A freeze-all strategy does not increase live birth rates in women of advanced reproductive age.

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: < 35, between 35 and 38, or > 38 years. Student's t test for independent samples and χ2 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 < 35 years group (43.7% vs 24%; p < 0.001). In both the 35-38 and > 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.

ALWAYS ICSI? A SWOT analysis.

PURPOSE: Intracytroplasmatic sperm injection (ICSI) is a common procedure used to improve reproductive results, even among couples without male factor infertility. However, the evidence available is still uncertain on the possible advantages and deficiencies that this procedure may have in patients with no formal indication for ICSI. METHODS: A SWOT (strengths, weaknesses, opportunities, threats) analysis examines the possible advantages and deficiencies of performing ICSI in these patients with no formal indication. RESULTS: The evidence suggests that ICSI is not justified for non-male factor infertile couples requiring in vitro conception. One of the major strengths associated to the procedure is the virtual elimination of cases further complicated by total fertilization failure and a combination between IVF and ICSI on sibling oocytes has been advised in the literature. Greater technical difficulties, higher costs and performing an unnecessary invasive technique in some cases represent some of the weaknesses of the procedure, and questions regarding safety issues should not be ruled out. CONCLUSION: Despite the widespread use of ICSI in patients without a formal diagnosis of male factor infertility, evidence demonstrating its effectiveness in this population is still lacking. Additional large and well-designed randomized controlled trials are needed to clarify definitive indications for ICSI in non-male factor infertility.

Hysteroscopic septum resection and reproductive medicine: A SWOT analysis.

Hysteroscopic septum resection in women with unfavourable reproductive and clinical outcomes has become common practice worldwide to improve reproductive results. No clear evidence on the possible advantages and drawbacks of this procedure has been published. In this opinion paper, based on a SWOT (strengths, weaknesses, opportunities, threats) analysis, the different aspects of this strategy are evaluated. Currently, no level 1 published evidence supports uterine resection in women with septate uterus. Clinical evidence from the studies analysed matches the more recent guidelines and suggests an improvement in reproductive outcomes after hysteroscopic resection of the septum, particularly in infertile women and women who have experienced recurrent miscarriages. In a patient with no history of infertility or prior pregnancy loss, it may be reasonable to consider septum incision after counselling about the potential risks and benefits of the procedure. Published clinical data in favour of the intervention, however, are based on studies with important methodological limitations. In this situation, the clinician and patient should reach an agreement together, based on the pros and cons of this intervention. Well-designed randomized controlled trials are required to confirm the clinical benefits and cost-effectiveness of this procedure.

There is no evidence that the time from egg retrieval to embryo transfer affects live birth rates in a freeze-all strategy.

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.

Position of the Spanish Menopause Society regarding the management of perimenopause.

Perimenopause is an imprecise period in woman over 40 years of age, which comprises the time between the moment that the first changes in the menstrual cycle appear and the year following the definitive cessation of the menses. Besides irregular bleeding, many women also complain of hot flashes and other characteristic symptoms of postmenopause. Moreover, most of them are concerned about the future impact that these events may have on their health, such as needing health exams or continuing to use contraceptive methods. A panel of experts from the Spanish Menopause Society has met to establish diagnostic and therapeutic guidelines for this period based on the best available evidence.

Can the Gail model increase the predictive value of a positive mammogram in a European population screening setting? Results from a Spanish cohort.

AIMS OF THE STUDY: The Gail Model (GM) is the most well-known model to assess the individual risk of breast cancer (BC). Although its discriminatory accuracy is low in the clinical context, its usefulness in the screening setting is not well known. The aim of this study is to assess the utility of the GM in a European screening program. METHODS: Retrospective cohort study of 2200 reassessed women with information on the GM available in a BC screening program in Barcelona, Spain. The 5 year-risk of BC applying the GM right after the screening mammogram was compared first with the actual woman's risk of BC in the same screening round and second with the BC risk during the next 5 years. RESULTS: The curves of BC Gail risk overlapped for women with and without BC, both in the same screening episode as well as 5 years afterward. Overall sensitivity and specificity in the same screening episode were 22.3 and 86.5%, respectively, and 46.2 and 72.1% 5 years afterward. ROC curves were barely over the diagonal and the concordance statistics were 0.59 and 0.61, respectively. CONCLUSION: The GM has very low accuracy among women with a positive mammogram result, predicting BC both in the concomitant episode and 5 years later. Our results do not encourage the use of the GM in the screening context to aid the referral decision or the type of procedures after a positive mammogram or to identify women at high risk among those with a false-positive outcome.

