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A total of 3,324 singleton pregnant women were screened for pre-term delivery and 128 women were finally randomised and analysed for outcome showing borderline cervical length (25-29 mm) and elevated cervico-vaginal interleukin 6 levels. To verify if vaginal administration of lactoferrin might have an influence on these variables, two groups of 64 patients were formed. Study cases were submitted to lactoferrin for 21 days; controls received no treatment. An inverse relation was found between interleukin 6 levels and cervical length. On day 30 from the beginning of the treatment, study cases showed a decrease in interleukin 6 levels and an increase in cervical length. A greater number of women with regular uterine contractions and reduced cervical consistency before the 37th week of gestation were found in the controls. Our data show that lactoferrin could play a role in reducing the number of women at risk for pre-term birth for shortened cervical length and elevated interleukin 6 levels.

Introduction: Weight loss amongst women with polycystic ovary syndrome (PCOS) is crucial to reduce the risk of endocrine, reproductive and metabolic complications including hirsutism, menstrual disturbances and cardiovascular disease. With approximately 50% of women with PCOS being overweight or obese, effective dietary management of weight in PCOS is essential. However, there is inconsistent evidence as to whether specifically modified diets (e.g. reduced carbohydrate diets) are more effective at achieving weight loss amongst women with PCOS than are conventional healthy hypocaloric diets. Material and Methods: A systematic review and meta-analysis of randomized controlled trials that had compared weight and BMI between women with PCOS who had undergone either a specifically modified diet or a conventional healthy hypocaloric diet were performed. Six electronic databases were searched, a manual search of the reference lists of the included studies was carried out and authors were contacted for additional information. Nine studies with a total of 395 participants (all with a body mass index [BMI] ≥30) were included in the meta-analysis. The effect size used was the mean difference in post-intervention weight and BMI between participants who had undergone a specifically modified diet and participants who had undergone a conventional healthy hypocaloric diet. Results: There were no differences between groups in post-intervention weight (mean difference 1.26, 95% confidence interval (CI) -0.92 to 3.43, p = .26; heterogeneity I2 = 50%, p = .04) or BMI (mean difference 0.15, 95% CI -0.93 to 1.23, p = 0.79; heterogeneity I2 = 44%, p = 0.10). Subgroup analyses according to the presence of a dietary run-in period (a period at the start of the study during which all participants are placed on an identical diet in order to equalize them on variables influenced by diet), intervention duration and type of diet and a sensitivity analysis according to study quality were not significant. Conclusions: Whilst the results should be interpreted in light of the moderate heterogeneity observed, they suggest that specifically modified diets offer no added benefit for weight loss in women with PCOS over conventional healthy hypocaloric diets. The findings of this meta-analysis may promote the unification of guidelines for the dietary management of PCOS and allow clinicians to be confident in prescribing conventional healthy hypocaloric diets for weight loss amongst their PCOS patients.

Our objective was to compare the effectiveness and safety of atosiban and ritodrine, in pregnancies obtained by intracytoplasmic sperm injection (ICSI) undergoing cervical cerclage. Data from a prospective study were compared with those from a retrospective study. Sixteen ICSI pregnant women, 20 - 24 weeks' gestation and maternal age >18 years, received atosiban (bolus dose 6.75 mg i.v., followed by 300 μg/min i.v. for 3 h and 100 μg/min i.v. for 45 h). Cervical cerclage was performed 3 h after starting atosiban. The control group (group B) of 16 ICSI pregnant women were matched and received ritodrine hydrochloride (100 - 350 μg/min) for 48 h. Cervical cerclage was performed after 24 h. Pre-term rupture of membranes occurred within 48 h of cervical cerclage in one woman receiving atosiban and in four women receiving ritodrine. There was no significant difference in terms of pregnancies not delivered at 48 h (short-term tocolysis) and at 7 days (long-term tocolysis). However, there was a significantly higher incidence of maternal tachycardia with ritodrine compared with atosiban (p

Purpose: To test the effects of type of embryo transfer catheter, transfer difficulty, and observations after the transfer procedure on pregnancy and implantation rates in an IVF programme.

