in singleton pregnancies resulting from IVF-OD versus IVF-AO. An electronic literature search in Pubmed, MEDLINE, and Cochrane database was performed. The main outcome measures were hypertensive disorders in pregnancy, preeclampsia, severe preeclampsia, pregnancy-induced hypertension, preterm birth, early preterm birth, low birth weight, and very low birth weight. RESULTS: Twenty-three studies were included. IVF-OD is associated with a higher risk of hypertensive disorders in pregnancy (OR 2.63, 2.17–3.18), preeclampsia (OR 2.64; 2.29–3.04), severe preeclampsia (OR 3.22; 2.30–4.49), pregnancy-induced hypertension (OR 2.16; 1.79–2.62), preterm birth (OR 1.57; 1.33–1.86), early preterm birth (OR 1.80; 1.51–2.15), low birth weight (OR 1.25, 1.20–1.30), very low birth weight (OR 1.37, 1.22–1.54), gestational diabetes (OR 1.27; 1.03–1.56), and cesarean section (OR 2.28; 2.14–2.42). There was no significant difference in the risk of preterm birth or low birth weight when adjusted for preeclampsia. CONCLUSIONS: IVF-OD patients should be considered an independent risk factor for some adverse perinatal outcomes, mainly hypertensive disorders in pregnancy, preeclampsia, and severe preeclampsia. Immunological and hormonal aspects may be involved in these results, and further research focusing in the etiopathogenesis of these pathologies are needed. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10815-019-01552-4) contains supplementary material, which is available to authorized users.

PURPOSE: The purpose of this study is to compare the results of ART treatment in patients with and without endometriosis in a large cohort of patients from different centers over an extented period of time. METHODS: This retrospective study is using data from patients undergoing 27,294 cycles of IVF/ICSI treatment between 1995 and 2011 that were registered in the database of the Latin American Registry maintained by the Latin America Network of Assisted Reproduction. RESULTS: The mean number of retrieved oocytes was higher in the control group, but the mean number of metaphase II oocytes was similar. Fertilization rate and transfer rate were higher in the control group. We observed higher pregnancy rates, per cycle initiated and per embryo transfer and higher live birth rate in the endometriosis group. In the group of patients with 25–35 years old, the number of oocytes, fertilization rate, and number of transferred embryos were significantly higher in the control group. However, pregnancy rate and live birth rate were higher in the endometriosis group. In the group of patients with 36–40 years old, the number of transferred embryos was higher in the control group, but the pregnancy rate and live birth rate were higher in the endometriosis group. In the group of patients with 41 to 42 years old, the number of transferred embryos and the transfer rate were higher in the control group, but the pregnancy rate was higher in the endometriosis group. CONCLUSION: Our results demonstrate that endometriosis does not affect the outcome of patients subjected to IVF/ICSI and although patients with endometriosis present lower number of oocytes and higher cancelation rate, these shortcomings do not reduce pregnancy and live birth rates.

Objectives To determine the efficacy of the physiological ICSI technique (PICSI) vs. conventional ICSI in the prognosis of couples with male factor, with respect to the following outcome measures: live births, clinical pregnancy, implantation, embryo quality, fertilization and miscarriage rates. Methods A systematic review of the literature, extracting raw data and performing data analysis. Patient(s): Couples with the male factor, who were subjected to in-vitro fertilization. Main Outcome Measures: rates of live births, clinical pregnancy, implantation, embryo quality, fertilization and miscarriage. Results In the systematic search, we found 2,918 studies and an additional study from other sources; only two studies fulfilled the inclusion criteria for this systematic review. The rates of live births, clinical pregnancy, implantation, embryo quality, fertilization and miscarriage were similar for both groups. Conclusion There is no statistically significant difference between PICSI vs. ICSI, for any of the outcomes analyzed in this study. Enough information is still not available to prove the efficacy of the PICSI technique over ICSI in couples with male factor.

