Increased circulating cell-derived microparticle count is associated with recurrent implantation failure after IVF and embryo transfer.

Cell-derived microparticles (cMPs) are small membrane vesicles that are released from many different cell types in response to cellular activation or apoptosis. Elevated cMP counts have been found in almost all thrombotic diseases and pregnancy wastage, such as recurrent spontaneous abortion and in a number of conditions associated with inflammation, cellular activation and angiogenesis. cMP count was investigated in patients experiencing unexplained recurrent implantation failure (RIF). The study group was composed of 30 women diagnosed with RIF (RIF group). The first control group (IVF group) (n = 30) comprised patients undergoing a first successful IVF cycle. The second control group (FER group) included 30 healthy women who had at least one child born at term and no history of infertility or obstetric complications. cMP count was significantly higher in the RIF group compared with the IVF and FER groups (P < 0.05 and P < 0.01, respectively) (RIF group: 15.8 ± 6.2 nM phosphatidylserine equivalent [PS eq]; IVF group: 10.9 ± 5.3 nM PS eq; FER group: 9.6 ± 4.0 nM PS eq). No statistical difference was found in cMP count between the IVF and FER groups. Increased cMP count is, therefore, associated with RIF after IVF and embryo transfer.

Assisted reproductive technologies are associated with cardiovascular remodeling in utero that persists postnatally.

BACKGROUND: Assisted reproductive technologies (ARTs) have been shown to be associated with general vascular dysfunction in late childhood. However, it is unknown whether cardiac remodeling is also present and if these changes already manifest in prenatal life. Our aim was to assess fetal and infant (6 months of age) cardiovascular function in ART pregnancies. METHODS AND RESULTS: This prospective cohort study included 100 fetuses conceived by ART and 100 control pregnancies. ART fetuses showed signs of cardiovascular remodeling, including a more globular heart with thicker myocardial walls, decreased longitudinal function (tricuspid ring displacement in controls: median, 6.5 mm [interquartile range, 6.1-7.1 mm]; tricuspid ring displacement in ART: 5.5 mm [interquartile range, 5.1-6.1]; P<0.001), impaired relaxation, and dilated atria (atrial area in controls, 1.46 cm(2) [interquartile range, 1.2-1.5 cm(2)]; atrial area in ART, 1.6 cm(2) [interquartile range, 1.3-1.8 cm(2)]; P<0.001). Additionally, ART infants showed persistence of most cardiac changes and a significant increase in blood pressure and aortic intima-media thickness (systolic blood pressure in controls, 74 mm Hg [interquartile range, 67-83 mm Hg]; systolic blood pressure in ART, 83 mm Hg [interquartile range, 75-94 mm Hg]; P<0.001; aortic intima-media thickness in controls, 0.52 mm [interquartile range, 0.45-0.56 mm]; aortic intima-media thickness in ART, 0.64 mm [interquartile range, 0.62-0.67]; P<0.001). We could not demonstrate that our findings were directly caused by ART because of their association with various confounding factors, including intrauterine growth restriction or factors related to the cause of infertility. CONCLUSIONS: Children conceived by ART manifest cardiac and vascular remodeling that is present in fetal life and persists in postnatal life, suggesting opportunities for early detection and potential intervention. The underlying mechanisms and the effect of potential confounders such as growth restriction or prematurity remain to be elucidated.

Benznidazole-induced drug reaction with eosinophilia and systemic symptoms syndrome in a patient with human leucocyte antigen (HLA)-A*68.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare but severe drug hypersensitivity reaction with potentially life-threatening consequences. It is characterised by fever, extensive maculopapular exanthema, lymph node enlargement, abnormal blood cell counts, and organ-related complications. Diagnosis can be challenging due to incomplete or non-specific symptoms, and it can sometimes manifest as a purely systemic disease. Discontinuation of the causative drug is essential. Treatment may involve corticosteroids and supportive care. Genetic screening for specific markers, such as human leucocyte antigen (HLA)-A*68, A11:01, and A29:02, can help identify individuals at risk for severe reactions to benznidazole, a drug used to treat Chagas disease. This case report describes the rarity and severity of DRESS syndrome, underscoring the potential benefit of genetic screening to prevent adverse reactions in patients with Chagas disease.

