Endometriosis: seeking optimal management in women approaching menopause.

The incidence of endometriosis in middle-aged women is not minimal compared to that in the reproductive age group. The treatment of affected women after childbearing age to the natural transition toward menopause has received considerably poor attention. Disease management is problematic for these women due to increased contraindications regarding hormonal treatment and the possibility for malignant transformation, considering the increased cancer risk in patients with a long-standing history of the disease. This state-of-the-art review aims for the first time to assess the benefits of the available therapies to help guide treatment decisions for the care of endometriosis in women approaching menopause. Progestins are proven effective in reducing pain and should be preferred in these women. According to the international guidelines that lack precise recommendations, hysterectomy with bilateral salpingo-oophorectomy should be the definitive therapy in women who have completed their reproductive arc, if medical therapy has failed. Strict surveillance or surgery with removal of affected gonads should be considered in cases of long-standing or recurrent endometriomas, especially in the presence of modifications of ultrasonographic cyst patterns. Although rare, malignant transformation of various tissues in endometriosis patients has been described, and management is herein discussed.

Genetics of Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome.

Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome, also referred to as Müllerian agenesis, is the second most common cause of primary amenorrhea. It is characterized by congenital absence of the uterus, cervix, and the upper part of the vagina in otherwise phenotypically normal 46,XX females. MRKH syndrome has an incidence of about 1 in 4,500-5,000 newborn females and it is generally divided into two subtypes: MRKH type 1, in which only the upper vagina, cervix and the uterus are affected, and MRKH type 2, which is associated with additional malformations generally affecting the renal and skeletal systems, and also includes MURCS (MÜllerian Renal Cervical Somite) characterized by cervico-thoracic defects. MRKH syndrome is mainly sporadic; however, familial cases have been described indicating that, at least in a subset of patients, MRKH may be an inherited disorder. The syndrome appears to demonstrate an autosomal dominant inheritance pattern, with incomplete penetrance and variable expressivity. The etiology of MRKH syndrome is still largely unknown, probably because of its intrinsic heterogeneity. Several candidate causative genes have been investigated, but to date only WNT4 has been associated with MRKH with hyperandrogenism. This review summarizes and discusses the clinical features and details progress to date in understanding the genetics of MRKH syndrome.

New minimally invasive technique for cystoscopic laser treatment of fetal ureterocele.

Prenatal ultrasound detection of fetal ureterocele with bilateral hydroureteronephrosis, obstruction of the bladder outlet and progressive amniotic fluid reduction have been associated with a significant risk of end-stage chronic renal disease after birth. Fetal cystoscopic laser incision of the ureterocele, using standard 3.5-mm fetoscopic access to the amniotic cavity and the fetal bladder with the aim of relieving the bladder outflow obstruction to preserve renal function, has been reported previously in a case with a favorable outcome. We report on two additional cases of fetal ureterocele treated by cystoscopic laser decompression. In the first case, a standard 3.3-mm uterine entry was used. In the second case, a new approach was adopted using an 'all-seeing needle' 1.6-mm endoscope. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Sphenofrontal distance on three-dimensional ultrasound in euploid and trisomy-21 fetuses at 16-24 weeks' gestation.

OBJECTIVE: To compare the distance between the sphenoid and frontal bones on three-dimensional (3D) ultrasound in euploid and trisomy-21 fetuses at 16-24 weeks' gestation. METHODS: We acquired 3D volumes of the fetal profile from 80 normal and 30 trisomy-21 fetuses at 16-24 weeks' gestation. We used the multiplanar mode to obtain the mid-sagittal plane and measured the sphenofrontal distance as the shortest distance between the most anterior edge of the sphenoid bone and the lowest edge of the frontal bone. RESULTS: In normal fetuses, the sphenofrontal distance increased linearly with gestational age, from 15.1 mm at 16 weeks to 18.2 mm at 24 weeks. In fetuses with trisomy 21, the mean sphenofrontal distance delta value was significantly smaller than in normal cases (-3.447 mm (95% CI, -5.684 to -1.211 mm); P < 0.01). The sphenofrontal distance was below the 5(th) and 1(st) percentiles of the normal range in 29 (96.7%) and 27 (90.0%) trisomy-21 fetuses, respectively. CONCLUSIONS: The sphenofrontal distance is shorter at 16-24 weeks' gestation in fetuses with trisomy 21 than in normal fetuses. A reduction in the growth of the anterior cranial base contributes to the mid-facial hypoplasia observed in fetuses with trisomy 21. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