Objective To ascertain whether perinatal outcomes are affected by vitrification and/or controlled ovarian hyperstimulation (COH). Design Register-based cohort study. Setting Not applicable. Patient(s) Women undergoing in vitro fertilization (IVF) between 2008 and 2012 using autologous or donated eggs who had a singleton pregnancy delivered from the 24th week onward. Intervention(s) Fresh embryo transfer (ET) or frozen-thawed ET in women undergoing IVF. Main Outcome Measure(s) Primary outcome birthweight, and secondary outcomes gestational age at delivery, small for gestational age, mode of delivery, and perinatal mortality. Result(s) In the autologous egg population, newborns from the fresh ET group had lower birthweight than the frozen-thawed ET group (3,152.9 ± 545.5g and 3,343.2 ± 532.3g, respectively), and this difference persisted even after adjusting for confounding factors, and the newborns had a higher risk of being small for gestational age (SGA). In contrast, among egg-donor recipients undergoing ET, the mean birthweight did not differ between the groups (3,165 ± 604.15 g and 3,143.60 ± 604.21g in the fresh and frozen-thawed ET groups, respectively); however, in the adjusted regression model birthweight was statistically significantly higher in the fresh ET group than the frozen-thawed ET group. The risk of SGA remained comparable between the fresh versus frozen-thawed ET groups. We observed no statistically significant differences in perinatal mortality between groups either in the autologous egg population or in the donor recipient group. Conclusion(s) Perinatal outcomes are negatively affected by COH and not affected by the vitrification process.

STUDY QUESTION Does the time from ovum pick-up (OPU) to frozen embryo transfer (FET) affect reproductive outcomes in a freeze-all strategy? SUMMARY ANSWER Our study did not detect statistically significant differences between first and subsequent cycles, clinically relevant differences are not ruled out and further and larger studies are required. WHAT IS KNOWN ALREADY Following controlled ovarian hyperstimulation (COH) delaying FET until the endometrium has returned to an optimal pre-stimulation state may have a significant emotional impact on patients, which adds to the stress and anxiety accompanying a standard IVF cycle. Currently there is no agreement on the best time to perform a FET after a freeze-all cycle in order to maximize reproductive outcomes for the patient. STUDY DESIGN, SIZE, DURATION: Retrospective cohort study of 512 freeze-all cycles, performed between January 2012 and December 2014. COH was performed by either a GnRH antagonist (n = 397) or a long GnRH agonist protocol (n = 115). Ovulation was triggered using either a GnRH agonist (n = 258) or hCG (n = 254). Endometrial preparation was performed in an artificial cycle by either oral (n = 238) or transdermal (n = 274) oestrogen. Differences were considered significant if P < 0.05. PARTICIPANTS/MATERIALS, SETTING, METHODS Reproductive outcomes between FETs which took place either within the first menstrual cycle following OPU (Cycle 1; n = 263) or afterwards (Cycle ≥2; n = 249) were compared. Student's t-test for independent samples, Mann-Whitney U-test and Chi-square analysis were used where appropriate. A multivariable logistic regression analysis was performed adjusting for maternal age, drug used for ovulation trigger, number of retrieved oocytes, number of embryos obtained, day of embryonic development at transfer, number of embryos transferred and type of endometrial preparation. Differences were considered significant if P < 0.05. MAIN RESULTS AND THE ROLE OF CHANCE Live birth rate (LBR) was significantly higher in FET performed during Cycle 1 vs Cycle ≥2 (37.6% vs 27.3%, respectively; P = 0.01) before adjusting for confounding factors. We found no difference for biochemical pregnancy (49.8% vs 43.8%; P = 0.17), clinical pregnancy (44.1% vs 36.1%; P = 0.07) or pregnancy loss (11.8% vs 16.1%; P = 0.16). A multivariable analysis found no impact of timing of elective FET on LBR (odds ratio, OR 0.73; 95% CI 0.49-1.08). The impact remained not significant after adjusting for number of retrieved oocytes, drug used for ovulation trigger (hCG vs GnRH agonist) and reason for cryopreservation. The factors that significantly affected LBR were: maternal age in both age categories (women between 35 and 40 years vs women below 35 years, OR 0.63, 95% CI 0.4-0.95; and women over 40 years vs women below 35 years, OR 0.34, 95% CI 0.2-0.7), day of embryonic development at transfer (day +4 vs +3; OR 1.7, 95% CI 1.1-2.8) and number of transferred embryos (OR 2.2, 95% CI 1.4-3.3) and oestrogen used for endometrial preparation (transdermal vs oral; OR 0.62, 95% CI 0.4-0.9). LIMITATIONS REASONS FOR CAUTION The main limitation of our study is its retrospective nature. Although we adjusted our statistical analysis for a number of known and suspected confounders, we cannot exclude the possibility of residual confounding factors. WIDER IMPLICATIONS OF THE FINDINGS According to our results, clinicians might not need to wait more than one menstrual cycle before performing FET. This allows us to reduce unnecessary delays in FET, without compromising reproductive outcomes. STUDY FUNDING/COMPETING INTERESTS No funding was sought for this study. Authors declare no competing interests. TRIAL REGISTRATION NUMBER NA.