Plasma homocysteine and vitamin B12 serum levels, red blood cell folate concentrations, C677T methylenetetrahydrofolate reductase gene mutation and risk of recurrent miscarriage: a case-control study in Spain.

BACKGROUND: Hyperhomocysteinemia and methylenetetrahydrofolate reductase (MTHFR) gene mutation have been postulated as a possible cause of recurrent miscarriage (RM). There is a wide variation in the prevalence of MTHFR polymorphisms and homocysteine (Hcy) plasma levels among populations around the world. The present study was undertaken to investigate the possible association between hyperhomocysteinemia and its causative genetic or acquired factors and RM in Catalonia, a Mediterranean region in Spain. METHODS: Sixty consecutive patients with ≥ 3 unexplained RM and 30 healthy control women having at least one child but no previous miscarriage were included. Plasma Hcy levels, MTHFR gene mutation, red blood cell (RBC) folate and vitamin B12 serum levels were measured in all subjects. RESULTS: No significant differences were observed neither in plasma Hcy levels, RBC folate and vitamin B12 serum levels nor in the prevalence of homozygous and heterozygous MTHFR gene mutation between the two groups studied. CONCLUSIONS: In the present study RM is not associated with hyperhomocysteinemia, and/or the MTHFR gene mutation.

Outcome from consecutive ICSI cycles in patients treated with recombinant human LH and those supplemented with urinary hCG-based LH activity during controlled ovarian stimulation in the long GnRH-agonist protocol.

Clinical results were compared in a well-established, assisted reproduction program during the cross-over from highly purified (HP)-human menopausal gonadotropin (hMG) to rhFSH/rhLH. We included the last 33 patients treated with HP-hMG and the first 33 patients receiving rhFSH/rhLH for ovarian stimulation in their first intracytoplasmic sperm injection cycle. Patient baseline characteristics were almost identical in the two groups. Ovarian stimulation characteristics (days of stimulation, total amount of FSH administered using a modest initial loading dose of 150 IU/d, patients with oocyte retrieval) were similar for the two groups. However, the number of total and leading follicles and E2 serum levels on the human chorionic gonadotropin injection day were significantly higher in the rhFSH/rhLH group. The oocyte yield was significantly higher in the rhFSH/rhLH group as well as the number of metaphase II oocytes, difference almost reaching the statistical significance. The number of oocytes fertilized was also higher in patients receiving rhFSH/rhLH treatment. Implantation and clinical pregnancy rates were similar in both the study groups. It is concluded that in women undergoing controlled ovarian hyperstimulation under pituitary suppression for ART, the recombinant combined product containing FSH and LH in a fixed 2:1 ratio is more effective than HP-hMG in terms of follicle development, oocyte yield and quality, and fertilization rates.

Risk of thromboembolic events after recurrent spontaneous abortion in antiphospholipid syndrome: a case-control study.

OBJECTIVE: To investigate whether patients having antiphospholipid syndrome (APS) as the only aetiological factor for recurrent spontaneous abortion (RSA) are at increased risk of thrombosis later in life. METHODS: A case-control study at a tertiary university referral centre. The study group consisted of 57 primary APS and RSA women (APS-RSA group). Control groups included: 86 patients with RSA of unknown aetiology (uRSA group), 42 patients with RSA and thrombophilic genetic defects as the only aetiologic factor for RSA (tRSA group) and 30 antiphospholipid antibody (aPL) positive but otherwise healthy women (aPL group). The main measurement was the thrombosis rate after long-term follow-up. RESULTS: APS-RSA patients had a significantly higher 12-year cumulative thrombotic incidence rate compared with the three comparator groups (19.3% vs 4.8%, 0.0% and 0.0%, respectively (log rank), p<0.001). Patients in the APS-RSA group had 25.6 thrombotic events per 1000 patient-years (95% CI 12.8 to 45.9). The OR of thrombosis in relation to the presence (APS-RSA group) or absence (uRSA and tRSA groups) of aPL in patients with RSA was 15.06 (95% CI 3.2 to 70.5). CONCLUSIONS: Our data indicate that a history of RSA associated with aPL is a risk factor for subsequent thrombosis in the long term.

