Ursodeoxycholic acid in the treatment of pregnancy cholestasis: a data-set available for Meta-analyses.

BACKGROUND: The recent literature on intrahepatic cholestasis of pregnancy raises questions on the best management of such a disease. Improved evidence might be achieved by meta-analyses. AIM: Providing data for allowing individual patients meta-analyses and aggregate data meta-analyses. METHODS: Data were collected retrospectively at the Fabia Mater Hospital of Rome (Italy), between 2013 and 2018. Several variables were collected and analyzed according to low-level bile acid (less than 40 µmol/L) and high-level bile acid (at least 40 µmol/L). Eighty-three cases of pregnancy cholestasis, diagnosed according to itching symptoms and excluding bile diseases, were collected and analyzed, both descriptively and inferentially. CONCLUSION: The analyzed data do not provide significant evidence supporting the use of ursodeoxycholic acid to prevent composite adverse fetal outcomes but they can be included in further meta-analyses.

Myoma and myomectomy: Poor evidence concern in pregnancy.

AIM: Summarize the results of the many, but often underpowered, studies on pregnancy complicated by myoma or myomectomy. METHODS: Survey of the electronic PubMed database for the last two decades was conducted. We selected reviews, meta-analyses, case series, case reports, clinical studies only with statistical analysis, and guidelines from scientific societies. RESULTS: Delaying childbearing leads to an increased incidence of pregnancy complicated by fibroids or previous myomectomy. Approximately 10-30% of pregnant women with myomas develop complications during gestation, at delivery and in puerperium. Submucosal, retroplacental, large and multiple myomas have a greater risk of complications. Cervical myomas, although rare, need careful management. The location and size of the fibroids should be assessed from the first trimester. Despite the increased risk of cesarean section, fibroids are not a contraindication to labor, unless they obstruct the birth canal or other obstetric conditions coexist. Myomectomy during pregnancy, in selected cases, is feasible and safe. Myomectomy cannot be considered a prophylactic measure prior to conception, but has to be individualized. Uterine rupture after myomectomy generally occurs in the third trimester or during labor and some associated risk factors have been identified. There is no consensus on the optimal interval between myomectomy and conception. CONCLUSIONS: Pregnancy in patients with fibroids or previous myomectomy should be considered as high risk, requiring a maternal-fetal medicine specialist. To date available literature is inconsistent on evidence-based management. Further research is needed for definitive recommendations.

Assessment of HPV-mRNA test to predict recurrent disease in patients previously treated for CIN 2/3.

BACKGROUND: The use of HPV-mRNA test in the follow-up after LEEP is still matter of debate, with regard to its capacity of prediction relapse. OBJECTIVE: The aim of the present study is to evaluate the reliability of HPV-mRNA test to predict the residual and recurrent disease, and its accuracy in the follow-up of patients treated for CIN 2/3. STUDY DESIGN: Multicenter prospective cohort study. Patients who underwent LEEP after a biopsy diagnosing CIN 2/3 were followed at 3, 6, 12, 24 and 36 months. Each check up included cytology, colposcopy, HPV-DNA test (LiPA) and HPV-mRNA test (PreTect HPV Proofer Kit NorChip). Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), of HPV-DNA test and HPV-mRNA test to predict relapse, recurrent and residual disease. Using multiple logistic regression, the statistical significant variables as assessed in univariate analysis were entered and investigated as predictors of relapse disease. RESULTS: The mRNA-test in predicting a residual disease had a sensitivity of 52% and a NPV of 91%, whereas DNA-test had 100% and 100%, respectively. On the contrary in the prediction of recurrent disease mRNA-test had a sensitivity and a NPV of 73.5% and 97%, whereas DNA-test had 44% and 93%. On the multivariate analysis, age, cytology, HPV DNA and mRNA test achieved the role of independent predictors of relapse. CONCLUSION: HPV-mRNA test has a higher sensitivity and a higher NPV in predicting recurrent disease, for this reason it should be used in the follow-up of patients treated with LEEP for CIN 2/3 in order to individualize the timing of check up.