Out-of-protocol concurrent use of cisplatin and radiation therapy in locally advanced cervical cancer: feasibility and survival.

PURPOSE OF INVESTIGATION: We assessed the feasibility, response rates, and overall survival of patients with locally advanced cervical cancer treated with cisplatin-based chemotherapy during radiation therapy on an out-of-protocol basis. METHODS: Sixty-nine consecutive newly diagnosed untreated patients with locally advanced cervical cancer who received chemoradiation between 1999 and 2003 were retrospectively reviewed. Treatment consisted in external beam radiation followed by one 137-cessium intracavitary application. Cisplatin was administered for six weeks during external beam radiation. RESULTS: Treatment was well tolerated, although 52 patients presented some degree of acute adverse toxicity (gastrointestinal 65%, hematological 48%, genitourinary 10%). The 3-year survival rate was 61.8% (95% CI 54.5-69.0), with a mean 41.8 months (95% CI 35.7-48.3). Overall survival after adjusting by FIGO Stage IB2-IIA and IIB-IVA was 73.9% and 50%, respectively (p = 0.1839). Overall survival according to Stages IB2-IIb and III-IVA was 74.8% and 34.9%, respectively (P = 0.0376). CONCLUSION: In patients with locally advanced cervical cancer, adding a weekly regimen of cisplatin to standard pelvic radiation in an out-of-protocol basis is feasible, effective, and showed no unexpected toxicity.

A porous PCL scaffold promotes the human chondrocytes redifferentiation and hyaline-specific extracellular matrix protein synthesis.

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.

A comparison of raloxifene and calcium plus vitamin D on vaginal atrophy after discontinuation of long-standing postmenopausal hormone therapy in osteoporotic women. A randomized, masked-evaluator, one-year, prospective study.

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 D3) (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<0.001) in the calcium (-51.8%) and raloxifene (-18.6%) groups compared with baseline and the estrogen/progesterone group. At 12 months, significant decreases of mean VMV in the calcium (-38.7%) and raloxifene groups (-32%) (P<0.001) were also observed. Serum estradiol levels and changes of VMV correlated significantly at 6 months (rho=0.361, P<0.01) and at 12 months (rho=0.269, P<0.035). A significantly higher number of patients complained of hot flushes and palpitations in the calcium and raloxifene groups than in the estrogen/progesterone group. Raloxifene-treated women reported a significantly higher number of adverse events at 6 months compared to the other treatment groups. 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.

Insulin-sensitizing agents: use in pregnancy and as therapy in polycystic ovary syndrome.

Treatment with insulin-sensitizing agents is a relatively recent therapeutic strategy in women with polycystic ovary syndrome (PCOS) and insulin resistance. The key areas addressed in this review include PCOS and the development of type 2 diabetes mellitus and gestational diabetes, as well as the use of insulin-sensitizing agents, particularly metformin, in the management of infertility in obese and non-obese PCOS women. Treatment with metformin in PCOS women undergoing IVF and the use of metformin during gestation will be discussed. The challenge for the health care professional should be the appropriate utilization of pharmacotherapies to improve insulin sensitivity and lower circulating insulin levels resulting in beneficial changes in PCOS phenotype. Further research into the potential role of other insulin-sensitizing agents, such as pioglitazone and rosiglitazone, in the treatment of infertile women with PCOS is needed.

Trends in the use of emergency contraception: an epidemiological study in Barcelona, Spain (1994-2002).

We conducted a retrospective review of the medical records of women requesting emergency contraception (EC) at our emergency department over a 9-year period (1994-2002). EC accounted for 5.9% of all visits (n = 95,288) and increased from 1.26% in 1994 to 9.82% in 2002 (p < 0.001). Reasons for EC were condom problems in 79.5% of cases. EC was used only once by 93% of women. The mean daily number of visits was significantly higher in August (2.46), July (2.01) and September (2.02) than in other months (p < 0.05), and was more frequent on Sunday (3.26), Saturday (2.92) and Monday (2.05) compared to other week days (p < 0.001). New Year's Day and the St. John's Night registered the highest number of visits (mean of 17.2 and 11.7, respectively), with significant differences compared to the remaining days of the year (p < 0.001).