The effect of maternal age on chromosomal anomaly rate and spectrum in recurrent miscarriage.

STUDY QUESTION: Is there any effect of maternal age on chromosomal anomaly rate and spectrum in recurrent miscarriage? SUMMARY ANSWER: There was no significant difference in the chromosome abnormality rate between sporadic and recurrent miscarriage but the chromosome abnormality rate increased significantly with maternal age. WHAT IS KNOWN ALREADY: About 50-70% of non-recurrent miscarriages occur because of a chromosomal anomaly, but no agreement about the effect of either maternal age or the number of previous miscarriages on the chromosomal anomaly rate has been reached. STUDY DESIGN, SIZE, DURATION: A retrospective cohort of 353 miscarriages successfully karyotyped in the same center between 2002 and 2011, grouped according to the number of miscarriages and maternal age. PARTICIPANTS/MATERIALS, SETTING, METHODS: Among the 353 women, 153 were below 35 years (73 with sporadic, 48 with two and 32 with recurrent miscarriage) and 200 were 35 years or more (81 with sporadic, 55 with two and 64 with recurrent miscarriage). The chromosomal anomaly rate and the anomaly spectrum were compared between sporadic and recurrent miscarriage, within the two maternal age groups, using the chi-square test and the Bonferroni correction for all the P-values. Risk of chromosomal anomaly was estimated for maternal age, number of miscarriages and previous live births by multivariate binary logistic regression analysis. MAIN RESULTS AND THE ROLE OF CHANCE: Sporadic and recurrent miscarriage did not show significantly different chromosomal anomaly rates (68 versus 60%) and maternal age was the only statistically significant predictor of the chromosomal anomaly risk we identified. Some trends were observed in the chromosomal anomaly spectrum when sporadic was compared with recurrent miscarriage: recurrent miscarriage exhibited a decrease in viable trisomies (37 versus 11%) and an increase in non-viable trisomies (38 versus 57%) in women >35 years, together with an increase in unbalanced structural anomalies (4.9 versus 29%) in younger women. LIMITATION, REASONS FOR CAUTION: The mixed origin of our study population, and the limited number of recurrent miscarriages, particularly in the younger group, limits statistical power to detect differences. WIDER IMPLICATIONS OF THE FINDINGS: The most commonly observed chromosomal anomaly type in recurrent miscarriage depends on maternal age: non-viable autosomal trisomies in older women and unbalanced structural anomalies in younger women. When a chromosomal anomaly is identified as the cause of miscarriage, additional maternal evaluation may be avoided. STUDY FUNDING/COMPETING INTERESTS: No competing interests declared.

Reduced plasma fibrinolytic potential in patients with recurrent implantation failure after IVF and embryo transfer.

BACKGROUND: Recurrent implantation failure (RIF) following embryo transfer (ET) is a major continuing problem in IVF. Women with haemostatic defects may be at increased risk of miscarriage and preclinical pregnancy loss. The fibrinolytic system is considered, at present, the key to new thrombotic pathogenic mechanisms. Patients with unexplained recurrent miscarriage have an impairment of fibrinolysis, as demonstrated by prolonged clot lysis time (CLT) in association with increased plasma levels of thrombin-activatable fibrinolysis inhibitor (TAFI). In this study, we investigated fibrinolytic potential in patients with RIF. METHODS: Three groups of patients were studied: 30 women with RIF (RIF group), 60 patients undergoing a first successful IVF-ET cycle (IVF group) and 60 healthy fertile women (FER group). Plasma CLT was measured using a global fibrinolysis assay. TAFI antigen plasma levels and polymorphisms in the TAFI gene (+505A/G and +1542C/G) were analysed using enzyme-linked immunosorbent assay and allele-specific PCR, respectively. RESULTS: CLT was significantly longer (P < 0.0001 and P < 0.0009, respectively) and TAFI antigen levels were significantly higher (both P < 0.0001) in the RIF versus the IVF and FER groups. A direct relationship between CLT and TAFI antigen levels (r = 0.40; P = 0.001) was detected in the whole study population. There were no differences in distribution of TAFI polymorphisms between groups. CONCLUSIONS: Patients with RIF have reduced plasma fibrinolytic potential, as shown by a prolonged CLT, and this may be explained, at least in part, by increased TAFI antigen levels.

