A cost-effectiveness modeling evaluation comparing a biosimilar follitropin alfa preparation with its reference product for live birth outcome in Germany, Italy and Spain.

BACKGROUND/OBJECTIVE: Although biosimilar drugs may be cheaper to purchase than reference biological products, they may not be the most cost-effective treatment to achieve a desired outcome. The analysis reported here compared the overall costs to achieve live birth using the reference follitropin alfa (GONAL-f) or a biosimilar (Ovaleap) in Spain, Italy and Germany. METHODS: Patient and treatment data was obtained from published sources; assisted-reproductive technology, gonadotropin, follow-up and adverse-event-related costs were calculated from tariffs and reimbursement frameworks for each country. Incremental cost-effectiveness ratios (ICERs) were calculated from the difference in costs between reference and biosimilar in each country, divided by the difference in live-birth rates. Mean cost per live birth was calculated as total costs divided by the live-birth rate. RESULTS: The published live birth rates were 32.2% (reference) and 26.8% (biosimilar). Drug costs per patient were higher for the reference recombinant human follicle-stimulating hormone in all three countries, with larger cost differences in Germany (€157.38) and Italy (€141.50) than in Spain (€22.41). The ICER for the reference product compared with the biosimilar was €2917.47 in Germany, €415.43 in Spain and €2623.09 in Italy. However, the overall cost per live birth was higher for the biosimilar in all three countries (Germany €8135.04 vs. €9185.34; Italy €8545.22 vs. €9733.37; Spain €14,859.53 vs. €17,767.19). Uncertainty in efficacy, mean gonadotropin dose and costs did not have a strong effect on the ICERs. CONCLUSIONS: When considering live birth outcomes, treatment with the reference follitropin alfa was more cost effective than treatment with the biosimilar follitropin alfa.

Uterine fibroid size modifications during pregnancy and puerperium: evidence from the first systematic review of literature.

PURPOSE: The influence of pregnancy on uterine fibroid size still remains an unsolved dilemma. Basing on current knowledge, physicians are not able to inform patients about the likelihood of uterine fibroids to modify their size during pregnancy. Study aim was to summarize available evidence concerning the size modifications of uterine fibroids during each trimester of pregnancy and during puerperium. METHODS: The review was reported following the PRISMA guidelines and registered in PROSPERO (registration number: CRD42017071117). A literature search was conducted in electronic database (PubMed, Embase, Sciencedirect, the Cochrane library and Clinicaltrials.gov) until July 2017. All studies evaluating fibroids' changes during pregnancy and puerperium by ultrasound or magnetic-resonance-imaging were included. Descriptive characteristics of studies and patients were collected. The modifications of uterine fibroid diameter and volume were the outcome measures. RESULTS: Concerning the first trimester of pregnancy, all authors reported a significant growth of uterine fibroids. Contradictory evidence was found about uterine fibroid modifications during the second and third trimesters, mainly supporting a slowdown during mid pregnancy and a subsequent size reduction during late pregnancy. Concerning the overall modifications during pregnancy and puerperium, poor evidence quality suggests that uterine fibroids do not modify their volume/slightly enlarge during pregnancy and subsequently reduce in size during puerperium. CONCLUSIONS: Uterine fibroids seem to be subject to a non-linear trend of modifications during pregnancy and puerperium, which may vary from myoma to myoma. Adequate evidence supports uterine fibroid systematic enlargement during the first trimester of pregnancy, while inconsistent evidence is available about the changes of uterine fibroids during second and third trimesters. In addition, the overall modifications of myomas during pregnancy and puerperium remain unclear.