A 32 year old woman, gravid 1, nulliparous, was admitted to our department at 11 weeks and 2 days of gestation after being diagnosed with cervical pregnancy. She was unsuccessfully treated with methotrexate for 5 days. On the fifth day after admission she underwent bilateral uterine artery angiographic embolization followed by vacuum evacuation and curettage of the cervical canal. A Foley catheter was also inserted in the cervical canal and left in place for 4 days. The patient was discharged in good condition on the seventh postoperative day.

Serum concentrations of soluble human leukocyte class I antigens (sHLA-I) and of the intercellular adhesion molecule-1 (sICAM-1) are increased in the early inflammatory stages of several immune-related diseases. These soluble molecules also exert immunomodulatory activity, including regulation of natural killer (NK) cell cytotoxicity. The aim of this study was to verify whether sHLA-I and sICAM-1 serum concentrations are related to the various stages of pelvic endometriosis, which is an immune-related disorder associated with impaired in-vitro NK cell activity. Serum sHLA-I and sICAM-1 concentrations were similar in patients and in healthy donors. However, when evaluated according to disease stage, sHLA-I and sICAM-1 concentrations were higher in patients with endometriosis stage I-II (revised American Fertility Society classification), or with non-pigmented peritoneal lesions. In conclusion, studies on sHLA-I and sICAM-1 may help to clarify the pathogenic mechanisms of endometriosis, and their serum concentrations may serve as additional markers for the early detection of recurrence of the disease during the monitoring of treatment outcome.

The aim of this multicentre, prospective, randomised, investigator blind, controlled clinical trial was to evaluate the clinical efficacy and tolerability of a highly purified human menopausal gonadotrophin (hMG) preparation (Merional-HG) when administered to patients undergoing controlled ovarian stimulation (COS) for in-vitro fertilisation (IVF) procedure enrolled in hospital departments. One hundred fifty-seven patients were randomised in two parallel groups: 78 started COS with Merional-HG and 79 with Menopur. Results of the study showed that both highly purified hMG preparations were equivalent in terms of number of oocytes retrieved (primary endpoint: 8.8 ± 3.9 versus 8.4 ± 3.8, p = 0.54). In the patients treated with Merional-HG, we observed a higher occurrence of mature oocytes (78.3% versus 71.4%, p = 0.005) and a reduced quantity of gonadotrophins administered per cycle (2.556 ± 636 IU versus 2.969 ± 855 IU, p < 0.001). Fertilisation, cleavage, implantation rates and the number of positive β-human chorionic gonadotrophin (hCG; pregnancy) tests and the clinical pregnancy rate were comparable in the two groups. Both treatments were well tolerated. In conclusion, the results of this study support the efficacy and safety of Merional-HG administered subcutaneously for assisted reproduction techniques. Efficiency of Merional-HG appears to be higher due to reduced quantity of drug used and the higher yield of mature oocytes retrieved.

Study question What is the effect of FSHB-211G>T together with the FSHR 2039 A>G on serum FSH in women? Summary answer Serum FSH levels are affected by the combination of genetic polymorphisms in FSHR and FSHB. What is known already The relationship between SNPs of the FSHR gene and serum FSH has not been completely clarified. Genetic variants of the FSHB gene have been associated with variation in gene transcription and serum FSH levels in men. No data have been published on the effect of the FSHB-211G>T in women, alone or in combination with the FSHR 2039 A>G. Study design, size, duration This study was a prospective study including 193 healthy women of reproductive age. Participants/materials, setting, methods Infertile and otherwise healthy eumenorrheic women (n = 193) with normal BMI and serum FSH levels were recruited for the study. In all women early follicular phase FSH and AMH were measured by commercial assays, and antral follicle count was measured by transvaginal ultrasound. Genomic DNA was purified from total peripheral blood and genotyping for the two SNPs was performed. Main results and the role of chance No significant gradients of increasing or decreasing Day 3 FSH across the FSHR 2039 (AA/AG/GG) and FSHB-211 (GG/GT/TT) genotypes, respectively, were observed. When women were stratified according to the FSHR 2039, and FSHB-211 genotypes a statistically significant reduction of d3 FSH was shown in the group of women with the FSHB-211 GT + TT/FSHR2039 AA genotype compared with the FSHB-211 GG/FSHR2039 GG genotype, hence confirming a possible additive effect of the different SNPs in FSHR and FSHB on regulating serum FSH. Limitations, reasons for caution This finding requires an independent confirmation. However, it confirms the relationship between serum FSH and FSHB together with FSHR gene polymorphisms already reported in males. Wider implications of the findings The knowledge of the FSHB/FSHR genotype combination is fundamental for the proper interpretation of serum FSH levels in women of reproductive age. Study funding/competing interests Merck Serono supported the study in the form of a research grant for the laboratory session. None of the authors have any competing interest to declare.