Osteopontin and alphavbeta3 integrin as markers of endometrial receptivity: the effect of different hormone therapies.

The osteopontin: alphavbeta3 integrin complex has been proposed as a means of distinguishing receptive from non-receptive endometrium in clinical practice, thus offering new directions for the development of contraceptive approaches targeted to the endometrium as well as a better understanding of occult causes of infertility in women. Histological dating and immunohistochemical study were performed in control and study cycles in seven groups of women including 10 subjects per group and who received clomiphene citrate, ovarian stimulation for IVF, oral contraception, dehydrogesterone for endometrial luteal phase defect, two different regimens of hormone replacement therapy, or no treatment. Ten healthy fertile women served as a general control group. Osteopontin and alphavbeta3 integrin expression in the human endometrium was closely related to endometrial maturation and this was irrespective of the endometrium being in-phase or out-of-phase and the hormonal treatment (or no treatment) received. In conclusion, immunohistochemical assessment of the endometrium indicates that the use of osteopontin and alphavbeta3 integrin or the osteopontin: alphavbeta3 integrin complex as targets for the development of contraceptive approaches or the understanding of the pathogenesis of female infertility offer little benefit compared with simple histological dating.

Transdermal testosterone may improve ovarian response to gonadotrophins in low-responder IVF patients: a randomized, clinical trial.

BACKGROUND: Studies in macaques have indicated that androgens have some synergistic effects with FSH on folliculogenesis. This study investigated the usefulness of pretreatment with transdermal testosterone in low-responder IVF patients. METHODS: Randomized clinical trial including 62 infertile women who had a background of the first IVF treatment cycle cancelled because of poor follicular response. Patients were randomized in two treatment groups in their second IVF attempt. In patients in Group 1 (n = 31), transdermal application of testosterone preceding standard gonadotrophin ovarian stimulation under pituitary suppression was used. In Group 2 (n = 31 patients), ovarian stimulation was carried out with high-dose gonadotrophin in association with a minidose GnRH agonist protocol. The primary end-point was the incidence of low-responder patients. The main secondary outcome was the incidence of patients reaching ovum retrieval. RESULTS: The percentage of cycles with low response was significantly lower in Group 1 than in Group 2 (32.2 versus 71% 95% confidence interval for the difference, 15.7-61.6; P < 0.05). The number of patients with ovum retrieval tended to be higher in Group 1 than in Group 2 (80.6 versus 58.1% P = 0.09), the difference reaching statistical significance (81.2 versus 41.1%; P < 0.05) when only patients having normal basal FSH levels (16 and 17 patients in Groups 1 and 2, respectively) were considered. CONCLUSIONS: Pretreatment with transdermal testosterone may improve the ovarian sensitivity to FSH and follicular response to gonadotrophin treatment in previous low-responder IVF patients. This approach leads to an increased follicular response compared with a high-dose gonadotrophin and minidose GnRH agonist protocol.

Comparison of GnRH agonist versus luteal estradiol GnRH antagonist protocol using transdermal testosterone in poor responders.