In women with singleton pregnancies conceived after assisted reproductive technologies, does the in vitro fertilization with oocyte donation (IVF-OD) affect the perinatal and maternal outcomes compared to autologous in vitro fertilization (IVF-AO)? Systematic review and meta-analysis of studies comparing perinatal and maternal outcomes in singleton pregnancies resulting from IVF-OD versus IVF-AO. An electronic literature search in Pubmed, MEDLINE, and Cochrane database was performed. The main outcome measures were hypertensive disorders in pregnancy, preeclampsia, severe preeclampsia, pregnancy-induced hypertension, preterm birth, early preterm birth, low birth weight, and very low birth weight. Twenty-three studies were included. IVF-OD is associated with a higher risk of hypertensive disorders in pregnancy (OR 2.63, 2.17–3.18), preeclampsia (OR 2.64; 2.29–3.04), severe preeclampsia (OR 3.22; 2.30–4.49), pregnancy-induced hypertension (OR 2.16; 1.79–2.62), preterm birth (OR 1.57; 1.33–1.86), early preterm birth (OR 1.80; 1.51–2.15), low birth weight (OR 1.25, 1.20–1.30), very low birth weight (OR 1.37, 1.22–1.54), gestational diabetes (OR 1.27; 1.03–1.56), and cesarean section (OR 2.28; 2.14–2.42). There was no significant difference in the risk of preterm birth or low birth weight when adjusted for preeclampsia. IVF-OD patients should be considered an independent risk factor for some adverse perinatal outcomes, mainly hypertensive disorders in pregnancy, preeclampsia, and severe preeclampsia. Immunological and hormonal aspects may be involved in these results, and further research focusing in the etiopathogenesis of these pathologies are needed.

Exposure to air pollution has been clearly associated with a range of adverse health effects, including reproductive toxicity, but its effects on male semen quality are still unclear. We performed a systematic review (up to June 2016) to assess the impact of air pollutants on sperm quality. We included 17 semi-ecological, panel, and cohort studies, assessing outdoor air pollutants, such as PM 2.5 , PM 10 , NOx, SO 2 , and O 3 , and their effects on DNA fragmentation, sperm count, sperm motility, and sperm morphology. Thirteen studies assessed air pollution exposure measured environmentally, and six used biomarkers of air pollution exposure (two did both). We rated the studies using the Newcastle-Ottawa Scale and assessed with the exposure method. Taking into account these factors and the number of studies finding significant results (positive or negative), the evidence supporting an effect of air pollution on DNA fragmentation is weak but suggestive, on sperm motility is limited and probably inexistent, on lower sperm count is inconclusive, and on sperm morphology is very suggestive. Because of the diversity of air pollutants and sperm parameters, and the studies' designs, we were unable to perform a meta-analysis. In summary, most studies concluded that outdoor air pollution affects at least one of the four semen quality parameters included in the review. However, results lack consistency, and furthermore, studies were not comparable. Studies using standardized air pollution and semen measures are required to obtain more reliable conclusions. PROSPERO Registration Number CRD42015007175.