The aim of this study was to correlate and compare Doppler and anatomical placental findings obtained from 48 normal and 35 intrauterine growth-retarded (IUGR) fetuses. The IUGR group consisted of 19 fetuses from pregnancies complicated by pre-eclampsia and 16 from healthy mothers. Color Doppler evaluation of umbilical, spiral and uterine arteries was performed. Placental specimens from both normal and growth-retarded fetuses were obtained at the time of delivery. Placental specimens were evaluated using histochemical and immunohistochemical techniques. A progressive decrease in the pulsatility index was observed in umbilical, spiral and uterine arteries throughout pregnancy in the normal-growth fetuses. High umbilical artery pulsatility index values were obtained in 29 out of the 35 growth-retarded fetuses, six of them showing absent or reversed end-diastolic umbilical artery flow pattern. A total of 13 IUGR fetuses showed high resistance uterine artery flow velocity waveforms. Increased pulsatility index values were obtained from the spiral arteries of 16 growth-retarded fetuses. Abnormal histological and histochemical placental patterns were observed in all the growth-retarded fetuses with umbilical artery Doppler abnormalities. The presence of a peculiar dendritic cell subpopulation, strongly resembling the Langerhans cells, expressing the HLA-DR+/CD1+ phenotype, was detected in all growth-retarded fetuses, whether there was maternal pathology or not. Our data show uterine and spiral artery data as being ineffective in the monitoring of IUGR fetuses. The placental extracellular matrix seems to play an important role in the regulation of the umbilical circulation. The presence of CD1+ cells as a sign of a possible immunological mechanism in the pathogenesis of the intrauterine growth retardation is discussed.

The aim of this observational preliminary trial was to estimate the association between the most common polymorphism of LH (LH-beta variant: v-betaLH), with different profiles of ovarian response to recombinant human FSH (rhFSH). A total of 60 normogonadotrophic patients undergoing a gonadotrophin-releasing hormone analogue long down-regulation protocol followed by stimulation with recombinant human FSH (rhFSH) for IVF/intracytoplasmic sperm injection, and in whom at least five oocytes were retrieved were retrospectively included. On the basis of the total rhFSH consumption, patients were divided into three groups: Group A: 22 women requiring a cumulative dose of rhFSH >3500 IU; Group B: 15 patients requiring 2000-3500 IU; Group C (control): 23 women requiring

[No abstract available]

One of the most frequent consequences of allogeneic haemopoietic stem cell transplantation (allo-SCT) in both males and females is gonadal insufficiency. We report the case of a 27-year-old myelodysplastic male who developed azoospermia after allogeneic transplantation of haemopoietic stem cells from his HLA-identical sister. Post-transplant azoospermia was alternated with intermittent severe oligospermia. The patient had a normal endocrine pattern and evidence of mild chronic graft-versus-host disease (cGVHD). Normal intratesticular spermatogenesis was revealed by bilateral fine needle aspiration (FNA) cytology. Inflammation was evident at semen analysis, but no infection was detected by microbiological examination and sperm culture. These findings, together with the re-appearance of sperm cells at semen analysis after a low-dose immunosuppressive treatment, suggested the presence of cGVHD of the urogenital tract, causing a reversible obstruction of the spermatic tract and cryptozoospermia. This is the first case report documenting a severe impairment of sperm count because of a reversible obstruction of the seminal tract, likely caused by cGVHD, in a long-term survivor of allo-SCT with normal endocrine pattern. An important practical consequence of this case report is the fact that azoospermia was cured using low-dose immunosuppressive therapy, and this allowed us to avoid expensive stimulatory treatments with gonadotrophins, which remain, however, ineffective if the obstruction of spermatic tracts is not removed. A spontaneous uncomplicated pregnancy occurred in the partner of the patient 3 months after the corticosteroid treatment withdrawal.