OBJECTIVE: Transdermal testosterone has been used in different doses and in different stimulation protocols in poor responders. The aim of the present study is to compare the luteal estradiol/GnRH antagonists protocol versus long GnRH agonists in poor responder patients according to the Bologna criteria, in which transdermal testosterone has been used prior to the stimulation with gonadotropins. METHODS: In this retrospective analysis, a total of 141 poor responder patients according to the Bologna criteria were recruited. All patients were treated with transdermal testosterone preceding ovarian stimulation with gonadotropins during 5 days. In 53 patients we used the conventional antagonist protocol (Group 1). In 88 patients (GrH pituitary suppression was achieved by leuprolide acetate according to the conventional long protocol (Group 2). We analyzed the ovarian stimulation parameters and IVF outcomes. RESULTS: Comparing groups 1 and 2, there were no significant differences between cancellation rates and number of oocytes retrieved. However the total gonadotropin dose used and the mean length of stimulation were significantly lower in group 1 when compared to group 2. There were no significant differences in pregnancy outcomes; however, there was a slight increase in the implantation rate in group 1 vis-a-vis group 2, although statistical significance was not achieved. CONCLUSION: TT in poor responder patients can be effective both with the conventional agonist's long protocol and with the conventional antagonist's protocol. However, short regimes with previous estradiol antagonists in the luteal phase facilitate ovarian stimulation by shortening the days of treatment and the consumption of gonadotropins.

Combined laparoscopic surgery and pentoxifylline therapy for treatment of endometriosis-associated infertility: a preliminary trial.

BACKGROUND: Surgical treatment has modest efficacy for the treatment of infertility associated with early-stage endometriosis. Immunomodulation with pentoxifylline is considered as a new strategy potentially useful in treating endometriosis. Thus, this study investigated the usefulness of combined laparoscopic surgery and pentoxifylline therapy in the treatment of infertility associated with minimal to mild endometriosis. METHODS: A prospective, randomized, controlled blind trial was conducted. Patients entered the study immediately after laparoscopic surgery and were randomly assigned to the treatment with either oral pentoxifylline (800 mg/day) (pentoxifylline group, n = 51) or an oral placebo (placebo group, n = 53). Patients were then observed for pregnancy for 6 months. RESULTS: Among 98 patients finally considered in the evaluation of the results, the 6 month overall pregnancy rates were 28 and 14% in the pentoxifylline and placebo groups, respectively. Thus, an absolute difference of 14% (95% CI -2 to 30) (Chi-squared test, P = 0.1) in the cumulative probability of pregnancy in 6 months after laparoscopic surgery in patients receiving pentoxifylline versus placebo post-operatively was observed. CONCLUSION: Our findings provide preliminary clinical evidence to suggest the new experimental treatment approaches, toward endometriosis, that are based on immunomodulation deserve further attention. Well-designed multicenter trials are warranted to confirm or refute our results.

Osteopontin and alphavbeta3 integrin expression in the endometrium of infertile and fertile women.

Osteopontin and its receptor alpha(v)beta(3) integrin have recently been proposed as a major complex to promote embryo attachment, and thus they would be useful as markers of endometrial receptivity. In the current study alpha(v)beta(3) integrin and osteopontin expression and co-expression in in-phase and out-of-phase endometrial biopsies from normal healthy women (n = 12) and infertile patients (n = 107) were investigated. Two endometrial biopsies (post-ovulatory day +6 to +8, and 4 days later) were performed during a single menstrual cycle in each subject. Oestradiol and progesterone serum concentrations were quantified on the same days as endometrial sampling. No statistically significant difference regarding alpha(v)beta(3) integrin and osteopontin expression and their coexpression was found between fertile controls and infertile patients irrespective of endometria being in-phase or out-of-phase, infertility factors detected or whether patients became spontaneously pregnant or not. Although a co-ordinate high concentration of both glycoproteins on post-ovulatory day 8 onwards was observed, there was an evident lack of temporal co-expression of these markers during the implantation window. It is concluded that the functional significance of the osteopontin:alpha(v)beta(3) integrin complex as a marker of endometrial receptivity and implantation potential in women seems to be untenable.

Patient safety and nursing implication: Survey in Catalan hospitals. / Seguridad del paciente e implicación de las enfermeras: encuesta en los hospitales de Cataluña.

