Maximum number of children per sperm donor based on false paternity rate.

PURPOSE: The aim of this study is to estimate the weight of each relevant factor in such unions of inadvertent consanguinity and to determine a "reasonable" limit for the number of children per donor, matching the probability of inadvertent consanguinity arising from the use of sperm donor in assisted reproduction with that of such a union arising from false paternity. METHODS: In this study, we applied to Spanish data a mathematical model of consanguineous unions, taking into account the following factors: maximum number of live births/donor, fertility rate, average number of births per donor in a pregnancy, donor success rate, matings per phenotype, number of newborns/year, and number of donors needed in the population/year and births by false paternity. RESULTS: In Spain, the number of inadvertent unions between descendants of the same donor in Spain has been estimated at 0.4/year (one every two and a half years), although this frequency decreases as the reference population increases. On the other hand, the frequency of unions between family members due to false paternity has been estimated at 6.1/year. Thus, only 6% of such unions are due to the use of donor sperm. CONCLUSION: A total of 25 children per sperm donor are needed to align the probability of inadvertant consanguinity arising from the use of assisted reproduction with that due to false paternity. Therefore, we consider this number to be the maximum "reasonable" number of children born per donor in Spain.

Patient safety and adverse events related with obstetric care.

PURPOSE: To determine the frequency and distribution of Adverse Events (AE) in obstetrics departments at Spanish hospitals. METHODS: We present a retrospective cohort study including 816 women admitted to the obstetrics departments at 41 hospitals that took part in the National Adverse Effects Study in Spain (ENEAS) and an extension of this study in all hospitals located in two Autonomous Regions. To identify AE, nurses from each participating hospital examined all medical records, and completed a validated screening guide. A team of external reviewers evaluated the medical records of all women who met at least one of the criteria in the screening guide to verify all AE. The main outcome measure was the incidence of AE during hospitalization. RESULTS: The cumulative incidence of patients with obstetric care-related AE was 3.6% (95% CI 2.3-4.8). The most frequent AE were those related with surgical interventions or procedures (59.4%). None of the AE detected were considered severe. 36.7% of the AE lengthened the woman's hospital stay, and 13.3% led to hospital admission. Additional procedures were needed after 71.9% of the AE, and additional treatment was needed after 59.4%. 56.3% of the AE were considered preventable. CONCLUSIONS: Obstetric care is characterized by generally younger ages among patients, their low frequency of comorbidities and high expectations for successful outcomes of care. However, some factors can increase obstetric risk and favor the appearance of preventable incidents and AE. Systems are needed to detect preventable AE, and measures are needed to reduce risks or attenuate their consequences.

Cumulative live birth rate after two single frozen embryo transfers (eSFET) versus a double frozen embryo transfer (DFET) with cleavage stage embryos: a retrospective cohort study.

PURPOSE: According to the latest ART report for Europe, about 13% of pregnancies after frozen embryo transfer are multiple. Our objective was to analyse the impact on the multiple pregnancy rate of two eSFET (elective single frozen embryo transfers) versus a DFET (double frozen embryo transfer) in women aged under 38 years, who had not achieved pregnancy in their fresh transfer and who had at least two vitrified embryos of A/B quality. METHODS: This study was conducted from January 2010 to June 2013 at a public hospital. The couples were divided into three groups. Group DFET: the first cryotransfer of two embryos (105 women); cSFET group: the only cryotransfer of a single vitrified embryo (60 women); eSFET group, individually vitrified embryos: 20 patients included in a clinical trial of single-embryo fresh and frozen transfer and 21 patients who chose to receive eSFET. RESULTS: The clinical pregnancy rate was 38.1% in the DET group and the cumulative clinical pregnancy rate was 43.3% in the eSFET group. There were no significant differences between the DFET and eSFET groups (30.0 vs 34.1%) in cumulative live birth delivery rate. The rate of multiple pregnancies varied significantly between the DFET and eSFET groups (32.5 vs 0%, p < 0.05). CONCLUSIONS: For good-prognosis women aged under 38 years, taking embryo quality as a criterion for inclusion, an eSFET policy can be applied, achieving acceptable cumulative clinical pregnancy and live birth rates and reducing multiple pregnancy rates.