Endometrial scratch injury before intrauterine insemination: is it time to re-evaluate its value? Evidence from a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To assess the impact of endometrial scratch injury (ESI) on the outcomes of intrauterine insemination (IUI) stimulated cycles. DESIGN: Systematic review and meta-analysis. SETTING: Not applicable. PATIENT(S): Infertile women undergoing one or more IUI stimulated cycles. INTERVENTION(S): Randomized controlled trials (RCTs) were identified by searching electronic databases. We included RCTs comparing ESI (i.e., intervention group) during the course of IUI stimulated cycle (C-ESI) or during the menstrual cycle preceding IUI treatment (P-ESI) with controls (no endometrial scratch). The summary measures were reported as odds ratio (OR) with 95% confidence-interval (CI). MAIN OUTCOME MEASURE(S): Clinical pregnancy rate, ongoing pregnancy rate, multiple pregnancy rate, ectopic pregnancy rate, miscarriage rate. RESULT(S): Eight trials were included in the meta-analysis, comprising a total of 1,871 IUI cycles. Endometrial scratch injury was associated with a higher clinical pregnancy rate (OR 2.27) and ongoing pregnancy rate (OR 2.04) in comparison with the controls. No higher risk of multiple pregnancy (OR 1.09), miscarriage (OR 0.80), or ectopic pregnancy (OR 0.82) was observed in patients receiving ESI. Subgroup analysis based on ESI timing showed higher clinical pregnancy rate (OR 2.57) and ongoing pregnancy rate (OR 2.27) in patients receiving C-ESI and no advantage in patients receiving P-ESI. CONCLUSION(S): Available data suggest that ESI performed once, preferably during the follicular phase of the same cycle of IUI with flexible aspiration catheters, may improve clinical pregnancy and ongoing pregnancy rates in IUI cycles. Endometrial scratch injury does not appear to increase the risk of multiple pregnancy, miscarriage, or ectopic pregnancy.

Hysteroscopic Morcellation of Submucous Myomas: A Systematic Review.

Hysteroscopic surgery is the actual gold standard treatment for several types of intrauterine pathologies, including submucous myomas (SMs). To date, the availability of Hysteroscopic Tissue Removal systems (HTRs) opened a new scenario. Based on these elements, the aim of this article is to review the available evidence about HTRs for the management of SMs. We included 8 papers (3 prospective studies and 5 retrospective studies). A total of 283 women underwent intrauterine morcellation of SM: 208 were treated using MyoSure and 75 using Truclear 8.0. Only 3 articles reported data about procedures performed in outpatient/office setting. Only half of the included studies included type 2 SMs. HTRs significantly reduced operative time compared to traditional resectoscopy in some studies, whereas others did not find significant differences. Despite the availability of few randomized controlled trials and the cost of the instrument, according to our systematic review, the use of HTRs seems to be a feasible surgical option in terms of operative time and complications. Nevertheless, the type of SM still remains the biggest challenge: type 0 and 1 SMs are easier to manage with respect to type 2, reflecting what already is known for the "classic" hysteroscopic myomectomy.

The Distribution of Stroma and Antral Follicles Differs between Insulin-Resistance and Hyperandrogenism-Related Polycystic Ovarian Syndrome.

INTRODUCTION: Although insulin resistance plays an important pathogenetic role in polycystic ovary syndrome (PCOS), no correlation between ultrasound PCOS pattern and insulin resistance has yet been reported. The aim of this retrospective observational study was to assess whether the ovarian ultrasonographic parameter differed between PCOS women with insulin resistance and those with a hyperandrogenic profile. MATERIALS AND METHODS: Women who fulfilled the Rotterdam criteria for PCOS were retrospectively studied. Anthropometric, biochemical, and clinical data were recorded. Women were divided into two groups based on specific transvaginal ultrasound parameters: subjects with more than half of the follicles measuring between 5 and 9 mm in diameter, an ultrasonographic determined stroma/total area (S/A) > 0.34 and a "necklace" sign of antral follicles (Group A); and subjects with more than half of the antral follicles measuring between 2 and 4 mm in diameter, an S/A ≤ 0.34; no "necklace" sign but ubiquitously distributed follicles determined by ultrasound (Group B). The association between these ultrasound patterns and the presence of insulin resistance was also evaluated. RESULTS: Seventy-eight patients were enrolled: 33 with ultrasound sound pattern A and 45 with pattern B. The latter pattern had a sensitivity of 88% and a specificity of 78% in predicting PCOS women with insulin resistance. There were no differences in age, Ferriman-Gallwey score, and serum gonadotropin or androgen levels between the two groups. Body mass index, the waist-to-hip ratio, and homeostasis model assessment were significantly higher in group B than in group A (p < 0.05). Conversely, sex hormone binding globulin levels and ovarian volume were significantly higher in group A (p < 0.05). Insulin resistance was more frequent in group B than in group A (36/41, 87.8% versus 7/32, 21.8%; p < 0.05). CONCLUSION: These results suggest that insulin resistance could be associated with a specific ultrasound pattern in PCOS patients.