Introduction Results of the effects of Roux-en-Y gastric bypass (GB) and sleeve gastrectomy (SG) on triglyceride and high-density lipoprotein (HDL) cholesterol levels are controversial. Moreover, previous meta-analyses focused on global dyslipidemia remission, but did not include the separate remission rates of the different lipid fractions. Hence, the aim of the present meta-analysis was to compare the outcomes (concentration change and remission rates) of GB and SG on diverse lipid disorders one year postbariatric surgery (BS). Evidence acquisition An exhaustive electronic search carried out on MedLine, Embase and The Cochrane Central Register of Controlled Trials (Central) until July 2016 yielded 2621 records, of which 17, totaling 4699 obese patients with one-year follow-up after BS were included in the meta-analysis. Evidence synthesis GB was superior to SG in terms of total cholesterol (mean difference= 19.77 mg/dL, 95% CI: 11.84-27.69) and low-density lipoprotein (LDL) cholesterol (mean difference: 19.29 mg/dL, 95% CI: 11.93-26.64) decreases as well as in hypercholesterolemia remission (RR: 1.43, 95% CI: 1.27-1.61). No differences were found between GB and SG in terms of HDL cholesterol increase or triglyceride concentration change after surgery, as well as in hypertriglyceridemia and low HDL remission rates. Conclusions The effect of GB on total and LDL cholesterol concentration decreases and remission was greater than that of SG, whereas no differences were observed with respect to HDL cholesterol and triglyceride concentration evolution. Conclusions cannot be drawn from hypertriglyceridemia and low HDL remission rates based on this meta-analysis.

To determine whether the transdermal route is equal or superior to the oral route, when preparing the endometrium with oestrogens for embryo transfer.Prospective, randomized controlled trial; 140 patients randomized; the pills group followed a protocol with oestradiol valerate pills and the patches group followed a protocol with oestradiol hemihydrate patches. The primary variable was endometrial thickness on day 10 ± 1 of treatment. Secondary variables were endometrial thickness on day 15 ± 1 of treatment, patient satisfaction, plasma levels of oestradiol, rates of pregnancy, miscarriage and delivery. Endometrial thickness was measured on day 10 ± 1 of the cycle, if the lining was 7 mm or less in thickness, another measurement was made on day 15 ± 1. Blood oestradiol levels were analysed on the day the endometrial lining was greater than 7 mm (day 10 ± 1 or day 15 ± 1). Patients completed a survey to evaluate comfort and side-effects.The patches group achieved significantly thicker endometrium by the first check-up on day 10 ± 1 (7.6 mm versus 7.0 mm; P = 0.026), with lower blood levels of oestradiol (159.2 pg/ml versus 237.1 pg/ml; P0.001) when the endometrial thickness was over 7mm. The pills group considered the treatment more comfortable, with less side-effects. No significant differences in the rates of pregnancy, miscarriage or live birth were found.Transdermal oestrogen treatment allows patients to reach a higher endometrial thickness after 10 days of treatment, with lower plasma levels of oestradiol, although it is not tolerated as well.

Infertile males with varicocele have the highest percentage of sperm cells with damaged DNA, compared to other infertile groups. Antioxidant treatment is known to enhance the integrity of sperm DNA; however, there are no data on the effects in varicocele patients. We thus investigated the potential benefits of antioxidant treatment specifically in grade I varicocele males. Twenty infertile patients with grade I varicocele were given multivitamins (1500 mg L-Carnitine, 60 mg vitamin C, 20 mg coenzyme Q10, 10 mg vitamin E, 200 μg vitamin B9, 1 μg vitamin B12, 10 mg zinc, 50 μg selenium) daily for three months. Semen parameters including total sperm count, concentration, progressive motility, vitality, and morphology were determined before and after treatment. In addition, sperm DNA fragmentation and the amount of highly degraded sperm cells were analyzed by Sperm Chromatin Dispersion. After treatment, patients showed an average relative reduction of 22.1% in sperm DNA fragmentation (p = 0.02) and had 31.3% fewer highly degraded sperm cells (p = 0.07). Total numbers of sperm cells were increased (p = 0.04), but other semen parameters were unaffected. These data suggest that sperm DNA integrity in grade I varicocele patients may be improved by oral antioxidant treatment.