Early embryonic morphology sonographically assessed and its correlation with yolk sac in missed abortion.

PURPOSE: To provide additional information about embryo morphology sonographic assessment and its correlation with yolk sac. METHODS: A systematic study in 200 consecutive cases of missed abortion <10 weeks diagnosed by transvaginal ultrasound. RESULTS: In 104 gestations of embryos with morphological abnormalities, 88 (84.6 %) were at least 1 week smaller than expected for gestational age and 16 (15.4 %) were the expected size. From 32 normal morphologic embryos, 7 (21.9 %) were at least 1 week smaller than expected for gestational age, and 25 (78.1 %) were the expected size (p < 0.005). Normal morphologic embryos are linked more frequently with normal yolk sac (62.5 %). Findings in anembryonic gestations (GD1) included an absent yolk sac (46.9 %) and a cystic yolk sac (25 %). Likewise, findings in GD2-3 embryos included more frequently a cystic yolk sac (42.9 %) and an absent yolk sac (32.5 %). GD4 embryos are associated with an echogenic yolk sac (40 %), a relatively small-hypoplastic- (40 %) and a relatively large-cystic- (20 %). In DI embryos, yolk sac appears cystic (62.5 %) or echogenic (37.5 %). CONCLUSIONS: Our study proves the correlation between morphology of conceptuses and yolk sac appearance in cases of missed abortion.

PGS-FISH in reproductive medicine and perspective directions for improvement: a systematic review.

INTRODUCTION: Embryo selection can be carried out via morphological criteria or by using genetic studies based on Preimplantation Genetic Screening. In the present study, we evaluate the clinical validity of Preimplantation Genetic Screening with fluorescence in situ hybridization (PGS-FISH) compared with morphological embryo criteria. MATERIAL AND METHODS: A systematic review was made of the bibliography, with the following goals: firstly, to determine the prevalence of embryo chromosome alteration in clinical situations in which the PGS-FISH technique has been used; secondly, to calculate the statistics of diagnostic efficiency (negative Likelihood Ratio), using 2 × 2 tables, derived from PGS-FISH. The results obtained were compared with those obtained from embryo morphology. We calculated the probability of transferring at least one chromosome-normal embryo when it was selected using either morphological criteria or PGS-FISH, and considered what diagnostic performance should be expected of an embryo selection test with respect to achieving greater clinical validity than that obtained from embryo morphology. RESULTS: After an embryo morphology selection that produced a negative result (normal morphology), the likelihood of embryo aneuploidies was found to range from a pre-test value of 65% (prevalence of embryo chromosome alteration registered in all the study groups) to a post-test value of 55% (Confidence interval: 50-61), while after PGS-FISH with a negative result (euploid), the post-test probability was 42% (Confidence interval: 35-49) (p < 0.05). The probability of transferring at least one euploid embryo was the same whether 3 embryos were selected according to morphological criteria or whether 2, selected by PGS-FISH, were transferred. Any embryo selection test, if it is to provide greater clinical validity than embryo morphology, must present a LR-value of 0.40 (Confidence interval: 0.32-0.51) in single embryo transfer, and 0.06 (CI: 0.05-0.07) in double embryo transfer. DISCUSSION: With currently available technology, and taking into account the number of embryos to be transferred, the clinical validity of PGS-FISH, although superior to that of morphological criteria, does not appear to be clinically relevant.

Reducing inter-observer variability in embryo evaluation by means of training courses.

PURPOSE: To study the utility of a training session offered to junior embryologists, comparing the results obtained with those reported by a group of senior embryologists. METHODS: The 62 junior embryologists participanting were asked to decide on the quality of the embryos and theg clinical decision to be taken. RESULTS: The junior embryologists' success rate following the training course was significantly higher than before for embryo classification (48.4% ± 20.4 vs. 59.7% ±16.7) (p < 0.05) and for clinical decision (54.7% ± 19.6 vs. 68.7% ± 17.6) (p < 0.005). Comparison of the degree of agreement between the categories assigned by the junior embryologists and those assigned by consensus among the group of senior embryologists revealed kappa values of k = 0.32 before the course and of k = 0.54 after it. The comparison between pre- and post-training junior and senior embryologists also reflected an improvement in the kappa index for clinical decision, from k = 0.54 to k = 0.68. CONCLUSIONS: Training courses are shown to be an effective tool for increasing the degree of agreement between junior and senior embryologists.