Determination of vitamin B(6) in cooked sausages.

A reverse-phase high-performance liquid chromatography (HPLC) method has been described for the determination of various active forms of vitamin B(6) in meat products. Different extracting agents were tested to solubilize fully the analyte for quantification. The best data were obtained by extracting the samples with 5% (w/v) metaphosphoric acid. Separation by HPLC was performed with fluorescence detection (excitation, 290 nm; emission, 395 nm), on a 10 cm x 0.46 cm i.d. Hypersil BDS C(18) 5 microm column using a mixture of 50 mM phosphate buffer (pH 3.2) and acetonitrile (99:1, v/v) as mobile phase. Precision of the method was 0.5% (within a day) and 4.3% (between days). The detection limits were 0.020 mg/100 g for pyridoxal and pyridoxamine, 0.017 mg/100 g for pyridoxamine phosphate, 0.500 mg/100 g for pyridoxal phosphate, and 0.033 mg/100 g for pyridoxol, with a signal-to-noise ratio of 3. The recovery ranged from 92.0 to 100.0%.

Simultaneous determination of nicotinic acid and nicotinamide in cooked sausages.

A simple and sensitive method for determining simultaneously nicotinic acid and nicotinamide content in cooked sausages by ion-pair reversed-phase liquid chromatography is described. Samples are extracted with ultrapure water, centrifuged, deproteinized with zinc hydroxide, filtered, and chromatographed with UV detection at 261 nm on a 25 cm x 4 mm i.d. Spherisorb ODS-2 cartridge using as mobile phase a mixture consisting of 5 mM heptanesulfonic acid adjusted to pH 3.3 with phosphoric acid and acetonitrile (75:25, v/v). Both vitamins are measured on a reversed-phase column with a single ion-pair reagent. Precision of the method was 0.5 and 1.0% (within a day) and 2.3 and 4.5% (between days) for nicotinic acid and nicotinamide, respectively. The detection limit was 0.300 mg/100 g. The recovery was >92% of nicotinic acid and nicotinamide added to samples of meats. Twenty samples of six different products have been analyzed in duplicate. The mean value for nicotinic acid ranged between 0.908 and 1.267 mg/100 g of fresh weight and for nicotinamide between 1.968 and 2.880 mg/100 g of fresh weight.

Tromboflebitis de la vena ovárica: a propósito de un caso / Thrombophlebitis of the ovarian vein: a case report

No disponible

Determination of total riboflavin in cooked sausages.

A simple and rapid method for determining riboflavin content in cooked sausages by ion-pair reversed-phase liquid chromatography has been set up. Samples were subjected to acid and enzymatic hydrolysis. Sample extracts were directly chromatographed, avoiding purification and concentration treatment. Final determination was performed by high-performance liquid chromatography with fluorescence detector (excitation, 227 nm; emission, 520 nm), on a 25 cm x 4 mm i.d. Spherisorb ODS-2 cartridge using a mixture of 5 mM heptanesulfonic acid adjusted to pH 2.7 with phosphoric acid and acetonitrile (75:25, v/v) as mobile phase. Precision of the method was 1.3% (within a day) and 2.6% (between days). The detection limit was 0.015 mg/100 g. The recovery was >95%.

Determination of thiamin in cooked sausages.

A reliable and rapid high-performance liquid chromatography (HPLC) method has been set up for the determination of total thiamin in difficult sample matrices such as cooked sausages. Different hydrolysis conditions and enzymes were tested to release the vitamin from its phosphate ester. The best data in the enzymatic digestion were obtained by incubating the samples with 6% clara-diastase at 50 degrees C for 3 h. After oxidation of thiamin to thiochrome, the sample extracts were purified by using a C(18) Sep-Pak cartridge. Final determination was performed by reversed-phase HPLC with fluorescence detector (excitation 360 nm, emission 430 nm), on a low-cost 25 cm x 4 mm i.d. Spherisorb C(8) cartridge using a mixture of 5 mM phosphate buffer pH 7.0 and acetonitrile (70:30, v/v) as mobile phase. Precision of the method was 1.5% (within a day) and 5. 2% (between days). The detection limit was 0.015 mg/100 g. All the recoveries from the different cooked sausages were better than 90% of thiamin hydrochloride added to samples of meats. In the samples analyzed, the mean value for thiamin was between 0.039 and 0.508 mg/100 g fresh weight.