A randomised controlled trial of intrathecal blockade versus peripheral nerve blockade for day-case knee arthroscopy.

We allocated 100 patients scheduled for day-case knee arthroscopy to unilateral spinal anaesthesia with 40 mg intrathecal hyperbaric prilocaine or to ultrasound-guided femoral-sciatic nerve blockade with 25 ml mepivacaine 2%, 50 participants each. The median (IQR [range]) time to walk was 285 (240-330 [160-515]) min after intrathecal anaesthesia vs 328 (280-362 [150-435]) min after peripheral nerve blockade, p = 0.007. The median (IQR [range]) time to home discharge was 310 (260-350 [160-520]) min after intrathecal anaesthesia vs 335 (290-395 [190-440]) min after peripheral nerve blockade, p = 0.016. There was no difference in time from anaesthetic preparation to readiness for surgery.

Fetal right ventricular contraction and relaxation times at 11-13 weeks' gestation on speckle tracking imaging.

OBJECTIVE: To examine the contraction time and relaxation time of the right ventricle at 11-13 weeks' gestation in trisomy 21 and euploid fetuses by speckle tracking ultrasound imaging. METHODS: Measurement of fetal nuchal translucency (NT) thickness, Doppler assessment for tricuspid regurgitation and reversed A-wave in the ductus venosus (DV) and fetal echocardiography were performed immediately before chorionic villus sampling for fetal karyotyping at 11-13 weeks' gestation. Digital videoclips of the four-chamber view of the fetal heart were recorded and analyzed offline using speckle tracking imaging software. The contraction time, which is the time between the highest and lowest peaks in the right ventricular area, and relaxation time, which is the time between the lowest and the subsequent highest area peak, were measured and expressed as a percentage of the duration of the cardiac cycle. Values in trisomy 21 and euploid fetuses were compared. RESULTS: Mean contraction time and relaxation time in 119 euploid fetuses were 52.1% (95% CI, 51.6-52.8%) and 47.8% (95% CI, 47.2-48.4%), respectively. In 21 trisomy 21 fetuses, mean contraction time was significantly higher (57.0% (95% CI, 55.2-58.9%); P<0.01) and relaxation time lower (42.9% (95% CI, 41.1-44.8%); P<0.01) than in euploid fetuses. Multiple regression analysis showed that significant contributions to contraction time and relaxation time were provided by fetal karyotype, NT and tricuspid regurgitation, but not by reversed A-wave in the DV or the presence of a cardiac defect. CONCLUSION: In first-trimester fetuses with trisomy 21 and in euploid fetuses with increased NT and tricuspid regurgitation there is evidence of increased right ventricular contraction time and shortening of the relaxation time.

Double uterus with obstructed hemivagina and ipsilateral renal agenesis: pelvic anatomic variants in 87 cases.