Cervical Pessary for Preventing Preterm Birth in Singleton Pregnancies With Short Cervical Length: A Systematic Review and Meta-analysis.

OBJECTIVES: To evaluate the effectiveness of cervical pessary for preventing spontaneous preterm birth (SPTB) in singleton gestations with a second trimester short cervix. METHODS: Electronic databases were searched from their inception until February 2016. We included randomized clinical trials (RCTs) comparing the use of the cervical pessary with expectant management in singletons pregnancies with transvaginal ultrasound cervical length (TVU CL) ≤25 mm. The primary outcome was incidence of SPTB <34 weeks. The summary measures were reported as relative risk (RR) with 95% confidence interval (CI). RESULTS: Three RCTs (n = 1,420) were included. The mean gestational age (GA) at randomization was approximately 22 weeks. The Arabin pessary was used as intervention in all three trials, and was removed by vaginal examination at approximately 37 weeks. Cervical pessary was not associated with prevention of SPTB <37 (20.2% vs 50.2%; RR 0.50, 95% CI 0.23 to 1.09), <34, <32, and <28 weeks, compared to no pessary. No differences were found in the mean of GA at, interval from randomization to delivery, incidence of preterm premature rupture of membranes and of cesarean delivery, and in neonatal outcomes. The Arabin pessary was associated with a significantly higher risk of vaginal discharge. CONCLUSIONS: In singleton pregnancies with a TVU CL ≤25mm at 200 -246 weeks, the Arabin pessary does not reduce the rate of spontaneous preterm delivery or improve perinatal outcome. Individual patient data meta-analysis may clarify whether cervical pessary may be beneficial in subgroups, such as only singleton gestations without prior SPTB or by different CL cutoffs.

Etiology, pathophysiology and biomarkers of interstitial cystitis/painful bladder syndrome.

PURPOSE: Interstitial cystitis/painful bladder syndrome (IC/PBS) is a chronic pain syndrome and a chronic inflammatory condition prevalent in women that leads to urgency, sleep disruption, nocturia and pain in the pelvic area, to the detriment of the sufferer's quality of life. The aim of this review is to highlight the newest diagnostic strategies and potential therapeutic techniques. METHODS: A comprehensive literature review was performed on MEDLINE, PubMed, and Cochrane databases gathering all literature about "Interstitial cystitis" and "Painful Bladder Syndrome". Visual analogue scales, epidemiological strategies, pain questionnaires and similar techniques were not included in this literature survey. RESULTS: The etiology, exact diagnosis and epidemiology of IC/PBS are still not clearly understood. To date, its prevalence is estimated to be in the range of 45 per 100,000 women and 8 per 100,000 men, whereas joint prevalence in both sexes is 10.6 cases per 100,000. There are no "gold standards" in the diagnosis or detection of IC/PBS, therefore, several etiological theories were investigated, such as permeability, glycosaminoglycans, mast cell, infection and neuroendocrine theory to find new diagnostic strategies and potential biomarkers. CONCLUSION: Due to the fact that this disease is of an intricate nature, and that many of its symptoms overlap with other concomitant diseases, it could be suggested to classify the patients with emphasis on the phenotype, as well as their symptom clusters, to tailor the diagnostic and management choices according to the observed biomarkers.

A novel hysteroscopic approach for ovarian cancer screening/early diagnosis.