BACKGROUND: Endometriosis has been described to impair fertility through various mechanisms. However, studies evaluating the reproductive outcomes of women undergoing assisted reproductive technologies show controversial results. The aim of this study is to assess whether the reproductive outcome is impaired among women with endometriosis-associated infertility undergoing IVF. METHODS: A retrospective cohort study was performed, including women undergoing IVF reported by the Red Latinoamericana de Reproduccion Asistida (Redlara) registry, between January 2010 and December 2012. The study group included women with endometriosis-associated infertility, and the control group women with tubal factor, endocrine disorders or unexplained infertility. Women above 40 years, severe male factor and premature ovarian failure were excluded. The reproductive outcomes of between both groups were compared. The primary outcome was live birth. Secondary outcomes included clinical pregnancy, miscarriage, number of oocytes retrieved and number of fertilized oocytes. Outcomes were assessed after the first fresh IVF cycle, and were adjusted for age and number of embryos transferred. RESULTS: A total of 22.416 women were included (3.583 with endometriosis and 18.833 in the control group). Mean age of patients in the endometriosis group and control group was 34.86 (3.47) and 34.61 (3.91) respectively, p = 0.000. The mean number of oocytes retrieved were 8.89 (6.23) and 9.86 (7.02) respectively, p = 0.000. No significant differences were observed between groups in terms of live birth (odds ratio (OR) 1.032, p = 0.556), clinical pregnancy (OR 1.044, p = 0.428) and miscarriage rates (OR 1.049, p = 0.623). Women with endometriosis had significantly lower number of oocytes retrieved (incidence risk ratio (IRR) 0.917, 95% CI 0.895-0.940), however, the number of fertilized oocytes did not differ among the two groups when adjusting for the number of oocytes retrieved (IRR 1.003, p = 0.794). An age-stratified analysis was performed, and no differences were observed in the reproductive outcomes between groups for women aged under 35 and 35 to 40. CONCLUSIONS: Reproductive outcomes among women undergoing IVF and diagnosed with endometriosis-associated infertility do not differ significantly from women without the disease. Although women with endometriosis generate fewer oocytes, fertilization rate is not impaired and the likelihood of achieving a live birth is also not affected.

Air pollution has gained considerable interest because of the multiple adverse effects reported on human health, although its impact on fertility remains unclear. A systematic search was performed to evaluate the impact of air pollutants on fertility. Controlled trials and observational studies assessing animal model and epidemiological model were included. Occupational exposure and semen quality studies were not considered. Outcomes of interest included live birth, miscarriage, clinical pregnancy, implantation, and embryo quality. Ten studies were included and divided into two groups: animal studies and human epidemiological studies including the general population as well as women undergoing in vitro fertilization and embryo transfer (IVF/ET). Results from this systematic review suggest a significant impact of air pollution on miscarriage and clinical pregnancy rates in the general population, whereas among subfertile patients certain air pollutants seem to exert a greater impact on fertility outcomes, including miscarriage and live birth rates. Besides, studies in mammals observed a clear detrimental effect on fertility outcomes associated to air pollutants at high concentration. The lack of prospective studies evaluating the effect of air pollution exposure in terms of live birth constitutes an important limitation in this review. Thus, further studies are needed to confirm these findings.

The aim of our study is to determine whether alcohol consumption affects the results of in vitro fertilization. A review of the literature was performed to find prospective cohort studies of couples undergoing in vitro fertilization in which alcohol intake was recorded. A primary search returned 389 studies, 2 of which were finally considered eligible. A total of 2908 couples were analyzed in terms of pregnancy outcomes depending on drinking habits. The risk of IVF failure increased 4.14-fold and 2.86-fold with an increased alcohol intake of 12 gr/d in women during the week and month before, respectively. The odds ratio (OR) of live birth rate in women who drank at least four drinks per week compared with women who drank fewer was 0.84; this difference was statistically significant. Paternal alcohol use levels 1 month, 1 week and during the attempts were also associated with worse reproductive effects. Our review, though including a small number of studies that were heterogeneous in design, revealed decreased rates of pregnancy and fertilization outcomes for couples who drank before or during their in vitro fertilization techniques. This suggests that couples undergoing IVF should be advised to abstain from alcohol prior to and during their procedures.

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.

Oocyte donation can satisfy the desire to have children in women with premature ovarian failure (POF) but little progress has been made to improve reproduction using the patients' own gametes. The aim of this study was to assess the effectiveness of alternative treatments to oocyte donation in patients with POF. A systematic search of MEDLINE, EMBASE and Cochrane databases from January 1988 to January 2012 using descriptors related to POF, ovulation induction, and pregnancy was made. Randomized clinical trials of women with POF undergoing various treatments to achieve ovulation induction, often compared with alternative treatment and placebo groups, were only selected. Outcomes of interest were those related to pregnancy (biochemical and live birth). Twelve trials were included and analysed for methodology, inclusion and exclusion criteria, number of patients included, characteristics and type of intervention, and results in terms of ovulation rate, pregnancy rate and ongoing pregnancy rate. The large methodological variability among studies prevented to combined data for a meta-analysis. None of the studies showed statistically significant differences between the study groups. The lack of case-control studies with a placebo group makes it impossible to establish differences between a treatment and no treatment.