STUDY QUESTION: What are the anatomic variants (and their frequencies) of double uterus, obstructed hemivagina and ipsilateral renal agenesis? SUMMARY ANSWER: Most cases examined (72.4%) were of the classic anatomic variant of the Herlyn-Werner-Wunderlich syndrome (with didelphys uterus, obstructed hemivagina and ipsilateral renal agenesis) but the 27.6% of cases are of a rare variant of the syndrome (with uterus septum or cervical agenesis), showing relevant clinical and surgical implications. WHAT IS KNOWN ALREADY: The extreme variability of anatomic structures involved in this syndrome (both uterus, cervico-vaginal and renal anomalies) is well known, even if a complete and uniform analysis of all its heterogeneous presentations in a large series is lacking. STUDY DESIGN, SIZE, DURATION: This is a retrospective study with 87 patients referred to our third level referral center between 1981 and 2011. PARTICIPANTS/MATERIALS, SETTING, METHODS: We analyzed the laparoscopic and chart records of 87 women, who referred to our institute with double uterus, unilateral cervico-vaginal obstruction and ipsilateral renal anomalies. MAIN RESULTS: Sixty-three of 87 patients had the more classic variant of didelphys uterus with obstructed hemivagina; 10/87 patients had septate bicollis uterus with obstructed hemivagina; 9/87 patients had bicornuate bicollis uterus with obstructed hemivagina; 4/87 patients had didelphys uterus with unilateral cervical atresia; 1/87 patients had bicornuate uterus with one septate cervix and unilateral obstructed hemivagina. LIMITATIONS: This is a retrospective study with a long enrolling period (30 years). WIDER IMPLICATIONS OF THE FINDINGS: New insights in the anatomic variants of this rare syndrome with their relevant surgical implications.

Surgical versus low-dose progestin treatment for endometriosis-associated severe deep dyspareunia II: effect on sexual functioning, psychological status and health-related quality of life.

STUDY QUESTION: Does surgical and low-dose progestin treatment differentially affect endometriosis-associated severe deep dyspareunia in terms of sexual functioning, psychological status and health-related quality of life? SUMMARY ANSWER: Surgery and progestin treatment achieved essentially similar benefits at 12-month follow-up, but with different temporal trends. WHAT IS ALREADY KNOWN: Conservative surgery and hormonal therapies have been used independently for endometriosis-associated deep dyspareunia with inconsistent results. STUDY DESIGN, SIZE, DURATION: Patient preference, parallel cohort study with 12-month follow-up. The effect of conservative surgery at laparoscopy versus treatment with a low dose of norethisterone acetate per os (2.5 mg/day) in women with persistent/recurrent severe deep dyspareunia after first-line surgery was compared. PARTICIPANTS/MATERIALS AND SETTING, METHODS: A total of 51 patients chose repeat surgery and 103 progestin treatment. Variations in sexual function, psychological well-being and quality of life were measured by means of the Female Sexual Function Index (FSFI), the Hospital Anxiety and Depression Scale (HADS) and the Endometriosis Health Profile-30 (EHP-30). MAIN RESULTS AND THE ROLE OF CHANCE: Four women in the surgery group and 21 women in the progestin group withdrew from the study for various reasons. Total FSFI scores, anxiety and depression scores and EHP-30 scores improved immediately after surgery, but worsened with time, whereas the effect during progestin use increased more gradually, but progressively, without overall significant between-group differences at 12-month follow-up. A tendency was observed towards a slightly better total FSFI score after surgery at the end of the study period. LIMITATIONS, REASONS FOR CAUTION: Treatments were not randomly allocated, and distribution of participants as well as of dropouts between study arms was unbalanced. However, the possibility of choosing the treatment allowed assessment of the maximum potential effect size of the interventions. WIDER IMPLICATIONS OF THE FINDINGS: Both surgery and medical treatment with progestins are valuable options for improving the detrimental impact of endometriosis-associated dyspareunia on sexual functioning and quality of life. Women should be aware of the pros and cons of both options to decide which one best suits their needs. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by a research grant from the University of Milan School of Medicine (PUR number 2009-ATE-0570). None of the authors have a conflict of interest.

Safety of SSRIs during pregnancy: a controlled study.

