An unusual familial Xp22.12 microduplication including EIF1AX: A novel candidate dosage-sensitive gene for premature ovarian insufficiency.

We report on the results of array-CGH and Whole exome sequencing (WES) studies carried out in a Tunisian family with 46,XX premature ovarian insufficiency (POI). This study has led to the identification of a familial Xp22.12 tandem duplication with a size of 559.4 kb, encompassing only three OMIM genes (RPS6KA3, SH3KBP1and EIF1AX), and a new heterozygous variant in SPIDR gene: NM_001080394.3:c.1845_1853delTATAATTGA (p.Ile616_Asp618del) segregating with POI. Increased mRNA expression levels were detected for SH3KBP1 and EIF1AX, while a normal transcript level for RPS6KA3 was detected in the three affected family members, explaining the absence of intellectual disability (ID). To the best of our knowledge, this is the first duplication involving the Xp22.12 region, reported in a family without ID, but rather with secondary amenorrhea (SA) and female infertility. As EIF1AX is a regulatory gene escaping X-inactivation, which has an extreme dosage sensitivity and highly expressed in the ovary, we suggest that this gene might be a candidate gene for ovarian function. Homozygous nonsense pathogenic variants of SPIDR gene have been reported in familial cases in POI. It has been suggested that chromosomal instability associated with SPIDR molecular defects supports the role of SPIDR protein in double-stranded DNA damage repair in vivo in humans and its causal role in POI. In this family, the variant (p.Ile616_Asp618del), present in a heterozygous state, is located in the domain that interacts with BLM and might disrupt the BLM binding ability of SPIDR protein. These findings strengthen the hypothesis that the additional effect of this variant could lead to POI in this family. Although the work represents the first evidence that EIF1AX duplication might be responsible for POI through its over-expression, further functional studies are needed to clarify and prove EIF1AX involvement in POI phenotype.

Hyperreactio luteinalis incidentally found in the second trimester of pregnancy with normal hCG levels: a case report.

Hyperreactio luteinalis (HL) is a rare entity in which both ovaries are multicystic and enlarged under the action of human chorionic gonadotropin (hCG), mostly seen in the third trimester of pregnancy. This benign condition is usually asymptomatic and doesn't need any specific treatment, as the ovaries spontaneously reduce in size after birth. This is a case report of a 33-year-old woman diagnosed with hyperreactio luteinalis during the second trimester of her induced pregnancy. An ultrasound scan at 22 weeks of gestation revealed bilateral multicystic enlarged ovaries along with multiple fetal malformations and hydropsfetalis. Usually, HL is most commonly seen in situations in which there are high levels of hCG, but our patient had normal levels of hCG during all her pregnancy, which makes our case even rarer. In conclusion, the most important challenge when faced with HL is to differentiate between it and other differential diagnosis especially malignant tumors, because unlike them, this benign condition doesn't need surgical treatment.

Perineal endometriosis: a rare case of a unique sizeable nodule.

Endometriosis is the presence of endometrial tissue in abnormal locations outside the uterine cavity. These locations are usually the ovaries, the peritoneum, and the uterine ligaments. Less frequently, the endometrial tissue can affect the perineum especially after surgical procedures or obstetric lesions. In this case report, we describe the case of a patient suffering from pain and swelling, with a sizeable nodule in an old episiotomy scar. Clinical examination, ultrasonography (USG) and magnetic resonance imaging (MRI) helped evoke the diagnosis of perineal endometriosis, and there were no signs of other endometriosis locations. Hormonal treatment was provided at first, but there was no clinical improvement after three months, so the treatment had to be surgical. Histopathological examination of the endometriotic mass confirmed the diagnosis. There were no immediate postoperative complications, and no clinical symptoms or recurrence signs six months and one year after.

Reversible Wernicke encephalopathy caused by hyperemesis gravidarum in the second trimester of pregnancy: a case report.