Ovarian stripping versus cystectomy: recurrence of endometriosis and pregnancy rate.

PURPOSE: To compare two different surgical techniques, stripping or cystectomy, in patients treated with the same post-operative medical therapy in terms of recurrence of endometrioma, recurrence of pain and spontaneous pregnancy rate within 2 years from surgery. METHODS: The inclusion criteria of this study were: (1) 25-40 years old; (2) ovarian endometrioma more than 3 cm of diameter detected by transvaginal ultrasonography (3) regular menstrual cycle (4) post-operative treatment with GnRH analogs, (5) tubal patency assessed by laparoscopic chromopertubation (6) normal human semen characteristics. Exclusion criteria were uterine myoma, previous medical treatment for endometriosis, presence of adenomyosis, previous surgery of ovarian endometrioma, multiple cysts, bilateral involvement, co-existence of deep endometriosis. Patients were assigned to two study groups: group A (N = 45) patients undergoing stripping technique and group B (N = 64) patients undergoing cystectomy technique for ovarian endometrioma. RESULTS: In group B the percentage of ultrasonographic recurrence (15.4 %, N = 15) is much lower than in group A (55.6 %, N = 25). (p value 0.001). In group B the percentage of symptomatic recurrence (21.8 %, N = 14) is much lower than in group A (53.3 %, N = 24) (p value 0.001). Spontaneous pregnancy rate in group A patients was of 4.4 % (N = 2) and in group B 22.3 % (N = 21), (p value 0.0072). However, the percentage of specimen with adjacent healthy ovarian tissue was lower in group A (26.6 %) than in group B (50 %) (p value 0.01). CONCLUSIONS: Among the different treatment options for surgical treatment of ovarian endometrioma, in our experience cystectomy appears to be the most appropriate treatment, both in terms of recurrence and pregnancy rate.

Multiple intraepithelial neoplasias of the lower female genital tract: the reliability of HPV mRNA test.

OBJECTIVE: Human papillomavirus (HPV) is the most important pathogenetic factor of intraepithelial neoplasias of the lower genital tract. HPV-DNA and mRNA tests are applied for the management of epithelial dysplasias. The aims of this multicentric retrospective study were to compare the 2 molecular tests before the onset of metachronous intraepithelial lesions and to analyze the different characteristics between synchronous and metachronous lesions and their relationship to the pathologic mechanisms. MATERIALS AND METHODS: The study concerns 55 cases of multiple intraepithelial neoplasias of the lower genital tract. Clinical features of patients with synchronous and metachronous lesions were analyzed. During a 3-year follow-up, HPV-DNA and mRNA tests were performed every 6 months after treatment of the initial lesion. HPV-DNA and mRNA results were analyzed 12 and 6 months before, at time of the onset of the metachronous lesion, and 6 months after its treatment. RESULTS: We observed 31 synchronous lesions and 24 metachronous lesions. Immunodeficiency and multiple genotypes were associated with the synchronous lesions (p = .04 and p = .02, respectively). During the follow-up, positive DNA and mRNA tests increased before the appearance of the metachronous lesion and decreased 6 months after; mRNA test was significantly better than the DNA test 6 months before the appearance of the lesion (p = .04) and at the time of its appearance (p = .02). CONCLUSIONS: Our results support the hypothesis that a positive HPV-mRNA test could be a marker of persistent infection and a risk factor for the onset of metachronous lesions.

Evaluation of serum anti-Mullerian hormone levels to assess the ovarian reserve in women with severe endometriosis.

OBJECTIVE: The aim of this study was to measure anti-Mullerian hormone (AMH) serum levels in women with severe endometriosis, in order to demonstrate the effect of the disease on ovarian reserve. STUDY DESIGN: Prospective case-control study. One hundred and ninety-five patients were enrolled: 130 fertile patients (group A) and 65 patients with stage III and IV endometriosis, diagnosed by laparoscopy and histological examination (group B). AMH serum levels were measured in both groups and were compared using Student's t-test. RESULTS: The two groups were homogenous for main demographic data. Group B had statistically significantly lower mean AMH serum levels (0.97±0.59ng/ml) than group A (1.72±0.63ng/ml) (p=0.001). CONCLUSIONS: This study is a demonstration of the damage of endometriosis on ovarian reserve, leading to a form of incipient ovarian failure, which is considered as an early sign of advanced ovarian depletion in young women. These findings suggest that AMH could be used in the follow-up of patients with endometriosis, in order to assess promptly the decrease of ovarian reserve.