OBJECTIVE: The objective of our study was to analyze the efficacy and the safety of SSRIs during pregnancy. METHODS: A group of 30 pregnant women affected by Major Depressive Disorder by SCID I interview (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Text Revision criteria) and treated with selective serotonin reuptake inhibitor (SSRI) were included in the study. They were matched to a comparison group of 26 pregnant women. RESULTS: There were no statistically significant differences in any of the pregnancy outcomes of interest between the treated women and comparison group. There was no statistically significant association in newborns of women treated with an SSRI and the control group in the first and fifth minute Apgar score, and no newborns were admitted to neonatal Intensive Care Units. CONCLUSIONS: No definitive association between use of SSRIs during pregnancy and an increased risk of birth defects or other adverse outcomes could be found.

Surgical versus medical treatment for endometriosis-associated severe deep dyspareunia: I. Effect on pain during intercourse and patient satisfaction.

STUDY QUESTION: Does surgical or medical treatment for endometriosis-associated severe deep dyspareunia achieve better results in terms of patients' satisfaction (main study outcome), variation of coital pain and frequency of intercourse? SUMMARY ANSWER: Surgery and progestin therapy were equally effective in the treatment of deep dyspareunia in women with rectovaginal endometriosis, whereas medical therapy performed significantly better than excisional treatment in those without deeply infiltrating lesions. WHAT IS KNOWN AND WHAT THIS PAPER ADDS: Conservative surgery and hormonal therapies have been used independently for endometriosis-associated deep dyspareunia with inconsistent results. This study reports a direct comparison between the two treatment options in women with severe pain during intercourse. DESIGN: Patient preference, parallel cohort study with a 12-month follow-up. The effect of conservative surgery at laparoscopy was compared with treatment with a low-dose of norethisterone acetate per os (2.5 mg/day) in women with persistent/recurrent severe deep dyspareunia after first-line surgery. PARTICIPANTS AND SETTING: A total of 51 patients chose repeat surgery and 103 progestin treatment. Patient satisfaction was graded according to a five-category scale. Variations in pain during intercourse were measured by means of a 100-mm visual analogue scale. MAIN RESULTS AND THE ROLE OF CHANCE: In the surgery group, a marked and rapid short-term dyspareunia score reduction was observed, followed by partial recurrence of pain. The pain relief effect of the progestin was more gradual, but progressive throughout the study period. At a 12-month follow-up, the frequency of intercourse per month (mean ± SD) was 4.6 ± 1.8 in the surgery group and 5.3 ± 1.5 in the norethisterone acetate group (P = 0.02). A total of 22/51 (43%) women were satisfied in the surgery group compared with 61/103 (59%) in the progestin group [adjusted odds ratios (OR), 0.36; 95% confidence interval (CI), 0.16-0.82; P = 0.015]. Corresponding figures in women with and without rectovaginal endometriotic lesions were, respectively, 13/24 (54%) versus 18/35 (51%; adjusted OR, 0.77; 95% CI, 0.22-2.67; P = 0.68), and 9/27 (33%) versus 43/68 (63%; adjusted OR, 0.23; 95% CI, 0.07-0.76, P = 0.02). BIAS, CONFOUNDING, AND OTHER REASONS FOR CAUTION: Treatments were not randomly assigned, and distribution of participants as well as of dropouts between study arms was unbalanced. However, the possibility of choosing the treatment allowed assessment of the maximum potential effect size of the interventions. GENERALIZABILITY TO OTHER POPULATIONS: Caucasian patients able to choose their treatment. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by a research grant from the University of Milan School of Medicine (PUR number 2009-ATE-0570). None of the authors have a conflict of interest.

Pregnancy outcome in women with peritoneal, ovarian and rectovaginal endometriosis: a retrospective cohort study.

We retrospectively assessed pregnancy outcome in 419 women who achieved a first spontaneous singleton pregnancy after surgery for endometriosis. A miscarriage was observed in 87 of 419 women (20.8%) and an ectopic pregnancy in eight (1.9%). Among the remaining 324 women, 14 (4.3%) experienced gestational hypertension/pre-eclampsia, 38 (11.7%) had a preterm delivery, five (1.5%) had placental abruption and 12 (3.7%) had placenta praevia. The incidence of placenta praevia was 7.6% in 150 women with rectovaginal lesions, 2.1% in 69 with ovarian endometriomas plus peritoneal implants, and 2.4% in 100 women with peritoneal implants only, whereas no case was observed in 100 women with ovarian endometriomas only.