During intermediate-late phases of human folliculogenesis, LH plays a key role in promoting steroidogenesis and growth of the leading follicle. Ovarian stimulation for assisted reproduction techniques usually consists of administering exogenous FSH in a low LH environment. Although an impairment in LH-dependent paracrine activities would be expected, multiple follicular growth is efficiently achieved in almost all patients. Thus, there appears to be a discrepancy between classical folliculogenesis models and data from IVF. This study examines the 'interface' between basic endocrinological and clinical evidence, in an attempt to answer two questions: is there an LH therapeutic window, and if there is, how can this be exploited in the practice of assisted reproduction? It also reviews the evidence that specific subgroups of women may benefit from LH supplementation during ovarian stimulation.

In approximately 12-14% of young normogonadotrophic women treated with a depot GnRH agonist long protocol, the initial ovarian response to recombinant human FSH (rFSH) can be suboptimal. We have tested the hypothesis that these women may benefit from recombinant human LH (rLH) supplementation in a multicentre, prospective, randomized trial compared with patients treated with an rFSH step-up protocol. METHODS: A total of 260 young normogonadotrophic women undergoing controlled ovarian stimulation with a GnRH agonist long protocol for IVF/ICSI were enrolled. The starting dose of rFSH was 225 IU. One hundred and thirty patients with serum estradiol levels 5 mm but none >10 mm on both day 5 and day 8 of stimulation were randomly allocated to two groups. From the eighth day of stimulation, women in group A (n=65) received 150 IU of rLH in addition to rFSH, while those in group B (n=65) had an increase of 150 IU in the daily dose of rFSH (step-up protocol). One hundred and thirty normally responding women continued monotherapy with rFSH and served as a further control population (group C). RESULTS: The mean number of cumulus-oocyte complexes retrieved in group A (9.0+/-4.3) was significantly higher (P

This study was designed to measure leptin concentrations in the peritoneal fluid (PF) of women with different aspects of pelvic endometriosis. Among 36 consecutive women undergoing laparoscopy, nine were diagnosed as having minimal-mild endometriosis (stage I-II). Among nine other subjects with advanced stage (III-IV) disease, six showed one or more ovarian endometriotic cysts as the only operative finding. The remaining 18 unaffected women constituted the control group. Patients with endometriosis had significantly higher PF leptin concentrations (32.6 +/- 16.2 versus 17.1 +/- 6.6 ng/ml, P = 0.002); this difference remained significant when corrected for body mass index (BMI) (PF leptin/BMI ratio 1.41 +/- 0.67 versus 0.76 +/- 0.28, P = 0.001). Furthermore, the PF leptin/BMI ratio was significantly higher in women with peritoneal implants than in those in whom no implant was found at laparoscopy (1.6 +/- 0.7 versus 0.83 +/- 0.33, P = 0.007). Conversely, patients with one or more ovarian endometriomata as the only finding, had a PF leptin/BMI ratio comparable with that in women where no cyst was found (1.05 +/- 0.4 versus 1.1 +/- 0.65). In women with stage I-II endometriosis, a higher mean PF leptin/BMI ratio was found compared with those affected by stage III-IV (1.78 +/- 0.68 versus 1.05 +/- 0.43, P = 0.01). These results show that during endometriosis the presence of peritoneal disease, and not of ovarian endometriotic cysts, influences leptin concentrations in PF. The data suggest that leptin may play a role in the development of peritoneal endometriosis, and that different biochemical phenomena might be involved in the pathogenesis of the ovarian form of the disease.

Ovarian stimulation in cases of poor ovarian responsiveness is an important challenge in in-vitro fertilization (IVF) programmes. Despite improvements in oocyte number and quality, an ideal ovarian stimulation strategy has yet to be defined. Here, the results of ovarian stimulation with recombinant follicle stimulating hormone (rFSH) in 28 poor responders to highly purified FSH (FSH-HP) with high basal concentrations of FSH are reported. The protocols used on the FSH-HP and rFSH cycles were identical with the sole exception of the FSH preparation: triptorelin 0.1 mg/day (gonadotrophin-releasing hormone, GnRH-agonist short protocol) and the starting FSH dose of 300 IU/day were administered from day 2 of the menstrual cycle. Ovarian outcome was classified as 'normal', 'intermediate' and 'poor', depending on the number of mature oocytes retrieved and the peak serum oestradiol concentration. Nine of the 28 subjects had an intermediate ovarian response to re-stimulation with rFSH. In the 26 patients who received human chorionic gonadotrophin on both cycles, re-stimulation resulted in a significant increase (P < 0.05) in the mean number of mature oocytes (2.4 +/- 1.4 versus 1.7 +/- 0.8), mean peak oestradiol concentration (606 +/- 252 versus 443 +/- 32 pg/ml) and fertilization rate (73.0 versus 53.3%). Four pregnancies were achieved. It is concluded that rFSH in a GnRH-agonist short protocol improves the ovarian outcome in poor responders to FSH-HP with high basal concentrations of FSH.