Effect of multivitamins on plasma homocysteine in patients with the 5,10 methylenetetrahydrofolate reductase C677T homozygous state.

The role of hyperhomocysteinemia (HHcy) as a cardiovascular risk factor remains a matter of debate, while it correlates with folates, it demonstrates inverse correlation with plasma homocysteine (Hcy) levels and vitamin B12 levels and reduces plasma Hcy levels following supplementation with multivitamins. The purpose of this study was to demonstrate that administering multivitamins at specific doses for 90 days restores normal plasma Hcy levels in women who are homozygous for the thermolabile variant of 5,10 methylenetetrahydrofolate reductase (MTHFR C677T). We enrolled 106 healthy females aged between 30 and 42 years, who were non-smokers, non-vegetarian, normotensive and who had no history of food abuse in the previous months. Only females were enrolled in order to rule out any bias due to the variation in Hcy plasma concentrations between males and females. Patient blood sampling was performed in order to determine plasma Hcy, serum folic acid and vitamin B12 levels. Furthermore, molecular characterization of the C677T polymorphism present in the MTHFR gene, was also performed. The results of this study demonstrated that supplementation with specific multivitamins restores normal plasma Hcy levels, regardless of the MTHFR genotype. Furthermore, it is unnecessary to adminster high doses of folate to reduce plasma Hcy levels, and administering high doses of folate may cause pro-inflammatory and pro-proliferative effects.

Pain in the upper anterior-lateral part of the thigh in women affected by endometriosis: study of sensitive neuropathy.

OBJECTIVE: To assess whether pain in the anterior-lateral part of the thigh in women affected by endometriosis is due to femoral nerve invasion by endometriotic implants. DESIGN: Case-control study. SETTING: Hospital. PATIENT(S): We enrolled 30 patients with endometriosis and leg pain in the anterior-lateral part of the thigh and 30 healthy women. INTERVENTION(S): Skin biopsy and neurologic examination for detection of neuropathy. MAIN OUTCOME MEASURE(S): Intraepidermal small fiber density reduction and positive neurologic examination agree with sensitive neuropathy. RESULT(S): Biopsy results showed no statistically significant difference between the case group and the control group. At neurologic examination nine patients in the study group (30%) showed positive results, none in the control group showed signs. These nine patients had reduced intraepidermal small fiber density, compared to the lower cutoff values of the control group, suggesting a sensitive neuropathy. CONCLUSION(S): When there is leg pain in women with endometriosis it is important to distinguish neuropathic from referred pain. Skin biopsy and neurologic examination should be introduced in the management of leg pain in endometriosis, due to their low invasiveness to diagnose a sensitive neuropathy. As a result early detection of nerve injury and planning for a prompt specific treatment would be possible.

Obstetric and neonatal outcomes of women with FGM I and II in San Camillo Hospital, Burkina Faso.

PURPOSE: Female genital mutilation (FGM) is still performed in the world. Women who underwent FGM have marked psychological, gynecological and obstetric consequences. This article contributes to the spread of knowledge about obstetric and neonatal outcomes in women with FGM I and II. METHODS: Our observational study compared the obstetric outcomes of 85 women with FGM I and II (case group) and 95 women without it (control group). We evaluated age, need of oxytocin during labor, duration of the expulsion phase, need of episiotomy, weight of the newborn, Apgar score at birth, resuscitation of the newborn, stillbirth. We observed the rate of cesarean sections and their main indications. We compared the rate of cesarean sections among the cases and the controls. RESULTS: Controls were younger than women who underwent FGM. Intravenous oxytocin injection was higher in cases. The expulsion phase was longer in women with FGM than in the controls. FGM is related to a higher risk of episiotomy. Apgar score 9/10 was more frequently assigned to babies from mothers without FGM. There were more resuscitated babies and more stillbirth in the group of cases. Ten percent of all women underwent cesarean section. FGM is related to a higher incidence of cesarean section. CONCLUSION: FGM is associated with a higher risk of gynecological and obstetrical consequences, acting on women's health and also on the economy of resource limited countries. Because of migration, health professionals could interface with women who underwent FGM and have to know their related complications.