Wernicke encephalopathy is a potentially life-threatening neurologic syndrome caused by acute thiamine (vitamin B1) deficiency. It is usually associated with excessive alcohol consumption. Less frequently, this syndrome can be caused by persistent vomiting. This is a case report of a 33-year-old woman diagnosed with Wernicke encephalopathy (WE) during the second trimester of pregnancy. The presence of neurological and ophthalmological symptoms in the context of hyperemesis gravidarum led us to evoke the diagnosis of WE, and it was confirmed when specific lesions were found in the brain magnetic resonance imaging (MRI). Luckily for our patient, WE was diagnosed promptly and the signs were reversible after thiamine supplementation. In conclusion, any first line care taker or midwife must know the symptoms of Wernicke encephalopathy because prompt diagnosis and treatment can lead to recovery.

Routine assessment of occupational exposure and its relation to semen quality in infertile men: a cross-sectional study.

BACKGROUND/AIM: Concerns about the detrimental effects of occupational and environmental exposure on male reproductive function have been raised by reports of declining sperm quality over the last decades. The aim of this study was to investigate the association between altered semen parameters and exposure to occupational risk factors as assessed by questionnaire. MATERIALS AND METHODS: We conducted a cross-sectional questionnaire-based study among a population of 2122 men who underwent andrological investigation for couple infertility. All participants were interviewed and their semen samples were analyzed. Information about medical history and occupational exposure was used to classify participants into exposed and unexposed groups. RESULTS: Exposure to pesticides was associated with a significantly higher risk of asthenozoospermia (adjusted odds ratio [OR] = 1.6; 95% CI, 1.0-2.4) and necrozoospermia (OR = 2.6; 95% CI, 1.4-4.7). Exposure to cement was found to be correlated with a higher risk of oligozoospermia (OR = 1.1; 95% CI, 0.9-1.4). There was no association between semen impairment and exposure to solvents, excess heat, or mechanical vibrations. CONCLUSION: We found an association between self-reported occupational exposure and altered semen parameters. These results support the usefulness of questionnaires for routine assessment and management of occupational exposures in infertile men.

Vulvar cancer in Tunisia: Epidemiological and clinicopathological features multicentric study.

OBJECTIVE: To describe for the first time the epidemiologic and clinico-pathologic characteristics of vulvar cancer in Tunisia. DESIGN: Two parts are distinguished in this study: Part1: Multicentric retrospective study about the characteristics of all cancer cases diagnosed during a 17-years period (January 1998-December 2014) in three departments of Gynecology and Obstetrics: one in south Tunisia and two in the capital. Part 2: To determine the Incidence trend of invasive vulvar cancer in North Tunisia 1994-2009, on the basis of North Cancer Registry of Tunisia. RESULTS: A total of 76 cases of vulvar cancer were recorded. The median age at diagnosis was 65.4years and 86.9% of patients were more than 55years old. The symptomatology was dominated by vulvar pruritus in 48.7%. The average size of the tumor was 3.96cm. Stage III was the most frequent (53.7%) followed by stage II (28.3%). Only 10.4% of tumors were at stage I. The most common histologic type of vulvar malignancy was squamous cell carcinoma (SCC) (94.7%). Standardized incidence varied from 1.2/100 000 (1994) to 0.5/100 000 (2009). There was significant decrease of Standardized incidence (APC of -8.8% per year, 95% CI: -5.5%, -9.0%-p<0.001). CONCLUSION: Vulvar cancer in Tunisia is a rare disease, occurs mostly in elderly women, and is diagnosed at advanced stages. Our findings emphasize that a greater effort should be made to facilitate early diagnosis, as treatment in earlier stages is less extensive and potentially curative.

The prognostic significance of pathological features in Her-2 overexpressing breast carcinomas: A single institution experience in southern Tunisia.