OBJECTIVE: This study aims to describe the implementation of the patient safety (PS) programs in catalan hospitals and to analyze the level of nursing involvement. METHOD: Multicenter cross-sectional study. To obtain the data two questionnaires were developed; one addressed to the hospital direction and another to the nurse executive in PS. The survey was distributed during 2013 to the 65 acute care hospitals in Catalonia. RESULTS: The questionnaire was answered by 43 nursing directors and 40 nurse executive in PS. 93% of the hospitals responded that they had a PS Program and 81.4% used a specific scoreboard with PS indicators. The referent of the hospital in PS was a nurse in 55.8% of the centres. 92.5% had a system of notification of adverse effects with an annual average of 190.3 notifications. In 86% of the centres had a nurse involved in the PS program but only in the 16% of the centres the nurse dedication was at full-time. The nurse respondents evaluate the degree of implementation of the PBS program with a note of approved and they propound as improvement increase the staff dedicated to the PS and specific academic training in PS. CONCLUSIONS: The degree of implementation of programs for patient safety is high in Catalan acute hospitals, while the organizational structure is highly diverse. In more than half of the hospitals the PS referent was a nurse, confirming the nurse involvement in the PS programs.

Age, independent from ovarian reserve status, is the main prognostic factor in natural cycle in vitro fertilization.

OBJECTIVE: To analyze natural cycle IVF (NC-IVF) results according to patient age, ovarian reserve status following the Bologna criteria, cause of infertility, and modification of the cycle with the use of GnRH antagonist. DESIGN: Retrospective cohort study. SETTING: Tertiary-care university hospital. PATIENT(S): Nine hundred forty-seven natural cycles carried out in 320 patients. INTERVENTION(S): Analysis of 947 NC-IVF outcomes performed in one single center between January 2010 and December 2014. MAIN OUTCOME MEASURE(S): Pregnancy rates per cycle started, per ET, and per patient, as well as ongoing pregnancy rate at a minimum of 12 weeks of gestation. RESULT(S): Among the three age groups analyzed (≤35 years, 36-39 years, and ≥40 years), pregnancy rates per cycle were significantly lower in the older group of patients (11.4% vs. 11.6% vs. 5.9%). In addition, miscarriage rate (7.7% vs. 34.4% vs. 50%) and ongoing pregnancy rate (10.6% vs. 7.6%vs. 3.0%) were negatively affected by patient age. However, no differences were observed according to patient ovarian reserve status, cause of infertility, or modification of the cycle with GnRH antagonist. The multivariate logistic regression confirmed that patient age was the only variable that could predict pregnancy in NC-IVF cycles (odds ratio, 0.93; 95% confidence interval, 0.88-0.98). CONCLUSION(S): NC-IVF is a feasible and "patient-friendly" option to be offered to young patients, independent of their ovarian reserve status.

Effect of halving the daily dose of triptorelin at the start of ovarian stimulation on hormone serum levels and the outcome of in vitro fertilization.

Halving the standard daily dose of triptorelin at the start of ovarian stimulation in down-regulated women stimulated with recombinant FSH is enough for pituitary suppression and was associated with higher LH serum concentrations in the follicular phase. However, this did not translate into higher serum concentrations of androstenedione and E2 and had no significant effect on ovarian response and the outcome of IVF/intracytoplasmic sperm injection.

Within-subject between-cycle variability of histological dating, alpha v beta 3 integrin expression, and pinopod formation in the human endometrium.

alpha v beta 3 integrin expression and pinopod formation have been proposed as a means of distinguishing receptive endometrium from nonreceptive in clinical practice. However, one of the most intriguing facts in infertility is whether one cyclic event may be representative of all patients' cycles, and no study has evaluated the cycle-to-cycle variability of the expression of any of these new proposed markers in human endometrium. We investigated histological dating, alpha v beta 3 integrin expression, and pinopod formation in 45 endometrial biopsy specimens obtained in 15 primary infertility patients. All patients underwent three endometrial biopsies in consecutive spontaneous cycles, regardless of the previous histological findings. All endometrial samples were obtained on postovulatory d 7 as determined by ultrasonography. Agreement between the repeated observations (first vs. second, and first vs. third biopsies) with regard to histological dating and the presence or absence of alpha v beta 3 integrin and pinopods in the endometrium was analyzed using the 2 x 2 frequency tables and Cohen's kappa coefficient. The kappa values ranged from a low of -0.39 (level of agreement, poor) for alpha v beta 3 integrin expression to a high of 0.32 (level of agreement, fair) for biopsy dating by anticipated window of implantation. Overall, these results demonstrate that all endometrial variables investigated had poor reproducibility and high variability cycle to cycle.