Objective To examine the available evidence to assess if cryopreservation of all embryos and subsequent frozen embryo transfer (FET) results in better outcomes compared with fresh transfer. Design Systematic review and meta-analysis. Setting Centers for reproductive care. Patient(s) Infertility patient(s). Intervention(s) An exhaustive electronic literature search in MEDLINE, EMBASE, and the Cochrane Library was performed through December 2011. We included randomized clinical trials comparing outcomes of IVF cycles between fresh and frozen embryo transfers. Main Outcome Measure(s) The outcomes of interest were ongoing pregnancy rate, clinical pregnancy rate, and miscarriage. Result(s) We included three trials accounting for 633 cycles in women aged 27–33 years. Data analysis showed that FET resulted in significantly higher ongoing pregnancy rates and clinical pregnancy rates. Conclusion(s) Our results suggest that there is evidence that IVF outcomes may be improved by performing FET compared with fresh embryo transfer. This could be explained by a better embryo-endometrium synchrony achieved with endometrium preparation cycles.

Background: The available evidence of air pollution exposure on fertility is scarce. In a previous analysis, we have shown that PM2.5 was associated with a higher risk of having use Assisted Reprod...

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.

Resumen Objetivo La aparicion de nuevas herramientas de estudio en el campo de la andrologia nos ha permitido evaluar nuevos marcadores de calidad seminal, como la presencia de vacuolas en el nucleo del espermatozoide, mediante el uso de microscopia de alta magnificacion, y el grado de fragmentacion del acido desoxirribonucleico (ADN) espermatico. Ambos marcadores de calidad pueden verse afectados por la presencia de radicales libres de oxigeno, que favorecen la oxidacion celular. En el presente estudio piloto se plantea valorar la utilidad de un tratamiento con antioxidantes para reducir tanto el indice de vacuolizacion espermatica, como el grado de fragmentacion del ADN de una forma significativa. Material y metodos Estudio prospectivo para el que se selecciono a un total de 65 pacientes, de los cuales 33 finalizaron el estudio. Cada paciente entrego dos muestras de semen y realizo un tratamiento con antioxidantes mediante Androferti®. Se evaluo el indice de vacuolizacion en el nucleo del espermatozoide y la fragmentacion del ADN espermatico en cada una de las muestras entregadas. Resultados Se observa un aumento estadisticamente significativo de espermatozoides con grados de vacuolizacion I y II despues de un mes de tratamiento, asi como tambien una disminucion del grado de fragmentacion del ADN espermatico. Conclusiones A pesar de que se trata de un estudio clinico no aleatorizado, parece concluyente la importancia del uso de un tratamiento antioxidante para aumentar el exito de un ciclo de reproduccion asistida, con el objetivo de disminuir la influencia negativa de malformaciones en el nucleo espermatico y de la fragmentacion del ADN.

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.

Background Letrozole is the third-generation aromatase inhibitor (AI) most widely used in assisted reproduction. AIs induce ovulation by inhibiting estrogen production; the consequent hypoestrogenic state increases GnRH release and pituitary follicle-stimulating hormone (FSH) synthesis. Methods A systematic search of the literature was performed for both prospective and retrospective studies. Meta-analyses of randomized clinical trials (RCTs) were performed for three comparisons: letrozole versus clomiphene citrate (CC), letrozole + FSH versus FSH in intrauterine insemination (IUI) and letrozole + FSH versus FSH in IVF. In the absence of RCTs, non-randomized studies were pooled. Results Nine studies were included in the meta-analysis. Four RCTs compared the overall effect of letrozole with CC in patients with polycystic ovary syndrome. The pooled result was not significant for ovulatory cycles (OR = 1.17; 95% CI 0.66-2.09), or for pregnancy rate per cycle (OR = 1.47; 95% CI 0.73-2.96) or for pregnancy rate per patient (OR = 1.37; 95% CI 0.70-2.71). In three retrospective studies which compared L + FSH with FSH in ovarian stimulation for IUI, the pooled OR was 1.15 (95% CI 0.78-1.71). A final meta-analysis included one RCT and one cohort study that compared letrozole + gonadotrophin versus gonadotrophin alone: the pooled pregnancy rate per patient was not significantly different (OR = 1.40; 95% CI 0.67-2.91). Conclusions Letrozole is as effective as other methods of ovulation induction. Further randomized-controlled studies are warranted to define more clearly the efficacy and safety of letrozole in human reproduction.