Vaginal intraepithelial neoplasia: a therapeutical dilemma.

Vaginal intraepithelial neoplasia (VaIN) represents a rare and asymptomatic pre-neoplastic lesion. Its natural history and potential evolution into invasive cancer are uncertain. VaIN can occur alone or as a synchronous or metachronous lesion with cervical and vulvar HPV-related intra epithelial or invasive neoplasia. Its association with cervical intraepithelial neoplasia is found in 65% of cases, with vulvar intraepithelial neoplasia in 10% of cases, while for others, the association with concomitant cervical or vulvar intraepithelial neoplasias is found in 30-80% of cases. VaIN is often asymptomatic and its diagnosis is suspected in cases of abnormal cytology, followed by colposcopy and colposcopically-guided biopsy of suspicious areas. In the past, high-grade VaIN and multifocal VaIN have been treated by radical surgery, such as total or partial upper vaginectomy associated with hysterectomy and radiotherapy. The need to maintain the integrity of reproductive capacity has determined the transition from radical therapies to conservative ones, according to the different patients' characteristics.

Identification of patients with defects in the globin genes.

INTRODUCTION: hemoglobinopathies constitute a major health problem worldwide. These disorders are characterized by a clinical and hematological phenotypic heterogeneity. The increase of HbA2 is an invaluable hematological marker of the beta-thalassemia heterozygosis and of double heterozygosis for the alleles of delta and alpha globin genes or for the alleles of delta and beta globin genes which can cause the increase of HbA2 up to normal or borderline values. CASE REPORT: we report the case of a 30-year-old woman (first pregnant) who was admitted to our Unit at 12 weeks for a screening for thalassemia. The outcomes of the biochemical and haematological exams (MCV, MCH, HbA2, HbF) highlighted that the patient was a carrier of a beta-thalassemic trait. Molecular analysis of the beta globin genes highlighted a ß(0)39C>T heterozygous mutation. Biochemical and hematological parameters of the husband (MCV, MCH, HbA2, HbF) were normal except for the level of HbA2 (3,6%). The molecular analysis of the beta globin genes highlighted a IVS2 nt844 C>G heterozygous mutation. Furthermore, the heterozygous mutation δ(+)cod.27G>T was detected in his δ globin gene. For this reason, he was diagnosed a δ+ß Thal. CONCLUSIONS: the aim of this paper is to highlight that biochemical diagnosis could not exhaustive and a molecular diagnostic widening is required to detect the genetic deficiency causing the thalassemic trait.

Clinical correlation between premature ovarian failure and a chromosomal anomaly in a 22-year-old Caucasian woman: a case report.

INTRODUCTION: Premature ovarian failure is defined as the cessation of ovarian activity before the age of 40 years. It is biochemically characterized by low levels of gonadal hormones (estrogens and inhibins) and high levels of gonadotropins (luteinizing hormone and follicle-stimulating hormone). CASE PRESENTATION: Our patient, a 22-year-old Caucasian woman under evaluation for infertility, had experienced secondary amenorrhea from the age of 18. No positive family history was noted regarding premature menopause. An examination of our patient's karyotype showed the presence of a reciprocal translocation, apparently balanced, which had the X chromosome long arm (q13) and the 14 chromosome short arm (p12) with consequent karyotype: 46, X, t(X; 14)(q13;p12). CONCLUSIONS: Our study has underlined that karyotyping is one of the fundamental investigations in the evaluation of amenorrhea. It highlighted a genetic etiology, in the form of a chromosomal abnormality, as the causal factor in amenorrhea.