I concentration. Cardiac troponin I (cTnI) is a specific marker of myocardial injury in adults and children. Perinatal asphyxia can cause cardiac dysfunction. Methods: Some 161 samples among fetuses from pathological pregnancies were collected. Twenty-two had an elevated level of cTnI (above 0.1 ng/mL). Disorders in pregnancy, date of gestation, Doppler flow velocimetry in the ductus venosus (DV) and umbilical artery (AU) and vein (DV), mode of delivery, Apgar score and respiratory status after birth were evaluated. cTnI was determined on a dimension clinical chemistry system. Results: There were 22 newborns with a raised level of TnI: seven (31.8%) with SGA, five (22.2%) with fetal cardiac problems (arrhythmia, structural and functional abnormalities), nine (40.9%) with abnormal biophysical test results (abnormal Doppler velocimetry, computerized cardiotocography, biophysical profile score) and six (27.2%) whose mothers who had disorders (diabetes mellitus, hypertension). Results are shown in the table. Median gestational age at delivery was 36.6 (range, 27–43) weeks. Seventeen (77.2%) patients had a Cesarean section. The range of TnI blood concentration was 0.11–6.66 ng/mL in this group. Five (22.7%) had umbilical pH below 7.25. Conclusions: A high level of cTnI was associated with several disorders that could have led to fetal asphyxia. More detailed fetal heart examination is necessary to prove that fetal asphyxia had an impact on heart function.

Introduction: The aim of the presence case-report study was to evaluate the nature of the depicted round subchorionic ‘‘tumor’’ of 81 mm at 12 week of gestation age versus a possible myoma of haematoma and possible affection of fetal growth. Background: We studied serially using color-Doppler technique all the parameters of fetal growth and the tumor was still depicted at 34th week of gestation age ultrasound with the same dimensions and peripheral vascularisation but the fetal measurements started at that time to stay 1 week of gestational age and 3 days behind. Results: From that time a close study of the previous pregnancy started and after the caesarean section at 37th week of gestational age a healthy boy of 2.200 grams was delivered. The neonate admitted in NICU for 7 days for medical care. Discussion: The nature of the removed ‘‘tumor’’ was an haematoma which remained so long time and affected at the end the fetal growth marginally. Three months after delivery the mother examined for endovaginal color-Doppler ultrasound in which increased vascularisation depicted at the site of the described ‘‘tumurous’’ haematoma. Conclusion: The persistence of the haematoma might to be due to specific uterine vascularisation conditions of the posterior uterine wall which permitted its extremely enlongated presence.

Objective: To investigate the role of power Doppler in differentiating septate and bicornuate uterus prior to perform office operative hysteroscopy. Methods: Ten patients with previous hystory of infertility were referred to our US Dept. At the admission, transvaginal US axial scan of the uterus showed that the endometrium was as divided in two parts separated by hypoechoic tissue. B scan alone was unable to differentiate bicornuate from septate uterus. No shows difference could be found in uterine fundal contour. Power Doppler evaluation of uterine vascularization was performed in all patients. All patients were submitted to diagnostic laparoscopy. Results: In six patients the main branches of uterine arteries appeared to converge, at the uterine midline, in a single median arterial vessel flowing between the two emiuteruses, mimicking the greak letter gamma. Irregular vascular spots, at the uterine midline, have been found in the remaining four patients. Laparoscopy revealed that the a (gamma) sign was peculiar in case of bicornuate uterus. Median irregular vascular spots had been found in case of septate uterus. Conclusions: Power Doppler study of uterine malformations and the presence of the gamma sign seem to be able to differentiate bicornuate uterus from septate uterus.