BACKGROUND: Breast cancer is the most frequent malignant neoplasm affecting Tunisian women. It represents 25 to 35% of all female cancers. There is no published study about the features of Her-2 overexpressing breast carcinomas in North African women. OBJECTIVE: The aim of this study is to assess the prognostic significance of pathological features in a cohort of a Her-2 overexpressing breast carcinoma originating from the region of south Tunisia. METHODS: This study investigated a series of 100 patients followed from January 2006 to December 2011 for a Her-2 positive invasive breast carcinoma. Pathological features included in this study were: histological type, histological grade, tumor size, vascular invasion, perineural invasion, mitotic index, lymph nodes stage, positive lymph node capsular effraction, inflammatory infiltrates, nipple involvement and hormone receptors status. RESULTS: Multivariate analysis showed that pT stage, pN stage, capsular effraction, vascular invasion, perineural invasion and Nipple involvement were independent prognostic factors for overall survival and disease free survival in patients free from distant metastasis at diagnosis. For patients with synchronous metastasis, there is no independent pathologic prognostic factor for survival. CONCLUSIONS: Our study demonstrates that pathological features are important prognostic factors for non metastatic Her-2 overexpressing breast carcinomas. This supports the idea that HER2-positive disease is a heterogeneous entity. We believe that these findings reinforce the need to identify molecular predictors of benefit and resistance to anti-Her-2 based therapies.

Assessment of chromatin maturity in human spermatozoa: useful aniline blue assay for routine diagnosis of male infertility.

During spermatogenesis, sperm chromatin undergoes structural changes and results in a high condensation. This nuclear compaction would be useful as a predictor of sperm fertilization capacity and pregnancy outcome. We purpose to evaluate firstly the relationship among chromatin maturity assessed by aniline blue staining (AB) and the semen parameters in infertile men. Secondly, we analyzed whether the sperm gradient density centrifugation is effective to select mature spermatozoa. Fifty-one ejaculates were investigated by semen analysis and stained for chromatin condensation with AB to distinguish between unstained mature sperm and stained immature sperm. AB was applied also on 12 ejaculates which proceeded by density gradient centrifugation to compare the rates of immature sperm before and after selection. Neat semen were divided into two groups: G1 (n = 31): immature sperm <20% and G2 (n = 20): immature sperm ≥20%. No significant differences were detected in sperm concentration, motility, and normal morphology between G1 and G2. However, the rates of some morphology abnormalities were higher in G2: head abnormalities (P = 0.01) and microcephalic sperm (P = 0.02). We founded significant correlation between sperm immaturity and acrosome abnormalities (r = 0.292; P = 0.03). Sperm selection has significantly reduced the rates of immature sperm. A better understanding of chromatin structure and its impact on the sperm potential is needed to explore male infertility.

[Prospective study of the relationship between heart rate fetal anomalies, pH umbilical cord at birth and Apgar]. / Etude prospective de la relation entre anomalie du rythme cardiaque fœtale, pH ombilical et Apgar à la naissance

BACKGROUND: The search for an acute fetal distress during labor remains one of the objectives of obstetrical surveillance. AIM: To find a relationship between different aspects of fetal heart rate (FHR) occurring during labor, Apgar score at first minute and the pH blood at birth. METHODS: A prospective study which involved 170 single-fetal pregnancies to term. RESULTS: In our population, by comparing the APGAR score in the first minute and umbilical pH, it was found that only 25.7% of newborns with Apgar at 1st minute less than 7 had an umbilical arterial pH <7.15. Thus in our study, the Apgar score did not predict umbilical acidosis and the difference was significant (p = 0.02). In the same population, by comparing the analysis of FCR and umbilical PH, we found that fetal bradycardia was associated with pH umbilical lowest with an average of 7008 and the difference was significant (p = 0.008). Other types of ERCF were also significantly associated with neonatal acidosis. CONCLUSION: Recording fetal heart rate is a limited review to assess the exact condition of the fetus. It has a good negative predictive value but there is little specific consideration. Combination with other techniques to better assess the fetal state.