The lethality of epithelial ovarian cancer (EOC) may be due to common misconceptions regarding etiology and the absence of effective screening and early diagnostic tools. Reviews of histopathological surveys performed on the resected fallopian tubes of breast cancer (BRCA) mutation carriers, who underwent risk-reducing salpingo-oophorectomy, unexpectedly revealed the presence of occult carcinomas of the fallopian tubes. This finding prompted studies that demonstrated the most accredited theory of type II EOC development, which suggests that a large proportion of these tumors are derived from the fallopian tube. At present, no diagnostic tools or screening programs have been demonstrated to be effective or cost-effective in improving the outcome of EOC; it is therefore imperative that the scientific community unite its efforts in the identification of a valid screening and/or early diagnostic method for the treatment of this lethal gynecological malignancy. To this end, the present paper proposes a novel tool for the screening/early diagnosis of EOC: The 'Tuba-check'. This novel approach is based on the possibility of acquiring specimens for tubal lumen cytology via hysteroscopy in a minimally-invasive outpatient setting. The present study protocol aimed to validate the technical feasibility and oncological accuracy of the proposed approach, commencing with a cohort of patients with an expected increased oncological risk, including BRCA mutation carriers or those with a gene expression profile of 'BRCA-ness'. If the data collected by the present study protocol validates this approach, the 'Tuba-check' may, in the near future, be extended for the treatment of all women, therefore reducing the number of victims of epithelial ovarian carcinoma.

A cost-effectiveness evaluation comparing originator follitropin alfa to the biosimilar for the treatment of infertility.

OBJECTIVES: To perform a cost-effectiveness evaluation comparing the originator follitropin alfa (Gonal-f®) to the biosimilar (Bemfola®) in the Italian and Spanish contexts, with an assessment of the German and UK backgrounds. METHODS: Starting from the study by Rettenbacher et al, a cost-effectiveness model was developed in the Italian and Spanish contexts. Clinical data on subjects, doses of gonadotropin, pregnancies, live-born children, and ovarian hyperstimulation syndrome were used to feed the model. Costs related to drugs, hospitalizations, specialist visits, and examinations were retrieved from Italian and Spanish tariffs. Gonadotropin acquisition costs for Germany and the UK were also taken into account to expand the economical assessment to the other countries. The evaluation was done based on the National Health Service perspective. Sensitivity analyses, both univariate and probabilistic, as long as scenario analyses, tested the robustness of the model. RESULTS: Originator follicle-stimulating hormone (FSH) costs were €3,663 and €6,387 in Italy and Spain, respectively, whereas biosimilar FSH costs were €3,483 and €6,342. The efficacy was found to be 0.52 for the originator and 0.47 for the biosimilar. The average cost per live birth was estimated to be €7,044 and €12,283 for the originator FSH and €7,411 and €13,494 for the biosimilar for Italy and Spain, respectively. Furthermore, the originator FSH generated an incremental cost-effectiveness ratio of €3,600 for Italy and €900 for Spain compared to the biosimilar. Sensitivity analyses confirmed the results of the base case model. CONCLUSION: This analysis indicated that the originator FSH is a cost-efficient treatment strategy for Italian and Spanish health services compared to the biosimilar and it would be worthwhile extending this evaluation to other countries.

Salpingectomy before assisted reproductive technologies: a systematic literature review.

Salpingectomy is largely used in case of hydrosalpinx in infertile women scheduled for assisted reproductive technologies (ART), whereas there is no consensus on its role in absence of hydrosalpinx. The current is a systematic literature review to collate all available evidence regarding salpingectomy as fertility enhancement procedure before ART in infertile patients. Our primary endpoint was to assess the impact of the surgical procedure on ovarian reserve, and secondary outcomes were to evaluate its benefits and harms on ART outcomes. We identified 29 papers of which 16 reporting data on the impact of tubal surgery on ovarian reserve and 24 (11 previously included) on ART outcomes. Available data suggested an absence of variation in ovarian reserve markers after unilateral salpingectomy while contradictory results were reported for bilateral surgery. Considering ART outcomes, data reported a significant improvement in ongoing pregnancy/live-birth rate in treated subjects without significant reduction in ovarian response to gonadotropin stimulation. In case of tubal disease, a surgical approach based on unilateral salpingectomy may be considered safe, without negative effects on ovarian reserve and ovarian response to controlled ovarian stimulation whilst having a positive effect on pregnancy rate. Data regarding bilateral salpingectomy and ovarian reserve are conflicting. Further trials are needed to confirm both the benefits of salpingectomy before ART and the safety of bilateral salpingectomy on ovarian reserve, and to clarify the role of uni- or bilateral surgery in case of tubal blockage without hydrosalpinx.