Factors influencing pregnancy outcome in women with type 2 versus type 1 diabetes mellitus.

AIM: To compare pregnancy outcome and factors related to adverse perinatal outcome in women with type 1 versus type 2 diabetes mellitus (DM). MATERIAL AND METHODS: Multicentre retrospective study. Some 404 women were studied, 257 with type 1 DM and 147 with type 2 DM. Main outcome measures were rates of prematurity, macrosomia, instrumental deliveries, congenital malformations, need for neonatal intensive care unit (NICU), and perinatal mortality. RESULTS: There were no significant differences in pregnancy outcome between women with type 1 and type 2 DM, except for an increased rate of instrumental deliveries in women with type 1 DM. In these women, duration of diabetes was a significant predictor of caesarean delivery (OR =1.06 (1.01-1.12); p=0.02). Chronic hypertension was positively related to prematurity (p=0.02), and proved to be a significant predictor of birth weight lower than 2,500 g (OR =3.54 (1.4-12.49); p=0.043) and perinatal mortality (OR =10.6 (1.15-117.6); p=0.04). In women with type 2 DM, third trimester higher glycosylated haemoglobin was related to both prematurity (OR 4.9 (1.7-14.4; p=0.004) and low birth weight. Macrosomia was a significant risk factor for caesarean section. First trimester glycosylated haemoglobin was related to congenital malformations and proved to be a significant predictor of perinatal mortality (OR =2.4 (1.02-5.74); p=0.04). CONCLUSIONS: Duration of DM and chronic hypertension were the most influential factors related to adverse perinatal outcomes in women with type 1 DM, and poor metabolic control and macrosomia in women with type 2 DM.

PERINATAL OUTCOMES OF PREMATURITY AND BIRTH WEIGHT ACCORDING TO MATERNAL CAFFEINE CONSUMPTION.

UNLABELLED: Objetive: identify whether there is an increased risk of adverse perinatal outcomes, like prematurity or decreased weight in newborns, associated with caffeine consumption during the first half of pregnancy in pregnant women of our population. METHODS: transversal study carried out in 1 175 patients from Virgen de las Nieves University Hospital of Granada (Spain). Information about caffeine consumption during first half of gestation and perinatal outcomes was obtained by personal interview, medical records and telephone call after delivery. The average caffeine intake was calculated from meals and drinks included in a validated questionnaire. RESULTS: there was no difference in caffeine consumption in pregnant women with birth weight ≥2 500 g and.

Objetivo: identificar si existe un aumento del riesgo en resultados perinatales adversos de prematuridad y disminucion del peso de los recien nacidos asociados al consumo de cafeina durante la primera mitad del embarazo en gestantes de nuestra poblacion. Métodos: estudio transversal llevado a cabo en 1.175 gestantes del Hospital Universitario Virgen de las Nieves de Granada (Espana). La informacion sobre el consumo de cafeina durante la primera mitad del embarazo y los resultados perinatales estudiados se obtuvieron mediante entrevista personal, consulta de la historia clinica y llamada telefonica tras el parto. La ingesta media de cafeina se calculo a partir de las comidas y bebidas incluidas en un cuestionario validado. Resultados: no hubo diferencias en el consumo de cafeina en gestantes con recien nacidos de peso ≥2.500 g y.

Assisted reproductive technology and obstetric outcome in couples when the male partner has a chronic viral disease.