Ultrasonography as a predictor of embryo implantation after in vitro fertilization: a controlled study.

OBJECTIVE: To investigate the predictive value of ultrasonographic parameters as prognostic indicators of implantation after IVF when measured on the day of embryo transfer. DESIGN: Comparative, observational study. SETTING: University teaching hospital. PATIENT(S): Two hundred eighty patients undergoing IVF. INTERVENTION(S): Ovarian stimulation, IVF. MAIN OUTCOME MEASURE(S): Variables related to patients' clinical characteristics, treatment characteristics, ovarian response, ovum retrieval, outcome of IVF and ICSI, embryo transfer, ultrasonographic and Doppler endometrial measurements, and uterine blood flow that have been proposed as potential predictive factors of implantation. All transvaginal ultrasonographic assessments were performed on the day of embryo transfer. RESULT(S): Among 240 patients finally evaluable, 67 (group 1) became pregnant after IVF, and 173 (group 2) failed to conceive. The 111 nonpregnant patients who had the same embryo score per replacement (group 3) as did patients in group 1 were selected for comparison purposes. The only significant differences between groups 1 and 3 were the type A endometrium and the absence of a protodiastolic notch in the uterine arteries, both of which were more frequently found in group 1. However, a considerable overlap existed between conception and nonconception cycles regarding both variables. CONCLUSION(S): Ultrasonographic parameters as predictors of implantation in assisted reproduction have a limited value in the clinical setting.

Evaluation of two doses of recombinant human luteinizing hormone supplementation in down-regulated women of advanced reproductive age undergoing follicular stimulation for IVF: a randomized clinical study.

OBJECTIVES: To evaluate the effects of mid-follicular recombinant human luteinizing hormone (rhLH) supplementation in down-regulated women of advanced reproductive age undergoing in vitro fertilization (IVF). STUDY DESIGN: This was a prospective, randomized parallel-group study (allocation 1:1) including 187 normogonadotrophic infertile patients aged ≥ 35 years. Subcutaneous triptorelin was used for pituitary desensitization, and ovarian stimulation was achieved with recombinant human follicle-stimulating hormone (rhFSH) either alone (Group 1) or in combination with rhLH in one of two daily doses: 37.5 IU (Group 2) or 75 IU (Group 3). Ovarian stimulation characteristics and IVF outcome were evaluated. The main outcome was pregnancy rate. RESULTS: A total of 62, 62 and 63 patients were randomized to groups 1, 2 and 3 respectively, and 56, 54 and 55 patients respectively were available for final analysis of the results. Follicular development and oocyte yield were significantly higher in group 1 patients compared with patients in groups 2 and 3. Oocyte maturity and number of oocytes fertilized were also higher in group 1 patients; this difference almost reached statistical significance. No significant difference in implantation and clinical pregnancy rates was found among the three treatment groups. CONCLUSIONS: rhLH supplementation is not a useful tool for patients of advanced reproductive age in ovarian stimulation protocols using an appropriate gonadotrophin-releasing hormone agonist and a step-down regimen of rhFSH.

Thrombin activatable fibrinolysis inhibitor and clot lysis time in women with recurrent miscarriage associated with the antiphospholipid syndrome.

Antiphospholipid syndrome patients with recurrent miscarriage have an impairment in fibrinolysis demonstrated by prolonged clot lysis time (CLT) that cannot be attributed to differences in thrombin activatable fibrinolysis inhibitor (TAFI) antigen levels. Patients with unexplained recurrent miscarriage have an impairment in fibrinolysis demonstrated by increased CLT, that can be at least partly explained by higher TAFI antigen levels.