New frontiers in human assisted reproduction ­ from research to clinical practice: Several considerations (Review).

In the era of very late, or advanced, motherhood, in which 'egg banks', 'social' egg­freezing, egg donation and surrogacy represent a potential solution to a number of obstacles to human reproduction, what is the role of scientists and clinicians involved in assisted reproduction? In light of the apprehension that, in the future, through fertility treatment infertility may be passed on to the offspring, boundaries of medical vs. 'social' infertility are being created. Scientists and clinicians are joining forces in a synergistic effort to improve the effectiveness of infertility care by introducing novel therapeutic protocols with the intent of customising care and improving cost­effectiveness, testing novel drugs and formulations, and searching for novel markers (for estimating biological age) and nomograms (to optimise the yield of a controlled ovarian hyperstimulation cycle). On the other hand, political, social and health institutions are doing little to educate young women with respect to disinformation and to increase their awareness regarding age as the predominant factor that contributes towards the decline in fertility. Nevertheless, despite the great advances that have been made, 38 years after the birth of the first baby via in vitro fertilisation, the intricate road leading from the antral follicle to the fully developed baby continues to be designated as being too 'expensive', 'empirical', 'mysterious' or 'bound by ethics', with few significant improvements in terms of real cost­effectiveness.

Embryo quality before and after slow freezing: Viability, implantation and pregnancy rates in 627 single frozen-thawed embryo replacement cycles following failure of fresh transfer.

Frozen embryo transfer cycles are now common practice, however, various aspects regarding the potential of frozen embryos remain unclear. The main goal of the present study was to assess embryo quality before and after slow freezing procedure, and more specifically blastomere loss and embryo quality as indicator of viability. A single center retrospective analysis of single frozen-thawed embryo replacements (s-FER) was performed. The embryo quality before and after slow freezing and thawing, implantation, and pregnancy rates were recorded. One hundred and twenty seven s-FER were included in the final analysis. The probability of achieving an ongoing pregnancy was significantly associated with embryo quality and the percentage of blastomere loss after thawing. Considering thawed embryos, a non-significant difference in term of implantation rate was observed, regardless to their post-thawing quality and the percentage of blastomeres loss. In conclusion, current data suggest that thawed embryos are capable of implantation regardless of their morphological quality and the degree of cryoinjury sustained.

Mineralocorticoid receptor is involved in the aldosterone pathway in human red blood cells.

We have recently demonstrated that excessive aldosterone (Aldo) secretion in primary aldosteronism (PA) is associated with red blood cells (RBC) senescence. These alterations were prevented/inhibited by cortisol (Cort) or canrenone (Can) raising the hypothesis that Aldo effects in RBC may be mediated by mineralocorticoid receptor (MR), though to date MR has never been demonstrated in human RBC. The aim of this multicenter comparative study was to investigate whether Aldo effects were mediated by MR in these a-nucleated cells. We included 12 healthy controls (HC) and 22 patients with PA. MR presence and activation were evaluated in RBC cytosol by glycerol gradient sedimentation, Western blotting, immuno-precipitation and radioimmunoassay. We demonstrated that RBC contained cytosolic MR, aggregated with HSP90 and other proteins to form multiprotein complex. Aldo induced MR to release from the complex and to form MR dimers which were quickly proteolyzed. Cort induced MR release but not dimers formation while Can was not able to induce MR release. In addition, RBC cytosol from PA patients contained significantly higher amounts of both MR fragments (p<0.0001) and Aldo (p<0.0001) concentrations. In conclusion, in RBC a genomic-like Aldo pathway is proposed involving MR activation, dimerization and proteolysis, but lacking nuclear transcription. In addition, dimers proteolysis may ensure a sort of Aldo scavenging from circulation by entrapping Aldo in MR fragments.

Prevention of primary caesarean delivery: comprehensive management of dystocia in nulliparous patients at term.