BACKGROUND: Assisted reproductive technology (ART) with washed semen can achieve pregnancy with minimal risk of horizontal and vertical transmission of chronic viral diseases (CVD) such as human immunodeficiency virus (HIV), hepati- tis C virus (HCV) and hepatitis B virus (HBV) among serodiscordant couples. How- ever, few studies have been made of the use made by these couples of ARTs or of the obstetric results achieved. MATERIALS AND METHODS: In this retrospective study, 93 men who were seropositive for HIV, HCV or HBV and who underwent assisted reproduction treatment at our centre (Hospital Universitario Virgen de las Nieves, Granada, Spain) were included. Washed semen was tested to detect viral particles. Non-infected women were tested before and after each treatment, as were the neonates at birth and after three months. RESULTS: A total of 62 sperm samples were washed, and none were positive for the detec- tion of viral molecules. Semen samples from 34 HBV positive males were not washed since the female partner had immunity to hepatitis B. In total, 38 clinical pregnancies were achieved (22% per cycle and 40.9% per couple) out of 173 cycles initiated, and 28 births were achieved (16.2% per cycle and 30.1% per couple), producing 34 live births. The rate of multiple pregnancies was 21.4%. Obstetric and neonatal results were similar in the groups of couples studied. At follow-up, no seroconversion was detected in the women or neonates. CONCLUSION: Sperm washing and intracytoplasmic sperm injection are shown to be a safe and effective option for reducing the risk of transmission or super infection in serodiscordant or concordant couples who wish to have a child. Pregnancies ob- tained by ART in couples when the male is CVD infected achieve good obstetric and neonatal results.

Randomised clinical trial comparing elective single-embryo transfer followed by single-embryo cryotransfer versus double embryo transfer.

OBJECTIVE: To analyze the impact of the eSET followed by single-embryo cryotransfer versus double embryo transfer in older women (<38 years) without taking into account embryo quality. STUDY DESIGN: This is a prospective randomised clinical trial performed on 194 couples attempting a first IVF cycle in a Public Hospital in Spain. The women in Group 1 received eSET plus a single-embryo cryotransfer, and those in Group 2 received a double embryo transfer (DET). RESULTS: In the intention-to-treat analysis, the cumulative live birth delivery rate in the eSET group was similar to the results obtained for the DET group (45.2% vs. 41.8%; p = 0.60). The rate of multiple gestation was significantly lower in the eSET group than in the DET group (0% vs. 26.4%; p < 0.05). The findings obtained in the per-protocol analysis were similar to those obtained in the intention-to-treat analysis. The per-protocol analysis revealed no significant differences in the rate of implantation (29.8% in eSET vs. 29.7% in DET; p = 0.98), in cumulative pregnancy rates per transfer (49.1% in eSET vs. 46.9% in DET; p = 0.80) or in the cumulative live birth delivery rate (38.6% in eSET vs. 42.2% in DET; p = 0.69). In the cycles with eSET, there were no twin pregnancies (0% in eSET vs. 27.6 in DET; p < 0.05). CONCLUSIONS: For women aged under 38 years with good prognosis, without taking embryo quality as a criterion for inclusion, an eSET policy can be applied, achieving acceptable cumulative clinical pregnancy rates and birth rates.

Pelvic abscess after oocyte retrieval in women with endometriosis: A case series.

BACKGROUND: Pelvic inflammatory disease with progression to pelvic abscess is a rare complication after oocyte retrieval during in vitro fertilization cycles. However, in patients with endometriosis the risk appears to be increased. Many authors agree on the need for antibiotic prophylaxis during the oocyte retrieval in these patients, but there is no consensus regarding the best antibiotic. CASE: We discuss 3 clinical cases of tubo-ovarian abscess in women with endometriosis after oocyte retrieval despite antibiotic prophylaxis between 2004 and 2011 at our center, and discuss our experience in the context of earlier reports. CONCLUSION: It is unclear whether antibiotic prophylaxis is necessary in these women, and which antibiotic is best. Only douching with povidone-iodine appears to decrease the rate of pelvic infection.

Obstetric and perinatal outcome in women with twin pregnancy and gestational diabetes.