OBJECTIVE: To assess the effectiveness of the Mirena levonorgestrel-releasing intrauterine system (LNG-IUS) in peri- and postmenopausal women with endometrial hyperplasia without atypia. DESIGN: All consecutive women with histologically documented endometrial hyperplasia without atypia recruited during a 1-year period participated in an open prospective single-center study. They were followed for at least 2 years after levonorgestrel-releasing intrauterine system insertion. The pattern of uterine bleeding was evaluated on a 4-point qualitative scale (1 = amenorrhea 2 = scarce 3 = normal 4 = abundant). RESULTS: The study population consisted of 15 women with a mean (SD) age of 49 (2.7) years. Compared with baseline bleeding decreased quantitatively from a mean score of 3 at baseline (normal bleeding) to 2 (scarce) at 3and 6 months and 1 (amenorrhea) at 24 months. Endometrial biopsies performed at 12 months revealed atrophicendometrium in 14 women (93.3%) and secretory endometrium in 1 (6.7%)(P < 0.001). At 24 months endometrial atrophy was documented in 100% of women. CONCLUSIONS: The levonorgestrel-releasing intrauterine system seems to be an effective and safe alternative in the treatment of peri- and postmenopausal women with (simple) endometrial hyperplasia without atypia.

The redifferentiation, proliferation, and hyaline-specific extracellular matrix (ECM) protein synthesis of chondrocytes cultured in a polycaprolactone (PCL) scaffold were analyzed. Gene expression of the type II collagen and aggrecan was assessed by real-time PCR in cells from PCL scaffolds, monolayer, and pellet cultures. The proliferative activity was assessed using Ki-67 immunodetection, and the chondrocytic differentiation was evaluated using S-100 immunodetection. The synthesis and deposition into scaffold pores of type II collagen and glycosaminoglycan were analyzed by immunohistochemistry and Alcian blue staining, respectively. All parameters were assessed throughout 28 days of cultures maintained in either fetal bovine serum-containing medium (FCM) or Insulin-Transferrin-Selenium-containing medium (ICM). Expression of the type II collagen gene was lower in FCM cultures than in ICM cultures for all culture systems (p < 0.05). Moreover, PCL scaffolds cultured in ICM were able to induce collagen gene expression more efficiently than pellet and monolayer cultures. Aggrecan gene expression did not vary significantly between mediums and three-dimensional system cultures, but in ICM cultures, the monolayer cultures had significantly higher levels of aggrecan gene expression than did either the PCL or pellet cultures. Chondrocytes cultured in PCL scaffolds or pellets with FCM did not proliferate to a great extent but did maintain their differentiated phenotype for 28 days. Levels of cartilage ECM protein synthesis and deposition into the scaffold pores were similar among PCL and pellet cultures grown in FCM and in ICM. In conclusion, chondrocytes seeded into PCL scaffolds, cultured in ICM, efficiently maintained their differentiated phenotype and were able to synthesize cartilage-specific ECM proteins.

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.