PURPOSE: Dystocia is the leading indication for primary caesarean sections. Our aim is to compare two approaches in the management of dystocia in labor in nulliparous women with a singleton fetus in cephalic presentation at term in spontaneous or induced labor. METHODS: Prospective cohort study. Four hundred and nineteen consecutive patients were divided into two groups: the standard management group (SM), in acceleration of labor was commenced at the "action line" in the case of arrested or protracted labor, and the comprehensive management group (CM) in which arrested or protracted labor was considered as a warning sign promoting further diagnostic assessment prior to considering intervention. RESULTS: Caesarean sections rate was 22.2 % in the SM group (216 patients) and 10.3 % in the CM group (203 patients) (p = 0.001). The rate of oxytocin use decreased from 33.3 % in SM group to 13.8 % in the CM group (p < 0.0005). The rate of amniotomy decreased from 41.7 % in the SM group to 7.4 % in the CM group (p < 0.0005). The percentage of newborns with 5-min Apgar score <7 and/or umbilical cord arterial pH ≤ 7.00 decreased from 2.3 % in SM cohort to 0.5 % in CM cohort (p = ns). The average length of labor did not differ between the two groups of patients (264 vs 277 min; p = ns). CONCLUSION: Comprehensive management of dystocia enabled us to achieve a reduction in iatrogenic interventions in labor while maintaining good neonatal outcomes.

Peri-incisional and intraperitoneal ropivacaine administration: a new effective tool in pain control after laparoscopic surgery in gynecology: a randomized controlled clinical trial.

BACKGROUND: A proportion of patients undergoing laparoscopic gynecological surgery experiences excessive post-operative pain, which results in high rescue analgesic treatment and prolonged hospitalization. The aim of our study was to evaluate the efficacy of intraoperative topical ropivacaine in the control of post-operative pain in the first 48 h after operative laparoscopy for benign adnexal or uterine pathologies . METHODS: We conducted a prospective, randomized, double-blind, placebo-controlled clinical trial. Patients received a standard dose of topical ropivacaine (injected at the three portal sites and atomized in the abdominal cavity) or placebo. The primary outcome was the evaluation of post-operative pain intensity 6 h after surgery. Secondary outcomes included the intensity of pain during the 48 h after surgery, shoulder tip pain and the request for rescue analgesics during the first 48 h after surgery, time to discharge from recovery room, time to mobilizing on the ward and time to return to daily activities. Patients were divided in two groups (Group_A: benign adnexal pathologies; Group_B: benign uterine diseases) and assigned to Subgroup_1 (receiving ropivacaine) and Subgroup_2 (receiving placebo). RESULTS: A total of 187 women were included: 93 in Group_A and 94 in Group_B. Forty-seven patients entered Subgroup_A1, 46 Subgroup_A2, 48 Subgroup_B1 and 46 Subgroup_B2. Subgroup_A1 experienced lower post-operative pain at 4 (p = 0.008) and 6 h (p = 0.001) as well as a faster return to daily activities (p = 0.01) in comparison with Subgroup_A2. Both Subgroup_A1 and Subgroup_B1 showed lower shoulder tip pain (respectively, p = 0.032 and p = 0.001) as well as shorter time to mobilizing on the ward after surgery (respectively, p = 0.001 and p = 0.01). The remaining variables analysis did not show significant results. CONCLUSIONS: Combined topical analgesia with ropivacaine could represent a new safe and effective tool in the control of post-operative pain in gynecological laparoscopic surgery. Given the greater benefits for adnexal surgery, this strategy may be more suitable for this class of patients.

In Estimated Good Prognosis Patients Could Unexpected "Hyporesponse" to Controlled Ovarian Stimulation be Related to Genetic Polymorphisms of FSH Receptor?