Conservative treatment of Herlyn-Werner-Wunderlich syndrome: Analysis and long-term follow-up of 51 cases.

OBJECTIVE: The purpose of this study is to analyze the precise anatomical characteristics of a large group of patients with Herlyn-Werner-Wunderlich syndrome together with the long-term follow-up and the reproductive performance. STUDY DESIGN: Retrospective analysis of prospectively collected data. In two tertiary medical centers, from 2008 to 2021, 51 patients with HWWS underwent surgery via the same technique. Presenting symptoms, preoperative investigations, operative management, and long-term follow-up with obstetric outcome were assessed. RESULTS: The surgical procedure was successful in all cases with no major complications recorded. Postoperative course was uneventful. The median follow-up was 6,5 years, with a range from 6 months to 13 years. After surgery, among 14 patients who sought pregnancies, 12 (85,71%) were successful. Of these 11 patients had a total of 22 pregnancies, resulting in spontaneous miscarriage in 27% (6/22), premature birth (<37 weeks) in 36% (8/22) and full-term birth in 36% (8/22). Overall the pregnancies demonstrated had a good course. CONCLUSIONS: Early diagnosis is essential in establishing prompt and correct surgical treatment.

[Congenital heart disease: contraception and management of pregnancy]. / Cardiopatie congenite: contraccezione e management della gravidanza.

The number of women with congenital heart disease reaching childbearing age is constantly increasing due to the advances achieved in cardiac surgery during the past decades. The significant physiological haemodynamic changes and adaptations of the cardiovascular system associated with pregnancy, birth and puerperium increases the cardiovascular risk to pregnant women with congenital heart disease. It is therefore necessary not only the awareness of these haemodynamic changes and risks, but also a multidisciplinary approach that involves preconception counseling, choosing the best contraceptive method, close surveillance during pregnancy, delivery and puerperium. The purpose of this article is to review the major risks associated with pregnancy in women with CHD and to provide an indication on the best contraceptive method and cares during pregnancy in these patients.

'Blood On The Tracks' from corpora lutea to endometriomas.

OBJECTIVE: To detect a direct transition from a haemorrhagic corpus luteum to an endometriotic cyst by serial transvaginal ultrasonographic scans. DESIGN: Prospective observational study. SETTING: An academic tertiary care and referral centre for women with endometriosis. POPULATION: One hundred and nine women younger than 40 years, with regular menstrual cycles, undergoing first-line surgery for endometriomas, and not wanting postoperative oral contraception. METHODS: Three-monthly transvaginal ultrasonography during the luteal phase for 2 years after surgery. MAIN OUTCOME MEASURE: Sonographic identification of progression from a haemorrhagic corpus luteum to a recurrent endometriotic cyst. RESULTS: A haemorrhagic corpus luteum was identified in 13 women. Serial ultrasonographic scans demonstrated transition to an endometriotic cyst in 11 (85%) instances and resorption in two. A unilateral endometriotic cyst without previous detection of a cystic corpus luteum was observed in 14 women. CONCLUSIONS: Bleeding from a corpus luteum appears to be a critical event in the development of endometriomas.

A possible mechanism for non-replication of allelic association between a single nucleotide polymorphism of the human beta T-cell receptor and autoimmune diseases.