To establish a ratio of the P level to the number of follicles (P/F ratio) on the day of human chorionic gonadotropin (hCG) administration and to evaluate whether this ratio is associated with in vitro fertilization (IVF) outcome.This study was conducted between January 2012 and June 2013. A total of 337 patients with cleavage-stage day-3 fresh embryo transfer with P levels ≤1.5 ng/mL on the day of hCG administration were included in the study. The main outcome was ongoing pregnancy rate.The P/F ratio was calculated according to the equation (P[ng/mL]/number of follicles) on the day of final oocyte maturation. Using ROC, we established a cut-off level of 0.075 for the P/F ratio. The area under the curve (AUC) (0.756; 95 % confidence interval [CI]: 0.704-0.807) indicated that it was a good prognostic test. In group 1 (patients under 36 years old), the ongoing pregnancy rates were 57 and 30 % for patients with P/F ratios ≤ .075 and .075, respectively, (p = 0.003). In group 2 (patients between 36 and 39 years old), the ongoing pregnancy rates were 58 % and 17 % (p = 0.001) for patients with P/F ratios ≤ .075 and .075, respectively. In group 3 (patients ≥ 40 years old), the ongoing pregnancy rates were 41.7 and 10.9 % (p = 0.001) for patients with P/F ratios ≤ .075 and .075, respectively.The P/F ratio is a good prognostic test for predicting IVF outcome that can correlate the P level with ovarian response.

Miguel A Checa,1,2 Mario Brassesco,2 Margalida Sastre,1 Manuel Gómez,2 Julio Herrero,3 Laura Marque,3 Arturo Brassesco,2 Juan José Espinós3 1Department of Obstetrics and Gynecology, Parc de Salut Mar, Universitat Autònoma de Barcelona, 2Centro de Infertilidad y Reproducción Humana (CIRH), 3Centro de Reproducción Asistida Sagrada Familia, Clínica Sagrada Familia, Barcelona, Spain Abstract: 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. Keywords: controlled ovarian hyperstimulation, GnRH antagonists, emergency fertility preservation, cancer patients

Objectives: We assessed the effects of the discontinuation of long-standing transdermal estrogen replacement therapy (>4 years) and substitution of this treatment by calcium or raloxifene on the vaginal epithelium and climateric symptoms in a study population of osteoporotic women. Methods: A total of 136 women (mean age 55.5 years) were randomized to calcium (500 mg elemental calcium, 400 IU Vitamin D 3 ) (n = 40), raloxifene (60 mg/day) (n = 48), or estrogen patches (3.9 mg estradiol) and progesterone (100 mg/day) (n = 48). Treatment was given for 1 year. The vaginal maturation value (VMV), serum estradiol levels, and climateric symptoms using a 12-item modification of the SF-36 quality of life questionnaire were evaluated at baseline and at 6 and 12 months. Results: At 6 months, mean VMV decreased significantly (P P ρ = 0.361, P ρ = 0.269, P Conclusions: Withdrawal and change of long-standing transdermal hormone replacement therapy by treatment with calcium or raloxifene resulted in worsening of vaginal atrophy assessed by the VMV, although it was not clinically perceived by the patients. However, increases in dyspareunia and urinary leaks were reported. Menopausal complaints related to vasomotor symptoms worsened in the calcium- and raloxifene-treated groups and persisted throughout the study period.

Objective: To assess differences between native Spanish and immigrant pregnant women in behaviour relating to the use of medications during pregnancy. Study design: This cross-sectional study was carried out at the department of obstetrics and gynaecology of an acute-care teaching hospital in the city of Barcelona, Spain. A total of 1103 women who gave birth at the hospital during a 1-year period were enrolled in the study. Each woman was interviewed by a gynaecologist during her stay in hospital after delivery, with special reference to drug use during the pregnancy. Drug exposure was assigned to trimesters, and drugs were divided into therapeutic groups, while the women taking part were divided up by nationality, educational level, parity and age. Data were analysed using bivariate, multivariate, and cluster analyses. Results: Slightly over half (55.7%) of the women were native to Spain and 44.3% were immigrants of other nationalities. About a quarter, or 25.4%, of pregnant patients had not taken any drugs during their pregnancies. The most frequent drugs taken by the others were vitamins, which were used mostly by Spanish women, followed by analgesics, which were mostly taken by non-Spanish western women. The largest group who had taken folic acid was made up of non-Spanish western women, while the Asiatic patients had taken this in the smallest proportion of cases. Conclusions: Spanish patients and immigrants from other western countries showed a similar behaviour in terms of drug intake during pregnancy, which was different from the behavioural patterns seen in pregnant patients from developing countries.

Background: A growing body of evidence has associated exposure to air pollution to adverse pregnancy outcomes and complications. However, the available evidence on such an impact on fertility is sc...