Gonadal dysgenesis and the Mayer-Rokitansky-Kuster-Hauser Syndrome in a girl with a 46, XX karyotype: A case report and review of literature.

Mayer-Rokitansky-Kuster-Hauser (MRKH) is a characteristic syndrome in which the Mullerian structures are absent or rudimentary. It is also associated with anomalies of the genitourinary and skeletal systems. Its association with gonadal dysgenesis is extremely rare and appears to be fortuitous, independent of chromosomal anomalies. We report such a case in a 21-year-old girl who presented primary amenorrhea and impuberism. The endocrine study revealed hypergonadotrophic hypogonadism. The karyotype was normal, 46, XX. No chromosome Y was detected at the fluorescence in situ hybridization (FISH) analysis. Internal genitalia could not be identified on the pelvic ultrasound and pelvic magnetic resonance imaging. Laparoscopy disclosed concomitant ovarian dysgenesis and MRKH syndrome. There were no other associated malformations. Hormonal substitution therapy with oral conjugated estrogens was begun. The patient has been under regular follow-up for the last two years and is doing well.

Antenatal macrosomia prediction using sonographic fetal abdominal circumference in South Tunisia.

INTRODUCTION: Identifying newborns who weight 4000 g or more is important because birth of macrosomic fetuses is associated with adverse peripartum outcomes. Ultrasound is widely used for this purpose Our objective was to evaluate the diagnostic value of sonographic measurement of fetal abdominal circumference (AC) over 350 mm for the prediction of fetal macrosomia and shoulder dystocia, to specify factors that could generate errors in its measure. METHODS: A retrospective clinical trial was conducted at the Department of Obstetrics and Gynecology, Hédi Chaker Hospital, Sfax, Tunisia. The study consisted of comparing two groups of singleton newborns: the first group (n=465) includes macrosomic babies and the second group (n=465) includes the non macrosomic ones. All women underwent sonographic measurements of the fetal abdominal circumference (AC) within 72 hours before delivery. The AC values were correlated to actual fetal birth weight. The cut-off value of AC for predicting of fetal macrosomia was analyzed. RESULTS: A cut-off value of abdominal circumference ≥ 350 mm, in predicting of fetal macrosomia., had a sensitivity, specificity, accuracy, positive predictive value, and negative predictive value: 78.7%, 76.8%, 77%, 92.6%, and 49.2%, respectively. In macrosomic group obesity was significantly more frequent when AC ≥ 350 mm. CONCLUSION: The fetal AC measurement was useful in predicting of fetal macrosomia. An AC measurement AC ≥ 350 mm could help to suspect shoulder dystocia.

[Endometrial thickness in in vitro fertilization. A study of 414 cases]. / Influence de l'épaisseur de l'endomètre sur l'implantation embryonnaire en fécondation in vitro. À propos de 414 cas.

BACKGROUND: Study of endometrial thickness is central to the monitoring of ovulation in in vitro fecondation (IVF). Actually, failures of in vitro fecundation are mainly due to implantation failure of embryo. AIMS: • To assess whether the endometrial thickness the day of the induction of ovulation influences or not the result of the IVF attempt. • To determine the endometrial thickness for which the chances of pregnancy are the highest. • To determine if there is any effect of the stimulation protocol or the gonadotrophin on the endometrial thickness. METHODS: A retrospective study at the Reproductive Medicine-Unit of Farhat Hached teaching hospital, Sousse-Tunisia, concerning all the cases of IVF conducted the year 2008. RESULTS: A total of 414 cycles of IVF were studied. The rate of pregnancies in our series was 23%. There was not statistically significant relation-ship between the women's-age and the endometrial thickness; nor between the rate of the ?stradiol before the IVF trial and the endometrial thickness. The endometrial thickness after ovarian stimulation was significantly linked to the rate of FSH before the IVF attempt (P=0.01). The total rate of pregnancies was significantly linked to the endometrial thickness before the ovulation induction (P=0.02). The best rate of pregnancy was reached with an endometrial thickness>2 mm (43%) and the chances of success in that case were roughly 3 times higher than if the endometrial thickness was ≤12 mm. With ICSI (277 cases), there was a statistically significant relation-ship between endometrial thickness and the pregnancy-rate (P=0.009). There was a statistically significant relation-ship between the endometrial thickness and the stimulation protocol used (P<0.001) and no statistically significant relation-ship between endometrial thickness and the gonadotrophin used for ovarian stimulation (hMG or recombinant FSH). CONCLUSION: There is a statistically significant relation-ship between the endometrial thickness and the success rate of ICSI attempt. A thickness higher than 12 mm seems to improve IVF results.