It has been reported that 10% to 15% of young normogonadotrophic women show suboptimal response to standard gonadotropin-releasing hormone-a long protocol. These patients require higher doses of exogenous follicle-stimulating hormone (FSH). This phenomenon could be associated with genetic characteristics. In this study, FSH receptor polymorphism was retrospectively evaluated in 42 normoresponder young women undergoing an in vitro fertilization/intracytoplasmic sperm injection cycle; patients were stratified according to recombinant human FSH (r-hFSH) consumption. We selected 17 normoresponder young patients who required a cumulative dose of recombinant FSH (rFSH) >2500 UI (group A). A control group was randomly selected among patients who required a cumulative dose of rFSH <2500 UI (group B). Follicle-stimulating hormone receptor (FSH-R) 307Ala and 680Ser variants were analyzed in all our patients. Our results show that the mean number of rFSH vials (36.3 ± 7.5 vs 28.6 ± 4.5, P = .0001) and days of stimulation (12.7 ± 2.4 vs 10.8 ± 2.8, P = .03) were significantly lower in group B, whereas the number of oocytes retrieved (7.1 ± 1.5 vs 9.6 ± 2.4; P = .0005) and the average number of embryos transferred (2.1 ± 0.7 vs 2.7 ± 0.4; P = .001) were significantly lower in group A. Estradiol serum levels on the human chorionic gonadotrophin day were significantly lower in group A (997.8 ± 384.9 pg/mL vs 1749.1 ± 644.4; P = .0001). The incidence of the Ser/Ser genotype was higher in patients with higher r-hFSH consumption (group A; P = .02). Based on our results, we hypothesize an association between the FSH-R polymorphisms and a "hyporesponse" to exogenous FSH.

Coexistence of adenomyosis and endometrioid endometrial cancer: Role in surgical guidance and prognosis estimation.

The aim of the current study was to diagnose the concomitant presence of adenomyosis (AM) in endometrioid endometrial cancer (EEC) in order to evaluate its value as an oncological prognostic marker. A retrospective analysis of 289 patients diagnosed with EEC who underwent total hysterectomy, bilateral salpingo-oophorectomy and pelvic-lymphadenectomy was conducted. The total cohort included 37 patients in Group A (those with concomitant AM and EEC) and 252 patients in Group B (those affected only by EEC). The following factors were evaluated: Presence or absence of AM, tumor grade, depth of myometrial invasion, tumor size, lymphovascular space involvement, lymph node status, peritoneal cytology, concomitant detection of endometrial atypical-hyperplasia or polypoid endometrial features and tumor stage according to the International Federation of Gynecology and Obstetrics (FIGO) classification. Uterine examination of different sections of uterine cervix, corpus, myomas and cervical or endometrial polyps was performed. The diagnosis of AM was confirmed when the distance between the lower border of the endometrium and the foci of the endometrial glands and stroma was >2.5 mm. Parametric and nonparametric statistical tests were performed when possible; continuous variables were analyzed using a Student's t-test, and categorical variables were analyzed by the χ2 test or Fisher's exact test. The association between FIGO stage and group was determined to be significant: 83.8% of Group A patients were categorized as FIGO stage I, vs. 68.7% of Group B patients. In addition, Group A was associated with lower grades in FIGO stage, myometrial invasion, lymphovascular space involvement, lymph node involvement and tumor size. The findings suggest that the intraoperative evaluation of the presence of AM in patients with EEC may aid surgeons in estimating oncological risk and in selecting the most appropriate surgical treatment.

Management of osteogenesis imperfecta type I in pregnancy; a review of literature applied to clinical practice.

PURPOSE: Osteogenesis imperfecta (OI) is a rare heritable heterogenous disorder characterized by bone fragility and susceptibility to fractures with a wide spectrum of clinical expression due to defects in collagen type I biosynthesis. The purpose of the review is to highlight the practical norms in pregnancies with osteogenesis imperfecta. METHODS: We carried out a literature review in MEDLINE on OI during pregnancy, focusing on diagnosis, therapy and delivery. We reviewed 28 articles (case reports, original articles and reviews). RESULTS: Pregnant women affected by type I OI should be closely monitored to assess fetal well-being and detect pregnancy-related complications associated with an increased risk for osteoporosis, restrictive pulmonary disease, cephalopelvic disproportion and other problems related to connective tissue disorders. Mode of delivery remains controversial and should be determined on an individual basis. CONCLUSION: In conclusion, women affected by type I OI represent a subset of patients whose pregnancies should be considered high risk and warrant a multidisciplinary approach in a referral center.