OBJECTIVE: The aim of this study was to evaluate pregnancy complications and obstetric and perinatal outcomes in women with twin pregnancy and GDM. STUD DESIGN: An observational multicentre retrospective study was performed and 534 pregnant woman and 1068 twins infants allocated into two groups, 257 with GDM and 277 controls, were studied. MAIN OUTCOME MEASURES: Pregnant women characteristics, hypertensive complications, preterm delivery rate, mode of delivery and birthweight were analysed. RESULTS: Pregnant women with GDM were older (p < 0.001) and had higher body mass index (p < 0.001) than controls. GDM was associated with higher risk of prematurity in twin pregnancy (odds ratio 1.64, 95% confidence interval [1.14-2.32], p = 0.005). This association was based on the association with other pregnancy complications. Birthweight Z-scores were significantly higher in the GDM group (p = 0.02). The rate of macrosomia was higher in the GDM group (p = 0.002) and small for gestational age (SGA) babies were significantly less frequent (p = 0.03). GDM was an independent predictor of macrosomia (p = 0.006). CONCLUSION: The presence of GDM in twin pregnancy was associated with a higher risk of hypertensive complications, prematurity and macrosomia, but significantly reduces the risk of SGA infants. Prematurity was related to the presence of other associated pregnancy complications.

Lowering the age at menarche and risk of early menarche in a population of Spanish postmenopausal women during the past two decades.

AIM: The purpose of this study is to confirm in our population the decreasing secular trend in the age of menarche (AAM) observed in other European countries. Another aim is to investigate the association between early menarche and breast cancer, metabolic disorders risk or early menopause. MATERIALS AND METHODS: We conducted a nationwide population-based study of 1980 Caucasoid Spanish postmenopausal women from 2003 to 2006 to investigate the AAM, the duration of the fertile period and the relation of early menarche with breast cancer and some metabolic disorders. RESULTS: Regression analysis of AAM demonstrates a trend towards the younger AAM in our population during the past decades (P > 0.001). Parallel to this decrease we observe a significant increase in the fertility period and the height of our population (P < 0.001). In the women with AAM less than 11 years, there is an increased risk of hypercholesterolaemia, being overweight and obesity. However, early menarche does not raise the risk of adult onset diabetes, hypertension or breast cancer. CONCLUSIONS: These data indicate a decreasing secular trend of AAM in a Spanish population in the last decades. Furthermore, hypercholesterolaemia and obesity, but not breast cancer, appears to be influenced by younger AAM. Only women who have their menarche at the age of nine years or less are more likely to have an earlier menopause.

Multigenic combination of estrogen-related genes is associated with age at natural menopause in a Spanish population.

OBJECTIVE: Age at natural menopause (ANM) can be considered a complex parameter that depends on the interaction of multiple factors. In the present study, the role of interaction between genetic variants within estrogen synthesis and signalling pathways in the ANM in Spanish women is studied. MATERIAL AND METHODS: Nine single nucleotide polymorphisms (SNPs) located at different candidate genes related to the estrogen signalling pathway were analysed in 1980 Spanish postmenopausal women. RESULTS: Independently, none of the nine markers were significantly associated with early ANM. Only heterozygosis at the NRIP rs2229741 locus could be associated with early menopause; however, this marker does not maintain statistical significance. In contrast, linear regression analysis suggests several epistatic interactions including these markers in relation to ANM, especially between ESR2, NRIP1 and BMP15. The genetic variant that appears most in these interactions is that of the BMP15 rs3897937. It was observed that AA-TC combined genotype for NRIP-BMP15 (rs3897937), respectively, appears to be associated with a lower ANM than other possible combinations of these SNP (46.1+/-5.9 versus 50.4+/-3.3; P = 0.002). In the multilocus analysis, the multigenic interaction formed by ESR2 (AA), BMP15 rs3897937 (TC) and NRIP1 (AA) has the lower ANM (45.37+/-6.8 versus 48.69+/-5; P = 0.038). CONCLUSIONS: The results suggest that epistatic interactions of estrogen-related alleles may contribute to variance in ANM in Spanish women. Moreover, BMP15 and NRIP1 also appear as attractive candidate genes for premature menopause but require further investigation to confirm them.