[Exploration of post-menopausal uterine bleeding. Hysteroscopy-histology correlation in 94 cases]. / Exploration des métrorragies postménopausiques par hystéroscopie : à propos de 94 cas.

INTRODUCTION: Post-menopausal uterine bleeding is the reason for nearly 70% of gynaecological consultations. Because the cause may be a malignant disease, a thorough work-up is necessary to attempt to identify an organic cause. PATIENTS AND METHODS: This retrospective study examined 94 cases of post-menopausal bleeding in which both a hysteroscopic and a histological examination were performed in the gynaecology and obstetrics department of the Hedi Chaker University of Sfax from 1 January 2004 to 28 February 2005. We examined correlations between the hysteroscopy and histology findings as well as the causes determined. RESULTS: By hysteroscopy, we observed atrophic uterine linings in 53 patients (56%), endometrial polyps in 43 patients (45%), endometrial hyperplasia in 23 patients (24%) and myomas in 24 patients (25.5%). This examination suggested malignancy in 12 patients, among 6 of whom endometrial cancer was confirmed histologically. The sensitivity and specificity of hysteroscopy were relatively poor for the diagnosis of endometrial atrophy (about 48.7% and 68.5%), acceptable for endometrial polyps (75% and 86.6%), endometrial hyperplasia (64.7% and 85.5%), and endometrial cancer (60% and 92.7%). CONCLUSION: Hysteroscopy is the most reliable technique for exploration, offering a direct view of the uterine cavity and allowing direct biopsy. Its sensitivity varies according to the indication and diagnosis and is sometimes very good. However, histology remains the reference examination for diagnosis of the cause of post-menopausal uterine bleeding.

[Management of postpartum vaginal haematomas by embolisation: two cases]. / L'embolisation radiologique dans le traitement du thrombus vaginal (à propos de deux observations).

Postpartum vaginal haematomas are a rare complication of delivery. The incidence of large haematomas is estimated at 1/4000 deliveries, and this complication can be life-threatening. We report two such cases. The diagnosis is suggested by shooting perineal pain with urinary tenesmus and vulvovaginal swelling or an unexplained haemorrhagic syndrome in the postpartum period. Rapid management is essential. Embolisation by interventional radiology is preferred to surgery. In the first case, arterial embolisation was performed after bilateral ligation of the hypogastric arteries failed. Arterial embolisation was the first-line treatment for the second patient. It was successful for both women.

Postpartum ovarian vein thrombophlebitis: Report of a case and review of the literature.

CONTEXT: Postpartum ovarian vein thrombophlebitis is an uncommon life-threatening situation. It should be systematically evoked in case of persistent fever during the postpartum. Diagnosis is often not immediately apparent clinically and there are many that mimic this condition. CASE REPORT: A 26-year-old female presented with fever and acute right loin pain during four days after delivery. Right ovarian venous thrombosis was demonstrated on sonography and confirmed with computed tomography. The patient was given antibiotics and anticoagulation therapy with good response. CONCLUSION: Search for postpartum ovarian vein thrombophlebitis should be undertaken in patients with persistent fever. Treatment is more often medical.