Gene polymorphisms, in particular single nucleotide polymorphisms (SNPs), have been associated to multifactorial diseases such as cancer, inflammation and autoimmunity. Indeed for some autoimmune diseases, it has been possible to identify critical residues that play a major role in susceptibility to diseases. The association of a common T/C polymorphism in the promoter region of the beta 2 constant chain of the T-cell receptor with autoimmune diseases, such as insulin-dependent diabetes, autoimmune hepatitis, IgA nephropathy, membranous nephropathy, Graves' disease and Hashimoto's thyroiditis, was described in the 1990 s. These reports have not been confirmed in the last few years. We also failed in a previous study to detect any difference between 70 normal subjects and 70 patients with primary biliary cirrhosis; however, we found a difference in allelic frequency between males and females. This finding led us to make an allele frequency study of this single nucleotide polymorphism between sexes in a new series of patients. We studied 165 subjects, 80 males and 85 females, and we found a significant difference between sexes especially for the CC homozygous genotype: 34% of females vs. 14% of males (P = 0.008). If the higher frequency of CC homozygous genotype (that is associated with an increased risk of autoimmune diseases) in females would be confirmed in normal population, this could be an explanation of the controversial results obtained by association studies made between this SNP and autoimmune diseases.

Different allelic distribution of a single SNP between sexes in humans.

We searched for a difference in allele distribution between males and females of a single nucleotide polymorphism located in the human beta T-cell receptor, in 500 subjects (200 males and 300 females). Genotype analysis gave the following results: among the males, 114 (57%) were heterozygous for the T/C polymorphism, 52 (26%) were homozygous (T/T), and 34 (17%) were homozygous (C/C). Among the females, 142 (47.3%) were heterozygous, 73 (24.3%) were homozygous (T/T), and 85 (28.3%) were homozygous (C/C). The allele frequency was significantly different between sexes (chi2 = 8.799, P = 0.012).

The laparoscopic Vecchietti technique for vaginal agenesis.

OBJECTIVE: To evaluate surgical, long-term anatomic and functional results of the laparoscopic Vecchietti procedure to treat women with vaginal agenesis. METHODS: Retrospective analysis of 86 women treated at the Department of Gynecology and Obstetrics at the University of Verona, Italy. Data were analyzed based on surgical results and postoperative sexual satisfaction. Depth and diameter of the neo-vagina was determined. The characteristics of the neo-vaginal mucosa were investigated by vaginoscopy. Patients reported frequency, satisfaction, and any difficulties found at intercourse. RESULTS: Functional success was obtained in 98.1% and anatomic success in 100%. In all patients, at 1 year, the mucosa was pink, trophic, and moist. Two fingers were introduced easily into the neo-vagina in all cases. All patients, which decided to have sexual intercourse, defined these as satisfying within 6 months. CONCLUSIONS: Laparoscopic procedure used in this study is simple, safe, and effective. Anatomical and functional results obtained suggest this laparoscopic procedure as the treatment of choice for this syndrome.

Heat Transfer Capability of (Ethylene Glycol + Water)-Based Nanofluids Containing Graphene Nanoplatelets: Design and Thermophysical Profile.

This research aims at studying the stability and thermophysical properties of nanofluids designed as dispersions of sulfonic acid-functionalized graphene nanoplatelets in an (ethylene glycol + water) mixture at (10:90)% mass ratio. Nanofluid preparation conditions were defined through a stability analysis based on zeta potential and dynamic light scattering (DLS) measurements. Thermal conductivity, dynamic viscosity, and density were experimentally measured in the temperature range from 283.15 to 343.15 K and nanoparticle mass concentrations of up to 0.50% by using a transient plate source, a rotational rheometer, and a vibrating-tube technique, respectively. Thermal conductivity enhancements reach up to 5% without a clear effect of temperature while rheological tests evidence a Newtonian behavior of the studied nanofluids. Different equations such as the Nan, Vogel-Fulcher-Tamman (VFT), or Maron-Pierce (MP) models were utilized to describe the temperature or nanoparticle concentration dependences of thermal conductivity and viscosity. Finally, different figures of merit based on the experimental values of thermophysical properties were also used to compare the heat transfer capability and pumping power between nanofluids and base fluid.